class1	haemophilus influenzae meningitis with prolonged hospital course  a retrospective evaluation of haemophilus influenzae type b meningitis observed over a 2 year period documented 86 cases  eight of these patients demonstrated an unusual clinical course characterized by persistent fever  duration  greater than 10 days   cerebrospinal fluid pleocytosis  profound meningeal enhancement on computed tomography  significant morbidity  and a prolonged hospital course  the mean age of these 8 patients was 6 months  in contrast to a mean age of 14 months for the entire group  two patients had clinical evidence of relapse  four of the 8 patients tested for latex particle agglutination in the cerebrospinal fluid remained positive after 10 days  all patients received antimicrobial therapy until they were afebrile for a minimum of 5 days  subsequent neurologic examination revealed a persistent seizure disorder in 5 patients  62 5    moderate to profound hearing loss in 2  25    mild ataxia in 1  12 5    and developmental delay with hydrocephalus which required shunting in 1  12 5    one patient had no sequelae  
class1	mucosal intussusception to avoid ascending cholangitis  many methods have been devised to prevent ascending cholangitis following kasai s hepatic portoenterostomy for biliary atresia  to investigate the effectiveness of mucosal intussusception in preventing ascending cholangitis  20 mongrel dogs were randomized to undergo roux en y cholecystjejunostomy and common bile duct ligation with or without mucosal intussusception  aeromonas hydrophila was instilled into the gastrointestinal tract  bacterial cultures were grown from samples taken from the gallbladders and lower jejunum  and blood chemistry and barium studies were performed  the barium studies showed satisfactory lack of reflux in all ten dogs with mucosal intussusception  only two of them had positive cultures for aeromonas from the gallbladder 3 days after bacterial instillation into the jejunum  all ten dogs in the control group had positive cultures for aeromonas from the gallbladder  our results showed that the mucosal intussusception group had a significantly lower rate of recovery of organisms from the gallbladder compared with the control group when the organisms were instilled into distal intestine  p less than 0 05   the method is worthy of clinical trial as a means of preventing or treating ascending cholangitis  
class1	gastrointestinal function and structure in hiv positive patients  we examined 19 patients  17 men  with human immunodeficiency virus  hiv  infection and gastrointestinal symptoms to determine whether those symptoms were due to either a gastrointestinal tract infection or a defect in mucosal absorption because of an enteropathy  the erythrocyte folate and serum vitamin b12 levels were within normal limits in all of the patients  the serum ferritin level was elevated in 12  the xylose absorption test results were abnormal in 8 of the 13 patients able to complete the study  none of the duodenal aspirates yielded a pathogen  light microscopy revealed nonspecific lymphocytic inflammation without infection in the stomach  in seven patients   the esophagus  in five   the duodenum  in two  and the rectum  in two   however  biopsy specimens were positive for candida albicans in the esophagus  four patients   cytomegalovirus in the esophagus  one  and the rectum  two   helicobacter pylori in the antrum  two   treponema infection in the rectum  two  and mycobacterium avium intracellulare in the small intestine  one   only three patients had a normal series of biopsy specimens  all of the patients had similar ultrastructural changes at the epithelial stromal junction of the antral glands and in the intestinal crypts  we conclude that abnormal biochemical and endoscopic findings are common in hiv positive patients with gastrointestinal symptoms  defects in carbohydrate absorption and ultrastructural changes may be responsible for some aspects of hiv enteropathy  
class1	epidemiology in bone and joint infection  the studies of community acquired infection indicate the importance of the environment in which the host pathogen interaction takes place  whereas the high incidence rates at the extremes of life are compatible with a hypothesis of diminished immune competence  the varying rates of acute osteomyelitis during growth  and its predominantly metaphyseal site  suggest that further studies of the molecular biology of this rather specific infection would be revealing  molecular biology has a role  too  in improving understanding of the epidemiology of resistance and pathogenicity in hospital acquired infections  although antibiotic prescription and other medical practices influence the environment profoundly  we should remember that we may be experiencing long term trends beyond our present understanding  as more and more reconstructive bone and joint surgery is carried out  careful observational epidemiology remains a vital tool  
class1	the diabetic foot  soft tissue and bone infection  diabetic patients  as a consequence of various neurologic  vascular  and metabolic perturbations  are at high risk for developing infections of the soft tissue and bones of the feet  the microbial etiology of soft tissue in infections is best determined by cultures of a tissue curetting or aspiration  rather than a swab  aerobic gram positive cocci are the major pathogens in diabetic foot infections  these may be the sole isolate s  in acute uncomplicated infections  but they are usually accompanied by aerobic gram negative bacilli or anaerobes in chronic or previously treated infections  carefully selected patients with mild infections can be treated as outpatients with oral antibiotics  but others require hospitalization and broad spectrum parenteral antibiotics  bone infections are frequently diagnosed on the basis of roentgenographs and nuclear medicine scans  but these methods are often inaccurate  and bone cultures should be obtained whenever possible  
class1	infection in total joint replacement  although a small number of infections in total joint replacements are blood borne from distant sources  most infections appear to have been derived at operation  strenuous attempts to reduce this risk by cleaning the air in the wound environment  coupled with prophylactic antibiotics  have reduced infection rates by an order of magnitude in a decade  during that time the potential for exchange arthroplasty in established infection has been shown  and the results are encouraging  rigorous infection control is the key to containing this difficult and expensive problem  
class1	analysis of the immune response to lipopolysaccharide  existence of an interspecies cross reactive idiotype associated with anti lipid a antibodies  lps is the major surface glycolipid on gram negative bacteria  in this work  we have idiotypically characterized the antibody response against lps in different species  to do this  we have produced mab against lps  binding of many of these antibodies to lps could be inhibited by lps and lipid a  indicating that the monoclonals are specific for lipid a  the toxic moiety of the lps molecule  one anti lipid a antibody  ic9  proved protective against gram negative bacteremia and endotoxic shock in murine protection models  we generated anti idiotypic antibodies against ic9  the binding of several of these anti id to ic9 was specifically inhibited by lipid a  we used these anti id to characterize the anti lps response  and the results revealed that the ic9 id is conserved in different species  the importance of an interspecies cross reactive id in the response to endotoxin and its relevance in vaccine development for septic shock are discussed  
class1	organ hypertrophy and responses of colon microbial populations of growing swine to high dietary protein  thirty two castrated male crossbred growing pigs  average initial wt 26 9 kg  were used to determine the effect of a high level of dietary protein  37   compared with a normal level of protein  15   on enterobacteria and campylobacter sp  inhabitation in the large intestine and on visceral organ hypertrophy and the interrelationships between these two factors  pigs were kept in pairs  eight pens of two pigs diet  and fed their respective diets and libitum  eight pigs  two pens of two pigs fed each diet  were killed at wk 4  8  12 and 16 without fasting  fecal samples were obtained every 2 wk from animals scheduled for necropsy at 16 wk  and colon contents were obtained from all pigs at necropsy  samples were enumerated individually for enterobacteria and campylobacter sp  weights of heart  lungs  liver  kidneys  perirenal fat and empty stomach  small intestine and large intestine were recorded at necropsy  stomach  cecum and proximal colon were sectioned for histopathologic examination  daily body weight gain was depressed by high dietary protein  but liver and kidneys were heavier in the high protein group than in controls at each time interval  mild lymphoid hyperplasia of peyer s patches in the small intestine in some pigs in both groups was indicative of antigenic stimulation but not of pathologic significance  there was no effect of diet on counts of enterobacteria or campylobacter sp  in feces or colon contents during the 16 wk experiment  we conclude that the hypertrophic response of the tissues of growing pigs to high dietary protein is not the result of the presence of campylobacter sp  or enterobacteria in the colon contents  
class1	normalization of plasma arginine vasopressin concentrations when children with meningitis are given maintenance plus replacement fluid therapy we hypothesized that plasma arginine vasopressin  avp  concentrations in children with meningitis are appropriate for the children s degree of hypovolemia  even though the concentrations were higher than expected for the serum osmolality  a randomized study was conducted to compare the effect on plasma avp concentrations of giving maintenance fluid requirements plus replacement of any deficit versus restricting fluids to two thirds of maintenance requirements for 24 hours  plasma avp concentrations and serum osmolality were measured before fluid therapy was begun and again after 24 hours  nineteen children  2 months to 17 years of age  were studied  13 had bacterial meningitis  12 with haemophilus influenzae type b   ten children  seven with bacterial meningitis  received a mean of 1 42 times the calculated maintenance fluid requirements  and nine  six with bacterial meningitis  were restricted to a mean of 0 65 times maintenance  children in the maintenance group also received significantly more sodium  mean   6 3 meq kg 24 hr  than children in the fluid restricted group  mean   2 0 meq kg 24 hr   the two groups were comparable for plasma avp concentration and serum osmolality before fluid therapy was begun  the plasma avp concentration was significantly lower after 24 hours of maintenance plus replacement fluids than after fluid restriction  p   0 005   and the change in avp concentration correlated with the amount of sodium given  p less than 0 02   this study supports the hypothesis that serum avp concentrations are elevated in patients with meningitis because of hypovolemia and become normal when sufficient sodium is given to facilitate reabsorption of water by the proximal tubule of the kidney  patients with meningitis can be given maintenance plus replacement fluids but should be monitored for the development of the syndrome of inappropriate secretion of antidiuretic hormone  
class1	impairment of neutrophil chemotactic and bactericidal function in children infected with human immunodeficiency virus type 1 and partial reversal after in vitro exposure to granulocyte macrophage colony stimulating factor  because polymorphonuclear neutrophils are the most important component of host defense against bacteria  we assessed their function in 13 children with asymptomatic and 12 with symptomatic infection with human immunodeficiency virus type 1  hiv 1   and compared their values with healthy adult control values  the functions assessed were  1  chemotaxis   2  bacterial phagocytosis   3  superoxide generation  and  4  bactericidal activity  chemotaxis of polymorphonuclear neutrophils toward the chemoattractant n formylmethionyl leucyl phenylalanine  fmlp  was significantly decreased in symptom free infected children compared with control subjects  p less than 0 0001   but was increased in children with symptomatic infection  p less than 0 025   bactericidal activity of the neutrophils against staphylococcus aureus was defective in 8 of 12 children with asymptomatic infection  p   0 016   and in 8 of 9 children with symptomatic infection  p less than 0 00001   superoxide generation by polymorphonuclear neutrophils on stimulation with fmlp and phagocytosis of s  aureus were normal  serum from patients with symptomatic hiv 1 infection was not as efficient in low concentrations as normal serum in the ability to opsonize s  aureus  the in vitro bactericidal defect was partially corrected by granulocyte macrophage colony stimulating factor  gm csf   the results suggest that both cellular  neutrophils  and humoral defects contribute to the increased incidence of bacterial infections in hiv 1 infected children  and that gm csf may improve the defective bactericidal activity of polymorphonuclear neutrophils in these patients  
class1	prevalence of hiv infection among patients with leprosy in african countries and yemen  screening for human immunodeficiency viruses types 1 and 2  hiv 1 and hiv 2  antibodies was carried out in the serum of 1 245 leprous patients and 5 731 controls selected in nine different centers from the congo  ivory coast  senegal  and yemen arab republic  in yemen  all sera were negative  in the congo  the seropositivity among patients and controls was  respectively  3 8 and 5 2   in senegal  it was 1 3 and 0 6   and in the ivory coast 4 8 and 3 9   differences were not statistically significant  even considering lepromatous or tuberculoid forms  3 6  and 3 7   respectively   hiv 2 antibodies were only detected in subjects from the ivory coast and senegal  using appropriate criteria for seropositivity  confirmation by western blot  reactivity to hiv envelope glycoproteins  and a large selection of patients  several countries with several centers   it appears that leprosy  and specially the lepromatous form  is not a factor for hiv infection  
class1	platelet activating factor  paf  and tumor necrosis factor alpha  tnf alpha  interactions in endotoxemic shock  studies with bn 50739  a novel paf antagonist  bn 50739  a new paf receptor antagonist  was tested in vitro and in vivo for its capacity to block paf  endotoxin and recombinant human tumor necrosis factor alpha  rtnf  mediated effects  in vitro  bn 50739 blocked paf induced platelet aggregation by 60 to 100  at 0 2 1 x 10  7  m  p less than  002   respectively  in the conscious rat  pretreatment  30 min  with bn 50739  n   5 13  dose dependently attenuated paf induced hypotension   5     5 vs    43     2 mm hg  p less than  01  and shortened the recovery time of mean arterial pressure  22     13 vs  325     46 sec  p less than  01   bn 50739  10 mg kg i p   n   5 11  prevented endotoxin  14 4 mg kg  induced hemoconcentration  54     1 vs  46     1   p less than  01  and reduced 24 hr mortality  100 vs  60   p less than  05   only partial protection was conveyed by bn 50739 against the hypotensive response to endotoxin  115     3 vs  91     4 mm hg  p less than  03   also  bn 50739 attenuated the lipopolysaccharide induced elevation of plasma thromboxane b2  21 2     0 8 vs  46 7     11 8 pg 100 microliters  p less than  01  and tumor necrosis factor alpha  7523     3983 vs  26 430     3541 u ml  p less than  05   whereas leukopenia and thrombocytopenia remained unchanged  
class1	hydroxyethyl starch pretreatment in bacteremic sheep  live bacteria were infused in a chronic ovine lung lymph model to determine if a preceding infusion of the colloid  hydroxyethyl starch  hes   exaggerated the cardiopulmonary dysfunction or impaired removal of bacteria by macrophages in the pulmonary circulation  hes was infused  3 ml kg hr  n   6  from 24 to 12 hr before the bacteria and decreased plasma protein content and increased pulmonary lymph to plasma protein concentration because of its oncotic properties  ringer s lactate  2 ml kg hr  was given after stopping hes and also to the control group  n   6   infusion of live ps  aeruginosa  2 5 x 10 8  ps  min for approximately 30 min  induced equivalent pulmonary hypertension  increased pulmonary microvascular permeability  and cardiovascular depression in the two groups  the removal of bacteria in the lungs was not affected  indicating that this measurement of the function of the mononuclear phagocytic system was not impaired by the preceding hes  
class1	the role of antibiotic therapy in the prevention of empyema in patients with an isolated chest injury  iss 9 10   a prospective study  the purpose of this study was to determine the impact of an antibiotic regimen on the incidence of empyema in patients admitted with isolated chest trauma  iss 9 10  and hemopneumothorax requiring tube thoracostomy  all patients with isolated chest trauma and hemopneumothorax  estimated iss 9 or 10  seen in our trauma center were considered eligible for this study  patients were excluded for the following reasons  age less than 18 years  presence of shock at the time of initial resuscitation  ongoing antibiotic therapy for unrelated disease  documented pre existing infection or documented abnormal immune status  ninety patients were randomized to two treatment limbs  antibiotics and tube thoracostomy or tube thoracostomy alone  all patients had the procedure performed in the trauma center in a standard fashion  wound care and tube care were identical  antibiotic therapy consisted of a first generation cephalosporin  cefazolin   one dose given just before the procedure and then q 6 h into the tube removal  injury severity scores were established as described by schwab after the manner of baker  statistical analysis was performed using fisher s exact test of binary outcome  in this study  antibiotics were able to reduce the incidence of empyema in patients with isolated chest trauma and for such patients antibiotic treatment appears justified  further work is required to determine the effect on patients with more severe injury and multisystem involvement  
class1	the direct costs of universal precautions in a teaching hospital  an analysis of the increase in expenditures for barrier isolation materials before and after the institution of universal precautions at our 900 bed university hospital was used to generate a national estimate of the cost of implementation of the new centers for disease control guidelines  following the institution of universal precautions  use of rubber gloves at our hospital increased from 1 64 million pairs of 2 81 million pairs annually  a 5 year review of hospital purchasing and supply records in both inpatient and outpatient areas indicated that the total annual costs for isolation materials increased by  350 900  this represented an increase from  13 70 to  22 89 per admission  60   after adjustment for inflation  the cost of isolation materials increased from  98 to  215 per 1000 outpatient visits  an adjusted increase of 92   two thirds of the increase  64   was due to rubber gloves and an additional 25  was due to disposable isolation gowns  universal precautions are estimated to have cost at least  336 million in the united states in fiscal year 1989 after adjustment for inflation  if expenditures for isolation materials at our medical center are representative  previous estimates may have significantly underestimated costs nationwide  
class1	epidemiologic  clinical  and laboratory findings of human ehrlichiosis in the united states  1988  in 1988  the centers for disease control and the oklahoma state department of health identified 40 patients who had a fourfold or greater change in antibody titer in response to ehrlichia canis  the median age of these patients was 42 years  83  were male  76  became ill between may and july  and 92  reported recent exposures to ticks  patients resided in or were exposed to ticks in 14 states  including five where ehrlichiosis had not been reported before 1988  thirty four patients  85   were hospitalized  and many had serious complications  including acute respiratory failure  seven patients   encephalopathy  six patients   and acute renal failure  four patients   pulmonary infiltrates were demonstrated in 14 patients  cerebrospinal fluid pleocytosis was seen in 10 patients  and elevated levels of serum creatinine were demonstrated in eight patients  two patients  both of whom had preexisting medical problems  died  nonhospitalized patients received tetracycline therapy earlier in the course of their illness than hospitalized patients  there was no significant difference in the interval from initiation of antibiotic therapy to the first day of defervescence between patients treated with tetracyclines and those treated with chloramphenicol  
class1	unsuspected syphilitic hepatitis in a patient with low grade proteinuria and abnormal liver function a 25 year old patient was found to have cholestatic liver enzyme abnormalities during assessment for asymptomatic low grade proteinuria at the us naval hospital in portsmouth  virginia  these abnormalities persisted for a 6 month period  and an extensive workup  including viral serologic studies  rapid plasma reagin test  iron studies  ceruloplasmin  antimitochondrial  antinuclear  and anti human immunodeficiency virus antibodies  endoscopic retrograde cholangiopancreatography  and liver biopsy  was unrevealing until serologic tests for syphilis were repeated to evaluate a new onset of urethral discharge  the patient had none of the more characteristic signs of secondary syphilis  the liver enzyme abnormalities rapidly resolved after treatment with penicillin  syphilis remains the great impostor and still must be considered in the differential diagnosis of unexplained liver enzyme abnormalities  even in a patient with no symptoms or signs of early syphilis  
class1	outbreak of diarrhoea due to escherichia coli o111 b4 in schoolchildren and adults  association of vi antigen like reactivity  during six days in november  1987  611 pupils  age range 7 19 years  and 39 adults  23 57  at a school complex in southern finland had diarrhoea due to escherichia coli o111 b4  diarrhoea developed in 137 other household members during the two weeks after the school outbreak  the source of the organism remains unknown  the outbreak strains  when incubated at 22 degrees c or exposed to ampicillin  lost the lipopolysaccharide o antigen and began to react with antisera against salmonella typhi vi antigen  the vi antigen like reactivity increased the adherence of the organisms to hep 2 cells  these results indicate that e coli o111 b4  and possibly other enteropathogenic e coli strains  should be considered in the diagnosis of all diarrhoea cases and not only in infantile diarrhoea  expression of vi antigen in e coli may play a part in virulence by enhancing adherence to the intestinal epithelium  
class1	ecology  life cycle  and infectious propagule of cryptococcus neoformans cryptococcus neoformans is a biotrophic smut like fungus  and the epidemiology of cryptococcosis can mainly be explained by exposure to an infective aerosolised inoculum  for c neoformans var gattii it is postulated that the principal infectious propagule is the basidiospore and that exposure to eucalyptus camaldulensis  the host tree  is required to initiate infection in man and animals  c neoformans var gattii may have been exported from australia by infected seeds of e camaldulensis containing dormant dikaryotic mycelium of the fungus  for c neoformans var neoformans both the basidiospore and desiccated encapsulated yeast cells are postulated to act as infectious propagules  the basidiospores showing a seasonal distribution in association with an as yet unidentified host plant  and the encapsulated yeast cells dispersed from accumulations of dried bird  mainly pigeon  droppings which act as a year round vector  
class1	gentamicin iontophoresis in the treatment of bacterial otitis externa in the guinea pig model  pseudomonas otitis externa is one of the most common infections treated by otolaryngologists  infections induced in 30 guinea pigs appeared similar to that seen in humans  the ears were then placed into four treatment groups  group a  which received a single cleaning  group b  which received a single cleaning followed by gentamicin drops 4 times daily  group c  which received a single cleaning followed by a single gentamicin iontophoresis treatment  and group d  the control group  which received no treatment  infections were analyzed by grading edema  purulence  and erythema  an average of 10 2 days was required for control group to return to normal appearance  groups a  b  and c had mean resolution times of 5 9  4 7  and 4 3 days  respectively  gentamicin iontophoresis appears to be promising  with results as good as drop therapy in otitis externa in the guinea pig model  
class1	bacterial meningitis  an update  antibiotics and improvements in supportive care have greatly reduced the mortality from bacterial meningitis  nevertheless  the incidence of neurodevelopmental sequelae remains unacceptably high  ampicillin and chloramphenicol remain the standard for antimicrobial therapy against which other agents must be compared  a number of adjunct therapies are being investigated for their possible effectiveness in reducing hearing loss and other neurologic effects of this disease  there continues to be a need for carefully performed follow up studies to assess any possible benefit of these agents  a significant percentage of children surviving an episode of bacterial meningitis have obvious or subtle neurodevelopmental deficits  the role of the pediatric neurologist should not end with management of acute problems such as seizures but should be expanded to aid in close developmental monitoring of these high risk children  
class1	borrelia burgdorferi infection of the brain  characterization of the organism and response to antibiotics and immune sera in the mouse model to learn more about the neurologic involvement in lyme disease  we inoculated inbred mice with the causative agent of lyme disease  borrelia burgdorferi  we cultured brains and other organs  and measured anti b burgdorferi antibody titers  we further studied a brain isolate for its plasmid dna content and its response in vitro to immune sera and antibiotics  one strain of b burgdorferi  n40  was consistently infective for mice  and resulted in chronic infection of the bladder and spleen  sjl mice developed fewer culture positive organs and had lower antibody titers than balb c and c57bl 6 mice  organism was cultured from the brain early in the course of infection  and this isolate  named n40br  was further studied in vitro  the plasmid content of n40br was different from that of the infecting strain  implying either a highly selective process during infection or dna rearrangement in the organism in vivo  n40br was very sensitive to antibiotics  but only after prolonged incubation  immune sera from both mice and humans infected with b burgdorferi were unable to completely kill the organism by complement mediated cytotoxicity  these data demonstrate that b burgdorferi infects the brain of experimental animals  and is resistant to immune sera in vitro but sensitive to prolonged treatment with antibiotics  
class1	reclosure of disrupted abdominal incisions  we evaluated prospectively a technique of delayed reclosure of disrupted abdominal incisions  forty one consecutive postoperative obstetric and gynecologic patients with abdominal incisions that had opened because of infection  hematoma  or seroma and had intact fascia participated in the study  all wounds were first managed identically  with surgical drainage and debridement  for a minimum of 4 days  the patients then were randomized to either wound reclosure by a standardized en bloc technique  35  or healing by second intention  six   reclosure was successful in 30 of 35 cases  85 7    the mean time to complete healing was 15 8 days in successful cases  67 2 days in failed cases  and 23 2 days for all patients who were reclosed  failure to heal after reclosure was due to subcutaneous infection in two patients and seroma in three  these women were significantly heavier than those in whom reclosure was successful  there were no other major complications of wound reclosure  patients randomized to healing by second intention required a mean of 71 8 days of wound care  the time to complete healing in the wound reclosure group was significantly shorter compared with the group that healed by second intention  p    002  log rank test   we conclude that en bloc reclosure of disrupted surgical incisions  compared with nonsurgical treatment  significantly decreases the time required for wound healing and has minimal morbidity  
class1	cefazolin for hysterectomy prophylaxis  efficacy data for single dose cefazolin prophylaxis at hysterectomy are meager  and there are none evaluating the impact of route of administration on efficacy  for these reasons  772 women undergoing elective abdominal or vaginal hysterectomy for benign diseases were given 1 g cefazolin either intramuscularly or intravenously in a randomized clinical trial  preoperative diagnoses and clinical  surgical  and outcome variables were similar by route of administration for each surgical approach  risk factors for infection after abdominal hysterectomy included younger age  lower postoperative hemoglobin concentration  and pelvic hematoma  women who developed infection after vaginal hysterectomy were heavier than those who remained uninfected and were more likely to have a pelvic hematoma  the overall incidence of major operative site infection requiring parenteral antimicrobial therapy in evaluable women was 7 2   7 6  for 539 women undergoing abdominal hysterectomy and 6 3  for 207 women undergoing vaginal hysterectomy  postoperative infection was unrelated to route of cefazolin administration  
class1	the effects of chlamydia trachomatis on the female reproductive tract of the macaca nemestrina after a single tubal challenge following repeated cervical inoculations  the effects of repeated cervical infections followed by a single direct tubal inoculation with chlamydia trachomatis  serovars d and f  were examined in 11 pig tailed macaques to test the hypothesis that tubal inoculation after cervical priming causes a more severe disease than primary tubal inoculation alone  animals were cervically inoculated between two and five times  fallopian tubes were inoculated with serovar d or f 1 week after the last cervical challenge  three control monkeys received only one direct tubal inoculation without previous cervical inoculation  infection was confirmed by isolating the microorganism from the endocervix in 13 of 14 monkeys and from the endosalpinx in four only after the tubal inoculation  antibody was detected in post infection sera of all 14  tubal edema occurred in seven of 11 animals after the first cervical inoculation  and uterine erythema occurred in 11 of 11 after the second cervical inoculation  peritubal adhesions were induced before the tubal inoculation in zero of seven given three or fewer cervical inoculations and four of four given five cervical inoculations  p less than  01   after direct tubal inoculation  peritubal adhesions became more prominent  and the 11 hysterectomy specimens showed plasma cell endometritis in nine and salpingitis in nine  two control monkeys developed minor adhesions  the other none  one tube in two of three controls showed mild plasma cell infiltrates  whereas no evidence of endometritis was observed in controls  histopathology in these monkeys was characteristic of chlamydial endometritis and salpingitis  however  the pathogenesis of these changes is uncertain because c trachomatis was not isolated from the endosalpinx after cervical inoculations alone  
class1	torulopsis glabrata vaginitis  clinical aspects and susceptibility to antifungal agents  torulopsis glabrata is second only to candida albicans in frequency of isolation from the vagina in both asymptomatic women and patients with yeast vaginitis  we retrospectively studied 33 patients from whom vaginal isolates of t glabrata were obtained  torulopsis glabrata caused symptomatic vaginitis in 42  of the patients but was unassociated with symptoms in 30   in 27  of patients  its importance was uncertain because of concomitant pathology  antifungal susceptibility testing was performed on 39 t glabrata strains isolated from 39 patients  the minimal inhibitory concentrations  mics  of the majority of t glabrata isolates fell within the sensitive range of the antimycotic drugs tested  however  no correlation was found between in vitro antifungal mics and the response to azole drug therapy  clinical success was achieved in 67  of the patients although mycologic cure occurred in only 33   a small number of patients developed recurrent and often chronic torulopsis vaginitis unresponsive to conventional therapy  limited experience suggests that vaginal boric acid therapy may be of value in these recalcitrant cases  
class1	evaluation of the gram stain as a screening tool for maternal carriage of group b beta hemolytic streptococci  the vaginal infections and prematurity study group  to determine the usefulness of the vaginal gram stain as a screen for maternal group b streptococcal carriage  we compared the presence of gram positive cocci on gram stain with a cervicovaginal culture in 7755 women at 23 26 weeks  gestation and in 1452 women at delivery  group b streptococci were isolated from 18 4  of women at 23 26 weeks and 14 9  of women at delivery  the sensitivity  specificity  positive predictive value  and negative predictive value of the gram stain were 28  69  17  and 81   respectively  in mid gestation and 34  72  18  and 86   respectively  at delivery  the presence of gram positive cocci on gram stain was strongly associated with the isolation of gardnerella vaginalis and with the presence of bacterial vaginosis  we conclude that most gram positive cocci seen on gram stain are probably anaerobes or micrococci and that the vaginal gram stain is neither sensitive nor specific enough to be of use as a tool in the diagnosis of maternal group b streptococcal carriage  
class1	enumeration of clue cells in rehydrated air dried vaginal wet smears for the diagnosis of bacterial vaginosis  among 235 women attending an outpatient clinic  the diagnosis of bacterial vaginosis was made using three of the following four criteria  typical discharge  ph more than 4 5  positive amine sniff test  and clue cells in a wet smear  these findings were correlated with the finding of clue cells in air dried wet smears rehydrated more than 1 month after the visit  the rehydrated specimens had the same microscopic appearance as a nonpreserved wet smear  the demonstration of clue cells in the rehydrated smears correlated with the composite diagnosis of bacterial vaginosis with a sensitivity of 96  and specificity of 98   in a busy multi physician setting  the scoring of clue cells in stored and rehydrated smears can be used to obtain consistent readings for wet smear diagnostics  thus simplifying teaching and increasing the utility of wet smears in clinical research  
class1	increased cell adherence of group b streptococci from preterm infants with neonatal sepsis  most women with group b streptococcus cervical colonization have uncomplicated pregnancies  but about 1  experience preterm premature rupture of membranes  prom  followed by neonatal group b streptococcal sepsis  in such cases  streptococcal adherence to and penetration of the membranes may be an important step in the pathogenesis  in the present study  chorionic epithelial cells were incubated with group b streptococci isolated from either children developing sepsis after preterm prom  complicated pregnancies  or from uncomplicated pregnancies  incubation periods varied  the numbers of adherent bacteria per chorionic epithelial cell were counted by microscopic examination  after 70 minutes  incubation  the number of adherent group b streptococci in complicated pregnancies was 38  compared with 14 in uncomplicated pregnancies  p less than  001   this difference in vitro might reflect the virulence of group b streptococci  
class1	a rapid method for detection of group b streptococcal colonization  testing at the bedside  vertical transmission of group b streptococci  the most frequent cause of early neonatal sepsis  can be interrupted by intrapartum antibiotics  however  rapid methods for detecting colonized women must be developed to limit the administration of antibiotics to those who are at risk of delivering an infected infant  the accuracy of a colorimetric test using starch serum medium on vaginal and rectal specimens from women with preterm labor or prolonged rupture of membranes was evaluated  the test was interpreted by labor and delivery room nurses without special microbiologic training  starch serum medium results were compared with those obtained from routine cultures  thirteen of 29 positive vaginal cultures  45   and eight of 18 positive rectal swabs  44   were identified by nurses using the rapid method  this was significantly different  p less than  001  from sensitivities of 93 and 95   respectively  for the same vaginal and rectal specimens interpreted by a bacteriology technologist  the specificity for the test from both sites was 95  for the nurses  the sensitivity was 53 and 36  for vaginal and rectal swabs  respectively  for a subgroup of mothers whose infants were assessed as clinically septic  the low sensitivity of starch serum medium as interpreted by nurses in the labor suite is inadequate to allow the test to replace cultures in identifying women colonized with group b streptococci  efforts to increase the sensitivity should be directed toward improving nursing staff interpretation rather than improving the medium itself  
class1	angiographic arterial embolization and computed tomography directed drainage for the management of hemorrhage and infection with abdominal pregnancy  hemorrhage during or after surgery  pelvic abscess  bowel obstruction  and prolonged febrile morbidity can complicate the puerperal course of the gravida after removal of an extrauterine fetus with nondisturbance of the extrauterine placenta  in this report we describe the successful angiographic arterial gelfoam embolization of the placental vascular bed to control heavy postoperative hemorrhage in a mother suffering adult respiratory distress syndrome after removal of the fetal portion of her abdominal pregnancy  six weeks later  computed tomography  ct  directed drainage by catheter of a placental abscess was performed  selective angiographic transcatheter embolization with gelfoam is a useful tool for the control of hemorrhage in the gravida who is an unfavorable operative candidate or who may present technical hemostasis problems peculiar to the placenta with abdominal pregnancy  later use of ct directed catheter drainage of the infected residual placental mass provided a nonoperative means of treatment  
class1	a clarification on endodontic flare ups  comment  in an article on endodontic flare ups by robert j  matusow  our research and publications are discussed  since we found what we consider to be distortions and misinterpretations of our work  it was decided to clarify the apparent discrepancies found in matusow s article  
class1	progressive osseous destruction as a complication of hiv periodontitis  a pathologic condition is described  characterized by rampant necrosis of gingival mucosa  periodontium  and related osseous structures associated with systemic infection with the human immunodeficiency virus  hiv   it is believed that this condition is an extension beyond the normal clinical course of hiv periodontitis  hiv p  and manifests itself in three progressive stages   1  hiv associated gingivitis   2  hiv p  and  3  an extension of hiv p to osseous necrosis  two cases of osseous destruction attending hiv p are reported  one of which led to initial diagnosis of hiv infection  they represent the final stage of disease progression with localized necrosis of gingiva  periodontium  and alveolar bone  
class1	safety and immunogenicity of haemophilus influenzae type b oligosaccharide crm197 conjugate vaccine in infants aged 15 to 23 months  a total of 268 infants aged 15 to 23 months received one dose of a vaccine composed of haemophilus influenzae type b oligosaccharides covalently linked to the nontoxic diphtheria toxin variant crm197  hboc  hibtiter   side effects associated with vaccination were infrequent  transient  and mild  one month after a single vaccination  the anti h influenzae type b capsular polysaccharide antibody concentration rose from a geometric mean prevaccination level of 0 20 microgram ml to 13 77 micrograms ml  of these infants  99  had a postvaccination level greater than or equal to 1 00 microgram ml  a level associated with long term protection  the immune response was long lived  all of the children who were monitored 17 to 27 months after vaccination had concentrations greater than or equal to 1 00 microgram ml  the anti h influenzae type b capsular polysaccharide antibody generated was predominantly of the igg isotype and igg1 subclass  the immune sera had bactericidal activity in vitro and conferred passive protection in the infant rat meningitis model  
class1	open lung biopsy in the critically ill newborn  experience with 17 open lung biopsies in critically ill premature neonates was reviewed  despite their small size  prematurity  and near maximal ventilator requirements  the infants suffered no significant complications  in three cases  an infectious agent was identified  in one case end stage lung fibrosis associated with persistent  greater than 3 months   severe respiratory failure prompted termination of support  in the remainder of the cases  definitively ruling out infection allowed the confident trial of a course of steroids in an attempt to treat bronchopulmonary dysplasia  unlike older patients  the definitive diagnosis of no infection in the premature neonate is just as informative as the diagnosis of an infection  used judiciously  open lung biopsy can be performed in the premature infant with acceptable morbidity and mortality  
class1	poor compliance with universal precautions  a universal phenomenon  an anonymous survey was conducted in order to examine compliance with universal precautions in the department of pediatrics at loyola university medical center in maywood  illinois  completed questionnaires were returned by 23 faculty members  29 residents  and 22 medical students  gloves were worn consistently during venipuncture or intravenous catheterization by 13  7  and 18  of attending physicians  residents  and students  respectively  most physicians wear gloves only occasionally and cite presence of high risk factors as their selection criterion  interference with the performance of procedures is the most common cause of noncompliance  in view of poor compliance with universal precautions  further efforts are needed in order to decrease the incidence of preventable exposure to blood borne infections  
class1	absent or minimal cerebrospinal fluid abnormalities in haemophilus influenzae meningitis  a case of haemophilus influenzae type b  hib  meningitis in which the diagnosis and treatment were delayed because of normal cerebrospinal fluid analysis is presented  a retrospective review was conducted at two children s hospitals to determine the frequency and clinical characteristics of patients with hib meningitis whose spinal fluid had a normal total white blood cell count  normal chemistries  and negative gram stain  but subsequent growth of hib in culture  of 379 cases of hib meningitis  two had completely normal csf  and two had csf containing small numbers of polymorphonuclear cells as the sole abnormality  in three of the four cases  the duration of symptoms was less than 24 hours  and appropriate therapy was significantly delayed because of benign appearing csf  normal csf cell counts  chemistries  and gram stain do not exclude the possibility of bacterial meningitis  and one should remain suspicious when a child has clinical findings suggesting meningitis  
class1	vaginitis  systematically solving a bothersome problem  vaginitis is a common cause of patient visits to primary care physicians  causes include allergic and irritative factors and infectious agents  diagnosis is readily made with use of simple office procedures such as wet smears  stains  and cultures  treatment with appropriate antibiotics or vaginal preparations is usually effective  
class1	infectious diarrhea  managing a misery that is still worldwide  infectious diarrhea is the largest single cause of morbidity and mortality in the world  bacteria  viruses  and protozoan parasites are the most common causative agents  treatment in most cases of bacterial and viral diseases consists of correcting fluid loss and electrolyte imbalance by oral or parenteral rehydration  antimicrobial therapy is reserved for very ill patients only  with the exception of cryptosporidium  for which no effective agent is yet available  all protozoan infections are treatable with metronidazole  
class1	bacterial or viral meningitis  measuring lactate in csf can help you know quickly  measurement of cerebrospinal fluid  csf  lactate is a useful test when properly applied to the appropriate clinical situation and can offer information other csf parameters cannot provide  except for gram s stain of csf  lactate level is the most important csf parameter in the early differentiation of viral  aseptic  and bacterial purulent meningitis  
class1	a study to assess the efficacy of chemoprophylaxis in the prevention of endoscopy related bacteraemia in patients aged 60 and over  five hundred and fifteen patients aged 60 and over  mean age 74 7  278 men and 237 women  underwent routine endoscopic procedures  gastroscopy  bronchoscopy and cystoscopy   alternate patients were given antibiotics before the procedure  as currently recommended  and blood was taken for culture from all patients within five minutes of completion of the procedure  of 74 patients who underwent bronchoscopy  only one culture  from one of 37 controls was positive  of 262 who underwent gastroscopy  cultures were negative in the 130 who received antibiotics but positive in 13 of the 132 controls  9 8 per cent p less than 0 001   cystoscopy was performed in 179  one culture was positive in the 88 given antibiotics  1 1 per cent  compared to 25 in the 91 controls  27 5 per cent  p less than 0 001   bacteraemia rates appear to be low following bronchoscopy  less than 5 per cent  but higher with gastroscopy  10 per cent  and cystoscopy  28 per cent   chemoprophylaxis was effective in reducing these rates in this patient group  
class1	oral findings in hiv infected patients attending a department of internal medicine  the contribution of intraoral examination towards the clinical management of hiv disease the occurrence of oral mucosal lesions was studied in 70 consecutive human immunodeficiency virus  hiv  infected patients  including 35 patients with aids  who had been admitted to a department of internal medicine  lesions of the oral mucosa were observed in 52 patients  74 per cent   oral candidiasis  50 per cent   hairy leukoplakia  14 per cent   periodontal disease  13 per cent   and oral kaposi s sarcoma  4 per cent  were the most common lesions  oral mucosal lesions suggestive of hiv infection were present in ten of 12 patients of unknown hiv status in whom pneumocystis carinii pneumonia was suspected  close cooperation between the medical and dental professions is recommended since accurate intraoral examination can make a valuable contribution towards the clinical management of hiv infected patients and may influence the cdc classification of this disease  
class1	endocarditis in the 80s in a general hospital in auckland  new zealand  the clinical and investigative features of 102 episodes of infective endocarditis were analysed retrospectively  the most frequent presenting symptoms  malaise  fever  sweats  myalgia  weight loss  were non specific  fever  cardiac murmur  tachycardia  vascular phenomena and a change in mental state were the most common physical signs at admission  anaemia was present in half the episodes and renal and liver dysfunction in about one third  streptococci  61  and staphylococci  31  were the causative organisms in all but 10 episodes  the commonest predisposing factors were underlying cardiac disease  52 per cent  and a preceding focus of infection  14 6 per cent   left ventricular failure  33 per cent  and focal neurological disease  29 per cent  occurred frequently  valvular surgery was performed in 20 episodes  with two in hospital deaths  overall hospital mortality was 27 5 per cent and death was most commonly neurological  11 28   a higher mortality was associated with elevated total white blood count  microscopic haematuria  renal or liver dysfunction at admission  s  aureus endocarditis  the development of left ventricular failure or focal neurological disease  age greater than or equal to 60 years and persistence of fever after one week of antibiotic therapy  the absence of both renal dysfunction at admission and subsequent microscopic haematuria identified a group with a very low hospital mortality  4 7 per cent   the three year mortality of the entire group was 43 5 per cent  
class1	derivation and validation of a clinical diagnostic model for chlamydial cervical infection in university women we developed and prospectively tested a logistic regression model for chlamydial cervical infection  study subjects included 2271 women receiving gynecologic care in our student health clinic  clinical data were collected in a standardized fashion  we identified cell culture  isolated chlamydia trachomatis from 133  9   of 1458 subjects in the derivation set and 73  10   of 729 subjects in the validation set  model variables included a new sexual partner within 2 months or more than one sexual partner within 6 months  cervical ectopy  cervical friability  at least 20 polymorphonuclear leukocytes per high power field in cervical secretions  white blood cells in vaginal secretions  and use of an antibiotic active against c trachomatis within a month  this model can distinguish women with low  medium  and high risks of chlamydial infection  on derivation set  receiver operating characteristic curve area  0 710  se  0 026  on validation set  area  0 698  se  0 035  using simple clinical information obtained in the office  
class1	health issues at the us mexican border with a rapidly growing population  increasing manufacturing activity  and increased interdependence  health issues on the us mexican border are demanding greater attention  it is unlikely that any other border in the world separates two nations having such variety in health status  entitlements  and utilization  binational initiatives in the areas of environmental health and sanitation are clearly needed  further cooperation between the united states and mexico in provision of health services is warranted and will probably require enhanced federal funding or subsidies to be successful  
class1	breast milk and neonatal necrotising enterocolitis in a prospective multicentre study on 926 preterm infants formally assigned to their early diet  necrotising enterocolitis developed in 51  5 5    mortality was 26  in stringently confirmed cases  in exclusively formula fed babies confirmed disease was 6 10 times more common than in those fed breast milk alone and 3 times more common than in those who received formula plus breast milk  pasteurised donor milk seemed to be as protective as raw maternal milk  among babies born at more than 30 weeks  gestation confirmed necrotising enterocolitis was rare in those whose diet included breast milk  it was 20 times more common in those fed formula only  other risk factors included very low gestational age  respiratory disease  umbilical artery catheterisation  and polycythaemia  in formula fed but not breast milk fed infants  delayed enteral feeding was associated with a lower frequency of necrotising enterocolitis  with the fall in the use of breast milk in british neonatal units  exclusive formula feeding could account for an estimated 500 extra cases of necrotising enterocolitis each year  about 100 of these infants would die  
class1	a randomized  double blind  placebo controlled trial of oral antibiotic therapy following intravenous antibiotic therapy for postpartum endometritis  one hundred thirty six patients were enrolled in a randomized  double blind  placebo controlled trial of oral antibiotic therapy  amoxicillin  versus placebo following successful intravenous  iv  antibiotic therapy for postpartum endometritis  no subjects were readmitted to the hospital for recurrent endometritis and there were no wound infections or recurrent fevers  minor side effects were seen in 10  of those taking amoxicillin and 14  of those taking placebo  compliance was fair  only 52  of those taking amoxicillin and 65  of those taking placebo completed therapy  the lack of infectious complications in this high risk population suggests that oral antibiotic therapy is unnecessary after successful iv antibiotic therapy for endometritis  
class1	haemophilus influenzae  an important cause of maternal and neonatal infections  although haemophilus influenzae is recognized as a major pathogen of infants  its role in maternal and neonatal infections is not as well appreciated  we analyzed the records of all mothers and neonates infected with h influenzae over a 10 year period  twenty eight mother neonate sets were identified in which at least one had documented infection with h influenzae  of the 18 mothers with documented infection  13 had chorioamnionitis  endometritis  or both  and two of these mothers were bacteremic with h influenzae  of the 23 infected neonates  15 presented with early sepsis and or pneumonia and nine had conjunctivitis  during the period of the study  only group b streptococci and escherichia coli were more common as causes of early neonatal bacteremia  under the conditions of this retrospective study  maternal infection predicted neonatal infection  however  prospective studies in which asymptomatic patients are cultured will be required to determine how well maternal colonization infection with h influenzae predicts neonatal infection  
class1	posterior infectious crystalline keratopathy with staphylococcus epidermidis  two cases of infectious crystalline keratopathy located in the posterior stroma after penetrating keratoplasty are presented  topical steroids and suture removal were risk factors in both cases  in the first case  a moderate anterior chamber reaction was present  crystalline infiltrates persisted on topical and systemic steroid therapy  in the second case  deep corneal ulceration  hypopyon  and vitreitis were noted  a vitreous aspirate showed rare gram positive cocci in pairs  the corneal ulceration and crystalline keratopathy persisted despite intravitreal and topical antibiotics  therapeutic penetrating keratoplasty was performed in both cases  staphylococcus epidermidis sensitive to vancomycin was isolated from corneal tissue  light microscopy documented aggregates of gram positive bacteria anterior to descemet s membrane  with an overlying keratitis  electron microscopy in the second case showed all bacteria within stromal keratocytes  no clinical recurrence was seen using topical vancomycin  as demonstrated in the cases presented  infectious crystalline keratopathy can occur exclusively in the deeper layers of the cornea  isolation of s  epidermidis  associated inflammation  and intraocular spread of organisms are rare findings  
class1	retained intraocular foreign bodies and endophthalmitis  retained intraocular foreign bodies  iofbs  are associated with endophthalmitis in approximately 7 to 13  of cases  the role of prompt surgical removal of the foreign body along with the use of intravitreal antibiotics in reducing this figure is uncertain  retained iofbs presenting to the medical college of wisconsin between july 1986 and june 1989 were reviewed  a total of 27 cases were evaluated and surgically treated  none of the 27 cases presented with or developed clinical signs of endophthalmitis  yet bacterial cultures of the removed intraocular material were positive in seven cases  foreign body in 5 cases  the aqueous fluid and the vitreous fluid in 1 case each   all eyes presenting within 24 hours of injury underwent immediate surgery  average  4 5 hours after presentation   of the seven eyes with positive intraocular cultures  all had pars plana vitrectomy removal of the iofb and three of these eyes received intravitreal antibiotics at the time of surgery over concern of a high risk of infection  two of these eyes eventually grew out the bacillus sp  all eyes received subconjunctival antibiotics and postoperative topical and systemic antibiotics  even after the positive cultures  no signs of clinical infection developed in any of the eyes  all seven eyes retained excellent visual acuity of 20 70 or better at an average of 10 months  follow up  follow up ranged from 1 to 31 months  prompt surgical intervention  the use of intravitreal antibiotics in high risk type injuries  and the possible use of vitrectomy surgery may reduce the incidence and severity of endophthalmitis  
class1	management of post tuberculous complex aspergilloma of the lung  role of surgical resection  of 14 patients with complex aspergilloma complicating healed tuberculosis  12 underwent lobectomy or pneumonectomy for recurrent haemoptysis  no deaths occurred  though one patient needed re exploration for bleeding  there was no postoperative worsening of dyspnoea despite a mean forced vital capacity  fvc  of 60  predicted for the patients undergoing surgery and of 20  predicted for two patients with severe restrictive defects  perhaps owing to the fact that there was little or no function in the resected part of the lung  as shown by preoperative isotope ventilation perfusion scanning  and that patients were under the age of 50 and generally fit  there has been no recurrence of haemoptysis during follow up  which has been from 12 to 33 months  surgical resection  provided that cases are carefully selected  offers the best chance of cure with low mortality and morbidity  
class1	lipid infusion increases oxygen consumption similarly in septic and nonseptic patients  this investigation compared the metabolic effects of lipid infusion in five septic and five nonseptic patients  oxygen consumption was determined by indirect calorimetry over 1 h of rest and during 2 h when intralipid  20   was infused  166 ml h  23 kj min  5 5 kcal min    septic patients had a resting metabolic rate 17  higher than that of their nonseptic control subjects and a significant  p less than 0 05  rise  13   in oxygen uptake was measured in both groups of subjects during the 2 h infusion of lipid  preinfusion respiratory quotient  rq  was 7  higher in the septic patients  p less than 0 05   and during the infusion period rq decreased similarly  approximately 6   p less than 0 05  in both groups  plasma catecholamines were elevated in the septic patients preinfusion and the concentrations remained unaltered during the infusion  norepinephrine rose significantly in the nonseptic group with the lipid infusion  the results show that sepsis has little or no influence on the characteristic rise in metabolic rate that occurs with intravenous lipid  
class1	a rabbit model for bacteria induced preterm pregnancy loss  bacterial infection has been implicated in premature labor in humans  to elucidate mechanisms and potential intervention strategies  we sought to develop a model of infection induced pregnancy loss in rabbits  on day 21  70  of gestation   each uterine horn was inoculated hysteroscopically with 0 2 ml containing saline solution of 10 6  cfu escherichia coli or bacteroides bivius or fusobacterium necrophorum  fetal viability was assessed  animals were sacrificed at various times or as delivery occurred  serum progesterone and amniotic fluid prostaglandins were measured  cultures and histologic sections were prepared  compared with the saline solution group  e coli and f  necrophorum inoculated rabbits were significantly more likely to deliver  16 of 16 and six of seven with mean times of 31 9     10 7 and 28 3     11 5 hours  respectively for e  coli and f  necrophorum   positive amniotic fluid cultures for the e  coli group were found in 11 of 12  92   and for the f  necrophorum group in three of three cases  100    histologic inflammation was seen heavily in both the e  coli and f  necrophorum groups  whereas it was absent in the saline solution group  inoculation with b  bivius led to a much lower pregnancy loss rate  eight of 32  and less histologic inflammation despite positive uterine cultures in most animals  this model may provide an opportunity to determine mechanisms of clinical or subclinical intraamniotic infection and to test intervention strategies  
class1	in vitro inhibition of esterase activity in amniotic fluid  comparison with bacterial cultures  assessment of leukocyte esterase activity in amniotic fluid for the rapid and reliable diagnosis of chorioamnionitis has been demonstrated previously  we compared in vitro inhibition of esterase activity in amniotic fluid with bacterial cultures to identify the origins of the specific esterases released by the infecting organisms  one hundred forty one samples were tested  90 uninfected  51 infected   each sample was evaluated for gram stain  cultures  and an in vitro esterase assay followed by ebelactone inhibition  forty two patients had positive amniotic fluid cultures  ebelactone produced varying degrees of inhibition of esterase activity  range  20  to 60   in the uninfected samples and in those infected with gram negative organisms  there was no inhibition in the samples infected with gram positive organisms  thus different groups of bacteria may elicit the production of different and specific esterases in infected amniotic fluid  as shown by the differences in in vitro inhibition  
class1	methicillin resistant staphylococcal colonization and infection in a long term care facility objective  to determine the natural history of colonization by methicillin resistant staphylococcus aureus  mrsa  among patients in a long term care facility  we specifically sought to determine if mrsa colonization was predictive of subsequent infection  design  cohort study  setting  long term veterans affairs medical center  patients  a total of 197 patients residing on two units were followed with regular surveillance cultures of the anterior nares  main outcome measurement  the development of staphylococcal infection  results  thirty two patients were persistent carriers of mrsa and 44 were persistent carriers of methicillin susceptible strains  mssa   twenty five percent of mrsa carriers had an episode of staphylococcal infection compared with 4  of mssa carriers and 4 5  of non carriers  p less than 0 01  relative risk 3 8  95  ci  2 0 to 6 4   the rate of development of infection among mrsa carriers was 15  for every 100 days of carriage  using logistic regression analysis  persistent mrsa carriage was the most significant predictor of infection  p less than 0 001  odds ratio  3 7   seventy three percent of all mrsa infections occurred among mrsa carriers  isolates of mrsa from 7 patients were typed  colonizing and infecting strains had the same phage type in all 7 patients and the same pattern of plasmid ecori restriction endonuclease fragments in 5 patients  conclusions  colonization of the anterior nares by mrsa predicts the development of staphylococcal infection in long term care patients  most infections arise from endogenously carried strains  colonization by mrsa indicates a significantly greater risk for infection than does colonization by mssa  the results offer a theoretic rationale for reduction in mrsa infections by interventions aimed at eliminating the carrier state  
class1	primary dapsone resistant hansen s disease in california  experience with over 100 mycobacterium leprae isolates we found that in the years 1978 through 1981 only one of 54 previously untreated patients with hansen s disease was found to harbor dapsone resistant mycobacterium leprae  that single strain was only partially resistant  ie  it was resistant to 0 0001  dapsone in a mouse diet but not to higher concentrations  during the years 1983 through 1988  m leprae from 47 previously untreated patients presenting to clinics in san francisco  calif  and los angeles  calif  grew in mice  none of these strains was found to be dapsone resistant  thus  from 1978 through 1988 only one of 101 m leprae isolates obtained from skin biopsy specimens from patients with leprosy was found to be resistant to dapsone  we have concluded that primary dapsone resistance still does not appear to be a significant problem in california  owing to the fact that our single resistant case and those reported from international sources are  in general  partially resistant  the potential importance of partial dapsone resistance is discussed  
class1	 cystic papilloma  in humans  demonstration of human papillomavirus in plantar epidermoid cysts  fourteen cases of plantar epidermoid cyst were studied immunohistochemically and five of them were also studied electron microscopically for the presence of human papillomavirus  in eleven cases  the test results were positive for papillomavirus antigens  and in five of them  papillomaviruslike particles were observed by electron microscopy  histological examination showed most of the cysts to contain intracytoplasmic eosinophilic bodies in cells of the cyst wall as well as the vacuolar structures in the keratinous mass within the cavity  these findings suggest an etiologic association between the papillomavirus and plantar epidermoid cysts  the  cystic papilloma  produced in rabbits by the shope papillomavirus has been clearly demonstrated  we propose that human papillomaviruses play an important role in the genesis of plantar epidermoid cysts  this is the first report on the possible existence of a cystic papilloma in humans  
class1	hepatic abscess  changes in etiology  diagnosis  and management  most recent reviews of pyogenic hepatic abscess emphasize percutaneous versus open surgical management and devote little time to studying the etiology or the clinical condition of the patient  in this study a detailed review was performed with a computerized analysis of multiple clinical parameters in 73 patients treated for pyogenic hepatic abscess during a 17 year period  the mean age of the patients was 55 years and 38 of them  52   were male  the mortality rate was comparable for solitary  17   and multiple  23   abscesses  the likelihood of death was higher with antibiotic treatment alone  45   or percutaneous treatment  25   than with surgical treatment  9 5    the primary determinant of outcome  however  was the underlying disease  i e   malignancy or an immunocompromised patient  rather than solitary versus multiple abscesses  in addition the incidence of hepatic abscess seen at this center has doubled from the first half to the second half of the review  reflecting a population of more severely ill patients  it is apparent that in current clinical practice several methods of management are effective  and the choice of therapy should be determined by individualized selection  the principle of timely diagnosis and prompt institution of treatment appropriate to the specific patient remains the standard of care in this potentially grave disease  
class1	streptococcal antibody cross reactivity with hla dr4 ve b lymphocytes  basis of the dr4 associated genetic predisposition to rheumatic fever and rheumatic heart disease   published erratum appears in br j rheumatol 1991 jun 30 3  222  b lymphocytes obtained from patients with either rheumatic fever or rheumatic heart disease and from normal subjects were reacted with serum obtained from rabbits immunized with streptococcal cell wall antigen  the presence of cytotoxicity was sought using an inverted phase microscope after differential uptake of eosin dye  the serum was found to be significantly more cytotoxic to hla dr4 containing cells of both patients and normals compared with dr4 negative cells  p less than 0 0001   
class1	immunologic evidence for the in situ deposition of a cytoplasmic streptococcal antigen  endostreptosin  on the glomerular basement membrane in rats  endostreptosin  ess  is an antigen derived from the cytoplasm and the plasma membrane of nephritogenic group a and to a lesser extent group c and g streptococci  it is immunologically not related to streptococcal exoenzymes or the streptococcal cell wall and can be detected on the endothelial side of the glomerular basement membrane of kidney biopsies of patients with acute poststreptococcal glomerulonephritis  asgn  during the early phase of the disease  highest and most persistent antibody titers to this antigen are found in patients with asgn  immunoaffinity isolated ess was injected i v  into the tail vein of wistar furth  w fu  rats for up to five successive days  the animals were sacrificed on days 1  2  3  4  5  8  9  10  11 and 12  frozen sections of the rat kidneys were tested by immunofluorescence against rabbit anti ess antibody and against sera from patients who had recently recovered from asgn as well as against anti rat igg and c3  the basement membranes of rat kidneys were positive for ess deposition starting from day one on  but were negative for anti rat igg and c3 during the first four days  rats sacrificed on days 8 12 showed increasing deposition of igg and c3 with decreased staining for ess  the sera of rats sacrificed on days 1 3 had no detectable anti ess antibodies  whereas animals from day 4 on had low levels of anti ess antibodies as determined by microcomplement fixation  control animals showed no staining for ess  igg  c3 as well as no detectable anti ess antibodies  
class1	decrease in mean platelet survival time in acute poststreptococcal glomerulonephritis  apsgn   in an attempt to study further the possible participation of platelets in the pathogenesis of acute poststreptococcal glomerulonephritis  apsgn   we studied the platelet survival time  as an index of platelet activation  in 22 patients with apsgn  mean platelet survival time was computed from the disappearance of radioactivity from blood  sampled serially after injection of autologous 51cr labelled platelets  c1q solid phase elisa and conglutinin  k  solid phase elisa were used to measure the serum levels of immune complexes  the platelet survival time in apsgn patients was 113     10 h vs 197     10 h in the control group  p less than 0 001   68  of the patients had a shortened platelet survival  lower than 95  confidence limit  there was a significant increase in the platelet survival in the six patients that were studied after recovery from acute nephritic syndrome  there was no significant association between the mean platelet times survival and cics  circulating immune complexes   similarly  no significant correlation was found between the mean platelet lifespan and the severity of the glomerular disease  as assessed by the serum creatinine level and the proteinuria  these results support evidence of platelet activation and consumption in apsgn and we suggest that this activation occurs in the glomeruli capillary wall  due to platelet vascular wall interaction  
class1	staphylococcus aureus infection of human endothelial cells potentiates fc receptor expression  vasculitis  a recognized complication of staphylococcal endovascular infections  may result in part  from the expression of fcr by staphylococcus aureus infected endothelial cells  fcr were measured using  51 cr labeled srbc preincubated with rabbit anti srbc igg  fcr were not detected on uninfected endothelial cells  but were demonstrated on s  aureus infected cells using igg  but not igm labeled srbc  fcr expression was dependent on the initial bacterial density  greater than or equal to 8 x 10 7  cfu ml  and on phagocytosis of the staphylococci  but not on new protein synthesis  igg labeled srbc binding was blocked by aggregated igg but not igm  srbc coated with the f ab  2 portion of igg did not bind  thus confirming that fcr were specifically involved in this interaction  fcr are expressed after s  aureus invasion of human endothelial cells and may contribute to the vasculitis which often accompanies s  aureus endovascular infections  
class1	immunogenicity and protective effect against oral colonization by streptococcus mutans of synthetic peptides of a streptococcal surface protein antigen  streptococcus mutans is known to be a major causative organism of human dental caries  a surface protein ag with a molecular mass of 190 kda of s  mutans  pac  is receiving attention as an anticaries vaccine  we have recently determined the complete nucleotide sequence of the gene for pac  in this study  four peptides were synthesized on the basis of amino acid sequence of pac  among these peptides  pac 301 319  corresponding to the alanine rich repeating amino acid region was the most strongly bound by polyclonal murine anti rpac antibodies  the peptide partially inhibited the binding of polyclonal anti rpac antibodies to rpac  the peptide induced the proliferation of t cells from balb c mice immunized with rpac  subcutaneous immunization with pac 301 319  or rpac emulsified in cfa ifa induced high serum igg responses to rpac and pac 301 319   in addition  serum igg responses to a surface protein ag with a molecular mass of 210 kda of streptococcus sobrinus were elicited in mice immunized by s c  injection with pac 301 319  or rpac  intranasal immunization with pac 301 319  coupled to cholera toxin b subunit  ctb  or with rpac and free ctb induced high serum igg responses to rpac  the immunization with pac 301 319  coupled to ctb or rpac and free ctb suppressed the colonization of murine teeth by s  mutans  these results suggest that intranasal immunization with the peptide or rpac may be effective for the prevention of dental caries  
class1	pneumococcal pneumonia in a rat model of cirrhosis  effects of cirrhosis on pulmonary defense mechanisms against streptococcus pneumoniae  to study alterations in host defense mechanisms that enhance pneumococcal virulence  a model of streptococcus pneumoniae pneumonia was developed in cirrhotic rats  cirrhosis  with or without ascites  was produced in rats by intragastric administration of carbon tetrachloride  ccl4   histopathologic and laboratory studies demonstrated that ccl4 induced cirrhosis was similar to alcoholic cirrhosis in humans  cirrhotic rats were more susceptible to type 3 pneumococcal pneumonia induced by intratracheal challenge than controls  and the presence of ascites was associated with the lowest ld50  more cirrhotic rats with ascites had bacteremia and elevated levels of circulating capsular antigen after challenge compared with cirrhotic rats without ascites or controls  pulmonary clearance of pneumococci was markedly reduced in rats with cirrhosis and ascites and was associated with reduced serum complement levels  this model may be useful in further studies of the pathogenesis and therapy of pneumococcal infections in the compromised host  
class1	the human antibody response to streptococcal c5a peptidase  an elisa was developed to measure antibody  both igg and iga  against the streptococcal c5a peptidase  scp   in human sera and saliva  generally  sera and saliva from young  uninfected children lacked antibody to scp  in contrast  most sera and saliva specimens from healthy adults had measurable levels of anti scp igg and scp specific secretory iga  anti scp siga   paired acute and convalescent sera from patients with streptococcal pharyngitis possessed significantly higher levels of anti scp igg than did sera from healthy individuals  sera containing high concentrations of anti scp immunoglobulin were capable of neutralizing scp activity  a survey of healthy adults and children also showed that the latter were significantly less likely to have anti scp siga in their saliva  detection of this antibody in greater than 90  of the saliva specimens obtained from children who had recently experienced streptococcal pharyngitis demonstrated that children can produce a secretory response  this is thought to be the first report of a secretory iga response in humans to a somatic antigen of streptococcus pyogenes  
class1	mediastinitis following coronary artery bypass surgery  a 3 year review  twenty cases of mediastinitis after coronary artery bypass graft operations in 1985 1987 were reviewed to determine risk factors  two distinct clusters with a methicillin resistant staphylococcus aureus  mrsa  strain occurred in 1986  one resident was exposed to six cases but to only 5 of 24 controls  p less than  008   cultures of his nares in january and november 1986 revealed the same mrsa strain as that of the cases  an attempt to eradicate the resident s nasal carriage of mrsa in january 1986 failed  eradication of his carrier state was achieved only after treatment with mupirocin  in a case control study examining patients exposed to the resident  a prolonged duration of surgery  p less than  05  and a preoperative albumin level of less than 3 0 g dl  p less than  009  were associated with mediastinitis with this mrsa  for the other 14 mediastinitis patients  who were not exposed to the resident  a preoperative albumin level of less than 3 0 g dl was also a risk factor  8 14 cases vs  8 43 controls  p less than  009   thus  this study suggests that it is important to follow mrsa disseminators and to recognize that preoperative serum albumin levels are a risk factor for mediastinitis  
class1	immunization of mice with antibiotic treated escherichia coli results in enhanced protection against challenge with homologous and heterologous bacteria  the murine immune response to escherichia coli exposed to subminimal inhibitory concentrations of four antibiotics was investigated  groups of mice were injected for 8 weeks with formalin killed bacteria and subsequently challenged with 10 x ld50 of viable e  coli  mice receiving saline only  controls  died within 24 h  the mortality of mice immunized with ciprofloxacin treated e  coli was significantly lower than that of mice immunized with e  coli untreated or treated with other antibiotics  sera from mice immunized with ciprofloxacin treated bacteria showed better bacteriostatic capacity and enhanced production of antibodies that bound to homologous and heterologous lipopolysaccharide isolated from several smooth and rough gram negative strains  the better protection observed in mice immunized with ciprofloxacin treated e  coli was probably due to an enhanced production of antibodies to epitopes on lipopolysaccharide that became better exposed and so more accessible after treatment with ciprofloxacin  
class1	predictive index for optimizing empiric treatment of gram negative bacteremia  in a survey of 296 episodes of gram negative bacteremia in 286 patients  aged 13 99 years   four clinical variables were found to predict both significantly and independently the subsequent isolation of a multiresistant strain  hospital acquisition of the infection  antibiotic treatment before the bacteremic episode  endotracheal intubation  and thermal trauma as the cause of hospitalization  these variables were combined in an index that served to classify the patients into four groups with an increasing prevalence of multiresistant strains  pseudomonas isolates  and isolates resistant to each of the antibiotic drugs in common use  for example  the percentage of isolates susceptible to cefuroxime in the four groups were 79   56   34  and 25   and to gentamicin  89   79   46   and 33   p less than  001 for both comparisons   the performance of the index was validated in a second group of 144 episodes of gram negative bacteremia  the index kept its discriminative power  compared with the prescriptions of the attending physicians  the index could probably have improved empiric antibiotic treatment in 24  of patients  
class1	instillation of vancomycin into a cerebrospinal fluid reservoir to clear infection  pharmacokinetic considerations  vancomycin instilled in an ommaya reservoir was used to treat a reservoir associated infection  vancomycin concentrations in cerebrospinal fluid  csf  were measured  and derivation of pharmacokinetic parameters allowed tailoring of dosing  first order kinetics were observed  the calculated half life of 3 52 h was less than reported by others  and the apparent volume of distribution  60 ml  was less than anticipated  the elimination constant was 0 197 h 1  empiric dosing based on schedules suggested in the literature would have led to high peak and low mean concentrations of intrareservoir vancomycin  patients with reservoir associated infections have a variety of pathophysiologic conditions that can result in alteration of normal csf dynamics  pharmacokinetic analysis is useful to individualize dosing and to optimize therapy with intrareservoir vancomycin  
class1	exacerbation of bacterial toxicity to infant ferrets by influenza virus  possible role in sudden infant death syndrome  published erratum appears in j infect dis 1991 jul 164 1  232  of several toxins examined  only staphylococcal alpha and gamma toxin  endotoxin  and diphtheria toxins were lethal for 5 day old ferrets  their toxicities were enhanced in animals infected at 1 day old with influenza virus  from 3 fold with staphylococcal gamma toxin through 14 fold for staphylococcal alpha toxin  84 fold for endotoxin  and 219 fold for diphtheria toxin  no increased viral replication occurred in any tissue  thus the effects of the toxins were exacerbated by the infection  not vice versa  neonates died suddenly without clinical symptoms as in human babies dying from the sudden infant death syndrome  sids   pathologic examination showed inflammation in the upper respiratory tract  lung edema and collapse  and early bronchopneumonia in the toxin  and influenza virus treated animals but not in those treated with toxin or virus alone  thus  bacterial toxins could play a role in sids  this being more likely with a concomitant influenza virus infection  
class1	divergent efficacy of antibody to tumor necrosis factor alpha in intravascular and peritonitis models of sepsis  the role of tumor necrosis factor alpha  tnf alpha  in the lethal consequences of intravascular lipopolysaccharide  lps  or escherichia coli sepsis was compared with that in bacterial peritonitis  intravenous administration of e  coli lps or e  coli  live or dead  resulted in large transient increases in serum tnf alpha levels  peaking at 90 min at 10 000 30 000 units ml  in contrast  the serum tnf alpha response following the induction of bacterial peritonitis was substantially less  peaking at 200 500 units ml  sterile peritonitis  essentially nonlethal  and bacterial peritonitis  greater than 60  lethal  elevated tnf alpha levels to 1000 2000 units lavage within the peritoneal cavity 2 h after challenge  passive immunization with neutralizing goat anti tnf alpha igg improved survival from 8  to 75  in rats administered lps intravenously but was completely ineffective in protecting rats from lethal e  coli peritonitis  thus significant differences exist in the role tnf alpha plays in systemic intravascular models of sepsis and bacterial peritonitis  
class1	tumor necrosis factor and severe malaria  to investigate the relation of tumor necrosis factor alpha  tnf alpha  to plasmodium falciparum infection  plasma tnf alpha concentrations were measured in zairian children with severe malaria  mild malaria  or other illnesses  the initial geometric mean plasma concentration of tnf alpha among 61 children with p  falciparum infection   71 pg ml  was higher than the level in 26 severely ill  aparasitemic children  10 pg ml  p less than  001   among 29 parasitemic children  initial geometric mean tnf alpha levels decreased from 77 to 5 pg ml  p less than  001  at day 7  tnf alpha levels increased with parasite density and were associated with hyperparasitemia  severe anemia  hypoglycemia  and young age but not with cerebral malaria or fatal outcome  however  tnf alpha levels were elevated equally in children with cerebral malaria and with other signs of severe malaria  with multiple linear regression  tnf alpha levels were elevated independently in children with hyperparasitemia  p    001  and severe anemia  p    04   in this study  high tnf alpha levels were associated with several manifestations of severe malaria and were not specific to cerebral malaria  
class1	shunt surgery for hydrocephalus in tuberculous meningitis  a long term follow up study  hydrocephalus is a common complication of tuberculous meningitis  case studies of 114 patients with tuberculous meningitis and hydrocephalus  who underwent shunt surgery between july  1975  and june  1986  were reviewed to evaluate the long term outcome and to outline a management protocol for these patients based on the results  seven factors were studied in each case  1  age at admission  2  grade on admission  i to iv  classified by the authors  grade i being the best and grade iv being the worst   3  duration of alteration of sensorium  4  cerebrospinal fluid  csf  cell content at initial examination  5  csf protein levels at initial examination  6  number of shunt revisions required  and 7  the necessity for bilateral shunts  during a long term follow up period ranging from 6 months to 13 years  mean 45 6 months   the mortality rate was 20  for patients in grade i  34 7  for patients in grade ii  51 9  for patients in grade iii  and 100  for patients in grade iv  only the grade at the time of admission was found to be statistically significant in determining final outcome  p less than 0 001   based on these results  the authors advocate early shunt surgery for grade i and ii patients  for patients in grade iii  surgery may be performed either if external ventricular drainage causes an improvement in sensorium or without selection  all patients in grade iv should undergo external ventricular drainage and only those who show a significant change in their neurological status within 24 to 48 hours of drainage  should have shunt surgery  
class1	the management of flail chest injury  factors affecting outcome  the records of 57 patients presenting with flail chest injury from 1981 through 1987 were reviewed to determine factors affecting morbidity and mortality  fifteen patients  26   had 8  rib fractures with a unilateral flail and seven  12   had multiple rib fractures with a bilateral flail  thirty two  56   had moderate severe pulmonary contusions and 44  77   required chest tubes for hemo pneumothorax  ventilatory assistance was used in 36  63    the major factors determining the need for ventilatory assistance were  an iss greater than or equal to 23  blood transfusions in the first 24 hours  moderate severe associated injuries  fractures  head injuries or truncal organs requiring operation   and shock on admission  p less than 0 001   an adverse outcome occurred in 15  28    nine required ventilatory assistance greater than or equal to 14 days and six died of sepsis with pneumonia  the main factors associated with an adverse outcome were  an iss greater than or equal to 31  p less than 0 001   moderate severe associated injuries  p less than 0 001   and blood transfusions  p less than 0 005   although the primary determinants of an adverse outcome were the associated injuries and blood loss  a bilateral flail  p less than 0 01  and age greater than or equal to 50 years  p less than 0 02  were contributing factors  
class1	treatment of candidosis in severely injured adults with short course  low dose amphotericin b  thirty three  0 7   of 4 818 trauma patients admitted between january 1  1987  and july 1  1989  developed invasive candidosis requiring iv antifungal therapy  all patients were seriously traumatized  before developing candidosis  all patients had documented bacterial infections  these infections were generally polymicrobial and were treated with multiple broad spectrum antibiotics  an average of 5 4 antibiotics for 17 2 days   twenty eight  85   of 33 patients received enteral feedings for an average of 11 days     1 5  sem  before developing candidosis and 24  73   received ng oral nystatin for an average of 7 6 days     0 9 before developing candidosis  all patients with candidosis were treated with intravenous amphotericin b  cumulative dose of 157 3 mg     31 3 mg given over 10 days     1 1  one patient developed recurrent candidosis despite ng oral prophylaxis and enteral feedings  six patients  18   died due to sepsis and multiple organ failure  the patients who died did not objectively differ from the survivors  candidosis is an infrequent infection in severely injured patients  candidosis was invariably preceded by treatment with multiple broad spectrum antibiotics for a variety of polymicrobial bacterial infections  ng oral nystatin and enteral feedings did not prevent candidosis  in contrast to widely accepted beliefs  amphotericin b therapy was safe  recurrent candidosis was unusual  candida infections had a high mortality rate associated with multiple blood transfusions and prolonged hospitalization  candidosis represents a sign of severe injury and illness but can be amenable to prompt  aggressive treatment  
class1	septic hip in pelvic fracture with urologic trauma  case report  urologic injuries occur in 10  of pelvic fractures and hip sepsis is a rare complication  the symptoms of a septic hip are often not as dramatic when found in the setting of an acute pelvic fracture and may be overlooked  a case is presented with a review of the literature  early recognition and aggressive surgical debridement are important to prevent the long term sequelae of septic arthritis  
class1	contaminant blood cultures and resource utilization  the true consequences of false positive results  to determine whether contaminant blood cultures increase resource utilization  we studied charge and length of stay data for episodes in which blood cultures were obtained from hospitalized adults  compared with 1097 negative episodes  94 false positive episodes were associated with increased subsequent length of stay  median  12 5 vs 8 days  and subsequent total charges  median   13 116 vs  8731   pharmacy charges  median   1456 vs  798   and laboratory charges  median   2057 vs  1426   in multivariate analyses  contaminants were independently correlated with 20  and 39  increases in total subsequent laboratory charges and intravenous antibiotic charges  respectively  thus  the true costs of contaminants may greatly exceed those of the test itself  identifying patients at very low risk of bacteremia and attention to sterile technique may reduce costs by decreasing the frequency of contaminants  
class1	surgical outcome in 435 patients who sustained missile head wounds during the iran iraq war  variables important in predicting the final postsurgical outcome of 435 patients who sustained missile head wounds during the iran iraq war were evaluated over a 99 month period  the type of projectile  site of injury  and presence or absence of foreign material did not seem to have a significant effect on the final outcome  of the patients with a perforating type of injury  48 8  had a poor surgical outcome as compared with 19 9  with a penetrating type and 15 6  with a tangential type  this difference is statistically significant  chi 2   14 7 and 17 1  respectively  p less than 0 001   the most important factor in predicting overall outcome was the glasgow coma scale  gcs  score at the time of admission  mortality and morbidity contributing to a poor surgical outcome were noted in only 6  of patients with a gcs score at admission of 13 to 15  in 24 6  of those with a gcs score of 9 to 12  in 57  of those with a gcs score of 6 to 8  and in 65  of those with a gcs score of 3 to 5  of the 71 patients who died  75  had a score of 3 to 8  perforating projectiles or those traversing two or more dural compartments were statistically significant in contributing to mortality and morbidity  chi 2   17 2  p less than 0 001   the incidence of focal neurological deficit was 100  90 6  88  and 52 2  in patients with gcs scores of 3 to 5  6 to 8  9 to 12  and 13 to 15  respectively  the two best predictors of mortality in this group of patients were a low gcs score and infection  
class1	bismuth subsalicylate in the treatment of acute diarrhea in children  a clinical study  bismuth subsalicylate  bss  and placebo were evaluated in a double blind  placebo controlled study as adjunct to rehydration therapy in 123 children  aged 4 to 28 months  hospitalized with acute diarrhea  the dosing regimen was 20 mg kg five times daily for 5 days  significant benefits were noted in the bss group compared with placebo as manifested by decreases in stool frequency and stool weights and an improvement in stool consistency  significant improvement in clinical well being  and shortening of the disease duration  patients treated with bss had a significant reduction in duration of hospital stay  6 9 days  compared with placebo treated patients  8 5 days   also  intravenous fluid requirements decreased significantly more rapidly and to a greater degree in the bss treated group  bismuth subsalicylate was associated with clearance of pathogenic escherichia coli from the stools in 100  of cases but was not different from placebo in rotavirus elimination  bismuth subsalicylate was well tolerated with no reported adverse effects  blood bismuth and serum salicylate levels were well below levels considered toxic  in this study  bss provided effective adjunctive therapy for acute diarrhea  allowing children to get well sooner with less demand on the nursing and hospital staff  
class1	bacteremia with otitis media  to investigate the occurrence and outcome of bacteremia associated with otitis media  charts were reviewed from patients who were 3 to 36 months of age  had temperatures greater than or equal to 39 degrees c  and were diagnosed with isolated clinical otitis media  a total of 2982 patients were identified  blood cultures were obtained from 1666  56    of the 1666 patients  who had blood drawn for cultures  50  3 0   had bacteremia  these included 39 with streptococcus pneumoniae  4 with haemophilus influenzae  2 with neisseria meningitidis  3 with salmonella species  and 2 with staphylococcus aureus  the incidence of bacteremia increased at higher temperatures  being 1 9  at temperatures less than or equal to 40 degrees c and 5 0  at temperatures greater than 40 degrees c  younger children were more likely to have bacteremia  3 7  less than or equal to 12 months of age  2 4  13 to 24 months of age  and 1 9  25 to 36 months of age had blood culture results that were positive  not significant   reevaluation of the 50 bacteremic patients showed that 9 patients had continued fever  3 patients had persistent bacteremia  pneumonia developed in 1 patient  and meningitis developed in 1 patient  it was concluded that  1  3  of young febrile children with otitis media have bacteremia at the time of evaluation  a rate comparable to that previously reported in children with no focus of infection   2  the incidence of bacteremia increases at higher temperatures  and  3  most febrile children with otitis media do well  the clinician must therefore weigh the potential benefit of drawing a blood culture to identify children at risk for complications against the inherent cost  inconvenience  and discomfort  
class1	risk of respiratory illness associated with day care attendance  a nationwide study  the risk of respiratory and other illnesses in children  age groups  6 weeks through 17 months  18 through 35 months  and 36 through 59 months  in various types of day care facilities was studied  children considered exposed to day care were those who were enrolled in day care with at least one unrelated child for at least 10 hours per week in each of the 4 weeks before the interview  unexposed children were not enrolled in any regular child care with unrelated children and did not have siblings younger than 5 years of age receiving regular care with unrelated children  although an increased risk of respiratory illness was associated with attending day care for children in all three age groups  this risk was statistically significant only for children 6 weeks through 17 months of age  odds ratio   1 6  95  confidence interval   1 1 to 2 4  and children 18 through 35 months of age who had no older siblings  odds ratio   3 4  95  confidence interval   2 0 to 6 0   in contrast  day care attendance was not associated with an increased risk of respiratory illness in children 18 through 35 months of age with older siblings  odds ratio   1 0   for children aged 6 weeks through 17 months  the exposure to older siblings was associated with an increased risk of respiratory illness  however  for children aged 36 through 59 months  older siblings were protective against respiratory illness  in addition  for the children in each age group currently in day care  increased duration of past exposure to day care was associated with a decreased risk of respiratory illness  
class1	pediatric emergency room visits  a risk factor for acquiring measles  in recent years  measles outbreaks have occurred among unimmunized children in inner cities in the united states  from may 1988 through june 1989  1214 measles cases were reported in los angeles  and from october 1988 through june 1989  1730 cases were reported in houston  more than half of cases were in children younger than 5 years of age  most of whom were unvaccinated  of cases of measles in preschool aged children  nearly one fourth in los angeles and more than one third in houston were reported by one inner city emergency room  to evaluate whether emergency room visits were a risk factor for acquiring measles  in los angeles  35 measles patients and 109 control patients with illnesses other than measles  and in houston  49 measles patients and 128 control patients  who visited these emergency rooms  were enrolled in case control studies  control patients were matched to case patients for ethnicity  age  and week of visit  records were reviewed to determine whether case patients had visited the emergency room during the period of potential measles exposure  which was defined as 10 to 18 days before rash onset  and whether control patients had visited 10 to 18 days before their enrollment visit  in los angeles  23  of case patients and 5  of control patients  odds ratio   5 2  95  confidence interval   1 7  15 9  p less than  01   and in houston  41  of case patients and 6  of control patients  odds ratio   8 4  95  confidence interval   3 3  21 2  p less than  01   visited the emergency room during these periods  
class1	pseudomonas aeruginosa bacteremia in patients undergoing liver transplantation  an emerging problem  in our institution  pseudomonas aeruginosa bacteremia appeared to occur with increasing frequency in patients undergoing liver transplantation  we thus conducted a prospective study to define risk factors and outcome in these patients  over a 19 month period 6  of liver transplants were followed by pseudomonas bacteremia  the mean age was 46 years  range  24 to 67 years   the interval between transplantation and onset of bacteremia was 3 to 372 days  mean  80   the incidence of pseudomonas bacteremia in liver transplants was three times that of other transplants  heart  lung  kidney   ninety one percent of infections were nosocomial  polymicrobial bacteremia occurred in 30  of episodes  the portal of entry was respiratory in 30   abdominal in 35   and biliary in 13   four patients had recurrent pseudomonas bacteremia  liver abscess  1   biliary obstruction  2   subhepatic abscess  1   survival at 14 days was 70   survival rates were significantly lower for patients with hypotension  on mechanical ventilators  and increasing severity of illness  p less than 0 05   survival was higher when bacteremia occurred within the first 30 days after transplantation compared to after 30 days  a large number  43 4   of pseudomonas bacteremias occurred after transplant surgery of biliary tract manipulation  while the patient was receiving a prophylactic regimen of cefotaxime and ampicillin  p  aeruginosa is an important pathogen in the liver transplant recipient  prevention may be possible for a subgroup of patients with the use of prophylactic antibiotics with activity against p  aeruginosa  
class1	cerebellar syndrome caused by isoniazid  treatment of tuberculosis in a hemodialysis patient with isoniazid  rifampin  and pyrazinamide resulted in the development of acute cerebellar dysfunction  this resolved rapidly following the discontinuation of isoniazid and pyrazinamide  reinstitution of isoniazid at a lower dose  and addition of pyridoxine  we discuss why we believe this syndrome was caused by isoniazid  patients with renal failure who undergo antituberculous therapy with isoniazid should receive supplemental pyridoxine to reduce the likelihood of isoniazid related neurotoxicity  
class1	griseofulvin  a new look at an old drug  griseofulvin is the oral antifungal agent of choice for the treatment of dermatophytoses  this article reviews the history  pharmacokinetics  adverse reactions  and traditional therapeutic applications of griseofulvin  in addition  reports since 1960 of the use of the drug in the treatment of raynaud s phenomenon  progressive systemic sclerosis  lichen planus  mycosis fungoides  herpes zoster  eosinophilic fasciitis  and molluscum contagiosum are discussed  noting the varying degree of therapeutic success  
class1	fluconazole  a new triazole antifungal agent  fluconazole is a fluorine substituted  bis triazole antifungal agent  its mechanism of action  like that of other azoles  involves interruption of the conversion of lanosterol to ergosterol via binding to fungal cytochrome p 450 and subsequent disruption of fungal membranes  activity against aspergillus spp   blastomyces dermatitidis  candida spp   coccidioides immitis  cryptococcus neoformans  histoplasma capsulatum  and paracoccidioides brasiliensis has been demonstrated in several animal models  fluconazole can be administered both orally and intravenously  mean peak serum concentrations achieved in human volunteers after 50 and 100 mg  oral  are 3 1 and 7 0 mumols l respectively  protein binding is low  11 percent  and cerebrospinal fluid to serum ratio is 0 58 to 0 89  serum half life is long  22 32 hours  and elimination is via renal clearance of unchanged drug  clinical trials and reports support the use of fluconazole in treatment of candidiasis  particularly oropharyngeal and esophageal infections in immunocompromised hosts  fluconazole is also approved for initial and suppressive therapy of cryptococcal meningitis  its role in management of systemic fungal infections will be further defined once results of other comparative trials become available  fluconazole is well tolerated and its effects on steroidogenesis are markedly less than those of ketoconazole  antipyrine clearance is not altered at low doses  50 mg  of fluconazole  however  drug interactions with the use of larger doses can be anticipated with agents such as cyclosporin  phenytoin  oral hypoglycemics  and warfarin  rifampin appears to decrease metabolic clearance of fluconazole  fluconazole is available as oral and parenteral formulations  once daily doses of 100 400 mg are recommended  dosage reduction is advised for patients with impaired renal function  
class1	acute phase reactants and risk of bacterial meningitis among febrile infants and children  study objective  to test the hypothesis that quantitation of either c reactive protein  crp  or the total peripheral wbc count can improve clinical detection of underlying bacterial meningitis among young febrile children  design  cross sectional survey of selected symptoms of central nervous system infection  signs of meningeal irritation and or elevated intracranial pressure  levels of crp in serum  and total peripheral wbc counts among unselected pediatric patients undergoing lumbar punctures for evaluation of acute febrile illnesses  setting  emergency department and acute care  walk in  clinic of an urban  university affiliated general hospital  participants  160 previously well  acutely febrile infants and children  median age  6 months   results  the prevalence of bacterial meningitis was 6   sensitivity of symptoms was 1 00 and specificity was 0 17  sensitivity of signs was 0 70 and specificity was 0 81  of the acute phase reactants  sensitivity of a crp level of more than 1 0 mg dl was 0 80  while that of a total peripheral wbc count of more than 15 000 mm3 was 0 40  the presence of signs and or a crp level of more than 1 0 mg dl correctly identified all children with bacterial meningitis  sensitivity  1 00   the absence of signs and a crp level of 1 0 mg dl or less correctly identified 71 of 150 children without bacterial meningitis  specificity  0 47   of 125 children without meningeal signs  the combination of symptoms and a crp level of more than 1 0 mg dl correctly identified all three children with bacterial meningitis  sensitivity  1 00   the absence of these symptoms and or a crp level of 1 0 mg dl or less correctly identified 80 of 122 children without bacterial meningitis  specificity  0 66   conclusion  quantitation of crp but not the total peripheral wbc count can increase the sensitivity of physical examination findings and the specificity of symptoms for the diagnosis of bacterial meningitis  measurement of crp in serum is useful as an adjunct to history and physical examination for the detection of acute bacterial meningitis in the acutely febrile child  
class1	transmission of  toxic strep  syndrome from an infected child to a firefighter during cpr  several cases of a toxic shocklike syndrome have been reported in the united states during the past five years in association with streptococcus pyogenes infection  we report a case of a firefighter exposed during attempted cpr to the secretions of an s pyogenes infected child  the firefighter developed an infection of the hand and subsequent febrile illness with hypotension  erythematous rash  renal failure  and hypocalcemia  bacterial isolates of blood and cerebrospinal fluid from the deceased child were identical in type and exotoxin production with isolates grown from the hand wound of the firefighter  this is the first reported case of documented transmission of s pyogenes  causing a toxic shocklike syndrome in an emergency medical technician  
class1	fatal capnocytophaga canimorsus septicemia in a previously healthy woman  a previously healthy 47 year old woman presented to the emergency department with septic shock five days after a small dog bite on the dorsum of her hand  capnocytophaga canimorsus was isolated from blood cultures  despite intensive therapy  multiple organ failure developed  and the patient died 27 days after admission  characteristics of capnocytophaga  formerly cdc group dysgonic fermenter 2  infection are briefly discussed  this unusual outcome in a previously healthy patient and the need for careful management of dog bite wounds  even if initially very small  is emphasized  
class1	yersinia enterocolitica in the synovial membrane of patients with yersinia induced arthritis  using a monospecific rabbit antibody against yersinia enterocolitica outer membrane protein 1  we examined synovial biopsy specimens from 7 patients with yersinia induced arthritis  yersinia were demonstrated in the synovial membrane by indirect immunofluorescence in 4 patients with yersinia induced arthritis  but not in 6 control patients with salmonella induced arthritis or with rheumatoid arthritis  these findings suggest the persistence of yersinia in the joints of patients with yersinia induced arthritis  
class1	double blind  placebo controlled study of three month treatment with lymecycline in reactive arthritis  with special reference to chlamydia arthritis  we conducted a double blind  placebo controlled  randomized study of 3 month treatment with lymecycline  a form of tetracycline  in reactive arthritis  rea   lymecycline therapy significantly decreased the duration of the illness in patients with chlamydia trachomatis triggered rea  but not in other rea patients  in 2 rea patients  c trachomatis was found in the throat  an uncommon locale for this organism  our results suggest that it is important to verify the triggering microbe and that it is beneficial to treat chlamydia arthritis patients with a prolonged course of tetracycline  
class1	application of the polymerase chain reaction and immunofluorescence techniques to the detection of bacteria in yersinia triggered reactive arthritis  leukocytes in synovial fluid and peripheral blood samples from patients with yersinia triggered reactive arthritis were analyzed after dna amplification using the polymerase chain reaction  the primers applied were specific for the virulence plasmid coded 1cre genes of yersinia enterocolitica o 3 and yersinia pseudotuberculosis iii  no yersinia dna was observed within the synovial fluid cells or peripheral blood cells by polymerase chain reaction techniques  however  yersinia antigens were detected in the synovial fluid cells by immunofluorescence techniques  these results suggest that only parts of the causative agents  not the entire microbe  can enter the joint and initiate the inflammation that leads to a reactive arthritis  
class1	human cytomegalovirus viraemia in hiv 1 seropositive patients at various clinical stages of infection  eighty two hiv 1 seropositive subjects were examined for the presence and quantification of human cytomegalovirus  hcmv  in peripheral blood polymorphonuclear leukocytes  pmnl  by polymerase chain reaction  culture and immunofluorescence in order to investigate the relationship between viraemia and immunosuppression  patients were divided into three groups   1  asymptomatic subjects with greater than 400 x 10 6  l cd4 lymphocytes  n   30    2  asymptomatic subjects with less than 400 x 10 6  l of cd4 lymphocytes and zidovudine  n   20   and  3  aids related complex  arc  aids patients on zidovudine  n   32   evidence of hcmv infection in circulating pmnl was found in 15 out of 29 arc aids patients examined  51 7    whereas no infection was detected among the 50 asymptomatic hiv 1 seropositive subjects  hcmv related symptoms were found only where the number of infected pmnl was greater than 50 per 2 x 10 5  cells  
class1	extrapulmonary and disseminated tuberculosis in hiv 1 seropositive patients presenting to the acute medical services in nairobi  we studied 506 consecutive adult acute medical admissions to hospital in nairobi  95  18 8   were seropositive for hiv 1  and 43 new cases of active tuberculosis  tb  were identified  tb was clearly associated with hiv infection  occurring in 17 9  of seropositive patients compared with 6 3  of seronegatives  odds ratio  or  3 2  95  confidence limits  cl  1 6 6 5   extrapulmonary disease was more common in seropositive than seronegative tb patients  nine out of 17 versus five out of 26  or 4 7  95  cl 1 01 23 6   this accounted for most of the excess cases of tb seen in seropositive patients  mycobacteraemia was demonstrated in two of eight seropositive tb patients but in none of 11 seronegative tb patients  no atypical mycobacteria were isolated  the world health organization  who  clinical case definition for african aids did not discriminate well between seropositive and seronegative tb cases  five out of seven seropositive women with active tuberculosis had delivered children in the preceding 6 months and were lactating  compared with only one out of eight seronegative tuberculous women  an association between recent childbirth  hiv immunosuppression and the development of tb is suggested  
class1	hiv 1 and pregnant women  associated factors  prevalence  estimate of incidence and role in fetal wastage in central africa  the major goals of this study were to measure the current prevalence and estimate the annual incidence of hiv 1 infection in young pregnant women from urban malawi  to identify factors that were associated with hiv 1 infection  and to examine adverse pregnancy outcomes  four hundred and sixty one consecutive pregnant women were studied when they presented for prenatal care  the overall seroprevalence for hiv 1 infection in these urban populations was 17 6   81 out of 461  during early 1989  based on previous seroprevalence in similar unselected pregnant women  the estimated annual incidence of hiv 1 seroconversion in urban pregnant women ranged from 3 to 4  per annum between 1985 and 1987 and from 7 to 13  between 1987 and 1989  hiv 1 infection was significantly associated with reactive syphilis serology  reported history of sexually transmitted disease was also correlated with hiv 1 infection but was not statistically significant  other variables  such as history of transfusion  history of tuberculosis  parity or occupation were not associated with hiv 1 infection  history of spontaneous abortion was significantly associated with reactive syphilis serology  hiv 1 infection and history of sexually transmitted disease  in logistic regression analysis  hiv 1 infection remained the only significant variable that was correlated with spontaneous abortion  this study suggests that hiv 1 infection may play a role in fetal wastage  
class1	audit of major colorectal and biliary surgery to reduce rates of wound infection  objective  to reduce the rates of wound infection for major colorectal and biliary surgery  design  prospective audit of antibiotic prophylaxis by keeping copies of typed notes of operations and annotating them at discharge and at first follow up visit and annual review of prophylactic regimen according to yearly rate of wound infection and modification if necessary  setting  the work of one consultant surgeon working in a district general hospital  patients  all patients having major colorectal resection during 1976 89  400  and cholecystectomy during 1981 9  500   main outcome measures  wound infection  defined as any discharge from the wound as detected by observation during inpatient stay and by specific questioning at the first follow up visit six weeks later  results  serial changes in prophylaxis for colorectal surgery resulted in a progressive reduction in the rate of wound infection from 43  in 1976  with no prophylaxis  to 1  during 1986 9 with single intravenous doses of metronidazole and cefuroxime intraoperatively and with lavage of the peritoneal cavity and wound with 0 1  tetracycline  during 1981 7  with no prophylaxis  the rate of infection in biliary surgery was 12  whereas in 1988 9  after the introduction of lavage with tetracycline alone  the rate was reduced to 2   implications and action  simple prospective audit identified the need for changes in antibiotic prophylaxis  successive rounds of audit resulted in improved rates of wound infection  and lavage with 0 1  tetracycline seemed to be a major factor in achieving this  
class1	adenine nucleotide changes in kidney  liver  and small intestine during different forms of ischemic injury  the purpose of this study was to better characterize renal adenine nucleotide pool responses to different forms of shock  contrast the changes to those found in other intra abdominal organs  the liver and small intestine   and assess whether these changes are closely mimicked by those produced by renal arterial occlusion  the usual method used to study ischemic acute renal failure  rats were subjected to hemorrhagic shock  septic shock  or cardiopulmonary shock of varying severities and durations  the liver consistently had the greatest energy depletion  followed by the kidney  and then the small intestine  however  only the kidney developed clear morphological damage  s3 brush border sloughing   kidney adenylate pools were better preserved during septic shock and cardiopulmonary shock than during hemorrhagic shock despite comparable blood pressures  only profound hemorrhagic shock  35 40 mm hg for 25 minutes  decreased total adenylate pools  atp   adp   amp   however  the degree of renal catabolite  nucleosides plus purine base  accumulation did not correlate with the amount of renal total adenine nucleotide depletion  partially because circulating catabolites contributed to intrarenal catabolite pools  purine base uric acid ratios differed among shocked organs  consistent with different degrees of xanthine oxidase activity  small intestine greater than liver greater than kidney   renal morphological damage decreased during the immediate  0 30 minutes  postshock period  and the extent of this improvement was not altered by xanthine oxidase inhibition  oxypurinol   suggesting that the immediate postshock period is not one of serious oxidative injury  shock  in comparison with renal arterial occlusion  caused only modest atp loss catabolite accumulation  very low purine base uric acid ratios  and no immediate reperfusion  0 30 minutes  resynthesis of the total adenylate pool  thus  ischemia induced renal adenylate changes may differ considerably  depending on the nature of the ischemic event  
class1	behavior of the pulmonary circulation at rest and during exercise in miliary tuberculosis  we studied the hemodynamic behavior of the pulmonary circulation at rest and during exercise in six patients with mtb  as a group  in contrast to advanced fibrocaseous tuberculosis  these patients exhibited normal pulmonary hemodynamics at rest and during exercise  only minor abnormalities in pulmonary vascular resistance at exercise  increased pad pwp gradient  were noted in two of the patients  the increase in rp during exercise does not appear to be related to acute hypoxic vasoconstruction but rather to functional changes  compliance or recruitment or both  of the pulmonary microvasculature  in the genesis of these functional changes  chronic alveolar hypoxia and the inflammatory fibrotic process might be interacting  
class1	endotoxemia in human septic shock  to evaluate the incidence  pattern and clinical importance of endotoxemia in septic shock  frequent  serial endotoxin determinations were made prospectively in patients with shock  detectable endotoxin occurred in 43 of 100 patients with septic shock  but in only one of ten patients with shock due to nonseptic causes  during septic shock  endotoxemia frequently occurred in the absence of gram negative bacteremia  using a logistic regression model  multiple organ failure occurred 10 3 times more frequently and depression of left ventricular ejection fraction  less than or equal to 45 percent  4 8 times more frequently in endotoxemic patients  in patients with positive blood cultures  endotoxemia was associated with a high mortality  we conclude that endotoxemia occurs frequently in septic shock and is associated with severe manifestations of this syndrome  including cardiac depression and multiple organ failure  this study suggests that endotoxin is an important mediator of septic shock and supports efforts to develop anti endotoxin therapies for treating patients with this disease  
class1	peripheral nerve function in sepsis and multiple organ failure forty three patients who had sepsis and multiple organ failure  critical illness  were studied prospectively to determine the incidence and severity of peripheral nerve function and to correlate such function with a number of variables  electrophysiologic studies indicated a primary axonal degeneration of motor and sensory fibers in 30  70 percent   fifteen  30 percent  had the clinical signs of difficulty in weaning from assisted ventilation  weakness of limb muscles  and reduced or absent deep tendon reflexes  full recovery from the polyneuropathy occurred among the 23  53 percent  who survived  except three who had a very severe polyneuropathy  a peripheral nerve function index  computed from electrophysiologic measurements  showed statistically significant  p less than 0 01  negative correlations with the time in the critical care unit  and the serum glucose value  the serum albumin level showed a positive correlation  multiple regression analyses indicated all three factors accounted for 47 percent  r2   0 4678  of all potential variables  in a separate analysis  the nerve function index correlated with the amplitude of the diaphragm compound muscle action potential  p less than 0 01   the results were consistent with the polyneuropathy being due to the same mechanisms that are currently postulated to cause dysfunction in this syndrome of other organ systems  including the neuromuscular respiratory system   
class1	rabbit skeletal muscle po2 during hypodynamic sepsis  we measured skeletal muscle tissue po2  pto2  in anesthetized rabbits  n   7  following infusion of an intravenous bolus of e coli endotoxin  an array of surface po2 microelectrodes was placed over the hindlimb biceps femoris muscle and sufficient readings were obtained to construct a pto2 histogram  changes in the histogram standard deviation were used to characterize micro circulatory maldistribution  systemic o2 consumption  vo2  was measured by the expired gas method  cardiac output  q  and systemic o2 transport  to2  were calculated  samples of arterial  right atrial  ra   and hindlimb venous blood  from a catheter placed in the infrarenal portion of the vena cava  were simultaneously obtained for measurement of blood gases and saturations  following the administration of endotoxin  there were decreases in q and to2 of approximately 50 percent  the vo2 initially decreased 23 percent  but returned to baseline levels 30 minutes after endotoxin administration  systemic o2 extraction ratio  ero2   vo2 to2  increased from 0 32      03 to 0 54      07  p less than 0 01   whereas hindlimb ero2 increased from 0 42      03 to 0 60      02  p less than 0 01   the arithmetic mean of the pto2 histograms decreased after endotoxin infusion  43     4 to 7     2 mm hg  p less than 0 01   but plo2 remained at baseline levels  35     2 vs  33     2 mm hg  p   ns   the standard deviation of the pto2 histograms remained constant during the experiment  this finding supports the notion that skeletal muscle microcirculatory heterogeneity does not increase during endotoxin induced hypodynamic sepsis  
class1	nonsurgical treatment of histoplasma endocarditis involving a bioprosthetic valve  endocardial involvement associated with disseminated histoplasmosis has been infrequently documented  especially among patients with prosthetic valves  the therapeutic approach to these patients is also not yet clearly defined  a 54 year old man with prosthetic valve endocarditis due to histoplasmosis was successfully treated with amphotericin b  a review of the literature suggests that the optimal form of therapy is likely a combination of surgical replacement of the involved valve and high dose amphotericin b  successful therapy with amphotericin b alone may  however  be achieved if surgery is not a viable option  
class1	the diagnostic utility of the antibody coated bacteria test in intubated patients  purpose  pilot study to determine if the presence of antibody coated bacteria  acb  in sputum specimens obtained from endotracheal tube suctioning would aid in the diagnosis of lower respiratory tract infection  lrti   patients and methods  all endotracheally intubated and mechanically ventilated patients for a two month period were recruited for study  the diagnosis of lrti was based on a clinical suspicion sufficient enough to start or change antibiotic therapy  specimens were obtained by blind endotracheal tube suctioning  after processing  sputum smears were stained with fluorescein labelled antibody to the fc portion of igg  igm  and iga  more than five fluorescein labelled bacteria per oil immersion field were considered positive smears  results  seventy one specimens were obtained from 36 patients  eighteen specimens were positive in 12 patients  all of whom had lrti  no specimen was positive in patients not diagnosed as having lrti  the acb test was positive in 12 of 25 patients with lrti  patients with lrti but negative acb were more likely to have received prior antibiotic therapy  p less than 0 001   acb was positive prior to the clinical diagnosis of lrti in seven of nine patients  av 4 1 days  range 2 6 days  and converted to negative in three specimens obtained seven or more days after starting appropriate antibiotics  while in three specimens it remained positive three six days post treatment initiation  conclusions  the acb test appears to be highly specific for the presence of lrti in intubated patients  sensitivity of the test may be adversely affected by prior antibiotic therapy  a positive acb test may predict the subsequent development of lrti  further study is warranted  
class1	diagnosis of campylobacter pylori gastritis  campylobacter pylori is a bacterium that inhabits gastric mucosa  it causes chronic active gastritis and is highly associated with duodenal ulcer  campylobacter pylori has a urease enzyme  not present in man   which allows diagnosis by a  14c urea breath test  we compared two noninvasive tests  the breath test and serum elisa  to biopsy and histologic diagnosis  twenty two patients who underwent gastroduodenoscopy for evaluation of possible peptic ulcer disease entered the study  the breath test detected the organism in eight of eight patients biopsy positive for the organism  sensitivity 100    the breath test was negative in 12 of the 14 patients who were biopsy negative  specificity 86    the elisa was performed in 14 patients  it was positive in 5 of 5 patients biopsy positive for the organism  sensitivity 100   and negative in 7 of 9 patients who were biopsy negative  specificity 78    we conclude that both the elisa and the  14c urea breath test are excellent noninvasive methods to detect campylobacter pylori  however  only the breath test is suitable for following the response to treatment  as it detects the presence of the organism rather than an immune response to it  
class1	zollinger ellison syndrome  relation to helicobacter pylori associated chronic gastritis and gastric acid secretion  since helicobacter pylori infects the gastric mucosa in most patients with chronic duodenal ulcer  infection with this organism has been implicated in the pathogenesis of this common disease  we postulated that if h  pylori is pathogenic in the usual type of duodenal ulcer  it should be less common when duodenal ulcer has another  specific etiology  such as zollinger ellison syndrome  gastric mucosa was compared from 18 patients with proven zollinger ellison syndrome  17 of whom had had duodenal ulcer disease  and 18 controls with chronic duodenal ulcer without such a diagnosis  all subjects  who were matched for age and sex  had undergone elective gastric resections  gastric tissues were stained by hematoxylin eosin and giemsa and were reviewed by an experienced pathologist who was unaware of the diagnosis  the frequency of h  pylori in patients with zollinger ellison syndrome  8 18  was lower than in controls with duodenal ulcer  16 18  p less than 0 02   moreover  chronic antral gastritis scores were higher in patients with duodenal ulcer  p less than 0 01   in zollinger ellison syndrome  peak acid output was lower in patients positive  median 22 meq 30 min  compared to those negative for h  pylori  median 32 meq 30 min  p less than 0 02  but serum gastrin was correspondingly lower in patients positive for h  pylori  p less than 0 05   h  pylori infection appears to be more frequent when duodenal ulceration is not associated with another etiology  such as acid hypersecretion in zollinger ellison syndrome  h  pylori infection in zollinger ellison syndrome may also be associated with decreased gastric acid secretion  
class1	helicobacter pylori and zollinger ellison syndrome  helicobacter pylori  previously campylobacter pylori  is almost invariably associated with chronic duodenal ulcer disease  the relationship between h  pylori infection and duodenal ulcer in zollinger ellison syndrome is unknown  we investigated the frequency of h  pylori infection in zollinger ellison syndrome and also what effect h  pylori infection had on gastric function in patients with zollinger ellison syndrome  h  pylori infection was diagnosed based on a specific serologic  elisa  assay based on high molecular weight cell associated proteins of h  pylori  we studied 20 patients with zollinger ellison syndrome  15 men and 5 women ranging in age from 24 to 71 years  median age 51  six zollinger ellison syndrome patients had h  pylori infection compared to 100 consecutive patients with chronic recurrent duodenal ulcer disease  p less than 0 05   pretreatment basal acid output in zollinger ellison syndrome patients ranged from 7 9 to 95 0 mmol hr  median 35 2  pentagastrin stimulated maximal acid output ranged from 8 5 to 132 mmol hr  median 52 7  acid secretion was lower in the h  pylori infected patients than the uninfected patients  bao 24 5     6 5 vs 45 4     6 6  and mao 44 3     11 8 vs 67 9     10 7  for h  pylori infected vs uninfected patients  respectively   the difference in bao was statistically significant  p less than 0 05   the present results indicate that h  pylori is not a major contributing factor in duodenal ulcer associated with zollinger ellison syndrome  the association of a reduced bao with h  pylori suggests that these findings may be related  
class1	enhancement of antibiotic concentrations in gastric mucosa by h2 receptor antagonist  implications for treatment of helicobacter pylori infections  we measured the effects of cimetidine on antibiotic concentrations in the luminal portion of gastric mucosa  guinea pigs were premedicated with cimetidine 4 mg kg intramuscularly  clindamycin  an antibiotic previously characterized under physiologic ph conditions  was administered intramuscularly and levels measured in serum and tissue using a high pressure liquid chromatography  hplc  technique  the luminal mucosa concentration of clindamycin at 1 hr  ph 5 9  was fivefold greater compared to the concentrations seen under physiologic  ph 2 0  conditions  81 5 micrograms g vs 15 9 micrograms g  p less than 0 05  and 10 fold greater at 2 hr  82 7 micrograms g vs 8 09 micrograms g  p less than 0 05   there was no difference in peak serum levels between the groups  the finding that an antibiotic with characteristics of a base is thus affected by a nonconservative acid inhibitor such as cimetidine supports the presence of an acidic storage pool as proposed by other investigators  h2 receptor antagonists may be useful therapeutic adjuncts in h  pylori infections by virtue of increasing gastric concentrations of antibiotics that behave as weak bases  
class1	helicobacter pylori and gastric acid output in peptic ulcer disease  helicobacter pylori is associated with peptic ulcer  and a causal relationship has been postulated  we investigated the association between helicobacter pylori and gastric acid output  two hundred forty one patients were studied  173 with duodenal ulcer  51 with gastric ulcer  41 corpus  10 prepyloric   and 17 with combined gastric and duodenal ulcer  in 194 patients  80    helicobacter pylori could be demonstrated histologically from gastric antral biopsies  the presence or absence of helicobacter pylori was not influenced by age  sex  or use of tobacco or analgesics  patients with duodenal ulcer or combined gastric and duodenal ulcer had similar gastric acid outputs irrespective of the presence or absence of helicobacter pylori  however  gastric ulcer patients with helicobacter had higher basal and maximal acid outputs when compared to patients without helicobacter  mean basal output  4 1 mmol hr vs 2 4  p less than 0 05  mean maximal output 19 5 mmol hr vs  14 4  p less than 0 05   although helicobacter pylori is associated with both gastric ulcer and duodenal ulcer  its significance may be different in the two diseases  
class1	penetration of lanthanum through the main pancreatic duct epithelium in cats following exposure to infected human bile  the main pancreatic duct epithelium acts as a barrier to the diffusion of molecules from the duct lumen into pancreatic acinar and interstitial tissue  we studied sequential ultrastructural characteristics of the loss of epithelial barrier function in the cat using lanthanum  an electron opaque tracer  following perfusion of the duct from the tail to the duodenum with infected human bile  tight junctions between duct epithelial cells were found to become permeable to the tracer as early as after 15 min of exposure  later  there was progressive disintegration of intercellular junctions and epithelial loss  lanthanum penetrated the duct epithelium exclusively on an intercellular path  loss of barrier function of the pancreatic duct epithelium was consistently associated with subsequent development of acute interstitial edematous pancreatitis  there was no association between the degree of duct epithelial damage and the severity of acute pancreatitis  both bile and a suspension of bacteria alone were not harmful to the pancreas  sequential perfusion produced acute pancreatitis only when at first bile and then the bacterial suspension was perfused  a reversed succession of perfusates produced no morphologic alterations  we conclude   1  increased tight junction permeability is an early lesion in acute bile induced pancreatitis   2  loss of duct epithelial barrier function is important for the initiation but not for the severity of the inflammation  and  3  bile renders duct epithelial intercellular junctions vulnerable to escherichia coli bacteria  
class1	a pilot study of the prevalence of herpes genitalis among selected groups of patients seeking care in a family practice center  herpes genitalis is typically studied in patient panels identified at specialized sexually transmitted disease clinics or with information obtained from herpes self help groups  this article reports the results of a descriptive pilot study of the prevalence of herpes genitalis in family practice  the feasibility of obtaining psychosexual information on sexually transmitted diseases from more than 600 patients from five family practice practices was assessed  these initial data show that in the family practices participating in this study  1  genital herpes is a low prevalence disease  2  psychosocial adjustment to the disease among infected persons is usually reported as good  apart from sexual effects  and 3  close to 30  of the study population reported having prior sexually transmitted diseases  problems involved in generalizing the results of this research and the limitations of conducting collaborative clinical research in family practice settings are reviewed  
class1	helicobacter pylori infection in pernicious anemia  a prospective controlled study  although some authors believe that helicobacter pylori is the etiologic agent in chronic nonspecific gastritis  it has also been suggested that the bacterium colonizes inflamed mucosa as a secondary event  this study documents the prevalence of h  pylori in 28 patients with pernicious anemia and compares the findings with those of a group of 28 age   race   and sex matched asymptomatic control subjects  all subjects underwent endoscopy with biopsy of the gastric antrum and corpus  a sample of serum was obtained before endoscopy for determination of antibodies  immunoglobulin a and immunoglobulin g  to h  pylori  the prevalence of h  pylori  by biopsy  in patients with pernicious anemia was significantly less than that in controls  11  vs  71   p less than 0 0001   all patients with pernicious anemia had abnormalities of corpus histology  inflammation and or atrophy   in addition  50  of patients with pernicious anemia had a lymphocytic infiltration of the antrum  all controls with h  pylori had gastritis  50  having active chronic gastritis  atrophic changes of the corpus were more commonly found in patients with pernicious anemia  75  vs  7   p less than 0 0001   serology and biopsy results correlated poorly in the patients with pernicious anemia  all 5 patients with positive serology results had negative biopsy results  whereas all 3 patients with positive cultures on biopsy had negative serological studies  in conclusion  patients with pernicious anemia are protected from infection with h  pylori  and h  pylori does not passively colonize mucosa inflamed by an unrelated process  
class1	selective intestinal decontamination prevents spontaneous bacterial peritonitis  in a prospective randomized study  selective intestinal decontamination with norfloxacin was performed during hospitalization in 32 cirrhotic patients with low ascitic fluid total protein levels  the incidence of infections was compared with that in a control group of 31 nontreated cirrhotic patients of similar characteristics  we found a significantly lower incidence of infections  1 32  3 1   vs  13 31  41 9    p less than 0 005  and spontaneous bacterial peritonitis  0 32  0   vs  7 31  22 5    p less than 0 05  in patients receiving norfloxacin  the lower incidence of extraperitoneal infections  1 32  3 1   vs  7 31  22 5    p   0 052  in the treated group did not reach statistical significance  the incidence of infections  1 28  3 6   vs  9 22  40 9    p less than 0 01  and spontaneous bacterial peritonitis  0 28  0   vs  5 22  22 7    p less than 0 05  in cirrhotic patients admitted because of ascites was also significantly lower in the treated group  the decrease in the rate of mortality observed in the group undergoing selective intestinal decontamination did not reach statistical significance  these data show that selective intestinal decontamination is useful to prevent spontaneous bacterial peritonitis and extraperitoneal infections in hospitalized cirrhotic patients with low ascitic fluid total protein levels  
class1	a rodent model of cirrhosis  ascites  and bacterial peritonitis  we sought to develop a rodent model of spontaneous bacterial peritonitis and report here the preliminary results of carbon tetrachloride induced cirrhosis in which ascites and bacterial peritonitis predictably develop  of 41 rats that survived the initial carbon tetrachloride toxicity  38  92 7   developed cirrhosis with ascites  of these 38  21  55 3   developed 24 episodes of ascitic fluid infection without iatrogenic colonization  no surgically treatable source of infection was identified at autopsy in any rat  therefore  the infections were presumed to be  spontaneous   eight  50   of the 16 rats with culture positive ascitic fluid at postmortem examination also had spontaneous pleural fluid infection with the same organism  escherichia coli and proteus sp  were the organisms most commonly isolated  this rodent model of cirrhosis with ascites appears to be the first high yield animal model of spontaneous bacterial peritonitis  ascitic fluid infection in these rats resembles ascitic fluid infection in humans  this model will allow further investigation of the mechanisms of pathogenesis of ascitic fluid infection and provide insight into the prevention and treatment of spontaneous bacterial peritonitis and pleural fluid infection in patients with cirrhosis  
class1	hepatic injury associated with small bowel bacterial overgrowth in rats is prevented by metronidazole and tetracycline  susceptible rat strains develop hepatobiliary injury following the surgical creation of self filling blind loops that cause small bowel bacterial overgrowth  luminal bacteria or their cell wall polymers were implicated in the pathogenesis of the lesions because sham operated rats and rats with self emptying blind loops  having only slightly increased bacterial counts  did not develop hepatic injury  in this study  antibiotics with different spectra of activities were continuously administered starting 1 day or 22 days after surgery to determine which intestinal flora may be responsible for the development of hepatic injury in rats with small bowel bacterial overgrowth  four weeks following surgery  lewis rats with self filling blind loops receiving no antibiotics had elevated liver histology scores  8 2     1 3 vs  0 7     0 4  and plasma aspartate aminotransferase levels  269     171 vs  84     24  compared with sham operated rats  p less than 0 001  oral gentamicin as well as oral and intraperitoneal polymyxin b  which binds endotoxin  did not prevent hepatic injury in rats with self filling blind loops  however  oral metronidazole and tetracycline therapy continuously administered beginning 1 day after surgery diminished hepatic injury  histology score 3 0     1 8  2 9     1 1  aspartate aminotransferase 87     25  98     34  respectively p less than 0 001 compared with self filling blind loops receiving no antibiotics   metronidazole also protected wistar rats that require 12 weeks to develop hepatic injury following experimentally induced small bowel bacterial overgrowth compared with rats with self filling blind loops that received no antibiotic treatment  histology score 10 4     1 3 vs  0 7     1 1  and aspartate aminotransferase 273     239 vs  76     20  p less than 0 001   when rats started metronidazole therapy 22 days after self filling blind loop surgery  elevated aspartate aminotransferase values decreased to normal during the next 77 days and final histology scores were normal  all rats with self filling blind loops had negative peritoneal  liver  spleen  and blood cultures but approximately 75  of mesenteric lymph node cultures were positive irrespective of antibiotic treatment  because bacteroides species have been implicated in causing vitamin b12 and disaccharidase deficiencies in rats with self filling blind loops  we documented the presence or absence of these organisms from blind loops using selective culture techniques  metronidazole and tetracycline eliminated bacteroides sp  from blind loops  but polymyxin b and gentamicin did not  abstract truncated at 400 words   
class1	managing prostatitis in the elderly  bacterial prostatitis is primarily a disease of elderly men  and it is the most common urinary tract infection seen in this age group  urosepsis from prostatitis or prostatic abscess occurs less frequently than with urological manipulation  but must always be considered in elderly men with prostatitis  this article focuses on the diagnosis and antibiotic treatment of bacterial prostatitis in the elderly  
class1	large diameter expanded polytetrafluoroethylene grafts for infrarenal aortic aneurysm surgery  the performance of an expanded polytetrafluoroethylene  eptfe  graft used for aortic aneurysm replacement was evaluated  eptfe grafts were implanted in 241 patients undergoing infrarenal abdominal aortic aneurysm  aaa  repair  sixty patients were operated as emergencies for aneurysm rupture and 181 electively  one hundred and fourteen bifurcated and 127 tube grafts were inserted  the transperitoneal approach was used in 64 cases and the remainder were placed using a retroperitoneal approach  there was a one month mortality of 2 8  in elective and 20  in emergency cases  median follow up was 26 months  specific graft complications included one infected graft resulting in a graft enteric fistula  no graft rupture  degeneration  dilatation  pseudoaneurysm or late graft limb thromboses were observed in up to 7 years of follow up  the aortic eptfe prosthesis demonstrated satisfactory performance over the period studied  
class1	campylobacter fetus infection of abdominal aortic aneurysm  a 61 year old man with campylobacter fetus infection of an abdominal aortic aneurysm treated surgically is presented herein  the fifth survival case reported in the literature  fever and back pain preceded the enlargement of atherosclerotic abdominal aortic aneurysm  the patient tolerated satisfactorily total excision of the aneurysm followed by axillo femoral prosthetic bypass  antibiotic therapy consisted of intravenous infusion of fosfomycin and gentamicin and oral administration of minocycline  the organism cultured from the aneurysmal wall and intraluminal thrombi was identified as campylobacter fetus from its typical characteristics  it is concluded that this organism should be considered in all cases of infected aneurysm in elderly or debilitated patients  
class1	wound infection following early repeat sternotomy for postoperative bleeding  an experience utilizing intraoperative irrigation with povidone iodine  a prospective observational study of median sternotomy wound infection was carried out in two consecutive groups of unselected patients undergoing early repeat sternotomy for postoperative haemorrhage  in group a the pericardial cavity and sternotomy wound layers were irrigated with aqueous povidone iodine prior to repeat closure  while group b did not receive povidone iodine  no median sternotomy infections were recorded in group a compared to 5 cases in group b  0 out of 22 vs 5 out of 21 patients  p less than 0 05   amongst the patients with wound infection  three developed sternal dehiscence and mediastinitis with one death  the data suggests that povidone iodine irrigation may be effective in reducing wound infection in patients undergoing early repeat sternotomy after cardiac surgery  
class1	infective endocarditis and an embolomycotic aneurysm in a 25 month old child  infective endocarditis in young children is uncommon  especially where there is no underlying structural heart disease  while septic embolization in adults occurs in up to 43  of the cases of endocarditis  there is little data on systemic embolization in cases of children  we present an unusual case of a 25 month old child with infective endocarditis and an embolomycotic aneurysm treated by mitral valve replacement and aortoiliac reconstruction  
class1	antibody coated bacteria in urine of patients with recent spinal injury  twenty patients with an acute spinal injury were prospectively studied to assess the clinical importance of antibody coated bacteria  acb  in the urine and the association among the different bacterial species with a positive antibody coated bacteria test  clinical urinary tract infection was associated with a positive acb test on 45  of occasions  three hundred and ninety nine urine samples containing 541 bacterial isolates were assessed for the presence of acb  13  were found to be positive and 87  negative for acb  67  of urines contained a single bacterial isolate  pseudomonas aeruginosa was most commonly associated with clinical urinary tract infection  found in 25  of episodes  followed by proteus mirabilis  17 5    klebsiella sp  12 5    and proteus morganii  10    providencia stuartii  however  was most commonly associated with a positive acb test  found in 17    other bacteria associated with a positive acb test included klebsiella sp  14    acinetobacter sp  12 5    pseudomonas aeruginosa  12    citrobacter sp  11 5    a positive acb test is not to be expected from a patient with spinal injury who has a catheter in place  and the test may provide a useful guide to identify those patients with an invasive infection  it is doubtful that a decision to treat or not treat bacteriuria could rest on the identification of the bacterial species alone  
class1	computer generated physician and patient reminders  tools to improve population adherence to selected preventive services  despite an emerging consensus on appropriate preventive services  a minority of patients receive them  a study was undertaken to assess the impact of computer generated reminders to adult patients  their physicians  or both patients and physicians on adherence to five recommended preventive services  cholesterol measurements  fecal occult blood testing  mammography  papanicolaou smears  and tetanus immunization  during the academic year 1988 1989  all 7397 adult patients and their 49 physicians in a university family medicine clinical practice were randomized by practice group into one of four study groups  control  physician reminders  patient reminders  and both physician and patient reminders  adherence was defined in community oriented terms  the percentage of patients within each group who had received the preventive service in the recommended interval  during the study period  adherence to four of the five preventive services increased significantly  with the largest increases in the physician and patient reminder group  cholesterol measurements increased from 19 5  to 38 1   fecal occult blood testing 9 3  to 27 0   mammography 11 4  to 27 1   and tetanus immunization 23 4  to 35 4   for each increase  p less than  0001  mcnemar s chi square test   in general  increases were greater in blacks and in patients with any form of insurance coverage  computer based physician and patient reminder systems have great promise of improving adherence to preventive services in primary care settings  
class1	a phase ii clinical trial of carboplatin infusion in high risk acute nonlymphoblastic leukemia  carboplatin  cbdca  is a second generation platinum drug that has been shown to be useful when used as a continuous infusion in treatment of refractory adult leukemia  we report on the effectiveness of continuous infusion cbdca  300 mg m2 d x 5 days  as evaluated in nine patients with secondary acute nonlymphocytic leukemia  anll   seven previous myelodysplastic syndrome and two treatment associated anll   three anll patients in first relapse  six refractory anll  and nine patients with blastic phase of chronic myelogenous leukemia  bp cml   all patients were considered assessable  the response rate was 44   eight complete remissions  crs   four partial remissions  prs    median duration of postchemotherapy neutropenia was 36 days  range  18 to 45   therapy was well tolerated  and toxicity was mainly hematologic and nondose limiting  despite prolonged neutropenia  severe infections were rarely seen  and most patients were managed as outpatients  twelve patients had nausea and vomiting  two had symptomatic hypomagnesemia  and one patient showed reversible ototoxicity  because of substantial antileukemic activity and unusual extrahematologic toxicity  cbdca appears to be an effective second line agent in the treatment of anll and should be considered for upgrading to first line treatment regimens  
class1	nosocomial pneumonia in adult patients undergoing bone marrow transplantation  a 9 year study  two hundred seventy five consecutive patients treated with bone marrow transplantation  bmt  during a 9 year interval were analyzed for the incidence and etiology of nosocomial pneumonia  cases included adults who acquired pneumonia during the first hospitalization period within 100 days of the transplant  fifty five  20   of the 275 patients developed nosocomial pneumonia  and the crude mortality during the hospitalization period was 74 5   an etiology was established in 67 3   37 of 55  of episodes  thirty six percent  20 of 55  of the cases were caused by aspergillus species  either as the sole agent  15 patients  or in association with others  the crude mortality for patients with aspergillus pneumonia was 95   elimination of 90  of aspergillus cases in our unit would have the effect of reducing the overall attack rate of nosocomial pneumonia to 13 4  and the associated crude mortality to 43 4   
class1	person to person transmission of brucella melitensis human brucellosis is primarily an occupational hazard in the usa  in the middle east and africa ingestion of contaminated dairy products is an important route of infection  whether human beings can become infected via person to person spread is uncertain  during an investigation of a commonsource  laboratory associated outbreak due to brucella melitensis  biotype 3  the wife of a microbiologist with serologically proven brucellosis became infected  her blood isolate was indistinguishable from the epidemic strain  in the absence of other risk factors  we suggest that sexual intercourse is a possible means of transmission  
class1	nd yag laser in the microsurgery of frontobasal meningiomas  forty three patients with big frontobasal meningiomas underwent a microsurgical removal of the tumor  the 1 32 microns nd yag laser has proved useful in this prospective series particularly with the contactless shrinkage of the tumors and the necrotization of the dural and bony attachments  tumor shrinkage was achieved by radiating the tumor surface with the nd yag laser  this technique facilitated the microsurgical dissection and reduced the blood loss by half  the nd yag laser necrotization of the dural and bony attachments reduced the recurrence rate following grade two resections from 20  to zero  the postoperative quality of life was excellent with a complete rehabilitation in 76  of the patients  the use of the 1 32 microns nd yag laser improved significantly the results of microsurgery for frontobasal meningioma  
class1	dexamethasone as an adjunct in oropharyngeal obstruction in a patient with leukemia  incipient airway obstruction due to fulminating bacterial infection of pharyngeal tissues requires prompt and definitive intervention  a case is presented in which dexamethasone was a key adjunct to antibiotic therapy in averting this problem in a severely neutropenic patient with acute leukemia  
class1	reactions of rat odontogenic tissues to heat  twenty four wistar rats were anesthetized and 200 degrees c heat was applied for 4 minutes to each mandibular left first molar  eight of these rats were then killed at 2  8  and 14 weeks  the subject and control teeth were radiographed and compared  they were then prepared for histologic evaluation and scored for levels of inflammation in both the pulpal and periradicular tissues  furcal  interproximal  and apical radiographic changes were found at all three time intervals  these changes involved progressively larger percentages of teeth at 8 and 14 weeks  histologically  complete necrosis and or abscess formation were found in the coronal portions of all experimental pulps  with time  inflammatory changes increased in intensity and progressed through the radicular pulps  resulting in necrosis or calcific changes and  finally  inflammatory changes in the periradicular areas  the pathosis created by the application of heat was devoid of microorganisms as evaluated by the brown and brenn stain  
class1	short course chemotherapy for childhood tuberculosis a prospective study  with an attempted 24 month post treatment follow up  of children with tuberculosis  tb  treated with short course chemotherapy  scc  for 6 months was carried out because published experience of scc in childhood tb was limited  all children in port moresby diagnosed as having tb between november  1984  and november  1986  entered the trial  of the 639 children 165  26   were younger than 2 years old  of these  227  35   had extrapulmonary tb  peripheral lymph node  110  central nervous system  43  abdominal  27  miliary  16  bone and joint  11  pleural  11  polyserositis  9   clinical response to scc was rapid  adverse drug reactions occurred in 15  2    mainly to streptomycin  twelve  2   died  38  6   transferred out and 145  28  of the 518 who did not die  transfer or live too far from a treatment centre  defaulted  three hundred seventy three  58   completed a 2 month course of daily rifampin  isoniazid  pyrazinamide and streptomycin followed by a 4 month course of twice weekly rifampin and isoniazid  a further 71  11   had their treatment modified because of their distance from a treatment center  only 70  19   of the 373 children available for post treatment follow up attended the every 3 month follow up visits for 24 months  although 223  60   attended one or more of the follow up visits  seven of the 373 children relapsed  mostly within 3 months  five of these children had been irregular with their treatment  scc for childhood tb is safe and effective for pulmonary and extrapulmonary disease  
class1	a randomized trial of fully intermittent vs  daily followed by intermittent short course chemotherapy for childhood tuberculosis fully intermittent short course chemotherapy regimens have been used successfully in adults but not in children  we report the results on 76 children with tuberculosis  excluding central nervous system tuberculosis and primary pulmonary complex  isoniazid  rifampin and pyrazinamide were used for treatment  they were randomly allocated to regimen a  52 doses  and regimen b  94 doses   overall efficacy of both schedules was greater than 95  in 27 children with lymphatic  43 with pulmonary and 6 with disseminated tuberculosis  compliance in 10 children after 2 to 4 months of therapy was poor because rapid improvement was mistaken by parents for cure  two children died  probably of underlying lung disease  follow up for up to 2 years did not reveal any case of relapse or recurrence of the disease  therapy for 6 months involving administration of only 52 or 94 doses of drugs was found to be economical  effective and safe for treating children with tuberculosis  
class1	cefotaxime and aminoglycoside treatment of meningitis caused by gram negative enteric organisms  we reviewed cases of gram negative enteric bacillary meningitis in infants and children treated with cefotaxime at texas children s hospital from january  1984  through june  1989  seventeen of 20 children had an underlying condition predisposing to the development of meningitis  the etiologic organisms in these 20 children  2 days to 12 years old  median  12 days old  were klebsiella sp  9  escherichia coli  4  enterobacter cloacae  3  citrobacter diversus  2  other  2  with the exception of one isolate of acinetobacter  all isolates were susceptible to cefotaxime  in addition to cefotaxime 17 children received an aminoglycoside intravenously  children with meningitis caused by klebsiella sp  or non klebsiella organisms received cefotaxime for 31     14 and 37     17 days  respectively  aminoglycosides were administered for 16     10 days in both groups  five children in each group also received intraventricular doses  1 to 25  of an aminoglycoside  9  or colistimethate  1   the mean durations of positive lumbar  ventricular cerebrospinal fluid or brain abscess cultures were 5 8     4 7 and 7 2     5 0 days after start of therapy in the klebsiella and non klebsiella meningitis patients  respectively  only three children were normal at the time of discharge or follow up  gram negative enteric meningitis remains difficult to treat despite the excellent in vitro activity of cefotaxime against gram negative enterics  in part as a result of the predisposing conditions resulting in the development of this infection  
class1	utility of collecting blood cultures through newly inserted intravenous catheters  we prospectively examined the utility of obtaining blood cultures through newly inserted intravenous catheters in 99 children who required both a blood culture and placement of an intravenous catheter  two blood cultures were collected from each patient  one through a freshly inserted intravenous catheter and another through a butterfly needle at a separate venipuncture site  a standardized technique of skin preparation with povidone iodine was used  the rate of contamination was 1 0   95  confidence intervals  0 to 3 0   for each method  ten patients had blood cultures yielding true pathogens  in five of these bacteremic children  only one of two sets of blood cultures was positive  we conclude that blood cultures can be collected through freshly placed intravenous catheters without increasing the risk of contamination  these results also raise the possibility that obtaining two blood cultures instead of a single culture may improve the detection of bacteremia in children  
class1	a ten year review of neonatal sepsis and comparison with the previous fifty year experience  records have been kept prospectively in our institution since 1928 of all positive blood cultures taken from neonates  using a modification of objective centers for disease control criteria to define sepsis  we reviewed the records of all neonates with positive blood cultures for the years 1979 to 1988 inclusive and found 270 cases of sepsis  the sepsis rate for infants less than or equal to 30 days of age was 2 7 cases 1000 live births  with a mortality rate from sepsis of 15 9   there was an increase in sepsis due to commensal species  cs  over the period  p less than 0 007   the number of infants in the nursery who developed sepsis when more than 30 days of age also increased  p less than 0 002   as did the rate of sepsis from cs in this group  p less than 0 001   isolation of cs from the blood with fulfillment of the modified centers for disease control criteria was associated with a 13 7  mortality rate  whereas isolation of cs without fulfillment was associated with a 4  rate  p less than 0 01   
class1	management of asymptomatic  term gestation neonates born to mothers treated with intrapartum antibiotics  intrapartum antibiotics are frequently administered to parturient women for suspected chorioamnionitis to treat infection in the mother and to prevent or treat infection in the baby  we sent a questionnaire to the 150 united states fellowship program directors in neonatology and pediatric infectious disease  focusing on recommendations for evaluation and therapy of apparently healthy  pretreated  term gestation infants  eighty three  55   of the completed responses were analyzed  sixteen  19   respondents do no initial laboratory evaluation but simply observe the baby  65  78   take a complete blood count as well as a platelet count  59  71   obtain blood cultures  41  49   check urine antigen for group b streptococcus  gbs  and 23  28   perform a lumbar puncture  only 39  of respondents would begin antibiotic therapy for all pretreated infants  if the evaluation were unremarkable 65 directors would treat for less than or equal to 3 days  if only the urine gbs antigen were positive 47 would treat for greater than or equal to 7 days  while if an elevated immature neutrophil total neutrophil ratio were the sole abnormality 19 would treat for greater than or equal to 7 days  forty four respondents thought that a combination of an elevated immature neutrophil total neutrophil ratio and a positive urine gbs antigen should always be considered indicative of bacteremia  given a different scenario  that of a mother treated with intrapartum antibiotics because of a positive cervical culture for gbs and a risk factor  e g  temperature greater than or equal to 38 degrees c   58 respondents would begin antibiotics  there is no consensus regarding management of pretreated  healthy appearing  term gestation neonates  
class1	syphilis  a new visit from an old enemy  syphilis has a number of stages  including a latent one  and may be overlooked or misdiagnosed if the possibility is not kept in mind  adequate treatment during the primary stage results in a very high cure rate  the latent stage may last for years  during which time a woman may still give birth to an infected child  symptomatic neurosyphilis occurs more often in men than women  penicillin g is preferred to treat all stages of the disease  other antibiotics can be used for patients sensitive to penicillin  
class1	the butterfly rash and the malar flush  what diseases do these signs reflect  the butterfly rash and malar flush are common facial manifestations of several disorders  systemic lupus erythematosus may produce a transient rash before any other signs  in pellagra  symmetric keratotic areas on the face are always accompanied by lesions elsewhere on the body  erysipelas produces brawny  fiery red facial lesions  and scarlet fever causes facial eruptions as part of a generalized eruption  lupus vulgaris and lupus pernio produce nodules that may spread in a butterfly pattern  and seborrheic dermatitis has a predilection for the malar prominences and other areas of the face  carcinoid syndrome often causes flushing attacks that vary in duration  and facial flushing that lasts throughout treatment may accompany chemotherapy if the patient has a hypersensitivity reaction  deep red rashes and or lichenoid lesions may be caused by graft versus host disease in a patient undergoing bone marrow transplantation  
class1	the neurologic workup in patients with cervical spine disorders  care must be exercised in interpreting the clinical and radiologic findings when assessing patients with cervical spondylosis and involvement of neural structures for surgery  if the clinical picture cannot logically be explained by the radiologic findings  further investigation is indicated to exclude a coexistent disorder  investigations may include electrophysiologic tests  transcranial magnetic stimulation  cerebrospinal fluid  csf  analysis  and magnetic resonance imaging  mri   only then can the indication for surgical intervention be properly determined  
class1	lumbar puncture frequency and cerebrospinal fluid analysis in the neonate  a prospective study was performed to assess the frequency and diagnostic utility of lumbar punctures in neonates both during their first week of life and thereafter  during the two 6 month periods from january 1  1985 to june 30  1985  and february 1  1986 to july 31  1986  712 neonates underwent 728 lumbar punctures during their first week of life primarily as part of the evaluation for suspected infection  either congenital or postnatal  there were eight patients with positive spinal fluid cultures in the first week of life  but only one patient simultaneously had a positive blood culture and a clinical course consistent with meningitis  in contrast  a considerably higher yield  approximating five times that of the first week of life  was obtained in patients undergoing a lumbar puncture after the first week of life  
class1	acute osteomyelitis in children  reassessment of etiologic agents and their clinical characteristics  one hundred thirty five children with acute osteomyelitis were identified by chart review during a 7 year period  january 1  1980  through december 31  1986  bacteriologic causes were detected in 75  55   of the patients  staphylococcus aureus  haemophilus influenzae type b  and pseudomonas aeruginosa were identified in 34  25    16  12    and eight  6   children  respectively  staphylococcus aureus occurred in all age groups  h influenzae type b occurred only in children younger than 3 years and was the number one cause of disease in this group  pseudomonas aeruginosa occurred exclusively in children older than 9 years  children with h influenzae type b had clinical and laboratory findings that were almost indistinguishable from a matched group of children with osteomyelitis due to other known bacteria  although children with h influenzae type b tended to have more joint effusions  63  vs 27    less lower extremity disease  22  vs 70    and fewer positive cultures from bone or joint aspirates  41  vs 89    unlike most pediatric cases of osteomyelitis  the ones due to p aeruginosa did not represent the hematogenous route of infection  penetrating injury to the foot was present in every case  children with p aeruginosa infections were older than 9 years  100    predominantly male  88    often afebrile  83    and never bacteremic  these data provide guidelines for the initial work up and management of osteomyelitis in children  
class1	pneumococcal osteomyelitis and arthritis in children  a hospital series and literature review  twenty nine children with pneumococcal osteomyelitis and or arthritis  11 of whom had osteomyelitis  were treated at cook county hospital  chicago  ill  in the past 20 years  they were mostly normal children with a single focus of infection  they represented more than 5  of the hospitalized children with a systemic pneumococcal infection  most of the pneumococcal isolates were serotyped  serotype 19  in particular  seemed to be unusually common in these children  twenty three of the 29 children with pneumococcal osteomyelitis and or arthritis had been hospitalized in the past 15 years  these 23 children were compared with 161 hospitalized children who had bone and joint infections with other isolated bacteria  the children with pneumococcal osteomyelitis and or arthritis were indistinguishable from most of the other children  except by age  all but three of the children with pneumococcal osteomyelitis and or arthritis were between the ages of 3 and 24 months  in this age group  pneumococcus was the common isolate from children with osteomyelitis  and second only to haemophilus influenzae from children with bacterial arthritis  pneumococcal osteomyelitis and or arthritis has never been rare  the medical literature describes at least 245 other children  most of whom were younger than 2 years  
class1	differences in expression of cystic fibrosis in blacks and whites  the recent identification of the cystic fibrosis  cf  gene confirms that genetic heterogeneity occurs in cf  a three base pair deletion in exon 10 resulting in a loss of the phenylalanine residue at amino acid position 508 of the gene product  termed the cf conductance regulator protein  accounts for 70  of cases of cf in white subjects  however  this gene defect occurs in only 37  of affected blacks  analysis of cf genes from american blacks has revealed a number of mutations  most of which are unique to that population  we therefore searched for potential differences in expression of cf between 24 black and 48 white patients with cf matched for birth date and gender  black patients more frequently presented with only respiratory symptoms  38  vs 10    black patients had fewer hospitalizations for pulmonary exacerbations  2 vs 6 9   a better mean forced vital capacity  77  vs 62  of predicted   and higher chest roentgenogram scores  18 2 vs 14 4  than white patients  complication rates were similar except for a higher incidence of hyponatremic dehydration  21  vs 2   and peptic ulcer disease  13  vs 0   in blacks  survival time appeared to be longer in blacks  but the difference was not statistically significant  we conclude that phenotypic differences exist between black and white patients with cf  which may be due to the genetic heterogeneity between these two populations  
class1	hemochromatosis and infection  alcohol and iron  oysters and sepsis  hemochromatosis  or primary iron overload  is a variably expressed genetic metabolic disorder greatly modified by sex  age  diet  and alcohol consumption  although a diagnosis has been made at the bedside by careful documentation of the slow resolution of subcutaneous iron pigment  clinical diagnosis is frequently overlooked  and even autopsy may fail to reveal hemochromatosis as the cause for cirrhosis  genetic linkage studies have confirmed the extremely high prevalence of this disorder  untreated patients may succumb to sepsis caused by organisms such as vibrio vulnificus  yersinia species  and others whose virulence is altered by iron availability  
class1	surgical removal of subfoveal neovascularization in the presumed ocular histoplasmosis syndrome  we treated two patients with presumed ocular histoplasmosis  subfoveal neovascular membranes  and progressive visual acuity loss to 20 400  vitreoretinal surgical techniques were used to remove the subfoveal membranes  visual acuity returned to 20 20 with seven months of follow up in one patient  case 1  and to 20 40 with three months of follow up in the other patient  case 2   no evidence of persistent or current subretinal neovascular membranes in either patient have been noted  these preliminary results suggest that vitreoretinal surgical techniques may be successful in mechanically removing subfoveal neovascular membranes with preservation of overlying neurosensory retina and thus preservation of central visual acuity  
class1	epidemiologic characteristics  predisposing factors  and etiologic diagnosis of corneal ulceration in nepal  corneal ulceration is one of the most frequent causes of blindness in developing countries  between september 1985 and august 1987  405 patients with corneal ulceration were examined at tribhuvan university teaching hospital in kathmandu  nepal  males and females were equally affected  the most common predisposing cause of ulceration was corneal trauma  usually with organic agricultural materials  microorganisms were grown from 324  80   of the ulcers  pure bacterial cultures were obtained from 256  63 2   of the patients  whereas pure fungal cultures were obtained from 27  6 7   of the patients  in 41 patients  10 1    corneal cultures yielded a mixed growth of bacteria and fungi  of a total of 398 bacterial isolates  124  31 1   were positive for streptococcus pneumoniae  the most commonly isolated organism in the series  other frequently isolated bacteria included staphylococcus epidermidis  s  aureus  and pseudomonas species  of 68 positive fungal isolates obtained  32  47 0   were identified as aspergillus species  candida species and fusarium species were less commonly seen  
class1	risks of intestinal anastomoses in crohn s disease  six hundred fifty eight intestinal anastomoses in 429 operations for crohn s disease were studied prospectively during an 8 year period to detect variables connected with perioperative morbidity  postoperative complications occurred in 9 7  of the patients  4  had to be reoperated on  and the overall mortality rate was 0 5   in multivariate analysis by stepwise logistic regression  the only variable significantly  p   0 03  associated with overall rate of complications was long term corticosteroid therapy  serious complications were more common in cases of intra abdominal abscesses  p   0 01  and preoperative steroid medication  p   0 03   the combination of both of these risk factors increased the rate of reoperations from 0 6   no steroids  no abscess  to 16   steroids and abscess   no significant association with postoperative complications could be found for age  sex  duration of disease  previous operations  nutritional status  emergency surgery  extent of disease  type  number  and localization of anastomoses  presence of proximal ileo  colostomy  or histologically inflamed margins of resection  
class1	metabolic changes in patients severely affected by tetanus  metabolic changes in six severely affected tetanus patients suffering from characteristic labile hypertension  maximum systolic blood pressure greater than 200 mmhg  maximum diurnal change in systolic pressure greater than 100 mmhg  were investigated  daily urinary excretion of urea nitrogen increased gradually from the onset of opisthotonus  reached a peak value  10 4 to 15 4 g m2  in 8 to 20 days  and decreased subsequently  average cumulative excretion in 30 days reached 239 6     32 7 g m2  urine catecholamine excretion was elevated in each patient and remained elevated during this period  plasma cortisol and glucagon concentrations were not increased markedly except in a case complicated other systemic bacterial infection  increased protein catabolism in these patients could not be explained by the metabolic effects of  stressed hormones  alone  and neurologic factors must be considered  
class1	role of granulocyte elastase in tissue injury in patients with septic shock complicated by multiple organ failure  to better understand the role of granulocyte elastase  ge  in mediating tissue injury during sepsis  ge levels were measured in plasma and bronchoalveolar lavage fluid  balf  in patients with septic shock  n   16  and hemorrhagic shock  n   30   granulocyte elastase levels were compared to levels of alpha 1 protease inhibitor  alpha 1 pi   results show that although plasma ge alpha 1 pi complex was initially elevated in patients with hemorrhagic and septic shock  elevations in plasma ge alpha 1 pi complex  831     241 micrograms l  persisted in septic shock patients  alpha 1 protease inhibitor levels in serum were increased  resulting in an inhibition of serum ge activity  granulocyte elastase activity in balf  however  was significantly higher in those patients with septic  as compared to hemorrhagic shock  31 4     25 8 versus 3 7     4 0 u l  respectively   in addition ge levels were compared to other parameters  including respiratory index  blood neutrophil count  and plasma levels of endotoxin  fibronectin  and coagulation factor xiii  significant correlations were observed between ge alpha 1 pi and increased endotoxin concentration and decreased fibronectin and coagulation factor xiii levels  significant correlation was found also between ge activity in balf and respiratory index  these findings suggest that severe tissue damage occurred in patients with septic shock complicated by multiple organ failure  although ge activity appeared to be adequately inhibited by alpha 1 pi in blood  increased ge activity in local tissues  such as lung alveoli  may be responsible for significant local tissue injury during septic shock  
class1	valve replacement in patients with endocarditis and cerebral septic emboli  cerebral septic emboli complicate the cases in 20  to 40  of patients with left sided endocarditis but the management of these patients who require a valvar operation remains unclear  from 1980 to 1988  the incidence of cerebral septic embolus was 42   n   45  among 106 patients with endocarditis who underwent valve replacement at the university of illinois hospital in chicago  of these 45 patients  69   n   31  had symptomatic cerebral septic infarctions and 31   n   14  were asymptomatic  findings on cerebral computed tomographic scans included ischemic infarcts  n   36  80    hemorrhagic infarcts  n   5  11    normal studies  n   2  4    and unknown  n   2  4    neurological complications after valve replacement included postoperative strokes  n   6  6    cerebral abscesses  n   2  2    and seizure  n   1  1    the presence of a hemorrhagic infarct preoperatively predisposed to a perioperative stroke  p less than 0 05   in conclusion  cerebral septic infarctions  both symptomatic and asymptomatic  are common among patients with endocarditis referred for valvar operation  in the absence of a hemorrhagic infarct  valve replacement can be performed with minimal risk of a perioperative stroke  
class1	empyema thoracis  14 year experience in a teaching center  one hundred two patients with empyema thoracis were managed at the royal melbourne hospital between 1976 and 1989  fifty five cases of empyema thoracis were postpneumonic  8 followed esophageal rupture  and 5 were associated with thoracic trauma  some form of systemic illness was a major contributing factor in the presentation of 29 patients  a single causal organism was found in 53 patients  the most common being staphylococcus aureus   multiple organisms in 36  and no growth in 13  during the years 1983 to 1989 there was an increased incidence of empyemas caused by multiple or antibiotic resistant organisms  operative drainage was required in 90 patients and 12 were managed by thoracentesis or intercostal tube drainage alone  the in hospital mortality rate for patients managed nonoperatively was 58   7 of 12 patients   it was 16   14 of 90 patients  for those receiving operative drainage  there were seven late deaths  four empyema related and three nonrelated  early adequate operative drainage is recommended for patients with empyema thoracis  
class1	acute rheumatic fever in west virginia  not just a disease of children  rheumatic fever is a poststreptococcal disease that is receiving renewed attention by the medical community  we describe a recent increase in the number of observed cases of acute rheumatic fever  arf  in west virginia  this is the fifth report of a recent increase in the incidence of arf in the ohio valley area in the last 4 years  in contrast to the other reports  nearly two thirds of our cases of arf were in adults  more than half of whom had suffered previous bouts of arf  in these adults with recurrences  none was taking prophylactic penicillin at the time of presentation  carditis was present in seven adults  two without a history of carditis  arthritis was present in all adult patients  these data indicate a possible geographic phenomenon related to the increased number of observed cases of arf and document that arf is not simply a disease of childhood  furthermore  our findings highlight the need for extended penicillin prophylaxis for secondary prevention of arf  especially for those with an increased risk of acquiring a streptococcal upper respiratory tract infection  
class1	gonococcal osteomyelitis  case report and review of the literature  we report the 11th case of gonococcal osteomyelitis in the postantibiotic era  this case demonstrates the classic presentation of osteomyelitis associated with gonorrhea  a subacute illness with minimal systemic symptoms  in addition  we present radiologic evidence of the pathogenesis of this unusual osteomyelitis from a contiguous joint infection  
class1	studies of the route  magnitude  and time course of bacterial translocation in a model of systemic inflammation  bacteria have been documented to translocate from the gut to systemic organs  yet the exact route by which they translocate remains unclear  to determine the route of bacterial translocation  different dosages of zymosan were used to activate complement and cause systemic inflammation  at a zymosan dose of 0 1 mg g  bacteria translocated only to the mesenteric lymph node complex  whereas at a dose of 0 5 mg g the bacteria translocated systematically  in rats receiving 0 5 mg g doses of zymosan  the bacteria appeared to reach systemic organs via the portal blood rather than via the mesenteric lymph  as bacteria were present in 87  of portal blood samples but only 25  of lymph samples  the number of bacteria exiting the portal vein was 11 500 times greater than the number exiting via the lymph  thus  both the route and extent of bacterial translocation varies based on the magnitude of the inflammatory insult  with the portal blood being the major route of bacterial translocation to systemic organs  
class1	fungal burn wound infection  a 10 year experience  to evaluate our experience with fungal burn wound infection  we performed a 10 year review for comparison with our experience with bacterial burn wound infection  during the study period  a marked decline occurred in bacterial wound infection but not in fungal wound infection  patients with either bacterial or fungal burn wound infection had massive injury  with burn size averaging greater than 50  of the total body surface area  factors that appear to have markedly reduced bacterial burn wound infection  including patient isolation  topical chemotherapeutic agents  and burn wound excision  do not appear to have had a similar effect on fungal wound infection  the mechanism of spread and colonization of fungi  and the lack of effective topical chemotherapeutic antifungal agents  may explain in part our findings  
class1	effect of aerosolized fibrin solution on intraperitoneal contamination  the potential deleterious effects of aerosolized fibrin on contaminated procedures were investigated in a rat model of peritonitis  one hundred forty rats were divided into two groups  in the control group  gelatin capsules containing feces  10 7  bacteria per milliliter  and barium sulfate at various dilutions were placed into the abdomen  in the second experimental group  a solution of cryoprecipitate  thrombin  and calcium was sprayed diffusely into the peritoneal cavity after similar fecal contamination  fecal inocula with low bacterial concentrations  0 01  0 1  and 0 15 ml  caused few deaths from peritonitis or abscess formation in either group  heavy peritoneal contamination  0 25  0 3  and 0 5 ml  caused early deaths from peritonitis in both groups  with 80  of the deaths due to sepsis in the first 48 hours  however  in the moderately contaminated rats  0 2 ml of fecal inoculate   fibrin aerosol reduced the 10 day mortality from 80  to 10   in all survivors in the fibrin treated group  intraperitoneal abscesses developed  with intraperitoneal bacterial concentrations of 2 x 10 6  organisms  early acute mortality from fibrinopurulent peritonitis is decreased at the expense of late  localized  nonlethal abscess formation  aerosolized fibrin solution must be used with caution in contaminated surgery  
class1	the epidemiologic features of nosocomial infections in patients with trauma  sepsis is a major cause of morbidity and mortality in patients with trauma  to elucidate factors that might lead to infection  we studied the epidemiologic characteristics of nosocomial infections in our patient population with trauma  during a 3 5 year period  2496 patients were entered into our hospital trauma registry and cross matched with hospital infection control surveillance information  two hundred twenty nine patients with trauma and nosocomial infections were identified  9 2    a figure that was nearly twice the nosocomial infection rate for the general hospital population  the majority of those infected were either orthopedic  51    general surgical  25    or neurosurgical  13   patients  the most common sites of first infection were urinary tract  61   or respiratory system  14    patients developing nosocomial infections were significantly older and had a higher injury severity score than those who did not  injury site was related to risk of infection with injuries of the spine  chest  and extremity showing the most significant relationship  the length of stay as well as hospital charges were significantly related to the occurrence of infectious complications  by determining the patient with trauma at risk for infection  treatment strategies can be designed to minimize septic complications  
class1	the febrile alcoholic in the emergency department  the authors retrospectively reviewed the charts of 31 alcoholic patients admitted with fever without a defined source  in our population 58  of patients were subsequently found to have an infectious cause for their fever  pneumonia was the most common infection  but occult urinary tract infections were seen surprisingly often  noninfectious but serious disorders  such as delirium tremens  prolonged postictal state  and subarachnoid hemorrhage  were also common  infectious and noninfectious causes commonly coexisted  the most common noninfectious cause was alcohol withdrawal  with or without seizures  the authors believe that indigent  malnourished  chronic alcoholics with fever for which a source cannot be readily identified  should usually be admitted to the hospital for observation and to await culture results  
class1	perianal streptococcal cellulitis with penile involvement  perianal streptococcal cellulitis is described occurring in a 5 year old boy  the condition also involved the penis and presented as a possible case of sexual abuse  the correct diagnosis was established by culturing beta haemolytic streptococci group a from the penile and perianal skin  
class1	neutrophil function and pyogenic infections in bone marrow transplant recipients  in a consecutive entry trial  the incidence and time course of decreased neutrophil function was assessed in 20 patients treated with allogeneic bone marrow transplantation  bmt   the aim of the study was to assess the prognostic value of low neutrophil function for late pyogenic infections  chemotaxis  superoxide production  and phagocytic bactericidal activity were studied before and 2  6  9  and 12 months after bmt  skin window migration was quantitatively assessed 2 months after bmt  infectious complications were recorded prospectively with preset criteria during 1 year  six of the 20 leukemic patients had defective neutrophil function before bmt  two months after bmt all 10 patients with greater than stage ii graft versus host disease  gvhd   and 6 of 10 patients with less than or equal to stage ii gvhd had at least one decreased function  at this time  patients with subsequent pyogenic infections had lower chemotaxis  p less than  05   phagocytic bactericidal activity  p less than  005   and superoxide production  p less than  025  than those without  defective skin window migration and combined defects were predictive for late pyogenic infections  at 9 months all tests were normal in seven patients surviving without gvhd  in contrast  at 9 months three of three patients  and at 1 year two of three with chronic gvhd had still decreased neutrophil function  in conclusion  neutrophil function is frequently impaired during the first months after bmt  combined neutrophil defects predispose to pyogenic infections and indicate the patient at risk  
class1	acute epididymitis  why patient and consort must be investigated  in this prospective study of 49 patients under 35 years of age with clinically diagnosed epididymitis  detailed microbiological investigation identified an infective cause in 67   chlamydia trachomatis was the commonest agent  present in 25 patients  but in 12 of these detection was based solely on raised antibody titres  20 of the 28 female consorts screened were partners of men with chlamydial epididymitis and 80  of them were also positive for this infection  isolating the micro organism from 14 of 16 consorts indicated active infection despite the negative swabs from the men  if this important infection is to be adequately treated we recommend that all patients in this age group with epididymitis and their partners should be referred to a specialist unit with access to full chlamydia laboratory facilities  
class1	a pilot study of intermediate dose methotrexate and cytosine arabinoside   spread out  or  up front   in continuation therapy for childhood non t  non b acute lymphoblastic leukemia  a pediatric oncology group study  one hundred six children with newly diagnosed non t   non b cell acute lymphoblastic leukemia  all  were treated in a pediatric oncology group  pog  pilot study in which six courses of intermediate dose methotrexate  mtx  and cytosine arabinoside  ara c   1 g m2 each  were added to a  backbone  of standard continuation therapy  the dose and sequence of mtx ara c administration were based on a preclinical model that demonstrated synergism between mtx and ara c  poor risk patients  n   49  were assigned to  up front  therapy  in which the mtx ara c courses were administered during the initial 15 weeks of remission  standard risk patients  n   57  were assigned to  spread out  therapy  in which the mtx ara c courses were interspersed at 12 week intervals within continuation treatment  toxicity after intermediate dose mtx ara c  principally neutropenia and fever  was judged significant but manageable  unexpectedly  the incidence of fever and neutropenia less than 500 mm3 was greater after  spread out  therapy  38   than after  up front  therapy  6    at 4 years  the kaplan meier estimate of event free survival  efs  is 71       7   for standard risk patients and 53       8   for poor risk patients  the results of this pilot study support the use of intermediate dose mtx ara c in additional studies  
class1	the role of infection in the morbidity and mortality of patients with head and neck cancer undergoing multimodality therapy  cancer of the head and neck is a common cancer worldwide  the majority of patients present with locally advanced disease  recently a great deal of improvement has been made in multimodality therapy of this disease  warranting more careful consideration of factors affecting quality of life  disease course  and treatment  infection is clearly a factor  analysis of 662 hospital admissions of 169 head and neck cancer patients was performed  a definite infection was documented in 86 febrile episodes  pneumonia contributed to 40   bacteremia to 13   skin and soft tissue infection to 12   and tracheobronchitis to 10   among the evaluated risk factors  foreign bodies  specifically intravenous  iv  cannulae and gastrostomy tubes  race  performance status  alcohol intake  and nutritional status were statistically significant variables that predicted for or were associated with infection  infection contributed to 44  of the deaths  
class1	once daily intramuscular ceftriaxone in the outpatient treatment of severe community acquired pneumonia in children  published erratum appears in clin pediatr  phila  1991 may 30 5  326  ceftriaxone  a broad spectrum third generation cephalosporin with a half life of six to eight hours  was evaluated prospectively in 147 children with severe community acquired bacterial pneumonia during the period 11 15 88 5 15 89  thirty nine of the children had been unsuccessfully treated with vanous oral antibiotics prior to admission  corrected   all the patients were initially hospitalized and started on once a day intramuscular ceftriaxone  mean duration of ceftriaxone therapy was five days  pathogens were recovered from blood cultures of 17  11 6   patients and included s  pneumoniae  13 patients   h  influenzae  three  all resistant to ampicillin  and s  viridans  1   corrected   all isolates were sensitive to ceftriaxone  an additional patient had l  pneumophila diagnosed by serology  cure was achieved in 142  96 6   patients  improvement was usually observed within 24 48 hours  after 48 hours  121  82 2   children could be discharged and continued the therapy on ambulatory basis  based on previous experience we estimated that 383 hospitalization days were saved  no serious side effects were observed  five patients were considered therapeutic failures  two of them developed empyema and one of them required repeated drainage procedures  a third patient experienced a relapse of pneumonia shortly after completion of therapy  the other two remained febrile for more than seven days  their subsequent improvement was unrelated to the antibiotic therapy  suggesting a viral or mycoplasmal syndrome  our data suggest that once daily intramuscular ceftriaxone can be successfully used for the outpatient treatment of most community acquired severe bacterial pneumonias in children  in our opinion it represents the treatment of choice for patients who failed treatment with other antimicrobials and are clinically stable enough not to require hospitalization  
class1	gastric epithelium in the duodenum  its association with helicobacter pylori and inflammation  duodenal biopsy specimens from 471 adults and 47 children were examined to determine the prevalence and distribution of gastric epithelium in the duodenal bulb in relation to age  gender  gastroduodenal inflammation  smoking  alcohol and consumption of nonsteroidal anti inflammatory drugs  nsaid   gastric metaplasia was present in the anterior wall duodenal biopsy specimen in 31   was significantly less common in patients under 17 than in adults  and was more common in males than females  in sixty two adults who underwent multiple radial duodenal biopsy gastric metaplasia was randomly distributed around the duodenal circumference  sixty three per cent of the patients with gastric metaplasia found on multiple biopsy were detected by just the anterior biopsy  gastric metaplasia was not obviously associated with alcohol  cigarette  or nsaid consumption  while the presence of gastric metaplasia was associated with adulthood  male sex  and low fasting gastric juice ph  its extent was associated with active duodenitis and helicobacter associated gastritis  on logistic regression  gastric metaplasia in the duodenum and gastric helicobacter pylori were independent predictors of active duodenitis  but were not significantly associated with inactive duodenal inflammation  h pylori was observed in duodenal biopsy specimens from 32 patients  all with active duodenitis  bacteria were present only on foci of gastric metaplasia  and were more likely to be seen when the metaplasia was extensive  it is proposed that inflammatory injury to the duodenal mucosa by h pylori may stimulate the development of further gastric metaplasia  and that the area of duodenum susceptible to colonisation with h pylori may therefore increase progressively until mucosal integrity is compromised and ulceration supervenes  
class1	helicobacter pylori in dyspeptic patients in kuwait  two hundred and four patients  mainly arabs  attending for upper gastrointestinal endoscopy at the gastroenterology clinic in mubarak al kabeer hospital  kuwait  were examined for evidence of infection with helicobacter pylori and associated inflammation  biopsy specimens of antrum  body  and duodenum  gastric juice  and antral mucosal brushings were investigated by microbiological  cytological  and histopathological methods  clinical conditions diagnosed at endoscopy included gastritis  gastric ulcer  duodenitis and duodenal ulcer  but half the patients had endoscopically normal gastric and duodenal mucosae  h pylori was detected by one or more of the procedures in at least one specimen from 197  96 6   of the patients  histological and cytological analysis showed equal sensitivity  but bacteriological culture was less reliable  the proportion of positive cases was high  compared with other reported series  which may have been accounted for by the variety of diagnostic techniques used in this study  the selected population  all with gastrointestinal symptoms  or genetic or environmental predisposing factors peculiar to the sample population  
class1	spontaneous bacterial peritonitis due to salmonella enteritidis in cirrhotic ascites  spontaneous bacterial peritonitis due to salmonella is uncommon  we report three patients with ascites infected by salmonella  all three patients had advanced chronic liver disease  typically cirrhosis with portal hypertension  salmonella enteritidis grew in the ascite fluid culture of the three patients  there was no clinical or microbiological evidence of salmonella infection other than in the ascitic fluid  one patient died before antibiotic treatment was started  but the other two were treated with different combinations of antimicrobial drugs  one of them died on the fourteenth day of hospitalization  and the other survived  
class1	total hip arthroplasty  periprosthetic indium 111 labeled leukocyte activity and complementary technetium 99m sulfur colloid imaging in suspected infection indium 111 labeled leukocyte images of 92 cemented total hip arthroplasties were correlated with final diagnoses  prostheses were divided into four zones  head  including acetabulum   trochanter  shaft  and tip  the presence  or absence  and intensity of activity in each zone was noted  and compared to the corresponding contralateral zone  though present in all 23 infected arthroplasties  periprosthetic activity was also present in 77  of uninfected arthroplasties  and was greater than the contralateral zone 51  of the time  when analyzed by zone  head zone activity was the best criterion for infection  87  sensitivity  94  specificity  92  accuracy   fifty of the arthroplasties were studied with combined labeled leukocyte sulfur colloid imaging  using incongruence of images as the criterion for infection  the sensitivity  specificity  and accuracy of the study were 100   97   and 98   respectively  while variable periprosthetic activity makes labeled leukocyte imaging alone unreliable for diagnosing hip arthroplasty infection  the addition of sulfur colloid imaging results in a highly accurate diagnostic procedure  
class1	technetium 99m human polyclonal igg radiolabeled via the hydrazino nicotinamide derivative for imaging focal sites of infection in rats  the biologic behavior of human polyclonal immunoglobulin  igg  radiolabeled with technetium 99m  99mtc  by a novel method  via a nicotinyl hydrazine derivative  was evaluated in rats  technetium 99m  and indium 111 igg were co administered to normal rats and biodistribution was determined at 2  6  and 16 hr  the inflammation imaging properties of the two reagents were compared in rats with deep thigh infection due to escherichia coli  blood clearance of both antibody preparations was well described by a bi exponential function   99mtc igg  t1 2   3 82     0 89 and 57 52     1 70 hr  111in igg  3 93     0 117 and 40 71     1 26 hr   biodistributions in the solid organs were similar  however  small but statistically significant differences were detected  99mtc igg greater than 111in igg in lung  liver  and spleen  99mtc igg less than 111in igg in kidney and skeletal muscle  p less than 0 01   at all three imaging times  target to background ratio and percent residual activity for the two compounds were remarkably similar  these studies establish that human polyclonal igg labeled with 99mtc via a nicotinyl hydrazine modified intermediate is equivalent to 111in igg for imaging focal sites of infection in experimental animals  
class1	management of infants at risk for occult bacteremia  a decision analysis  because febrile infants with no obvious source of bacterial infection may have bacteremia  and because bacteremia is difficult to diagnose on clinical grounds  we used decision analysis to evaluate whether such infants should be treated with antibiotics  tested further  or sent home  using a simple decision tree  we found that the decision to give empiric antibiotic treatment is the decision of choice  the difference in quality adjusted life expectancy between the  best  and  worst  decisions was only 11 days  however  this difference translated to prevention of death or permanent disability in 60 cases per 100 000 febrile children  further  empiric treatment remained the best management alternative unless the probability of bacteremia was less than 1 4   less than any published prevalence   or the efficacy of treatment was less than 21   our analysis demonstrated that a test with far greater sensitivity than leukocyte count or other tests currently in use is needed to justify testing rather than treating empirically  further  an enormous patient population would be needed to find a difference of both clinical and statistical significance between treated and untreated patients in a controlled trial  in the absence of such trials  we recommend blood culture and empiric antibiotic treatment of all infants at risk for occult bacteremia  
class1	risk factors for multiorgan failure  a case control study  the aim of this study was to identify factors associated with multiple organ failure  mof   and assess possible interactions between the risk factors identified as such  we studied 40 mof cases and 120 controls  out of all the surgery and trauma patients who needed intensive care at our institution in a 24 month period  the univariate analyses showed that age  hypovolemic shock  massive volume administration  mva   sepsis  and time of evolution before arriving to the hospital  te  were significantly associated with mof  logistic regression analysis showed that neither age nor mva were independently associated with mof after adjusting for all of the other variables  interactions seemed to be present between age  sepsis  and shock  we conclude that in our surgery and trauma icu adult patient population  hypovolemic shock  sepsis  and te are independent risk factors for mof  the importance of the association between shock and sepsis is discussed  as well as the possible relevance of te as a risk factor  
class1	improvement of septic syndrome after administration of recombinant human growth hormone  rhgh   twenty patients with generalized sepsis were studied prospectively to evaluate the effects of recombinant human growth hormone  rhgh  administration  five patients had developed sepsis after major abdominal surgery  15 patients after multiple trauma with head injury  hti iss 38     2 and glasgow coma scale 4     1   the urea production rate  upr  could be significantly reduced by the intramuscular administration of 1 5 iu of rhgh kg bodyweight  bw  per day  upr day  5  62     6 7 gm d vs  upr day  10  42 6     5 9 gm d   the catabolic index of bistrian  bi  was significantly lower after rhgh therapy on day 10 compared to day 5  igf 1 increased significantly after the administration of rhgh  the nitrogen balance  however  did not become positive  despite the administration of rhgh  the changes in sepsis were estimated by the scoring system according to elebute and stoner on days 3  5  7  10  and 13  in those patients who were available for post treatment evaluation the parameters had returned to baseline values after the withdrawal of rhgh  results indicate that this therapy might ameliorate the nitrogen intake  but has no influence on the course of sepsis  compared to previously published results in nonseptic patients  the somatomedin inhibitors as well as the split products of the complement system and the metabolites of arachidonic acid may have been responsible for this weak effect of rhgh and igf 1 in septicemia  
class1	ureteric catheterization in the diagnosis of pyelonephritis  an experimental evaluation  experimental models of renal infections have been used to determine the accuracy with which the cellular and microbiologic components of ureteric and voided urine reflected the pathologic status of the kidney in pyelonephritis  in acute pyelonephritis  the composition of the ureteric urine reflected the pathologic status of the kidney  although in a few cases ureteric samples were either sterile or cell free  animals with chronic pyelonephritis in which the lesions were either infected or sterile commonly had sterile ureteric urine  pyuria  however  was demonstrable in both these situations  in subclinical pyelonephritis  ureteric samples from infected kidneys were variably culture positive  although pyuria was a common observation  discriminate function analysis based on actual renal status and ureteric data gave an overall correct classification rate of 67  and demonstrated at least 80  agreement in four of the five classification groups  
class1	fatal fungal pericarditis after cardiac surgery and immunosuppression  the cases of two patients with fulminant pericarditis after cardiac surgery are reported  both fungal infections developed after rethoracotomy for open chest cardiac resuscitation and high dose glucocorticoid treatment  although the time course of both infections from the inoculation of fungi during rethoracotomy and immunosuppression with glucocorticoids to the lethal outcome was strikingly similar  histopathologic studies disclosed the disparate character of the two fungal pathogens responsible  the yeast candida albicans and the angiotropic mold aspergillus fumigatus  
class1	serological identification of escherichia coli o157 h7 infection in haemolytic uraemic syndrome  to test the value of serological tests as an adjunct to bacteriological methods and toxin testing in haemolytic uraemic syndrome  hus   60 patients with the disorder were examined for evidence of faecal escherichia coli producing verocytotoxin  vtec   particularly of serogroup o157  they were also tested for serum antibodies reacting with the lipopolysaccharide of e coli o157 by means of an enzyme linked immunosorbent assay  elisa  and immunoblotting  for faecal vtec by means of dna probes hybridising with the genes encoding verocytotoxins vt1 and vt2  and for  free  faecal vt  strains of e coli serotype o157 h7 were isolated from 9 patients  and faecal vt2 was detected in 3 of them  strains of e coli of serotypes 05 h   o55 h10  o105ac h18  and o163 h19 were isolated from 4 patients  but faecal vt was not detected  faecal vt2 was present in 1 patient from whom vtec were not isolated  antibodies to the lipopolysaccharide of e coli o157 were detected in serum samples from 44 patients  the 9 patients with faecal o157 h7 all had high titres of these antibodies  but serum samples from 16 healthy control children were negative  serological testing of patients with hus for antibodies to the lipopolysaccharide of e coli o157 provides evidence of infection with e coli o157 when faecal bacteria or vt cannot be detected  
class1	antimicrobial resistance of pneumococci in children with acute lower respiratory tract infection in pakistan 87 strains of streptococcus pneumoniae isolated during three winter seasons  1986 89  from the blood of children with acute lower respiratory tract infection  alri  in pakistan were serotyped and tested for susceptibility to a range of antimicrobial agents  97  of isolates were resistant to at least one antimicrobial drug  62  had decreased susceptibility to co trimoxazole  trimethoprim sulphamethoxazole   31  were fully resistant  and 39  were resistant to chloramphenicol  all isolates were susceptible to erythromycin  cefaclor  cephalothin  ceftriaxone  cefuroxime  rifampicin  vancomycin  and clindamycin  29  of isolates were neither vaccine types nor vaccine related types  serotype distribution and antimicrobial susceptibility varied significantly during the three winter seasons  no single serotype was found in all three winters  the findings highlight the need for surveillance of antimicrobial resistance and serotype distribution of s pneumoniae in developing countries as a guide both to the choice of agent for treatment of pneumococcal infections  especially alri  and to the formulation of new pneumococcal conjugate vaccines for use in young children  
class1	mycobacterial infection after renal transplantation  report of 14 cases and review of the literature  during a nine year period  14 cases of mycobacterial infection  tuberculosis  developed in 403 renal transplant recipients at the king faisal specialist hospital and research centre in riyadh  saudi arabia  an incidence of 3 5 per cent  the annual incidence of tuberculosis was about 50 times higher than that in the general population  infection was disseminated in nine  64 3 per cent   pulmonary in four  28 6 per cent   and genitourinary in 1  7 1 per cent   in one patient tuberculosis was transmitted by the donor s kidney  the clinical manifestations were often ill defined and not different from that in the normal host  cultures from all patients grew mycobacterium tuberculosis  concomitant infection with other organisms was present in five patients  35 7 per cent   two of 18 patients  group 1  with positive pretransplant tuberculin skin test developed tuberculosis after transplantation  11 per cent   and neither received isoniazid prophylaxis  three of 70 patients  group 2  with negative skin tests developed tuberculosis after transplantation  4 3 per cent   the difference between the two groups was not statistically significant  review of all published cases of mycobacterial infections in renal transplant recipients revealed 130 cases  tuberculosis was disseminated in 38 7 per cent  pulmonary in 40 2 per cent  cutaneous in 12 per cent  and miscellaneous in 9 4 per cent  atypical mycobacteria were responsible for 29 per cent of disseminated infections  8 per cent of pulmonary infections and all cases of cutaneous and articular tuberculosis  invasive procedures were needed to establish the diagnosis in 21 of 33 disseminated cases but in only three of 47 cases of pulmonary tuberculosis  p less than 0 0001   the mortality rate from disseminated disease was 37 per cent and from all other forms of tuberculosis was 11 per cent  p less than 0 005   these findings  1  confirm the higher incidence of tuberculosis in renal transplant recipients  compared to the general population   2  suggest that pretransplant skin testing probably has little value in identifying patients at risk   3  show that disseminated tuberculosis is common after renal transplantation and requires invasive procedures for diagnosis   4  confirm that the donor kidney may be an important source of infection  and  5  indicate that concomitant infection with other organisms is common  
class1	bacteremia due to escherichia coli  a study of 861 episodes  escherichia coli accounted for 861  23 9   of 3 605 episodes of bacteremia in an 18 year prospective survey at st  thomas  hospital  a proportion that changed little during the survey  the most common focus of infection leading to nosocomial and community acquired bacteremia due to e  coli was the urinary tract  twenty six percent of adult female patients with e  coli bacteremia resulting from a urinary tract infection were diabetic  the o antigen serotypes identified most often were o6  o2  o1  o4  o15  and o75  the multiply resistant o15 serotype of e  coli was implicated in a community outbreak of urinary tract infection  ampicillin resistance in strains causing community acquired infection increased to the same level as that of strains causing nosocomial infection  almost 50    the overall mortality was 20 7  and was greater in the presence of shock  52 4  vs  15 3    death due to infection occurred in 2 6  and 10 3   respectively  of cases with urinary tract and non urinary tract foci  the adverse influence of inappropriate initial therapy on outcome was more marked in the latter half of the study  
class1	urinary tract infection caused by corynebacterium group d2  report of 82 cases and review  corynebacterium group d2  cgd2  is a slow growing  urea splitting  multiantibiotic resistant microorganism that is frequently isolated from urine samples and that  in certain circumstances  produces infection of the lower urinary tract  acute and chronic cystitis  and the upper urinary tract  pyelonephritis   this paper analyzes  by means of a retrospective and partially prospective clinical protocol  our experience with 82 patients with cgd2 bacteriuria  the infection was symptomatic in 62  of cases  and the clinical diagnoses included acute and chronic cystitis and pyelonephritis with or without bacteremia  because cgd2 infection of the urinary tract may require specific antimicrobial treatment and because cgd2 is a fastidious microorganism  we recommend prolonged incubation of urine cultures  up to 48 72 hours   especially if the routine culture is negative  when patients are symptomatic  have alkaline urine  or have struvite crystals in the urine sediment  
class1	modern chemotherapy for brucellosis in humans  the most effective  least toxic chemotherapy for human brucellosis is still undecided  in vitro  the antibiotics most active against brucella include the tetracyclines  the aminoglycosides  the aminopenicillins  some cephalosporins  trimethoprim sulfamethoxazole  erythromycin  rifampin  and some new fluorinated quinolones  because brucella species are facultative intracellular parasites  the penetration of drugs into and within phagocytes and phagosomes can be problematic and can best be studied in experimental animals or tissue cultures  in humans  the effectiveness of various regimens of chemotherapy has been compared best in acute bacteremic infections by assessment of the control of symptoms  bacteremia  complications  and relapses  the standard therapy against which all other therapies have been judged is a combination of tetracycline and streptomycin  which is almost universally effective but fails to prevent relapse in 10  of cases  a combination of oral doxycycline and rifampin is convenient and currently popular  it is highly effective  with an average relapse rate of only 8 4   trimethoprim sulfamethoxazole is less effective in controlling bacteremia and other manifestations  in collected series  5 7  of cases did not respond and 12  relapsed  drug resistant brucella strains are rarely a cause of therapy failure  localized brucellosis poses special problems  often requiring surgery in addition to prolonged combined chemotherapy  
class1	extrapulmonary pneumocystosis  the first 50 cases  over the last 35 years  50 cases of extrapulmonary infection with pneumocystis carinii have been reported in the literature throughout the world  use of prophylactic aerosolized pentamidine may have facilitated the relative prevalence of extrapulmonary disease because of its inadequate systemic distribution  an increase in reported cases of infections due to p  carinii has been seen in conjunction with aids  but extrapulmonary pneumocystosis represents less than 1  of all cases of infection with p  carinii  several organs or tissues may be involved  but the most common sites are lymph nodes  spleen  liver  and bone marrow  extrapulmonary spread of p  carinii infection occurs via both lymphatic and hematogenous routes  while all patients with disseminated forms of this infection die rapidly  survival for patients with aids is possible if systemic treatment is provided  if a single extrapulmonary site is involved  and if no concomitant pneumonia is present  because of the increasing frequency of this condition in patients who do not have pneumonia due to p  carinii  extrapulmonary pneumocystosis should be included among the aids defining criteria  
class1	antifungal and surgical treatment of invasive aspergillosis  review of 2 121 published cases  published erratum appears in rev infect dis 1991 mar apr 13 2  345  no controlled trials of therapy for invasive aspergillosis have been done  this review appraises 2 121 cases reported in 497 articles in the literature and analyzes 440 courses of treatment of infection at various body sites in 379 patients  the exclusion of early failures of therapy skews the results toward a favorable outcome  the rate of response to amphotericin b is 55   mortality from pulmonary aspergillosis in bone marrow transplant recipients exceeds 94  regardless of therapy  as does that from cerebral aspergillosis in all hosts  amphotericin b  1 mg  kg d   with flucytosine lowers mortality in neutropenic patients with pulmonary aspergillosis who did not receive a bone marrow transplant  relapse is common  surgical debridement of aspergillus maxillary sinusitis is usually curative in nonimmunocompromised patients  whereas it increases mortality among neutropenic patients  valve replacement is essential for aspergillus endocarditis  both vitrectomy and intravitreal amphotericin b treatment are essential for aspergillus endophthalmitis  flucytosine is somewhat useful clinically  itraconazole shows efficacy in the treatment of pulmonary  skeletal  and pericardial aspergillosis  although liposomal amphotericin b is less toxic than standard preparations of the drug  relevant data are limited  the proposed potentiation of amphotericin b by rifampin is unsupported by clinical data  despite  conventional  therapy  mortality from invasive aspergillosis remains high  new approaches must be investigated  
class1	severity of meningococcal disease  assessment by factors and scores and implications for patient management  results from our own and other published series of cases of meningococcal disease were used to study prognostic factors and to compose scores for assessment of severity of disease on admission to the hospital  the difference in risk for fatality was designated the factor fatality difference  ffd   the ffd was determined by subtracting the percent fatality for factor negative patients from the percent fatality for factor positive patients  ffd was useful for selection of good indicators of severity of disease  blood ph of less than 7 35 was the best single factor  low platelet count came next  followed by low blood pressure  cyanosis  ecchymosis  and low blood leukocyte count  new scores were constructed based on multiple regression analyses  several older and new scores seemed to be comparable  by combining age adjusted systolic blood pressure  less than 100 mm hg   cyanosis  ecchymosis  diarrhea before or at admission  cold extremities  absence of nuchal or back rigidity  and rectal temperature of greater than or equal to 40 degrees c  a simple bedside percentage score  the menopp bedside clinical score  moc   was devised  cross evaluations on test materials generally confirmed the choice of score  the simplicity of this score made it more clinically suitable than laboratory or mixed laboratory and bedside scores  
class1	nosocomial infections due to xanthomonas maltophilia  pseudomonas maltophilia  in patients with cancer  from december 1985 to may 1986  xanthomonas maltophilia  formerly known as pseudomonas maltophilia  was isolated at an increased rate at our institution  52 isolates of x  maltophilia were obtained in cultures of clinical specimens from 38 patients during that time  the records of 35 of these patients form the basis of this study  twelve  71   of the 17 infected and nine  50   of the 18 colonized patients had received or were receiving antimicrobial therapy  eleven of 17 patients  three of seven with septicemia  three of five with pneumonia  three with urinary tract infection  and two with wound infection  responded to antimicrobial therapy  microbiologic studies of the potential environmental sources revealed growth of x  maltophilia in two water faucets and in one water sample from the medical intensive care unit  x  maltophilia is emerging as an important nosocomial pathogen in immunocompromised patients  especially those receiving broad spectrum antimicrobial therapy  
class1	indigenous cases of lyme disease diagnosed in north carolina  between january 1984 and december 1989  102 indigenous cases of lyme disease were reported in north carolina  lyme disease was reported in each of the three major geographic regions of the state  mountain  piedmont  and coastal plain  one or more diagnoses were made in 42 of 100 counties  patients ranged in age from 5 months to 78 years  median  27 years   58 patients  57   reported a history of tick exposure within 1 month of the onset of symptoms  erythema migrans was reported by 93 patients  91    arthritis  30    neurologic symptoms  10    and cardiac abnormalities  7   were observed  thirty of the 102 cases were confirmed serologically by indirect fluorescence microscopy or enzyme linked immunosorbent assay  
class1	anal submucosal injection  a new route for drug administration  vi  chronic prostatitis  a new modality of treatment with report of eleven cases  the anal submucosal route was used for the treatment of chronic bacterial prostatitis in 11 patients  prior to presentation  the patients had received different antimicrobial agents  the symptoms disappeared only to recur whenever the drug was discontinued  after repeated failure  the patients were treated with gentamicin to which the organisms were sensitive  via the anal submucosal route  a daily injection was given for ten days on an outpatient basis  the technique of injection is described  the patients were followed up clinically and by segmented cultures for three years  no anorectal complications were encountered as had been demonstrated experimentally  the symptoms of chronic prostatitis disappeared  and culture was negative by the end of treatment and for two to three years thereafter in all patients  it appears that the antimicrobial agent  via anal route  reaches the prostatic tissues at a higher concentration than that of the serum  the route adopted by the drug to reach the prostate from the anal submucosa is presented  
class1	spontaneous abortion  spontaneous abortion  or the early termination of pregnancy without outside interference  may be caused by fetal  maternal or external factors  in many cases  a specific etiology may never be identified  a variety of clinical presentations are possible  ranging from imperceptible loss to profound life threatening shock  physicians should be able to diagnose and manage the six recognized types of spontaneous abortion  threatened  inevitable  incomplete  complete  missed and septic  in all cases  uterine evacuation  avoidance of complications and psychologic support of the family are important  the prognosis for a subsequent successful pregnancy is good  except in cases of habitual abortion  
class1	chronic upper lobe cavitary lung disease  chronic upper lobe cavitary lung disease may be caused by infections  emphysema  cystic fibrosis  lung cancer  sarcoidosis and rheumatologic syndromes  the diagnostic evaluation includes a complete history  a physical examination  a chest radiograph  and sputum examination and culture  in some cases  computed tomographic scanning and biopsy are required  
class1	colonoscopic fine needle aspiration cytology in the diagnosis of ileocecal tuberculosis  two cases of ileocecal tuberculosis are presented  the diagnosis was achieved by endoscopic fine needle aspiration cytology  fnac   while endoscopic biopsies and brush cytology were negative  the usefulness of endoscopic fnac in the diagnosis of gastrointestinal tract tuberculosis is highlighted  
class1	whipple s disease can mimic chronic aids enteropathy  previous case reports have demonstrated that the intestinal pathology of mycobacterium avium intracellulare  mai  infection in the acquired immune deficiency syndrome  aids  has a light microscopic appearance similar to whipple s disease  this case report describes a 52 yr old male patient with a clinical picture suggestive of aids  including diarrhea  weight loss  oral thrush  and intestinal cryptosporidiosis  the intestinal biopsy showed light microscopic features compatible with either mai or whipple s disease  but electron microscopy confirmed the presence of the whipple bacillus  markers of human immunodeficiency virus  hiv  infection were absent  although immune abnormalities have been reported in whipple s disease  this is the first report of opportunistic infections complicating this condition  a useful clinical pearl emerges from this and other cases  aids can mimic whipple s disease  whipple s disease can mimic aids  
class1	disseminated pneumocystis carinii infection with hepatic involvement in a patient with the acquired immune deficiency syndrome  extrapulmonary infection with pneumocystis carinii  p  carinii  in aids patients is uncommon  and is often described only at postmortem examination  although most antemortem cases involve spread to the bone marrow or spleen  p  carinii involvement of other organs has only recently been described  despite the frequency of liver enzyme abnormalities in aids patients with a history of p  carinii pneumonia  p  carinii has been observed only rarely in the liver  we present a well documented case of p  carinii involving the liver in an aids patient with p  carinii pneumonia and progressive liver enzyme abnormalities  we suggest that p  carinii infection should be considered in the differential diagnosis of aids related liver disease  
class1	etiology and pathophysiology of pyelonephritis  escherichia coli is the most frequent cause of pyelonephritis  its possible virulence factors include the ability to adhere and colonize the urinary tract  an important initiating factor in all urinary tract infections  utis   the importance of p fimbriae in this adhesion is stressed and the evidence for its importance in pyelonephritis is presented in epidemiologic studies of patients  as well as in animal studies  it appears that both host receptor density and the nonsecretor state is responsible for susceptibility to urinary tract infection  vesicoureteral reflux can be responsible for ascending upper tract infection  but infection with p fimbriated e coli may lead to ascending pyelonephritis without reflux because of the paralytic effect of lipid a on ureteral peristaltic activity  renal ischemia leads to renal damage following infection by reperfusion damage due to the release of superoxide  experimentally  this ischemic damage can be prevented by allopurinol  a xanthine oxidase inhibitor  the acute inflammatory response can produce renal damage because of the respiratory burst of phagocytosis  which while killing phagocytosed bacteria also damages renal tubules  an amelioration of the inflammatory response by treatment with superoxide dismutase or corticosteroids has been shown to modulate renal damage  vaccination with p fimbriae has been shown experimentally to prevent the initiation of the disease  however  since vaccines are not clinically available  the clinical and animal studies on therapy of acute disease are stressed  acute pyelonephritis during the first 3 years of life more often produced the renal damage that could lead to end stage renal disease  
class1	successful prophylaxis for fungal peritonitis in patients on continuous ambulatory peritoneal dialysis  six years  experience  published erratum appears in am j kidney dis 1991 jun 17 6  726  fungal peritonitis as a serious complication of continuous ambulatory peritoneal dialysis  capd  is often associated with severe morbidity  capd  drop out  and  occasionally  death  most episodes of fungal peritonitis occur during or after a period of antibiotic treatment of various bacterial infections  usually bacterial peritonitis  from april 1979 to december 1982  period i   10 episodes of fungal peritonitis occurred during 415 patient months  ie  10 5  of all peritonitis episodes recorded in our capd program  after the introduction of oral prophylaxis with 3 x 500 000 iu  corrected  nystatin during every course of antibiotic treatment  only four episodes of fungal peritonitis occurred during 2 102 patient months  ie  3 1  of all peritonitis episodes from january 1983 to march 1989  period ii   this difference between the first and second periods is significant  p less than 0 05   moreover  none of the four patients who contracted fungal peritonitis in the second period received nystatin prophylaxis  thus  the simple measure of oral prophylaxis using this nonabsorbable antifungal agent in every case of an antibiotic treatment largely eliminates the risk of fungal peritonitis in patients on capd  
class1	successful antepartum treatment of listeriosis  a pregnant patient had a flulike illness at 27 weeks  listeria monocytogenes infection was diagnosed by blood cultures  electronic monitoring suggested the fetus was stressed  use of tocolytics inhibited uterine contractions while the mother was treated with intravenous ampicillin  four days later when labor began because of chorioamnionitis  the infant was delivered in good condition  
class1	a comparative study of gastrointestinal infections in united states soldiers receiving doxycycline or mefloquine for malaria prophylaxis  a double blind study of daily doxycycline  100 mg  vs  weekly mefloquine  250 mg  was performed on united states soldiers training in thailand to assess the effect of doxycycline malaria prophylaxis on the incidence of gastrointestinal infections  during a 5 week period  49   58 119  of soldiers receiving doxycycline and 48   64 134  of soldiers receiving mefloquine reported an episode of diarrhea  infection with bacterial enteric pathogens was identified in 39   47 119  of soldiers taking doxycycline and 46   62 134  of soldiers taking mefloquine  forty four percent  59 134  of soldiers receiving mefloquine and 36   43 119  of soldiers receiving doxycycline were infected with enterotoxigenic escherichia coli  etec   while 9   12 134  of soldiers receiving mefloquine and 4  of soldiers receiving doxycycline were infected with campylobacter  side effects from either medication were minimal  after 5 weeks in thailand  the percent of non etec strains resistant to greater than or equal to 2 antibiotics increased from 65   77 119  to 86   95 111  in soldiers on mefloquine and from 79   84 106  to 93   88 95  in soldiers on doxycycline  doxycycline prophylaxis did not prevent or increase diarrheal disease in soldiers deployed to thailand where etec and other bacterial pathogens are often resistant to tetracyclines  
class1	a positron emission tomographic comparison of pulmonary vascular permeability during the adult respiratory distress syndrome and pneumonia  we measured extravascular density  evd  and the pulmonary transcapillary escape rate  ptcer  for 68ga transferrin using positron emission tomography in 14 normal volunteers and 29 patients with radiographic infiltrates  including six patients with congestive heart failure  chf   eight patients with the adult respiratory distress syndrome  ards   and 15 patients with focal pneumonia  contralateral  radiographically normal regions were also evaluated in the patients with focal pneumonia  mean evd was elevated in the patients with chf  ards  and pneumonia in regions of radiographic infiltrate compared with values from normal subjects  p less than 0 05   but it was not significantly different among the three patient groups  ptcer in normal subjects and in patients with chf was not significantly different  21     11 versus 44     16 x 10  4  min 1  respectively  p   ns   ptcer was elevated in regions of infiltrate because of either pneumonia  173     99  or ards  170     79   ptcer was also elevated in regions contralateral to those with focal infiltrate during pneumonia  even though these regions were radiographically normal and had normal evd values  these results suggest that ptcer is a sensitive but nonspecific index of abnormal pulmonary vascular permeability  which may be useful for classifying patients in clinical studies of pulmonary edema  
class1	sepsis induced lung injury and the effects of ibuprofen pretreatment  analysis of early alveolar events via repetitive bronchoalveolar lavage  current knowledge of alveolar pathophysiology during early sepsis induced acute lung injury  ali  and the role of resident alveolar macrophages  am  in mediating alveolar inflammatory events during sepsis is limited  further  the effects of ibuprofen pretreatment upon alveolar pathophysiology and am function during early sepsis induced ali is unclear  utilizing repetitive bronchoalveolar lavage  bal  in a porcine model of sepsis induced ali  we studied changes in alveolar cellular constituents  bal protein content and molecular composition  and am superoxide anion  o2    generation during early sepsis  the neutrophil percentage of recovered alveolar cells  17     8   t   300 min versus 2     1   t   0  p   0 06  and the bronchoalveolar lavage total protein content  493     110 micrograms ml  t   300 min versus 109     18 micrograms ml  t   0  p less than 0 05  increased in septic animals  increases in bal fluid total protein were primarily due to low molecular weight plasma protein  indicating relative preservation of alveolar capillary membrane size selectivity  alveolar macrophages harvested following 300 min of sepsis generated significantly less o2   following phorbol myristate acetate  pma  stimulation compared to am harvested at baseline  ibuprofen pretreatment of septic animals completely blocked leakage of plasma proteins into the alveoli and attenuated neutrophil migration but did not prevent downregulation of am o2   generation  increased alveolar capillary membrane permeability  neutrophil migration into the alveoli  and downregulation of am oxidant generation occur within hours of the onset of sepsis  ibuprofen pretreatment significantly attenuates early sepsis induced ali without altering sepsis induced am dysfunction  
class1	the intracolonic bypass tube for left colon and rectal trauma  the avoidance of a colostomy  traumatic perforations of the left colon and rectum are most frequently managed by procedures that include the formation of a colostomy  primary repair without colostomy is much less commonly employed  we report nine patients with traumatic perforations of the left colon and rectum treated with the intracolonic bypass tube  icbt  without concomitant colostomy  in all these patients we believe the standard treatment would have included fecal diversion  four patients sustained blunt trauma and five sustained penetrating trauma  healing of the colonic anastomosis occurred in all cases  and the icbts were passed per rectum between the tenth and nineteenth days postoperatively  on the basis of this study  we conclude that the icbt has a role in the treatment of selected injuries of the left colon and rectum as a safe means of avoiding a colostomy  
class1	parapoxvirus infections acquired after exposure to wildlife  the histopathologic and electron microscopic findings in two patients with skin lesions that developed after exposure to deer and other wildlife were consistent with a parapoxviral infection  human infections that were morphologically similar to parapoxvirus infection have been previously described concerning exposure to cervids  deer and related animals   ours are the first reported cases in which viral particles were demonstrated by electron microscopy  
class1	absence of bacteremia during nasal septoplasty  episodes of staphylococcal bacteremia resulting in metastatic infection have occurred in association with nasal septoplasty  and this has suggested the possible need for antimicrobial prophylaxis  in a study designed to measure the actual frequency with which transient staphylococcal bacteremia occurs during nasal septoplasty  50 healthy patients had blood cultures drawn immediately prior to and during the procedure  although 46  of the 50 patients studied had their nasal mucosa colonized with staphylococcus aureus  some of the blood cultures obtained from the 50 patients showed bacterial growth  the authors conclude that staphylococcal bacteremia during nasal septoplasty is a rare occurrence  and that antimicrobial prophylaxis is unnecessary  
class1	assessment of middle ear status during experimental otitis media using magnetic resonance imaging  magnetic resonance imaging has proved to be a useful tool for in vivo imaging of a variety of tissues  in this study  magnetic resonance imaging was applied to the middle ear of experimental animals with otitis media  results showed that the presence and distribution of effusion within the middle ear space could be readily determined  moreover  following injection of gadolinium diethylenetriaminepentaacetic acid  a contrast agent  the inflamed middle ear mucosa could be resolved  a comparison between magnetic resonance imaging and tympanometry with respect to the diagnosis of effusion showed that negative pressure tympanograms were equivocal  50  effusion  and that flat or normal tympanograms were in error in approximately 20  of the observations  these data document a role for magnetic resonance imaging in in vivo studies of the pathogenesis of otitis media with effusion  
class1	correlation of gross and microscopic appearance of skin buttons in total artificial heart animals  pneumatic artificial hearts are powered by compressed air that is delivered through percutaneous tubes  a stress relief device  termed a skin button  surrounds these tubes as they exit from the recipient s tissues  the skin button is designed to protect the tissues from damage and provide a secure material tissue interface  prevention of superficial and invasive infection is the primary goal of the skin button  eight calves were studied prospectively to identify gross or microscopic infection with the skin button  all animals who survived more than sixty days  62 136  had both gross and microscopic evidence of infection  all animals surviving less than 60 days  13 43  had no gross evidence of infection but one had subcutaneous microscopic abscess formation  no animal died secondary to a skin button infection  skin buttons cannot prevent infection but they can contain the pathologic process in the superficial tissues with no evidence of systemic effects  
class1	the effects of three serotypes of ureaplasma urealyticum on spermatozoal motility and penetration in vitro  published erratum appears in fertil steril 1991 jun 55 6  1214  the effects of incubation of spermatozoa with three serotypes of ureaplasma urealyticum on spermatozoal motility and penetration in vitro were investigated  using computer assisted video microscopy  three parameters of motility were determined  individual path lengths  individual vectorial distances  and percentage motility  polyacrylamide gels were used as a medium for assessment of spermatozoal penetration  ureaplasma infected spermatozoa did have significantly greater path lengths and individual distances than did uninfected controls  but ureaplasma infection had no significant effect on percentage motility  overall  there were no significant differences in penetration distances between ureaplasma infected spermatozoa and their corresponding uninfected controls  our conclusion is that the ureaplasmas did not adversely affect motility or penetration when spermatozoa were incubated with ureaplasmas for 45 minutes at ureaplasma sperm ratios as high as 100 1  
class1	tumor necrosis factor independent il 6 production during murine listeriosis  we report that tnf  il 6  and ifn alpha beta are produced by mice during either sublethal or lethal listeria monocytogenes infections  the quantities of these cytokines in infected spleens increase and decrease in concordance with bacterial numbers in these organs  while all of these cytokines were present in listeria infected spleens  only il 6 and ifn alpha beta were found in the peripheral circulation  inasmuch as tnf has been reported to be responsible for the production of il 6 in vivo following the inoculation of a lethal dose of the gram negative bacterium  escherichia coli  fong et al   1989  j  exp  med  170  1627   experiments were undertaken to determine whether il 6 production elicited by the gram positive bacterium  l  monocytogenes  was also tnf dependent  it was found that the passive immunization of mice with neutralizing antibodies specific for tnf shortly before i v  injection of a lethal or sublethal listeria inoculum resulted in the complete neutralization of endogenously produced tnf  and in the progressive multiplication of bacteria in infected organs  it was also found that the anti tnf igg treatment resulted in a progressive increase in the amounts of listeria induced il 6 present in spleen and blood  until the death of the host  these findings indicate that listeria induced il 6 production in mice occurs primarily through a tnf independent pathway  and correlates directly with the severity of the infection  
class1	the effects of nonthyroid disease and drugs on thyroid function tests  serious nonthyroid illness and caloric deprivation  which so often accompany systemic illness  have diverse and still incompletely understood effects on thyroid hormone economy  we have discussed the pathophysiologic basis for the most common pattern of alterations in routine thyroid function tests  a decreased serum t3 concentration  normal or  in critically ill patients  a low total serum t4 level  and a normal free t4 concentration  another  less frequent pattern  high total and free t4 with a normal serum t3  can be encountered transiently in the acutely ill medical or psychiatric patient  with the recent advent of sensitive assays for tsh and better methods for serum free t4  it is now possible to define more quickly and accurately the thyroid metabolic status of most of these sick patients  the vast majority are euthyroid  certain drugs confound the picture  the most important of these include dopamine and high dose glucocorticoids  both of which suppress tsh secretion from the pituitary and may actually cause a state of central hypothyroidism  other drugs have multiple effects on thyroid hormone indices  e g   amiodarone   knowledge of all of the ways in which systemic illness  starvation  and certain drugs may influence thyroid function tests is crucial in assessing the thyroid status of patients with serious nonthyroid disease  
class1	mycobacterium chelonei keratopathy with visual rehabilitation by a triple procedure  we report a chronic keratouveitis following an eye injury  the etiology of which remained obscure despite repeated corneal scrapings and cultures  eventually  the diagnosis was established by culturing mycobacterium chelonei from a corneal biopsy specimen  topical amikacin resolved active inflammation  but dense corneal scarring and a cataract remained  visual rehabilitation was achieved through a combined penetrating keratoplasty  extracapsular cataract extraction  and intraocular lens implantation  this case illustrates that there should be a high index of suspicion of atypical mycobacteria when faced with any unusual keratitis  particularly following penetrating injuries and corneal grafts  
class1	ehrlichiosis in children  tick borne rickettsiae of the genus ehrlichia have recently been recognized as a cause of human illness in the united states  in the years 1986 1988  10 cases of ehrlichiosis were diagnosed in children in oklahoma  fever and headache were universal  myalgias  nausea  vomiting  and anorexia were also common  rash was observed in six patients but was a prominent finding in only one  leukopenia  lymphopenia  and thrombocytopenia were common laboratory abnormalities  six patients were treated with tetracycline  three with chloramphenicol  and one was not treated with antibiotics  all recovered  the onset of illness in spring and early summer for most cases paralleled the time when amblyomma americanum and dermacentor variabilis are most active  suggesting that one or both ticks may be vectors of human ehrlichiosis in oklahoma  
class1	premature rupture of the membranes and sepsis in preterm neonates  this investigation was designed as a historical cohort study using data abstracted from medical records  five hundred seven preterm neonates  26 35 weeks gestation  born alive from singleton pregnancies complicated by premature rupture of the membranes  prom  were selected  each neonate was matched on gestational age  gender  ethnicity  and date of delivery to a neonate without prom  a matched pairs analysis was done using risk ratios  rr  to measure strength of the association and risk differences  rd  to measure absolute effect  analysis revealed that preterm births complicated by prom were at significantly higher risk of neonatal sepsis  rr   3 5  and infection  rr   2 4   the rds indicated that prom exposure contributed an excess of 5 cases of sepsis per 100 infants  rd   0 05   prom was not significantly associated with neonatal mortality  but when prom had existed over 48 hours there was a higher risk of sepsis and infection  birth of a neonate over 1500 grams or 33 weeks gestation was the most important factor in reducing risk of infection in prom deliveries  
class1	detection of streptococcus pneumoniae and haemophilus influenzae type b antigens in the serum and urine of patients with pneumonia in papua new guinea  comparison of latex agglutination and counterimmunoelectrophoresis  latex agglutination  la  was compared with counterimmunoelectrophoresis  cie  for the diagnosis of pneumonia due to streptococcus pneumoniae or haemophilus influenzae type b in children less than 6 years old in papua new guinea  neither la nor cie was sufficiently sensitive for the detection of pneumococcal antigens  cie was superior to la but had a sensitivity of only 60   six of 10  in concentrated urine and a specificity of 90   54 of 60   la for the detection of h  influenzae type b had a sensitivity of 100   eight of eight  relative to that of blood culture and a specificity of 99   112 of 113  when urine diluted fivefold was tested  as compared with a sensitivity of 100   nine of nine  and a specificity of 92   56 of 61  in undiluted urine  undiluted and concentrated urine specimens were unsuitable for la because of the many false positive reactions that resulted from nasal carriage of h  influenzae type b and nasal carriage of the cross reactive s  pneumoniae type 6  cie for the detection of h  influenzae type b had a sensitivity of only 44   four of nine  in concentrated urine  
class1	bacterial colonization of the upper respiratory tract and its association with acute lower respiratory tract infections in highland children of papua new guinea  acute lower respiratory tract infection  alri  is the major cause of death among children in papua new guinea  this longitudinal study reports the bacteriologic findings for children observed in their hamlets  a total of 1 449 nasal swab specimens from 158 children less than 5 years of age who were studied intensively for 18 months were examined  non serotypable strains of haemophilus influenzae were isolated from 91  of specimens  and serotypable strains were isolated from 35   8  h  influenzae type b  of specimens  all children had acquired streptococcus pneumoniae by the age of 3 months  the most frequently occurring serotypes of s  pneumoniae were 6  19  and 23  children more frequently carried invasive pneumococci during an episode of alri than when they were healthy  also  children more frequently carried serotypable strains of h  influenzae during the 2 weeks preceding an episode of alri than when they were healthy  between children analyses showed that children who were susceptible to attacks of alri and those who were not susceptible had similar rates of carriage of bacteria  
class1	diversity of outer membrane protein profiles of nontypable haemophilus influenzae from children from papua new guinea and the philippines  we determined capsular serotypes and  with use of sds page  patterns of outer membrane proteins  omp  of haemophilus influenzae isolates from specimens of blood  lung  or csf from children with acute respiratory tract infections or meningitis who were hospitalized in papua new guinea or the philippines  among 72 isolates from papua new guinea  72  were type b  14  were other encapsulated serotypes  and 14  were nontypable  the respective frequencies among 43 isolates from the philippines were 56   7   and 37   the type b isolates could be subdivided into at least eight outer membrane subtypes  most of which have been described previously  in contrast  omp profiles of the nontypable h  influenzae isolates from children in both countries were highly heterogeneous  these results differ markedly from those previously found for isolates from children with acute respiratory tract infections in pakistan  for which encapsulated h  influenzae strains other than serotype b were not observed  95  of type b isolates were of a single omp subtype  and nontypable isolates showed evidence of clonal restriction  candidate vaccines for use in developing countries as protection against disease caused by h  influenzae will need to include both capsular and noncapsular antigens and investigators must take into consideration regional differences among strains  
class1	clinicopathologic studies of children who die of acute lower respiratory tract infections  mechanisms of death  clinicopathologic correlations for 71 cases of fatal pneumonia in children were determined  the mechanism of death for these patients was multifactorial  severe pneumonia alone accounted for 11 deaths  15 5    pneumonia associated with sepsis occurred in 42 children  59 2    heart failure  8 5    hypovolemia  4 2    and nosocomial infection  12 6   were also seen in children with fatal acute lower respiratory tract infection  extensive consolidation  squamous metaplasia  and hyaline membranes were present in the lungs of these children  patients with severe disease must receive  in addition to antibiotics for acute episodes  individualized intensive respiratory and supportive care  since these types of care are not available in poor communities  vaccination against measles and vitamin a supplementation for malnourished children may ameliorate the conditions that appear to predispose these children to severe or fatal disease  
class1	etiologic  clinical  and pathologic analysis of 31 fatal cases of acute respiratory tract infection in argentinian children under 5 years of age  during a 3 year survey of 805 children with acute lower respiratory tract infection  alri  who were admitted to three hospitals in buenos aires  31 fatal cases were recorded  a fatality rate of 3 8   of the 31 children who died  77  were less than 1 year of age  48  were boys  58  were malnourished  29  had previous respiratory disease  and 22  had previous congenital disease  all children who died had clinical diagnoses of pneumonia  71   or bronchiolitis  29    autopsies were performed in 14 of the cases  viral etiology was determined by both cell culture and indirect immunofluorescence  iif  assay of either nasopharyngeal aspirates  npa  or lung tissue and bacterial etiology was determined by isolation of organisms from blood  lung tissue  and or pleural fluid  npa was examined for bordetella pertussis by iif  pathogens were identified in 65  of fatal cases  seven cases were bacterial  seven cases were viral  and six cases resulted from mixed infections  lung tissue yielded positive etiologic results in 10 of 13 cases  histopathologic examination performed on specimens from the 14 autopsied children revealed necrotizing bronchiolitis with intranuclear inclusions  n   5  and multifocal pneumonia  n   9   
class1	etiologic and clinical evaluation of acute lower respiratory tract infections in young argentinian children  an overview  this paper summarizes the first study on clinical  etiologic  and epidemiologic features of acute lower respiratory tract infection  alri  in children in argentina  a total of 1 003 children less than 5 years of age  805 inpatients and 198 outpatients  presenting with alri were studied during a 40 month period  nasopharyngeal aspirate  npa   blood  urine  and throat swab samples were collected when each child was first seen for care  virologic studies were performed on the npa by means of indirect immunofluorescence and isolation of virus in cell culture  bacteriologic studies primarily were done by means of culture of blood or pleural fluid  when available   bordetella pertussis and mycoplasma pneumoniae  however  were searched for by the use of immunofluorescence and complement fixation testing  respectively  in paired sera  respiratory syncytial virus was the most commonly isolated virus  followed by adenovirus  parainfluenza virus  and influenza virus  streptococcus pneumoniae was the most frequently isolated bacterium  followed by b  pertussis and haemophilus influenzae type b  overall  the patient fatality rate was 3 8  among inpatients with pneumonia or bronchiolitis  
class1	acute lower respiratory tract infections in hospitalized patients with diarrhea in dhaka  bangladesh  this study focused on 401 children less than 5 years old who were hospitalized with acute lower respiratory tract infection  alri  and diarrhea in dhaka  bangladesh  and who were investigated for the presence of both bacterial and viral respiratory tract pathogens as well as for selected diarrheal pathogens  the most common manifestations of alri were pneumonia  374 cases   bronchiolitis  12 cases   and tracheobronchitis  11 cases   the majority  77   of the illnesses were in children less than 2 years of age  and 88  of the children were malnourished  a respiratory tract pathogen was identified in 30  of the patients  and a diarrheal pathogen was identified in 34   the overall case fatality rate in children with alri and diarrhea was 8   the case fatality rate was 14  in children with bacterial pneumonia and diarrhea  3  in those with viral pneumonia and diarrhea  and 14  in malnourished children with shigellosis and alri  the most common respiratory tract pathogens were respiratory syncytial virus  streptococcus pneumoniae  influenza viruses  and haemophilus influenzae type b  
class1	diagnoses of acute lower respiratory tract infections in children in rawalpindi and islamabad  pakistan  a hospital based inpatient and outpatient study of 1 492 cases of acute lower respiratory tract infection  alri  was conducted from november 1986 to march 1988 in two hospitals in rawalpindi and islamabad  pakistan  specimens of nasopharyngeal aspirate were processed for viral studies in all cases  blood cultures were performed in 1 331 cases  and urine was obtained for detection of bacterial antigen in 378 cases  but 227 of these samples had bacterial contamination and were discarded  respiratory syncytial virus was identified in 33  of cases  and haemophilus influenzae and streptococcus pneumoniae were identified in 9 6  and 9 9  of cases  respectively  nonencapsulated h  influenzae accounted for 32  of the haemophilus isolates  and type b was the only encapsulated h  influenzae strain identified  of the s  pneumoniae serotypes isolated  31  are not included in the currently available polyvalent pneumococcal vaccine  no clinical characteristic was demonstrated to be a reliable indicator for bacterial alri  
class1	microbial agents associated with pneumonia in children from uruguay  the etiology of severe pneumonia  not frequently encountered in a community based study  was determined in 204 hospitalized children less than 5 years of age  potential pathogens were identified in 41  of episodes  viruses were isolated or antigen was detected in 36 3  of cases  82 4  of these cases were due to respiratory syncytial virus  bacteria or bacterial antigens were identified in 13 2  of cases  streptococcus pneumoniae and haemophilus influenzae were the most frequently identified bacterial pathogens isolated from blood and or pleural effusions  mixed infections were identified in 4 9  of the episodes  among the 17 patients with pleural effusion whose pleural space was drained  the etiology was suggested for 10  58 8    a clear cut seasonal variation was seen  with the highest prevalence between may and october  viral infections were more common in the first 6 months of life  although viral and bacterial infections were distributed throughout the first 5 years of life  
class1	etiology of acute lower respiratory tract infection in children from alabang  metro manila  the etiology of acute lower respiratory tract infection  alri  was identified in 235  43 8   of 537 hospitalized children less than 5 years of age  clinical evidence of measles was found in 258  48 0   patients  of whom 59 had a second viral infection  a viral agent was identified in an additional 121 patients  so that a total of 379  70 6   had viral infections  after measles  respiratory syncytial virus was the most common respiratory virus  bacteremia was noted in 72 children  13 4    occurring as frequently in children with measles  14 8   as in those without  12 1    haemophilus influenzae and salmonella typhi were predominant in the former  and h  influenzae  staphylococcus aureus  and streptococcus pneumoniae were prominent in the latter  the presence of bacterial antigen in urine was not helpful in identifying bacterial infection  extrapulmonary and intrapleural complications  concomitant measles  complicated alri  female gender  and malnutrition were associated with increased mortality among children with alri  the importance of measles immunization  vitamin a supplementation for alleviation of defects associated with malnutrition  and timely antimicrobial therapy is emphasized  
class1	acute respiratory tract infections among a birth cohort of children from cali  colombia  who were studied through 17 months of age  for this study  340 children less than 18 months old from a low income  urban neighborhood in cali  colombia  were observed from birth by means of weekly home visits to detect cases of acute respiratory tract infection  all suspected cases were confirmed by trained doctors in a special clinic  information on symptoms  signs  and potential risk factors was documented prospectively  etiologic agents were identified in cases of lower respiratory tract infection  lri   the overall incidence of acute respiratory tract infection was 6 6 cases per child year at risk  the incidence of upper respiratory tract infection was 4 9 cases per child year at risk and that of lri was 1 7 cases per child year at risk  crowding in the home was found to be significantly associated with an increased incidence of lri  respiratory syncytial virus was the viral agent most frequently isolated from cultures of nasopharyngeal aspirates of children with lri  staphylococcus aureus was the bacterial agent most frequently isolated from the blood of patients with lri  
class1	rational use of antibiotics in the critically ill patient  despite the advent of newer broad spectrum antibiotics  infection in critically ill patients still is associated with significant morbidity and mortality  for these patients  who frequently receive inappropriate and excessive empiric antibiotic therapy  it is important to develop rational drug usage criteria  current economic forces  including personnel shortages and the effects of diagnosis related groups  are also a critical factor in this patient population  criteria for rational antibiotic selection are based on patterns of infection and knowledge of the pharmacokinetic and pharmacodynamic properties of individual antibiotics  the development and use of treatment protocols  or algorithms  will provide quality patient care for the lowest overall cost  
class1	pathophysiology  monitoring  and management of the ventilator dependent patient  considerations for drug therapy  emphasis on stress ulcer prophylaxis  adult respiratory distress syndrome  ards   or noncardiac pulmonary edema  is a form of acute hypoxemic respiratory failure  the goals of treatment for patients with ards are to provide supportive therapy  to reverse the underlying etiology or pathology  and to prevent subsequent complications  supportive therapy consists of supplemental oxygen  positive end expiratory pressure  and  often  mechanical ventilation  the reversal of the underlying pathology varies according to the etiologic origin of ards  complications from ards include stress ulcers  which occur when gastric aggressive and defensive functions become unbalanced  antacids and cytoprotective agents are used for stress ulcer prophylaxis  but histamine h2 receptor antagonists are now regarded as the standard of care  because all the marketed h2 receptor antagonists are efficacious  choice of the agent is based on the adverse effect profile and drug interactions  no definitive data currently exist linking stress ulcer prophylaxis regimens that raise intragastric ph to a significant risk for nosocomial pneumonia  
class1	a prospective longitudinal study of observation versus surgical intervention in the management of necrotizing pancreatitis  pancreatic necrosis is now recognized as a principal determinant of survival in acute pancreatitis  however  it is currently unknown how frequently pancreatic necrosis develops in acute pancreatitis  how often pancreatic necrosis becomes secondarily infected  and whether sterile pancreatic necrosis represents an indication for surgery or can be treated by conservative means  in 194 patients with unequivocal acute pancreatitis  pancreatic necrosis developed in 38  20    as documented by dynamic pancreatography  and was confirmed by histologic diagnosis at surgery in 28  all patients were prospectively treated by medical means  patients with pancreatic necrosis who remained persistently febrile underwent fine needle aspiration for bacterial culture  infected pancreatic necrosis was demonstrated in 27 of the 38 patients  71   with pancreatic necrosis and was treated by open drainage  yielding a mortality rate of 15   all 11 patients with demonstrated sterile pancreatic necrosis  including 6 with pulmonary and renal insufficiency  were successfully treated without surgery  pancreatic necrosis occurs in approximately 20  of patients with acute pancreatitis and is necessary for the development of secondary pancreatic infection  however  pancreatic necrosis by itself  even when accompanied by organ failure  is not an absolute indication for surgery  a trial of medical treatment for all patients with sterile pancreatic necrosis is in order  
class1	lymphoproliferative responses to borrelia burgdorferi in lyme disease  objective  to compare lymphocyte proliferative responses to borrelia burgdorferi in healthy controls and patients with lyme disease  patients  twelve patients fulfilling case definition criteria for lyme disease  twelve healthy volunteers and two newborns served as controls  measurements  antibodies to b  burgdorferi were measured by enzyme linked immunosorbent assay  elisa   proliferation of peripheral blood lymphocytes cultured for 5 days with b  burgdorferi  recall antigens  or pokeweed mitogen was measured by radioactive thymidine uptake  results  lymphocytes from 11 patients with lyme disease  8 healthy seronegative controls  and two newborns showed elevated responses when stimulated with b  burgdorferi  when a patient and a control were studied on the same day  the patient s lymphocyte response to b  burgdorferi exceeded the control s in only 5 of 12 cases  lymphocytes from both patients and controls responded to b  burgdorferi isolates from three different sources  conclusions  heightened lymphocyte responses to b  burgdorferi are found in patients with lyme disease but elevated responses also frequently occur in healthy controls  at present  the interpretation of a positive lymphocyte response to b  burgdorferi would be difficult in ambiguous clinical situations  
class1	aspergillus terreus endophthalmitis in a patient with chronic lymphocytic leukemia  a 65 year old woman with a 7 year history of chronic lymphocytic leukemia presented with acute visual loss  pain  and redness in her right eye  results of stains and cultures of anterior chamber fluid were negative  neurologic problems  bronchopulmonary pneumonia  recurrent skin lesions  and a low grade fever developed  progressive respiratory distress ensued  and the patient died 1 month after presentation  cultures from antemortem sputum and skin samples were positive for aspergillus terreus  postmortem histologic results showed extensive a terreus invasion of the posterior vitreous  retina  choroid  and anterior optic nerve  this organism was also found in histologic sections from the right adrenal gland  left kidney  thyroid  urinary bladder  right lung  skin  esophagus  sputum  vessels of the myocardium  and brain  to our knowledge  a terreus endophthalmitis has not been reported previously  
class1	the incidence of ulcerative keratitis among aphakic contact lens wearers in new england  we conducted a population based incidence study in five new england states to quantify the risk of ulcerative keratitis associated with contact lens use among aphakic persons  all practicing ophthalmologists in the five state area were surveyed to identify prospectively all new cases of ulcerative keratitis during a 4 month period  the number of aphakic persons using specific types of contact lenses was estimated through a telephone survey of 4178 households identified by random digit dialing  the annualized incidence of ulcerative keratitis among aphakic persons using contact lenses was estimated to be 52 cases per 10 000 aphakic contact lens wearers  95  confidence interval  ci   31 1 to 86 9   the risk of ulcerative keratitis varied substantially by lens use  with extended wear having an estimated sevenfold greater risk relative to daily wear  95  ci  1 6 to 30 2   rates of ulcerative keratitis in aphakic persons using contact lenses were much greater than rates among cosmetic wearers of the same lens type  for daily wear lenses  aphakic persons were estimated to have 6 3 times the risk of cosmetic wearers  95  ci  1 9 to 21 0   and for extended wear lenses  aphakic persons were estimated to have 8 7 times the risk of cosmetic wearers  95  ci  3 5 to 21 9   these risks are useful in assessing the benefits and risks of contact lens wear as an alternative to other methods of aphakic correction  
class1	endophthalmitis from contaminated donor corneas following penetrating keratoplasty  we encountered six  0 2   cases of endophthalmitis resulting from contaminated donor corneas between january 1983 and july 1990 following a total of 3000 consecutive penetrating keratoplasties  causative organisms in the three cases of fungal endophthalmitis were torulopsis glabrata  candida albicans  and aspergillus flavus  the three cases of bacterial endophthalmitis were due to klebsiella pneumoniae  staphylococcus aureus  and enterococcus faecalis  all organisms were resistant to gentamicin in the preservation media  a significantly higher incidence of endophthalmitis was noted in patients receiving corneas from a sri lankan eye bank  1 25   than in those receiving us eye bank tissue  0 14    donor rim cultures are important to identify those patients at increased risk of developing endophthalmitis  enabling earlier diagnosis and more specific treatment should endophthalmitis occur  
class1	chronic postoperative endophthalmitis associated with actinomyces species  actinomyces species  gram positive  non spore forming anaerobic bacilli were isolated from intraocular fluid obtained from four otherwise healthy patients with a delayed onset of postoperative endophthalmitis  one patient had a mixed anaerobic infection with recovery of both actinomyces israelii and propionibacterium acnes  in all four patients  early postoperative visual acuity was good but was eventually markedly reduced by intraocular inflammation that was first observed between 21 days and 4 months following uneventful extracapsular cataract extraction and posterior chamber intraocular lens implantation  inflammation was characterized by anterior segment and vitreous cellular debris in all cases  all eyes responded to therapy that included intraocular  topical  and systemic antibiotics as well as pars plana vitrectomy and partial iridectomy  these cases further illustrate the need for microbiologic investigation  including anaerobic cultures  in all cases of chronic postoperative inflammation following extracapsular cataract extraction  regardless of the time of onset  
class1	penetrating ocular injury from contaminated eating utensils  although the rate of infectious endophthalmitis following penetrating ocular injury is generally less than 10   certain settings may carry a greater risk of infection  one such setting is penetrating injury resulting from eating utensils contaminated with oral flora  we reviewed six of these injuries  culture positive bacterial endophthalmitis developed in four of the six eyes  only one of the eyes retained reading visual acuity  greater than 20 50  and two eyes lost light perception  the potential for infection and limited visual outcome in this series warrants aggressive prophylaxis and treatment  the unexpected isolation of haemophilus influenzae in two of the four infections suggests that broad spectrum antibiotic treatment should be considered in all such injuries since less common organisms may be encountered  
class1	increase in native valve endocarditis caused by coagulase negative staphylococci  an anglo french clinical and microbiological study  native valve endocarditis caused by coagulase negative staphylococci has become more common  a study of 35 cases showed that the infections were usually acquired in the community and occurred in men  mean age 51 years   a pre existing cardiac abnormality  mitral leaflet prolapse in a third of patients  was detected in 26  74    the source of the organisms in the community acquired infections was assumed to be the skin  though lesions were seldom demonstrated  most hospital acquired infections resulted from intravenous devices  community acquired organisms were usually sensitive to penicillin  whereas those acquired in hospital were often multiresistant  most infections were caused by staphylococcus epidermidis  the frequency of acute presentation  26   and of major neurological abnormality  23    together with the need for valve replacement  often emergency   51   and the mortality  36   suggest that coagulase negative staphylococci can be virulent aggressive pathogens  mimicking staphylococcus aureus  
class1	early antibiotic treatment of reactive arthritis associated with enteric infections  clinical and serological study  objective  to find out whether a 10 14 days  course of antibiotics early in the course of reactive arthritis associated with enteric infections could reduce the severity and duration of the disease and whether the antibody response in patients with reactive arthritis associated with yersinia infection differed between those treated and those not treated with the antibiotics  design  prospective multicentre trial in which patients were randomised to treatment or no treatment with antibiotics  patients were seen at three and six weeks and three  six  nine  12  and 18 months after their first visit  setting  departments of infectious diseases in three hospitals in linkoping  malmo  and stockholm  sweden  patients  40 consecutive patients who had had symptoms of reactive arthritis associated with enteric infection for less than four weeks  interventions  20 patients were allocated to treatment with antibiotics and 20 patients did not receive antibiotics  all patients received non steroidal anti inflammatory drugs  and four also received intra articular steroid injections after at least six weeks  observation  main outcome measures  arthritic symptoms assessed clinically and by using ritchies  index  blood measurements reflecting inflammatory activity  serum igg  igm  and iga antibody titres  hla tissue type  results  no difference was observed concerning duration of arthritis  grade of inflammation  and number of joints affected between patients treated and those not treated with antibiotics  furthermore  there was no significant difference between the two groups in erythrocyte sedimentation rate and haptoglobin  igg  and iga concentrations  all values had returned to normal within three months  no patient developed chronic arthritis  but sustained slight arthralgia occurred in three patients  the hla b27 antigen was found in 23  58   of the patients  and its presence did not affect clinical outcome  the igg  igm  and iga antibody responses were similar in patients treated with antibiotics and those not treated  conclusion  short term antibiotic treatment has no beneficial effect on the clinical outcome of reactive arthritis associated with enteric infection  
class1	effect of steroids on cerebrospinal fluid penetration of antituberculous drugs in tuberculous meningitis  sixteen patients with oral isoniazid  pyrazinamide  rifampin  and intramuscular streptomycin for tuberculous meningitis were studied  the concentrations of isoniazid  pyrazinamide  rifampin  and streptomycin in cerebrospinal fluid  csf  obtained 3 hours after administration were 2 40  34 78  0 29  and 3 78 micrograms ml  respectively  the csf concentrations of isoniazid and pyrazinamide were well above the minimum inhibitory concentration for mycobacterium tuberculosis  concentrations of rifampin and streptomycin were above the minimal inhibitory concentration initially but declined below the minimal inhibitory concentration at later times  the csf penetration of isoniazid  pyrazinamide  rifampin  and streptomycin was about 89   91   5   and 20   respectively  in eight patients who received antituberculous drugs in combination with steroids  the mean csf and serum concentrations  as well as csf serum ratios at various intervals of treatment  were not statistically different  p greater than 0 05  from those of the eight patients who did not receive steroids  
class1	endothelin immunoreactivity in mice with gram negative bacteraemia  relationship to tumour necrosis factor alpha  1  to investigate the role of endothelin in gram negative bacteraemia and the possible involvement of tumour necrosis factor alpha in its pathophysiology  we measured plasma and tissue  lung  kidney and spleen  immunoreactive endothelin levels in gram negative bacteraemic mice  with and without passive immunization by anti  tumour necrosis factor alpha  antibody  2  plasma immunoreactive endothelin levels were greatly increased after the escherichia coli injection  pretreatment with anti  tumour necrosis factor alpha  antibody did not suppress elevated plasma immunoreactive endothelin levels  p greater than 0 1   3  lung tissue immunoreactive endothelin levels in mice were increased 16 h after the e  coli injection and were not affected by prior passive immunization with anti  tumour necrosis factor alpha  antibody  immunoreactive endothelin in spleen and kidney was undetectable  less than 34 fmol g wet weight   4  injection of rmu tumour necrosis factor alpha into mice did not increase plasma immunoreactive endothelin levels  5  antibody to endothelin given 30 min after a 90  lethal dose challenge with e  coli did not affect mortality  6  we conclude that the rise in plasma and tissue endothelin that occurs in gram negative bacteraemia is independent of tumour necrosis factor alpha  
class1	non invasive assessment of the cardiovascular eicosanoids  thromboxane a2 and prostacyclin  in randomly sampled males  with special reference to the influence of inheritance and environmental factors  1  we studied  in a random sample of 385 nonsmoking men born in 1968 1969 and 31 men born in 1913 or 1923  whether inheritance and environmental factors influenced platelet activity and vessel wall prostacyclin formation  as reflected non invasively by the urinary excretion of the 2 3 dinor metabolites of thromboxane a2  2 3 dinor thromboxane b2  tx m  and prostacyclin  2 3 dinor 6 keto prostaglandin f1 alpha  pgi m   respectively  2  fathers of young men with high platelet activity did not excrete more tx m than fathers of young men with low platelet activity  men born in 1913 or 1923 displayed higher tx m  563 versus 128 pg mg of creatinine  p less than 0 001  and pgi m  163 versus 130 pg mg of creatinine  p less than 0 01  excretion than those born in 1968 1969  excretion of both tx m and pgi m was correlated to the urinary output of noradrenaline and adrenaline  3  well trained subjects did not differ in their excretion of tx m or pgi m from those who did not exercise regularly  a recent acute infection was also unrelated to the excretion of tx m or pgi m  pgi m excretion was  however  significantly correlated to tx m excretion  r   0 51  p less than 0 001   4  this study provides the first non invasive evidence that advancing age and sympathoadrenal tone are positively correlated to platelet activity in randomly sampled men  and that paternal inheritance  physical fitness and recent infection lack correlation to platelet activity  
class1	malassezia furfur fungemia associated with central venous catheter lipid emulsion infusion  malassezia furfur has been associated with fungemias in infants after prolonged intravenous lipid emulsion alimentation  most cases of m  furfur fungemia reported in the literature involved neonates and required catheter removal for cure  m  furfur is probably an underreported problem in neonates as well as adults with central venous catheters  receiving lipid emulsions  because the organism requires selective enrichment media for growth  for example  sabouraud s dextrose agar with sterile olive oil overlay  this case report of m  furfur fungemia in a neonates is unique because the neonate recovered on discontinuation of the lipid emulsion  without removal of the central venous catheter  
class1	failure of therapy with 2 3 dihydroxybenzoic acid to modify the course of sepsis induced lung injury  oxidant induced injury of the pulmonary microvasculature reportedly contributes to an increase in microvascular permeability and pulmonary hypertension  both of which are principal features of acute lung injury  ali   we tested the hypothesis that antioxidant therapy with 2 3 dihydroxybenzoic acid  dhb   initiated in awake sheep after the development of sepsis induced ali  would ameliorate the progression of these lesions  dhb has many actions that suggested to us the potential for demonstrating benefit in ali complicating sepsis  it is a nontoxic hydroxyl radical scavenger that also inhibits the cyclooxygenase pathway and acts as a weak iron chelator  in preliminary experiments  we demonstrated that pretreatment with dhb prevented an increase in mean pulmonary arterial pressure  plasma thromboxane a2  measured as its metabolite thromboxane b2  and lymph total protein clearance that otherwise followed an infusion of zymosan activated plasma  zap  in sheep  in subsequent experiments  12 additional sheep were rendered septic by cecal ligation and perforation  twenty four to 36 h after cecal ligation and perforation  an increase in lung microvascular permeability was confirmed  because pulmonary lymph flow had increased by 82  while the mean lymph to plasma total protein ratio was unchanged from baseline  at this point  six sheep were then treated with parenteral dhb and six with dhb vehicle for the subsequent 24 h  in contrast to the demonstrated benefit of dhb pretreatment in preventing ali secondary to an infusion of zap  the progressive increase in lymph total protein clearance that complicated septic lung injury in the dhb vehicle group throughout this 24 h study period was not ameliorated in the dhb treatment group  however  dhb did prevent a modest increase in mean pulmonary arterial pressures that was demonstrated in the dhb vehicle group throughout this 24 h treatment period  although pretreatment prevented ali after a zap infusion  we conclude that dhb only incompletely modified disease progression when administered after the onset of sepsis induced ali because it ameliorated the pulmonary hypertensive response without concurrently modifying an increase in lung microvascular fluid flux  
class1	cofactors in male female sexual transmission of human immunodeficiency virus type 1  in a study of human immunodeficiency virus type 1  hiv 1  uninfected african prostitutes  83  67   of 124 seroconverted to hiv 1  oral contraceptive use  odds ratio  or   3 1  95  confidence interval  ci   1 1 8 6  p less than  03   genital ulcers  mean annual episodes  1 32     0 55 in seroconverting women vs  0 48     0 21 in seronegative women  p less than  02  and chlamydia trachomatis infections  or  3 6  ci  1 3 11 0  p less than  02  were associated with increased risk of hiv 1 infection  condom use reduced the risk of hiv 1 infection  or  0 11  ci  0 05 0 27  p less than  0001   stepwise logistic regression analysis confirmed independent associations between hiv 1 infection and oral contraceptive use  condom use  genital ulcers  and c  trachomatis  the presence of other sexually transmitted diseases may in part explain the heterosexual hiv 1 epidemic in africa and may represent important targets for intervention to control hiv 1 infection  
class1	the prevalence and incidence of clinical and asymptomatic lyme borreliosis in a population at risk  a past history of clinical lyme borreliosis and the 6 month incidence of clinical and asymptomatic lyme borreliosis was studied prospectively in a high risk population  in the spring  blood samples were drawn from 950 swiss orienteers  who also answered a questionnaire  igg anti borrelia burgdorferi antibodies were detected by elisa  positive igg antibodies were seen in 248  26 1    in contrast to 3 9  6 0  in two groups of controls  n   101   of the orienteers  1 9  3 1  had a past history of definite or probable clinical lyme borreliosis  six months later a second blood sample was obtained from 755 participants  558  73 9   of whom were seronegative initially  45  8 1   had seroconverted from negative to positive  only 1  2 2   developed clinical lyme borreliosis  among all participants  the 6 month incidence of clinical lyme borreliosis was 0 8   6 755  but was much higher  8 1   for asymptomatic seroconversion  45 558   in conclusion  positive lyme serology was common in swiss orienteers  but clinical disease occurred infrequently  
class1	randomized comparison of ceftriaxone and cefotaxime in lyme neuroborreliosis  in this prospective  randomized  open trial  33 patients with lyme neuroborreliosis were assigned to a 10 day treatment with either ceftriaxone  2 g intravenously  iv  every 24 h  n   17   or cefotaxime  2 g iv every 8 h  n   16   of the 33 patients  30 were eligible for analysis of therapeutic efficacy  neurologic symptoms improved or even subsided in 14 patients of the cefotaxime group and in 12 patients of the ceftriaxone group during the treatment period  at follow up examinations after a mean of 8 1 months  17 of 27 patients examined were clinically asymptomatic  in one patient borrelia burgdorferi was isolated from the cerebrospinal fluid  csf  7 5 months after ceftriaxone therapy  csf antibiotic concentrations were above the mic 90 level for b  burgdorferi in nearly all patients examined  patients with lyme neuroborreliosis may benefit from a 10 day treatment with ceftriaxone or cefotaxime  however  as 10 patients were symptomatic at follow up and borreliae persisted in the csf of one patient  a prolongation of therapy may be necessary  
class1	antipneumococcal activity of ciprofloxacin  ofloxacin  and temafloxacin in an experimental mouse pneumonia model at various stages of the disease  the efficacy of temafloxacin against streptococcus pneumoniae in an experimental murine pneumonia model was compared with that of ofloxacin and ciprofloxacin  erythromycin and amoxicillin were used as reference agents  subcutaneous administration of antibiotics every 12 h for 3 days was initiated at various times after infection  the cumulative survival rates of mice treated with temafloxacin at 50 mg kg were 100   92   81   and 50  with treatment beginning 18  48  72  and 96 h after infection  respectively  the activity of temafloxacin at 50 mg kg was not significantly different from that of erythromycin and amoxicillin but was superior to that of ofloxacin and ciprofloxacin  the maximum cumulative survival rates of mice treated with ofloxacin and ciprofloxacin at 100 mg kg were 67  and 50   respectively  with treatment beginning 18 h after infection  treatment with ofloxacin and ciprofloxacin at 50 mg kg 18 h after infection did not significantly increase survival rates compared with those of untreated controls  
class1	dependence among host response parameters used to diagnose urinary tract infection  the host response parameters fever  c reactive protein  crp   and erythrocyte sedimentation rate  esr  are activated in concert by cytokines such as interleukin 6  il 6   il 6 is secreted in response to escherichia coli infection of the urinary tract  this study tested the hypothesis that the level of fever  crp  and esr is coregulated in individual patients  body temperature  crp  esr  pyuria  and renal concentrating capacity were analyzed in 692 children with first time urinary tract infections  the association of the parameters was evaluated by correlation and multiple regression analysis  the body temperature  crp  and esr were significantly correlated  r    54   58  and  58  p less than  001   and variation in crp and esr explained approximately 40  of the variation in fever  in contrast  the renal concentrating capacity and pyruia were weakly or not at all correlated with the febrile response  r     22  p less than  001   and less than 10  of the variation in renal concentrating capacity was explained by the other parameters  the results suggest that fever  crp  and esr describe the same aspect of the host response to uti  
class1	comparison of functional activities between igg1 and igm class switched human monoclonal antibodies reactive with group b streptococci or escherichia coli k1  the influence of valence and heavy chain on antibody activity was investigated using transfectoma derived  class switched igg1 and igm human monoclonal antibodies  mabs  reactive with the bacterial pathogens escherichia coli k1 and group b streptococcus species  igg igm pairs were compared in vitro for antigen binding and opsonic activities and in vivo for protective efficacy in neonatal rats  for the anti e  coli pair  the igm mab was 1000 fold more potent in all assay formats  importantly  the 50  protection dose  pd50  of the igm mab was 10 20 ng rat  while 100 micrograms of the igg mab was only minimally protective  for the group b streptococcal mabs  the igm was 100  and 4500 fold more potent in binding and opsonization assays  respectively  however  while 20 micrograms of igm protected neonatal rats  100 micrograms of igg mab was partly protective  these experiments demonstrate the utility of recombinant dna technology for creating a panel of antibodies that may aid in selecting potential immunotherapeutic candidates  
class1	macrophage  and oxidant mediated inhibition of the ability of live blastomyces dermatitidis conidia to transform to the pathogenic yeast phase  implications for the pathogenesis of dimorphic fungal infections  conidia  produced by the mycelial phase of dimorphic fungi  are thought to represent the infectious form of the organism but must complete a transition to the tissue invasive  yeast like phase for infection to ensue  preventing such transition should effectively eliminate pathogenicity  using blastomyces dermatitidis as a target  murine bronchoalveolar macrophages preferentially blocked phase transition after 4 h of incubation with conidia  relatively sparing the ability of conidia to produce hyphae  h2o2  in relatively high concentrations  demonstrated the same activity  the effects of h2o2 seem irreversible  since h2o2 treated conidia that germinated at 48 h at 25 degrees c were still unable to produce yeasts over the next 5 days when incubated at 37 degrees c  catalase could not reverse the macrophage induced inhibition of phase transition  suggesting that nonoxidative defense mechanisms may be operative in vivo  since conidia do not form mycelia at temperatures found in mammalian hosts  these effects may represent a novel host defense mechanism against dimorphic fungal pathogens  
class1	three new serovars of chlamydia trachomatis  da  ia  and l2a  three new chlamydia trachomatis serovars were identified by several monoclonal antibodies in the microimmunofluorescence test and are proposed to be called da  ia  and l2a  each was clearly distinguishable from the related serovars d  i  and l2  to date  7  41  and 4 isolates of the respective serovars have been identified  each appears to be distributed worldwide  the findings meet previously established criteria for establishment of new serovars  
class1	molecular epidemiologic techniques in analysis of epidemic and endemic shigella dysenteriae type 1 strains  during 1988 the number of shigella dysenteriae type 1 infections reported in the united states increased fivefold  to determine if recent isolates from mexico were related to those that caused epidemics of dysentery worldwide  southern hybridization analysis was done with shiga toxin and ribosomal rna gene probes  western hemisphere and eastern hemisphere strains differed by the size of a single ecori fragment carrying the shiga toxin genes  three ribosomal dna  rdna  patterns were observed  which correlated with the strain s continental origin for 81 of 83 isolates tested  together the shiga toxin and rdna probe results indicated that recent mexican isolates were chromosomally similar to earlier central american isolates and distinct from asian and african strains  this suggests there has been no significant exchange of organisms between continents in recent decades and that the 1988 outbreak in mexico was caused by strains present in central america since at least 1962  
class1	combined use of released proteins and lipopolysaccharide in enzyme linked immunosorbent assay for serologic screening of yersinia infections  an elisa for the screening of serum antibodies to yersinia species was developed using plasmid encoded released proteins of yersinia enterocolitica o 8 and lipopolysaccharide of y  enterocolitica o 3 as a combined antigen  of 43 sera from patients infected with one of six different yersinia serotypes  40  93   were positive in this assay  when tested using six serotype specific elisas with the corresponding yersinia bacteria as antigens  38  88   were positive  this screening elisa detects antibodies to all virulent yersiniae in one assay and offers the possibility for diagnosis of infections caused by yersinia serotypes seen only occasionally and not usually included in the serotype specific elisas  thus  this elisa offers a substantial advantage by saving time and money in routine laboratory work  
class1	indium 111 labeled leukocyte scan in detection of synthetic vascular graft infection  the effect of antibiotic treatment  to determine the sensitivity and specificity of the indium 111  111in  labeled leukocyte scan for prosthetic vascular graft infection in patients treated with antibiotic therapy  a retrospective study was performed  of 41 consecutive 111in labeled leukocyte scans performed to evaluate possible vascular graft infection  23 scans were performed in patients treated with antibiotics  the average duration of antibiotic therapy was 21 days  twelve positive and 11 negative scans for graft infection were found  by surgical and autopsy correlation of all positive cases  and clinical correlation  of all negative cases   there were 10 true positive  11 true negative  2 false positive  and no false negative scans for graft infections  for an overall sensitivity of 100  and specificity of 85   
class1	indium 111 chloride and three phase bone scintigraphy  a comparison for imaging experimental osteomyelitis  to investigate the utility of indium 111 chloride  111in cl  imaging in detecting osteomyelitis complicating surgical or fracture sites  the proximal tibia of 11 dogs were experimentally infected with staphylococcus aureus after creation of a cortical defect  the contralateral limb served as a sham operated control  animals were serially imaged by radiography  three phase technetium 99m methylene diphosphonate  99mtc mdp  scintigraphy  and 111in cl scintigraphy  there was a significant difference between infected  1 93  and noninfected  1 32  limb s tibia femur count density ratios on 24 hr  p   0 0001  and 72 hr  p   0 0001  111in cl images  a smaller difference was found for 99mtc mdp bone phase tibia femur ratios  p   0 0199   using receiver operator characteristic analysis of tibia femur ratios  a sensitivity of 61   specificity of 88   and positive  75   and negative  79   predictive values were determined for the 24 hr 111in cl images  indium 111 chloride was superior to 99mtc mdp in differentiating infected and noninfected operative sites  
class1	roentgenologic features of pulmonary blastomycosis  in 35 cases of pulmonary blastomycosis  the roentgenologic features were as follows  consolidation 26   mass 31   intermediate sized nodules 6   miliary pattern 11   solitary cavity 9   fibrotic and cavitary changes 6   interstitial pattern 6   diffuse alveolar involvement 3   and mixed alveolar and interstitial infiltrate 3   all symptomatic cases of consolidation were acute  symptoms for less than 1 month   and most were in young patients  mean age  34 years   consolidation constituted 58  of the acute cases in this series  two of the nine cases of consolidation were asymptomatic epidemic cases detected by screening  a pulmonary mass was the most common initial manifestation in this series  it tended to occur in patients with chronic symptoms  more than 1 month   the mass was considered suggestive enough of bronchogenic carcinoma to necessitate resection in 55  of cases  the military form of pulmonary blastomycosis occurred in older patients with disseminated disease  fibrotic and cavitary disease was chronic in nature  the presence of intermediate sized nodules elsewhere in the lung proved to be a helpful diagnostic finding in several patients with consolidation  mass  or cavitary disease  hilar adenopathy  postinfectious calcification  chest wall invasion  and pleural effusion occurred infrequently or not at all in this series  
class1	children born to women with hiv 1 infection  natural history and risk of transmission  european collaborative study  600 children born to hiv infected mothers by june 15  1990  in ten european centres were followed to study the natural history of hiv infection and the vertical transmission rate  they were seen at birth  every 3 months up to 18 months of age  and every 6 months thereafter  at last follow up  64 children were judged to be hiv infected and 343 had lost antibody and were presumed uninfected  the initial clinical feature in infected children was usually a combination of persistent lymphadenopathy  splenomegaly  and hepatomegaly  though 30  of children presented with aids  or with oral candidosis followed rapidly by aids  an estimated 83  of infected children show laboratory or clinical features of hiv infection by 6 months of age  by 12 months  26  have aids and 17  die of hiv related disease  subsequently  the disease progresses more slowly and most children remain stable or even improve during the second year  the vertical transmission rate  based on results in 372 children born at least 18 months before the analysis  was 12 9   95  cl 9 5 16 3    virus has been repeatedly isolated in an additional small proportion of children  2 5   95  cl 0 7 6 3   who lost maternal antibody and have remained clinically and immunologically normal  without a definitive virological diagnosis  the monitoring of immunoglobulins  cd4 cd8 ratio  and clinical signs could identify hiv infection in 48  of infected children by 6 months  with a specificity of more than 99   
class1	association of escherichia coli hep 2 adherence patterns with type and duration of diarrhoea  373  59   out of 636 faecal specimens obtained during the first 2 years of life of 72 mexican children yielded adherent escherichia coli  hep 2 cells   strains with localised adherence were significantly associated with acute non bloody diarrhoea  whereas strains with aggregative adherence were significantly associated with persistent diarrhoea  half the strains with localised adherence were not enteropathogenic e coli serotypes nor did they hybridise with an enteropathogenic e coli adherence factor dna probe  all strains with localised adherence gave a positive fluorescent actin staining  fas  assay  irrespective of serotype  one third of children colonised by aggregative strains had bloody diarrhoea  isolation of strains with diffuse adherence was not related to type or duration of diarrhoea but was generally associated with isolation of another pathogenic organism  
class1	fungal tracheobronchitis  report of 9 cases and review of the literature  clinical  roentgenographic and pathologic findings are described in 9 patients with fungal tracheobronchitis and comparison is made with 25 additional cases in the literature  two morphologic patterns were identified  the first appears as a pseudomembrane of necrotic tissue  exudate  and fungal hyphae involving more or less the entire circumference of the bronchial wall or as mucus fungus plugs completely occluding the airway lumen  the second consists of single or multiple discrete plaques on the airway wall  sometimes associated with invasion of the adjacent lung parenchyma or pulmonary artery  as with more invasive forms of fungal infection  a compromise in host defenses is probably the most important factor leading to fungal colonization and subsequent local invasion  malignancies of the hematologic and lymphoreticular systems  solid neoplasms  granulocytopenia  and a history of a protracted course of broad spectrum antibiotics  corticosteroids  and chemotherapy were present in most of our patients and in those reported in the literature  despite this  there is some evidence that tracheobronchitis may occur in individuals with a relatively lesser degree of host defense impairment  local damage to the airway wall such as occurs with prolonged mechanical ventilatory support  neoplastic infiltration  or nonfungal infection may also be a factor predisposing to fungal colonization and invasion  in 4 of our patients  the fungal infection of the tracheobronchial tree probably contributed significantly to the development of terminal respiratory failure  although recognition of the infection may not have altered the course of the underlying disease in some of our patients  in others identification and early treatment might have been life saving  thus  culture and histologic examination of bronchoscopically identified tracheobronchial mucus plugs and necrotic material should be performed in all immunocompromised individuals  
class1	treatment of gram negative bacteremia and septic shock with ha 1a human monoclonal antibody against endotoxin  a randomized  double blind  placebo controlled trial  the ha 1a sepsis study group background  ha 1a is a human monoclonal igm antibody that binds specifically to the lipid a domain of endotoxin and prevents death in laboratory animals with gram negative bacteremia and endotoxemia  methods  to evaluate the efficacy and safety of ha 1a  we conducted a randomized  double blind trial in patients with sepsis and a presumed diagnosis of gram negative infection  the patients received either a single 100 mg intravenous dose of ha 1a  in 3 5 g of albumin  or placebo  3 5 g of albumin   other interventions  including the administration of antibiotics and fluids  were not affected by the study protocol  results  of 543 patients with sepsis who were treated  200  37 percent  had gram negative bacteremia as proved by blood culture  for the patients with gram negative bacteremia followed to death or day 28  there were 45 deaths among the 92 recipients of placebo  49 percent  and 32 deaths among the 105 recipients of ha 1a  30 percent  p   0 014   for the patients with gram negative bacteremia and shock at entry  there were 27 deaths among the 47 recipients of placebo  57 percent  and 18 deaths among the 54 recipients of ha 1a  33 percent  p   0 017   analyses that stratified according to the severity of illness at entry showed improved survival with ha 1a treatment in both severely ill and less severely ill patients  of the 196 patients with gram negative bacteremia who were followed to hospital discharge or death  45 of the 93 given placebo  48 percent  were discharged alive  as compared with 65 of the 103 treated with ha 1a  63 percent  p   0 038   no benefit of treatment with ha 1a was demonstrated in the 343 patients with sepsis who did not prove to have gram negative bacteremia  for all 543 patients with sepsis who were treated  the mortality rate was 43 percent among the recipients of placebo and 39 percent among those given ha 1a  p   0 24   all patients tolerated ha 1a well  and no anti ha 1a antibodies were detected  conclusions  ha 1a is safe and effective for the treatment of patients with sepsis and gram negative bacteremia  
class1	doppler systolic diastolic ratios in pregnancies complicated by syphilis  maternal infection with syphilis can result in focal areas of vasculitis and  similarly  placental villitis and obliterative arteritis  we hypothesized that doppler systolic diastolic ratios  s ds  in pregnancies complicated by maternal syphilis infection might reflect an increased resistance to placental perfusion  doppler velocity waveform analysis was used to study the uterine and umbilical arteries in third trimester pregnancies complicated by maternal syphilis infection  a control group of similarly studied normal pregnancies was used for comparison  statistically significant increases were found in the mean s ds of both the uterine and umbilical arteries in the syphilis group compared with the normal group  indicating an increased resistance to perfusion of the placenta in pregnancies complicated by syphilis  this difference was even greater in association with the identification of spirochetes in the amniotic fluid by dark field microscopy  indicating that the s d results are related to the presence of intrauterine infection  serial s ds in a small subgroup of patients correlated with the clinical courses  including an apparent acute vascular resistance change associated with treatment  probably due to the jarisch herxheimer reaction  because of these post treatment vascular events  the pre treatment s d alone may have a limited clinical predictive value for treatment efficacy in congenital syphilis  
class1	upper genital tract isolates at delivery as predictors of post cesarean infections among women receiving antibiotic prophylaxis  the introduction of antibiotic prophylaxis for cesarean delivery has decreased the risk of postpartum endometritis and wound infection  but factors that contribute to prophylaxis failure are not understood  to determine factors that might contribute to postpartum infections following antibiotic prophylaxis  we cultured amniotic fluid  decidua  and chorioamniotic membrane specimens for anaerobic and facultative bacteria and for genital mycoplasmas at cesarean delivery  women were assessed daily for the development of infections  and if endometritis developed  a protected endometrial culture was obtained  postpartum endometritis developed in 16 and wound infection in four of 102 women  infection rates were similar for women receiving cefotetan  n   50  or cefoxitin  n   52  for prophylaxis  the isolation of group b streptococcus  p less than  001  or enterococcus faecalis  p    03  from the upper genital tract at delivery was significantly associated with postpartum endometritis  antibiotic resistant organisms  other than enterococci  were recovered uncommonly at delivery or with postpartum infections  group b streptococcus was susceptible to the prophylactic agents used  suggesting that virulence factors other than antibiotic resistance are important for the development of postpartum endometritis  group b streptococcus  e faecalis  and bacteria associated with bacterial vaginosis were recovered from the endometrium at the time of postpartum endometritis  
class1	evaluation of two rapid group b streptococcal antigen tests in labor and delivery patients  two rapid group b streptococcal antigen tests were compared with nonselective blood agar culture in 1062 unselected patients admitted to labor and delivery  vaginal specimens taken from each patient on admission were used to perform each of two rapid tests and corresponding cultures  the rapid tests were the streptex latex agglutination assay and the equate strep b test  which uses a solid phase immunoassay  overall  105 patients  9 9   had at least one positive culture  the sensitivities for the rapid tests were 15 1  for streptex and 21 5  for equate  specificities were 99 3 and 98 7   respectively  sensitivity was minimally increased in the setting of ruptured membranes for both tests  likewise  use of separate swabs for streaking the culture plate and performing the rapid test increased the sensitivity  but this was not significant for either test  in control experiments  the limit of sensitivity of both rapid tests was 5 x 10 6  colony forming units  we conclude that at present  these tests are not sensitive enough for routine use in this type of clinical setting  
class1	aerobic and anaerobic microbiologic factors and recovery of beta lactamase producing bacteria from obstetric and gynecologic infection  specimens obtained from 736 patients with obstetric and gynecologic infections were studied for aerobic and anaerobic bacteria  bacterial growth was present in 714 specimens  these included 53 specimens of infected fallopian tubes  470 of infected endometrium  94 of infected amniotic fluid  57 of aspirates of cul de sacs in instances of pelvic inflammatory disease  14 labial and vaginal abscesses and 26 of bartholyn s cyst abscess  a total of 2 052 isolates  2 9 per specimen   1 139 anaerobes  1 6 per specimen  and 913 aerobic or facultative  1 3 per specimen  were recovered  the most commonly isolated anaerobic bacteria was bacteroides species  566 isolates   which included bacteroides bivius  151   bacteroides fragilis group  130   bacteroides melaninogenicus group  110  and bacteroides ureolyticus  47   others included an anaerobic gram positive cocci  391   clostridium species  48  and fusobacterium species  36   the most frequently recovered aerobic and facultative bacteria were lactobacillus species  169   escherichia coli  85   neisseria gonorrhoeae  62   staphylococcus aureus  59  and group b streptococcus  55   three hundred and sixty five  18 per cent  of the isolates recovered from 276  39 per cent  patients were beta lactamase producing organisms  blpo   222  61 per cent  anaerobes and 143  39 per cent  aerobes or facultatives  the most common blpo were b  fragilis group  b  bivius  b  melaninogenicus  b  disiens  enterobacteriaceae and s  aureus  these data illustrate the polymicrobial nature and important role of blpo in obstetric and gynecologic infection  
class1	lyme disease  neurologic and ophthalmic manifestations  lyme disease is tick borne infection which produces early and late manifestations in many organ systems  prominent symptoms and signs occur in skin  heart  joints and nervous system  many ocular and neuro ophthalmic abnormalities recently have been attributed to lyme disease  but some cases have not been well established as direct sequelae  this review of the contemporary state of knowledge about lyme disease was undertaken so that more rigorous criteria can be applied in future diagnosis  
class1	improved results with combined donor specific transfusion  dst  and sequential therapy protocol  a combined dst sequential cya therapy protocol has been described that results in optimum graft survival for 1  and 2 haplotype mismatched living related donor recipient combinations  in addition to the excellent graft survival obtained through 4 years  lower prednisone and cya dosage levels are achieved with significantly decreased infection rates during the posttransplant period  
class1	topical vancomycin for the treatment of staphylococcus epidermidis and methicillin resistant staphylococcus aureus conjunctivitis  staphylococcus aureus and staphylococcus epidermidis are organisms that frequently cause conjunctivitis or blepharoconjunctivitis  we describe a patient with methicillin resistant s  aureus and s  epidermidis conjunctivitis who was treated successfully using an extemporaneously prepared topical ophthalmic solution of vancomycin hydrochloride 31 mg ml  studies describing the preparation  stability  and comfort of this solution  as well as reports pertaining to efficacy  are reviewed  controlled clinical trials evaluating the safety and efficacy of vancomycin ophthalmic solution have not yet been performed  
class1	drugs for treatment of vulvovaginal candidiasis  comparative efficacy of agents and regimens  various agents are available for the treatment of vulvovaginal candidiasis  imidazole agents  clotrimazole  miconazole  butoconazole  and terconazole  are preferred because of their greater efficacy  shorter treatment regimens  and ease of administration  although the various imidazole compounds are equally efficacious  different treatment schedules are recommended depending on clinical situations  additionally  different formulations are available that provide clinicians and patients with the opportunity to select the most appropriate agent  
class1	risk factors for nosocomial pneumonia after coronary artery bypass graft operations we attempted to determine risk factors for nosocomial pneumonia in patients undergoing a coronary artery bypass graft operation  we reviewed the microbiology and medical records for any patient with a sputum culture who had undergone a coronary artery bypass graft operation in 1988 to identify patients with pneumonia according to a standard clinical definition  we found 19 cases of pneumonia through our initial review  complete medical records were found on 15 cases  gram negative bacilli predominated as the most common etiologic agent causing pneumonia in this cohort  there were no clusters noted  mortality was 26 6   pneumonia occurred approximately 4 days after the operation  thirty six controls were randomly selected from patients undergoing coronary artery bypass graft operations in 1988  logistic regression analysis revealed that a history of chronic obstructive lung disease  duration of more than 2 days of mechanical ventilation after operation but before diagnosis of pneumonia  and receipt of gastric acid inhibitors  antacids or h2 blockers  were independent risk factors for nosocomial pneumonia  only the last risk factor was amenable to intervention at the time of operation  
class1	diagnosis of poststernotomy infection  comparison of three means of assessment  of 737 adults undergoing cardiac operations through a median sternotomy over a 2 year period  january 1988 to january 1990   sternal substernal space infection requiring mediastinal exploration developed in 8  six of these patients as well as 18 additional patients were evaluated for possible poststernotomy wound infection by computed tomography  4 true positive  4 false positive  10 true negative  2 false negative   indium 111 leukocyte scanning  5 true positive  0 false positive  18 true negative  1 false negative   and epicardial pacer wire cultures  6 true positive  1 false positive  12 true negative  0 false negative   on the basis of this experience it is suggested that in addition to computed tomography  indium 111 leukocyte scanning and epicardial pacer wire cultures may be useful in the diagnosis of poststernotomy deep wound infection  
class1	percutaneous balloon pulmonic valvuloplasty following treated endocarditis in a patient with congenital pulmonary valve stenosis  a 36 year old woman with congenital pulmonary valve stenosis developed the rare complication of endocarditis of the valve  after successful sterilization of the valve  the patient underwent percutaneous balloon pulmonic valvuloplasty at a later date  the procedure successfully reduced the peak pulmonary valve gradient from 94 to 45 mm hg  percutaneous balloon valvuloplasty is the procedure of choice for treatment of congenital pulmonary valvular stenosis  even in the unusual patient who has healed endocarditis of the pulmonary valve  
class1	balloon valvuloplasty for fungal endocarditis induced stenosis of a bioprosthetic tricuspid valve  palliative treatment was provided without complications by double balloon valvuloplasty of a stenotic porcine tricuspid valve in a patient with fungal endocarditis  with two 15 mm diameter valvulotomy balloons the peak tricuspid gradient decreased from 21 to 7 mm hg and valve area increased from 0 3 to 1 2 cm2  after the procedure the patient clinically improved  however  valve replacement was not performed as planned because the patient developed an intracranial hemorrhage  she subsequently died of complications of fungemia  the present report demonstrates the possible use of valvuloplasty as a palliative procedure in selected patients with valvular stenosis involved with endocarditis  
class1	use of the pediatric risk of mortality score to predict nosocomial infection in a pediatric intensive care unit  objective  to define infection rates in patients with pediatric risk of mortality  prism  scores greater than and less than 10 on admission to the pediatric icu  picu   design  descriptive  setting  an 18 bed picu admitting patients of all ages except nonsurgical neonates  within a 585 bed tertiary care pediatric hospital  patients  patients admitted to the picu from july 1987 to february 1988 inclusive  of 685 admitted  480 were followed for greater than or equal to 72 hr  methods  the baseline state of the patients on admission was determined by a designated intensivist using the prism score  other variables included age  length of stay  and hospital day of onset of infection  infections were identified by a designated intensivist who undertook prospective daily bedside observation  chart  radiographic  and laboratory review  measurements and main results  equal portions of patients had prism scores less than and greater than 10  significantly more infections occurred in the high prism population  10 8  vs  3 4   p less than  001   this association held through age  service  and length of stay  sensitivity  specificity  positive and negative predictive values of a prism score greater than 10 were 75   53   11   and 97   respectively  bacteremias accounted for 36  of infections  skin eye drain site 22   respiratory 16   wound 15   and urine 9   the most prevalent organisms were coagulase negative staphylococci  32    pseudomonas aeruginosa  23    candida sp   20    and s  aureus  9    conclusions  a prism score greater than 10 on picu admission characterizes a population within the picu at increased risk of infection  however  93  of patients did not develop infection and thus  a negative predictive value of 97  yields little additional information  
class1	reliability of the bronchoscopic protected catheter brush in the diagnosis of pneumonia in mechanically ventilated patients  objective  to assess the usefulness of the telescoping plugged catheter in the diagnosis of nosocomial pneumonia  design  prospective study  patients  a total of 103 ventilated patients with suspected pneumonia were prospectively studied over 20 months  results  the quantitative cultures of the protected brush specimen detected pulmonary bacterial infection  greater than 10 3  cfu ml  in 49  47 5   patients  subsequent follow up confirmed pneumonia in 41 patients  in only one patient was a positive protected brush specimen culture established as a false positive result  there were 54 patients with less than 10 3  cfu ml and the diagnosis was excluded in 36 of them  we identified eight patients with false negative protected brush specimen cultures  the results obtained by this technique allowed us to modify treatment in 49  47 5   patients  conclusions  the telescoping plugged catheter demonstrated significant bacterial infection in a relatively small proportion of patients in whom bacterial lung infection was suspected  this technique can be safely performed and is a sensitive and specific method to establish the cause of pneumonia  thus allowing specific treatment and the avoidance of inappropriate antibiotic therapy  
class1	systemic and muscle oxygen uptake delivery after dopexamine infusion in endotoxic dogs background and methods  this study was designed to test whether dopexamine  a dopaminergic and beta 2 adrenergic agonist  would a  increase systemic oxygen delivery  do2  in endotoxic dogs  and b  interfere with the ability of resting skeletal muscle to extract oxygen  there were three treatment groups  n   6 in each group   control  endotoxin alone  e  4 mg kg iv  and endotoxin   dopexamine  e   d  12 micrograms kg min  data were analyzed between and within groups by split plot analysis of variance with significance of identified differences tested post hoc by duncan s multiple range test  donor rbc and dextran were used after endotoxin to maintain adequate perfusion pressures  with hct kept near 40   blood flow to left hindlimb muscles was decreased in controlled steps of 15 min each after stabilization  results  in e group  cardiac output  qt   mean arterial pressure  map   systemic do2  and oxygen uptake  vo2  decreased despite blood volume expansion  in e   d group with similar volume expansion  dopexamine maintained qt  systemic do2  and vo2 near the control levels  although map and systemic vascular resistance were reduced  in comparison with control subjects  endotoxin increased critical do2 in the isolated limb muscles from 4 6 to 7  ml kg min and decreased critical oxygen extraction from 81  to 68   the pressure flow relationship in the limb became flattened  indicating loss of vascular reactivity  in the e   d group  there was no further change in the pressure flow curve nor in the critical oxygen extraction level  conclusions  dopexamine provided hemodynamic support for endotoxic dogs  thereby increasing total do2 and vo2  while not altering oxygen extraction in the muscle  
class1	comparative study of legionella pneumophila and other nosocomial acquired pneumonias  we studied  in a prospective way  the characteristics of definitively diagnosed nosocomially acquired pneumonias in our hospital over 36 months  out of 55 cases  27 were due to legionella pneumophila and 28 to other  non legionella bacteria  the cases of legionellosis concentrated in july  august  and december  the only risk factors that showed significant differences  p less than 0 05  were general anesthesia and surgery and immunosuppressive disease  which were more frequent in the non legionella group  as were chronic liver disease and lowering of consciousness level  the absence of severe underlying disease  chronic or not  was uncommon in both groups  but more frequent in the legionella group  we observed no differences in the clinical features of the two groups  mean values of gamma glutamyltranspeptidase and total bilirubin were higher  p less than 0 05  in the non legionella group  the only x ray data that showed significant difference were pleural effusion  more frequent in the non legionella group  p less than 0 02   the mortality rate of legionellosis was 14 6 percent compared to 35 7 percent for the non legionella group  p less than 0 05   we conclude that a sure differential diagnosis based on clinical  roentgenographic and analytical features of both groups is not possible  the relatively low mortality rate of the legionella group  when compared to other series of nosocomial legionellosis  could be due to the standard use of erythromycin in the therapeutic approach to nosocomial acquired pneumonia in our hospital  
class1	adenosine deaminase in the diagnosis of tuberculous pleural effusions  a report of 218 patients and review of the literature  the activity of adenosine deaminase in the pleural fluid of 218 consecutive patients was studied  according to the etiology of exudative pleural effusions  the patients were divided into the following five groups   1  tuberculosis   2  lung cancer   3  pneumonias   4  miscellaneous  and  5  idiopathic  patients with pleural tuberculosis presented significantly higher ada activity than patients with nontuberculous pleural effusions  p less than 0 0001   the results indicated that in a population with a relatively high prevalence of tuberculosis  the analysis of ada levels in pleural effusions constitutes a useful marker for the diagnosis which  in addition  can be made quickly and cheaply  additionally  a comprehensive review of the literature on the role of ada in the diagnosis of tuberculous pleural effusions is presented  
class1	utility of bronchoscopic sampling techniques for cryptococcal disease in aids  although cryptococcal pneumonia is a well recognized complication of the acquired immunodeficiency syndrome  optimal diagnostic approaches remain to be defined  during a 32 month period  october 1984 to june 1987   11 patients were diagnosed with cp at our institution  the diagnosis was established in all 11 patients from specimens obtained via fiberoptic bronchoscopy  ten  and or double lumen catheter lavage  one   direct stains of sedimented bronchoalveolar lavage were positive for organisms characteristic of cryptococcus neoformans in nine of 11 patients  transbronchial biopsies were positive  special histologic stains  in six of eight patients  bronchial washings were positive  direct smear  in seven of ten patients  the bronchial brushings were positive on stain in six of nine patients  and in one patient  a wang transbronchial needle aspirate was positive on stain  fungal cultures were positive on the bal in seven of 11 patients  and on the bronchial washings in four of ten patients  the tbbx culture samples were all negative  zero of three   the serum cryptococcal antigen titer was elevated  median   1 1024  in all eight patients in which it was assayed  our data suggest that bal and bronchial washings have a combined sensitivity on smear equal to that of tbbx and superior to that of tbbx fungal culture  the tbbx does not appear to be necessary in this setting  in addition  an elevated serum cryptococcal antigen titer appears to be an important adjunct in the evaluation of pulmonary infiltrates in aids  
class1	endobronchial actinomycosis simulating bronchogenic carcinoma  diagnosis by bronchial biopsy  five cases of actinomycosis of the main bronchi or trachea which were suggestive clinically of bronchogenic carcinoma are described  in four patients the correct diagnosis was made by a bronchial biopsy or wash  or both  three of them recovered following antibiotic treatment  and one died a few days after bronchoscopy  in one case the actinomyces were found in the bronchial wash retrospectively following diagnosis of pulmonary actinomycosis in the lobectomy specimen  a concomitant endobronchial lipoma was found in one of the patients  the diagnosis of pulmonary actinomycosis by bronchial biopsy may save the patient major surgical intervention  
class1	gram negative infection increases noninsulin mediated glucose disposal  peripheral glucose uptake can occur by either insulin  or noninsulin mediated mechanisms  and the two pathways appear to be regulated independently  using the euglycemic hyperinsulinemic clamp technique  we have previously demonstrated that sepsis induces whole body insulin resistance  the purpose of the present study was to determine whether infection also alters noninsulin mediated glucose uptake  nimgu  and  if so  which tissues are affected  studies were performed in chronically catheterized conscious rats under either basal  6 mm glucose  30 microu ml insulin  or insulinopenic conditions to determine nimgu  hypermetabolic sepsis was induced by sc injections of live escherichia coli  and 24 h later a tracer amount of  u 14c deoxy 2 glucose was injected for the determination of the in vivo glucose metabolic rate  rg  in selected tissues  our results indicate that nimgu is the predominant route of glucose disposal in both septic and nonseptic rats  accounting for 79 83  of the total rate of glucose disposal  because the rate of whole body glucose disposal was increased by sepsis  the absolute rate of nimgu was 46  higher in septic rats than in nonseptic animals  this increase was the result of the elevated rg in liver  spleen  ileum  and lung  sepsis also increased whole body insulin mediated glucose uptake by 88  under basal conditions  and this was due to an enhanced glucose uptake by muscle and skin  in insulinopenic animals in which the plasma glucose concentration was elevated to 17 mm  whole body glucose disposal increased by 107  in nonseptic animals  but by only 32  in septic rats  the hyperglycemic induced increment in organ rg was smaller in all tissues examined from septic animals  however  the absolute rate of whole body and tissue glucose utilization was not different between the two groups  these results indicate that gram negative infection increases whole body nimgu  which results from an enhanced rate of glucose utilization by tissues rich in mononuclear phagocytes  including the liver  spleen  ileum  and lung  but not by muscle  
class1	pathogenesis and pathophysiology of meningitis  advances in the understanding of the pathogenesis and pathophysiology of meningitis have occurred primarily through the use of experimental animal models  these models have proven to be particularly valuable in experimental bacterial meningitis  focusing on the bacterial virulence factors responsible for the initiation of infections  cns invasion  and induction of sas inflammation  recent studies have examined the formation of host inflammatory cytokines in response to these virulence factors  these cytokines may be responsible for many of the pathophysiologic consequences of bacterial meningitis  eg  increased bbb permeability  cerebral edema  and increased intracranial pressure   meningitis due to c  neoformans occurs most commonly in patients with defects in cell mediated immunity  eg  aids   and the depletion of t helper cells in aids patients may allow unrestricted cryptococcal growth  viral meningitis is an illness of low prevalence when compared with the overall occurrence of viral infections at other sites  cns infection usually occurs by means of traversal across barriers that normally exclude viral invasion of the cns  primarily through hematogenous dissemination from initial sites of infection  these advances in the pathogenesis and pathophysiology of bacterial  fungal  and viral meningitis may lead to the development of innovative treatment strategies for these disorders  
class1	bacterial meningitis in neonates and children  a high index of suspicion of meningitis is needed when evaluating neonates and young infants because clinical findings can be minimal and are often subtle and nonspecific  analysis of the csf constitutes the most effective method to document meningeal bacterial infection  although overlap with normal csf values can occur  especially in newborns and very young infants  the introduction of highly active third generation cephalosporins  ceftriaxone  cefotaxime  and their safety and efficacy in treating a broad array of bacterial pathogens that cause meningitis in all age groups has simplified selection of initial antibiotic therapy  in neonates  however  conventional antibiotic therapy with ampicillin and an aminoglycoside is appropriate because of its proven record of safety and efficacy  and because routine use of cephalosporins in the hospital nursery could lead to selection of resistant strains among gram negative enteric bacilli  despite the availability of modern intensive care management of infants and children with bacterial meningitis and the advent of potent antibiotics  case fatality rates and morbidity remain high  because of this  recent research has focused on the complex interaction between bacteria and the host and on means to attenuate the meningeal inflammatory response  the clinical benefits demonstrated recently with the use of dexamethasone therapy in infants and children with bacterial meningitis underscore the importance of anti inflammatory therapy to reduce audiologic and neurologic sequelae  future studies of new methods to modulate meningeal inflammation such as the use of monoclonal antibodies directed against cytokines or of agents that interfere with leukocyte endothelial interactions are indicated  the implication of routine h  influenzae type b immunization in young infants with the conjugated vaccines and optimal intrapartum prophylaxis against group b streptococcal disease in newborns will have an important impact on the incidence of meningitis in infants and children  
class1	bacterial meningitis in adults  bacterial meningitis continues to be an important cause of morbidity and mortality despite the availability of effective bactericidal antibiotics  penicillin or ampicillin remains the drug of choice for meningitis caused by streptococcus pneumoniae and neisseria meningitidis  the third generation cephalosporins have revolutionized the treatment of gram negative meningitis  future therapy for bacterial meningitis will use recent developments in the understanding of pathogenic and pathophysiologic mechanisms underlying this disease  
class1	general principles of therapy of pyogenic meningitis  in bacterial meningitis  several pharmacodynamic factors determine therapeutic success when defined as sterilization of the csf   1  local host defense deficits in the cns require the use of bactericidal antibiotics to sterilize the csf   2  csf antibiotic concentrations that are at least 10 fold above the mbc are necessary for maximal bactericidal activity  protein binding  low ph  and slow bacterial growth rates are among the factors that may explain the high antibiotic concentrations necessary in vivo   3  high csf peak concentrations that lead to rapid bacterial killing appear more important than prolonged suprainhibitory concentrations  probably because very low residual levels in the csf prevent bacterial regrowth  even during relatively long dosing intervals   4  penetration of antibiotics into the csf is significantly impaired by the blood brain barrier and thus  very high serum levels are necessary to achieve the csf concentrations required for optimal bactericidal activity  beyond these principles  recent data suggests that rapid lytic killing of bacteria in the csf may have harmful effects on the brain because of the release of biologically active products from the lysed bacteria  since rapid csf sterilization remains a key therapeutic goal  the harmful consequences of bacterial lysis present a major challenge in the therapy of bacterial meningitis  currently  dexamethasone represents that only clinically beneficial approach to reduce the harmful effects of bacterial lysis  and novel approaches are required to improve the outcome of this serious infection  
class1	spirochetal infection of the central nervous system  four spirochetal diseases frequently involve the central nervous system  syphilis  leptospirosis  relapsing fever  and lyme borreliosis  in particular  syphilis and lyme borreliosis are increasing problems  during the spirochetemic phase there is seeding of the nervous system  after a quiescent latent period  there may be late disease flareups producing a variety of neurologic syndromes  cerebrospinal fluid examination is very helpful in these infections  
class1	tuberculous meningitis  tuberculous meningitis is an uncommon but potentially devastating form of tuberculosis  current antituberculous drugs are highly effective when treatment is initiated early  before the onset of altered mentation or focal neurologic deficits  because the clinical outcome depends greatly on the stage at which therapy is initiated  early recognition is of paramount importance  patients with the meningoencephalitis syndrome and csf findings of low glucose levels  elevated protein levels  and pleocytosis should be treated immediately if there is evidence of tb elsewhere in the body  or if prompt evaluation fails to establish an alternative diagnosis  examination of csf is the best diagnostic approach  with sufficient diligence  serial afb smears and cultures will usually yield positive results  even days after therapy has been started  the ct scan is an important and highly effective tool for the diagnosis and management of patients with tbm  in a patient with compatible clinical features  the combination of basilar meningeal enhancement and any degree of hydrocephalus is strongly suggestive of the diagnosis of tbm  serial evaluation by ct scanning is useful for following the course of hydrocephalus and tuberculoma  particularly in reference to the need for  or response to  adjunctive therapy with corticosteroids and surgery  the decision to administer corticosteroids should be based on careful correlation of the clinical and radiographic features of the case  surgical shunting should be considered early in the patient with hydrocephalus and symptoms of raised intracranial pressure  tuberculomas are best treated medically  often in conjunction with corticosteroids where cerebral edema is believed to contribute to neurologic decline  the recommended chemotherapy regimen is isoniazid and rifampin in all patients  together with pyrazinamide for the first 2 months  
class1	fungal meningitis  fungal meningitis tends to be a subacute or chronic process  however  it may be just as lethal as bacterial meningitis if untreated  there are many similarities between the pathogenic fungi  most of the fungi are aerosolized and inhaled  and initiate a primary pulmonary infection which is usually self limited  hematogenous dissemination may follow the initial infection  with subsequent involvement of the cns  rarely  trauma or local extension provides the route to cns infection  the host is frequently  although not always  immunosuppressed  the hyphae of molds generally cause focal disease with hemorrhagic necrosis secondary to vascular thrombosis  the yeasts tend to cause a more diffuse process with the base of the brain being primarily affected  such that hydrocephalus is seen as a frequent complication of chronic disease  diagnosis may be difficult  as the csf may be normal  with negative smears and sterile cultures  although more often there is at least one abnormality indicating disease  serologies  if available  depending on the fungus  may point towards the proper diagnosis  as may a careful travel history  currently  amphotericin b is still the drug of choice in most situations  however  the newer azole antifungal agents offer great promise  especially in the treatment of cryptococcal meningitis  the precise role of such agents will remain unclear until appropriate large scale studies of their effectiveness have been completed  the treatment of the unusual cns mycoses will continue to be based on clinical experience  and reports of the use of new azoles in these diseases need to be critically evaluated  
class1	treatment of beta hemolytic streptococcal pharyngitis with cefaclor or penicillin  efficacy and interaction with beta lactamase producing organisms in the pharynx  the recommended treatment for group a beta hemolytic streptococcal pharyngitis has continued to be penicillin given in parenteral or oral form  treatment failures  as determined by the continued presence of the streptococcal organism in the pharynx  however  do occur in 6  to 25  of patients treated with penicillin  furthermore  beta lactamase produced by other bacteria in the pharynx could potentially inactivate the penicillin  resulting in increased treatment failures or infection relapses  a study was undertaken to compare the efficacy of cefaclor  which is relatively resistant to inactivation by beta lactamase  with penicillin for eradicating the group a beta hemolytic streptococcal organism from the throats of 93 patients with pharyngitis  additionally  extensive cultures for potential beta lactamase producing organisms were conducted on 37 patients  27  of these had one or more pharyngeal organisms that were producing beta lactamase  no statistically significant difference was found between the clinical responses or the bacteriological cure rates of those treated with cefaclor and those treated with penicillin when stratified by the presence or absence of beta lactamase producing organisms  the prevalence of beta lactamase producing organisms in the pharynx  however  was increased after treatment with penicillin  whereas no change was noted following treatment with cefaclor  
class1	terconazole for the treatment of vulvovaginal candidiasis  a double blind  randomized trial was conducted to evaluate the efficacy and safety of terconazole for vulvovaginal candidiasis  treatment consisted of daily intravaginal application of one of the following regimens  80 mg terconazole suppositories for 3 days  miconazole nitrate suppositories for 7 days or placebo suppositories for 7 days  the terconazole and miconazole nitrate groups had significantly higher therapeutic cure rates than did the placebo group  evaluation of vaginal secretions with microscopic examination showed no evidence of leukocyte proliferation  proline aminopeptidase activity  present in patients who have bacterial vaginosis  could not be detected in the vaginal secretions from patients with yeast vulvovaginitis  
class1	role of cephamycins in obstetrics and gynecology  infections of the female upper genital tract are usually polymicrobic  often involving mixed aerobic  facultative  and anaerobic bacteria  optimal therapy provides coverage against aerobes  both gram positive and gram negative and especially the enterobacteriaceae  and anaerobes  especially the beta lactamase producing gram negative species  such as bacteroides   a variety of antibiotics provide the broad spectrum of activity needed for these infections  including clindamycin plus an aminoglycoside  cephalosporins and cephamycins  imipenem  extended spectrum penicillins and the beta lactam agents combined with a beta lactamase inhibitor  the cephamycins  cefoxitin  cefotetan and cefmetazole  have been shown to have a high rate of clinical efficacy and bacteriologic response  the cephalosporins are usually used for prophylaxis at the time of obstetric and gynecologic surgery  the cephamycins have recently undergone extensive evaluation for prophylaxis and have demonstrated comparable microbiologic and clinical efficacy  a pharmacokinetic comparison of cefoxitin  cefotetan and cefmetazole points to cefmetazole as a cost effective alternative to cefoxitin and cefotetan for both prophylaxis and treatment of pelvic infections  
class1	role of new cephamycins in the management of obstetric and gynecologic infections  the results of in vitro and in vivo studies of cefmetazole  a second generation cephamycin  were reviewed  cefmetazole s spectrum of activity includes clinical coverage of many enterobacteriaceae  staphylococci  streptococci  haemophilus species  pathogenic neisseria organisms  moraxella  branhamella  catarrhalis and anaerobic bacteria  cefmetazole is generally two to eight times more potent than cefoxitin against organisms within their spectra and is most active against staphylococci  minimal inhibitory concentration90   2 0 micrograms ml   methicillin resistant staphylococcus aureus strains are more susceptible to cefmetazole  alone or in combination with fosfomycin  than to any other cephamycins  and cefmetazole is remarkably resistant to the beta lactamases produced by aerobic and anaerobic bacteria  the incidence of adverse drug reactions is low  8 8  in the united states  2 2  in japan   and the drug has been demonstrated to have cost containment potential  
class1	the challenge of prophylaxis in cesarean section in the 1990s  physicians have evaluated the role of antibiotics in the prevention of perioperative infections since these drugs were discovered  but not until it was determined that antibiotics prevented staphylococcal wound infections in the animal model did surgeons consider their use for prophylaxis  in the 1970s  improved techniques in isolating and identifying anaerobic microorganisms and the unacceptably high incidence of infection related complications convinced obstetricians to study  and ultimately accept  the use of perioperative antibiotic administration to prevent these infections  recent progress has included refinement of the guidelines for patient selection and drug regimens  although a single dose of an antibiotic given to the patient undergoing primary cesarean section has been demonstrated to be effective prophylaxis when administered after clamping the umbilical cord  this practice has not been widely accepted  with the discovery of cephamycins the role of these broad spectrum antibiotics in obstetric and gynecologic surgery was investigated  one of the studies compared the efficacy of cefmetazole with that of cefotetan in preventing post cesarean section infection  eighteen patients in each group received a 2 g dose of one of the two drugs when the umbilical cord was clamped  predetermined elevations in temperature were used to evaluate the presence of ensuing infections  four subjects in each group developed some type of morbidity  postoperative complications included wound infection  endometritis  bladder infection and cellulitis  cefmetazole and cefotetan seemed equally effective in preventing post cesarean section infections  
class1	cefmetazole and cefonicid  comparative efficacy and safety in preventing postoperative infections after vaginal and abdominal hysterectomy  a single 1 g dose of cefmetazole was compared with a single 1 g dose of cefonicid for prophylaxis in vaginal and abdominal hysterectomy to determine their efficacy and safety  the antibiotics were administered intramuscularly 15 90 minutes before the incision was made  cefmetazole and cefonicid had similar activity against most of the aerobic organisms recovered  but cefmetazole was significantly more active against anaerobic gram negative microorganisms  the patterns of regrowth of vaginal flora were similar in the two treatment groups  patient demographic characteristics and surgical procedures were similar in both groups  the difference in primary prophylactic failure  e g   cuff cellulitis  with the two study drugs  1 of 53  1 9   with cefmetazole and 2 of 28  7 1   with cefonicid  did not reach statistical significance  and the results were similar for the two routes of hysterectomy  cefmetazole  at a dose of 1 g intramuscularly preoperatively  is a safe and effective agent for prophylaxis during hysterectomy  
class1	therapeutic dilemmas in the treatment of pelvic infections  the identification of pathogens and the early recognition of pelvic infections in patients after hysterectomy  cesarean delivery and vaginal delivery were analyzed  criteria for administering cephamycin therapy were established  as were guidelines for evaluating the progress of the infection  in a comparative study of the safety and efficacy of cefmetazole and cefoxitin in 145 hospitalized patients with pelvic infections there were no significant differences between either the bacteriologic or clinical cure rates of the two antibiotics  both were efficacious and safe for the treatment of obstetric gynecologic soft tissue infections  
class1	improved detection of rotavirus shedding by polymerase chain reaction  to improve identification of children excreting rotavirus a method for the amplification of rotavirus rna by the polymerase chain reaction  pcr  was developed  the assay was compared with a solid phase enzyme immunoassay in the detection of rotavirus shedding by infants in hospital during the winter peak of rotavirus infections  forty children were studied in an intermediate care unit after transfer from intensive care units  only two were admitted primarily because of diarrhoea  the other thirty eight were admitted for management of various other disorders  rotavirus shedding was detected by enzyme immunoassay in twenty of the infants  and nine of these  aged 1 week to 8 months  remained in hospital for more than 5 days after the initial detection of rotavirus and could be studied long term  of 103 faecal samples from the nine infants  60  58   contained rotavirus rna detected by reverse transcriptase  rt  pcr  whereas only 37  36   were positive for rotavirus antigen by the immunoassay  chi 2   10 3  p less than 0 002   the geometric mean time of rotavirus shedding was 9 5  range 1 19  days as detected by rt pcr and 5 7  range 1 17  days by the immunoassay  p less than 0 018   in five of the nine children  rt pcr detected rotavirus shedding for 2 7 days longer than the immunoassay and in four children rt pcr was positive 1 or more days before rotavirus antigen was detected  further studies should attempt to find out whether infected infants are capable of spreading wild type virus during periods when they are not shedding antigen as detectable by enzyme immunoassay  
class1	changes in the differential white blood cell count in screening for group b streptococcal sepsis  we compared several previously defined scoring systems using white blood cell indices as part of a retrospective evaluation of infants with early onset group b streptococcal  gbs  sepsis  nineteen newborns were diagnosed with gbs sepsis between january  1988  and april  1990  case controls  n   33  were selected from patients admitted to the neonatal intensive care unit for suspected sepsis  complete blood counts obtained at admission and between 12 and 24 hours of age were reviewed  there was a significant change in the ratio of immature to total neutrophils in the gbs group over time  scoring systems for neonatal sepsis by manroe et al   rodwell et al  and spector et al  had poor sensitivity  specificity  positive predictive value and negative predictive value when initial white blood cell count criteria were used  but scoring systems by manroe and rodwell were 100  sensitive and had 100  negative predictive value when applied to the repeat white blood cell count  we conclude that a single early complete blood count may not be an adequate screening tool for early onset gbs sepsis and should not be used to rule out infection  optimal screening for gbs sepsis requires a repeat complete blood count within the first 24 hours of age  
class1	sexually transmitted viral disease in women  during the past decade  the incidence of sexually transmitted viral diseases has increased dramatically  in many cases  diagnosis is difficult  consequences are severe  and curative therapy is not available at present  in this article  drs peaceman and gonik review current evidence about sexual transmission of viruses and discuss the latest methods of diagnosis  management  and prevention  
class1	klebsiella pneumonia in the modern era  clinicoradiographic correlations  a classic clinical and radiographic picture of klebsiella pneumonia has emerged in the literature  patients are typically male  older than 48 years  and have a history of chronic alcoholism  the majority of these pneumonias are community acquired  bulging interlobar fissures and cavitation are radiographic findings said to be distinctive for klebsiella pneumonia  we prospectively studied 15 cases of bacteremically proven klebsiella pneumonia and found clinical and radiographic features strikingly different from those described in the literature  immunosuppression  from corticosteroids  cytotoxic chemotherapy  neutropenia  hematologic malignancy  and transplantation  now rivals alcoholism as the primary risk factor  cases tended to be nosocomial rather than community acquired  neither bulging interlobar fissure nor cavitation was seen in any case  the right upper lobe was involved in 11 of our 15 cases  pneumonia due to klebsiella oxytoca was more likely to be isolated from patients with bilateral infiltrates  while klebsiella pneumoniae was more likely in patients with unilateral infiltrates  
class1	adenotonsillectomy in children with sickle cell disease  the pediatric patient with sickle cell disease risks having a vasoocclusive episode during adenotonsillectomy under general anesthesia  with proper patient selection and appropriate perioperative management  adenotonsillectomy can be accomplished safely in children with sickle cell disease  we review the management of 10 children with sickle hemoglobinopathies who had adenotonsillectomy  indications for surgery were recurrent streptococcal infections in four and obstructive sleep apnea in six of these children  no complications resulted from any of these procedures  and the mean length of postoperative hospitalization was 2 4 days  the principal feature of preoperative management was the transfusion of red blood cells to suppress the patient s endogenous erythropoiesis and to reduce the concentration of sickle cell hemoglobin to less than 30   though a prospective  multi institutional clinical trial will ultimately be required to settle the issue of the safest preoperative management of children with sickle cell disease  balancing the risks of transfusion related complications against anesthesia related complications  our experience supports the operative safety of hypertransfusion therapy in children with sickle cell disease  
class1	reactional states in hansen s disease  practical aspects of emergency management  hansen s disease  leprosy   though not a common condition in the united states  can be found in some localities among patients who come to the emergency room for treatment  hansen s disease  hd  is a chronic systemic infectious granulomatous disease involving principally the skin  mucosa  nerves  and eyes  the causative organism  mycobacterium leprae  is neither highly contagious nor aggressive  but rapid alterations in the immunologic response to m leprae in affected tissues can result in acute exacerbations termed  reactions   since most of the symptoms and morbidity in hd are a consequence of these reactional states  they must be recognized and treated early to prevent permanent sequelae  especially neurologic and ophthalmologic  drug therapy  physical therapy  and sometimes surgery all play a role in minimizing the injury caused by reactions  
class1	preventing group b streptococcal infection in newborns  group b streptococci  commonly found in the maternal gastrointestinal and genitourinary tracts  can be transmitted to the neonate at the time of rupture of membranes and during delivery  current management strategies include early detection of group b streptococcal carriers and the administration of intrapartum prophylactic antibiotics to prevent maternal fetal transmission  several tests are now available to rapidly identify group b streptococcal carriers  physicians should be able to recognize patients at high risk for colonization and the situations in which prophylactic antibiotics should be employed  proper use of antibiotics during labor can eliminate group b streptococcal sepsis in neonates  early group b streptococcal meningitis carries a mortality rate of almost 50 percent  despite medical support from neonatal intensive care units  
class1	cytokines and glucocorticoids in the regulation of the  hepato skeletal muscle axis  in sepsis  sepsis results in muscle catabolism and peripheral release of amino acids with a concomitant uptake of amino acids in liver and acute phase protein synthesis  in addition  there appears to be a cytokine induced process that blocks muscle amino acid uptake in sepsis  further diverting amino acids from the periphery to the liver  in this article  evidence that cytokines and glucocorticoids play an important role in the regulation of hepatic and muscle protein metabolism during sepsis is presented  
class1	germfree animals and technics in surgical research  germfree animals have been reared to a size  weight  and age permitting the performance of major surgical procedures and the pursuit of a variety of surgical research problems  germfree dogs have been maintained in the isolator system through three generations  indicating that life  reproduction  and growth are all possible in the absence of microbial contamination  the value of the germfree approach to surgical problems has been utilized in studies of a variety of gastrointestinal problems  shock  cancer  immunology  burns  wound healing  and in direct patient application  patients have been maintained in isolator environments for prevention of infection  for operative procedures  for treatment of extensive burns  and for management of immune suppressed individuals  we conclude that germfree animals and germfree technics provide a valuable addition to the armamentarium of the surgeon in both research and clinical applications  
class1	an outbreak of tuberculosis in a shelter for homeless men  a description of its evolution and control  an outbreak of tuberculosis at a shelter for homeless men was studied in detail to further the understanding of the epidemiology of tuberculosis in this setting  the shelter provides evening accommodations for men aged 50 yr and older  the capacity is approximately 200 clients  and the client pool is approximately 1 000 men yr  during a 6 wk period in december 1986 and january 1987  seven cases of tuberculosis were diagnosed in shelter clients  nine cases were reported in clients during the preceding 12 months  and four cases in the year previous to that  the majority of outbreak cases were pulmonary tuberculosis  sputum smear positive  drug resistance was rare  phage typing of 15 mycobacterium tuberculosis isolates revealed one predominant type and four other types  the goals of the control plan  and the steps taken to achieve them  were to render known infectious cases noninfectious  directly observed therapy   to find undiagnosed infectious cases  repetitive mass screenings   to protect exposed clients  repetitive tuberculin skin testing and isoniazid preventive therapy   and to make the shelter environment safe  exclude infectious  noncompliant clients and improve the shelter s ventilation system   implementation of this plan rapidly terminated the outbreak  following the first mass screening in january 1987  at which six asymptomatic cases were detected  only five additional cases occurred in shelter clients during a 2 yr period of follow up  the investigation suggested that the outbreak evolved during 1986 as a result of the presence at the shelter of an increasing number of men with undiagnosed infectious pulmonary tuberculosis  
class1	early post treatment with pentoxifylline or dibutyryl camp attenuates escherichia coli induced acute lung injury in guinea pigs  we examined effects of early post treatment with the methylxanthine pentoxifylline  ptxf   or the cell permeable adenosine 3   5  cyclic monophosphate  camp  analog dibutyryl camp  db camp  on escherichia coli induced acute lung injury in guinea pigs  acute lung injury was assessed by measurements of lung water  lung wet dry weight ratio  w d ratio   the concentration ratio of 125i albumin in bronchoalveolar lavage  bal  fluid and lung tissue compared with plasma  albumin index  bal ai or tissue ai   and total differential leukocyte count in bal fluid  mean arterial pressure  pa  and peripheral wbc counts were monitored continuously over the 8 h experiment  septicemia was induced by a bolus injection of 2 x 10 9  kg live e  coli  thirty minutes later the animals received a bolus injection followed by continuous infusion of ptxf  20 mg kg   20 mg kg h  n   8  or db camp  2 mg kg   2 mg kg h  n   8  or saline  septic control  n   8   nonseptic control groups were also studied  the lung w d ratio  bal ai  lung tissue ai  and bal leukocyte count increased significantly in the septic control group  the ptxf septic and db camp septic groups showed no significant increase in lung w d ratio  bal ai  and lung tissue ai  however  there was no difference in bal total and differential leukocyte count as compared with the septic control group  ptxf and db camp had no effect on e  coli induced changes in peripheral wbc count and pa  comparison in vitro experiments demonstrated that ptxf and db camp inhibited the endotoxin induced  e  coli  chemiluminescent response of isolated guinea pig polymorphonuclear leukocytes  pmn   
class1	hypersensitivity pneumonitis versus invasive pulmonary aspergillosis  two cases with unusual pathologic findings and review of the literature  two brothers simultaneously exposed to moldy hay  who developed differing forms of aspergillus related lung disease  are presented  patient 1 developed a true case of hypersensitivity lung disease  whereas his brother developed invasive aspergillosis with bronchoalveolar lavage eosinophilia and unusual pathologic features including tissue eosinophilia  the possible overlap between hypersensitivity pneumonitis and invasive aspergillosis in the immunocompetent host is discussed  
class1	culture positive allergic fungal sinusitis  allergic aspergillus sinusitis is a well defined clinical and histologic entity  although surprisingly few reported cases have yielded any fungal growth on culture  taking advantage of recent changes in the identification and classification of certain groups of fungi  we were able to identify a specific fungal organism in 19 of 22 consecutive patients with a histologic diagnosis of allergic fungal sinusitis over the past 2 1 2 years  aspergillus was found in only one patient  while an organism in the family of dematiaceous fungi was found in 18 patients  of these patients  the genus bipolaris was the most commonly represented  while exserohilum  curvularia  and alternaria species were seen with less frequency  thus  it appears that aspergillus may not be the most common etiologic agent in allergic  aspergillus  sinusitis  allergic fungal sinusitis is not unusual and its incidence may be increasing  on initial clinical evaluation it may be easily mistaken for malignancy or invasive fungal disease with the potential for overly aggressive treatment  preoperative suspicion of allergic fungal sinusitis based on clinical and roentgenographic findings along with careful communication with the mycology laboratory about the possibility of dematiaceous fungal growth are necessary for proper diagnosis  
class1	role of prophylactic antibiotics in uncontaminated neck dissections  the use of perioperative prophylactic antibiotics in uncontaminated head and neck surgery remains controversial  we performed a retrospective analysis of 192 patients undergoing uncontaminated neck dissections from 1976 to 1989  wound infection developed in 10   10 99  of patients who did not receive antibiotics  while only three  3 3   of 93 patients who received antibiotics developed infections  this difference was not statistically significant  we correlated the use of flaps  length of surgery  prior radiation treatment  and postoperative complications with rate of wound infection  the difference was not statistically significant for any of these variables  our beta error was  however  greater than 0 2  our data do not demonstrate efficacy of prophylactic antibiotics in uncontaminated neck dissections with statistical significance  however  a trend exists suggesting its possible value  
class1	pupil cycle time and early autonomic involvement in ocular leprosy  ocular complications of leprosy patients often develop insidiously and with few if any symptoms  this study involves measurement of the pupil cycle time  pct  to evaluate the autonomic nerve system of the iris to determine the presence of subclinical intraocular involvement  the study included 19 lepromatous  ll   19 borderline lepromatous  bl   and five borderline tuberculoid  bt  leprosy patients and involved 25 healthy volunteers  10 patients with pulmonary tuberculosis and eight with duhring disease  the pct was measured in these groups  in all leprosy groups included in the study the pct was higher than in the control groups  moreover  the pct of the leprosy patients without any intraocular involvement was higher than in the controls  these results show that in the ophthalmic examination of leprosy patients without any symptoms the fact that autonomic nerve system of the eye is affected by the leprosy can often be determined by measuring the pct  
class1	serological evidence of infection with helicobacter pylori may predict gastrointestinal intolerance to non steroidal anti inflammatory drug  nsaid  treatment in rheumatoid arthritis  specific circulating antibodies to the spiral gastric organism  helicobacter pylori  hp  were detectable in 43  of 68 patients with rheumatoid arthritis by complement fixation test  cft  and enzyme linked immunosorbent assay  elisa   a frequency comparable with that of a normal  age matched population  presence of these antibodies correlated strongly with a previous history of peptic ulcer disease  pud  and to the severity of nsaid related dyspeptic symptoms  the latter often leading to multiple drug intolerance  this contrasts with short term  prospective nsaid toxicity data  which show little relationship between ulceration and hp carriage  this result suggests  however  that hp may have a definite role in the pathogenesis of symptomatic pud associated with more chronic nsaid usage  and may have important implications for ulcer prophylaxis in these patients  
class1	diagnosis and prevalence of persistent chlamydia infection in infertile women  tissue culture  direct antigen detection  and serology  specimens for chlamydial culture  direct fluorescent antibody  dfa  test  two enzyme immunoassays  eia  for antigen detection  and serum for chlamydial antibodies were collected from 256 infertile women  specimens were taken from the tubes during tuboplasty and from the cervix and endometrium during laparoscopy or tuboplasty  antibodies to chlamydia trachomatis were found four times more often in patients with signs of prior pelvic inflammatory disease  pid  than in infertile women with normal pelvic findings  only 48  37   of 131 patients with signs of prior pid had a history of pid  ten or more c  trachomatis elementary bodies  ebs  per smear were found in 21  8 2   of 256 patients  six patients had a positive culture or a positive antigen eia test  all six had high numbers of ebs in the dfa test  we conclude that routine culture and eia antigen tests detect only a minority of persistent chlamydia infections in this population  but subjective factors in the interpretation of dfa methods must be considered  
class1	endoscopic and histologic appearance of the gastric mucosa in patients with portal hypertension  to assess reliability of the endoscopic and histologic appearance of the gastric mucosa for diagnosing portal hypertension  50 patients with portal hypertension and 1323 controls were studied  endoscopic evidence of mild gastritis was seen more frequently in patients with portal hypertension than in the control group  42  vs  13 1   p less than 0 001   the mosaic sign was also seen more frequently in patients with portal hypertension compared with controls  14  vs  0 9   p less than 0 001   however  the mosaic sign was found to be nonspecific  and the sensitivity for diagnosis of portal hypertension was only 14   biopsy specimens from the stomach of all patients with portal hypertension and 100 controls with a normal endoscopic appearance revealed mucosal vascular congestion in 72  of patients with portal hypertension compared with 59  of controls  ns   there was no correlation between endoscopic and histologic evidence of congestive gastropathy  similarly  there was no correlation between the severity of mucosal vascular congestion and the degree of inflammatory changes observed in the biopsy specimens  both in the control  r   0 1  and in patients with portal hypertension  r   0 14   it is concluded that endoscopic and histologic features of the gastric mucosa in patients with portal hypertension are of low sensitivity and nonspecific and cannot be used to diagnose portal hypertension  
class1	endoscopic findings in yersinia enterocolitica enterocolitis  the endoscopic findings in the colon and terminal ileum in eight cases of yersinia enterocolitica enterocolitis infection were studied  the diagnosis was based on the isolation of y  enterocolitica in the feces and or elevated serum antibody titers to the organism  total colonoscopy was performed between 7 and 38 days  mean  24 days  after the onset of symptoms  in all patients  the terminal ileum was affected  followed by frequent involvement of the ileocecal valve and the cecum  and less frequently  the ascending colon  in the terminal ileum  round or oval elevations with or without ulcers were detected  small ulcers were detected on the ileocecal valve and in the cecum  these findings were observed even 4 to 5 weeks after the onset of symptoms  suggesting a relatively long course for this disease  
class1	why aging leads to increased susceptibility to infection  the elderly are predisposed to various infections through a multitude of factors  although intrinsic  unalterable defects occur in the aging immune system and nonspecific host defenses  there are factors that physician and patient can concentrate on to reduce the risk of infection  for example  meticulous attention to skin care can reduce the risk of soft tissue infection  improvement in oral hygiene and relief of xerostomia might promote recolonization with normal oral flora  correction of urinary tract obstruction where possible  relying on the use of indwelling urinary catheters only when necessary  can significantly reduce the risk of utis  medications that impair cognitive function should be prescribed judiciously  since they can promote aspiration with subsequent pneumonia  xerostomia  and urinary retention  correction of protein malnutrition may improve cell mediated immunity and skin integrity  thereby reducing the risk of infection  the signs and symptoms of infection in the aged may be subtle  therefore  the primary care physician should approach this susceptible population with a heightened clinical suspicion  thus expediting possibly life saving early diagnosis and treatment  
class1	helicobacter pylori infection rates in relation to age and social class in a population of welsh men  the seroprevalence of igg antibodies to helicobacter pylori was determined using a standard enzyme linked immunosorbent assay in a population of 749 randomly selected men  aged 30 75 years  from caerphilly  south wales  the overall prevalence of h pylori was 56 9   increasing sharply in middle age from 29 8  in those aged 30 34 to over 59  in those aged 45 or older  p less than 0 0001   age standardised seroprevalence rates were lowest in combined social class categories i and ii  49 2    intermediate in categories iiin and m  57 5    and highest in categories iv and v  62 2    p   0 01   in those aged 30 34 years  the prevalence rate for those in combined social class categories iv and v was 57 9    double the rate for social class categories iiim and n  28 3   and five times the prevalence rate in those in social class categories i and ii  11 1    these differences in the infection patterns of h pylori by social class are consistent with patterns of peptic ulcer disease and gastric cancer  
class1	mycobacterium paratuberculosis and crohn s disease  the possible aetiological role of mycobacterium paratuberculosis in crohn s disease was investigated  the immunological response was studied using an enzyme linked immunosorbent assay  elisa   western blotting  and immunocytochemistry  the antibody response to two protoplasmic antigen preparations of m paratuberculosis in the sera of patients with inflammatory bowel disease was measured by elisa  igg and igm antibodies to these antigens were measured in serum samples from 52 patients with crohn s disease  15 patients with ulcerative colitis  and 41 control patients without inflammatory bowel disease  although there was wide variation in the concentrations of antibody detected  patients with crohn s disease had concentrations that were not significantly different from those of the other two groups  in addition  mycobacterial antigens were separated by sodium dodecyl sulphate polyacrylamide gel electrophoresis and the immune response to each antigen was then examined separately and assayed for igg and igm in 10 patients from each of the three groups  an indirect peroxidase test was also used to detect m paratuberculosis in sections of tissue from 18 patients with crohn s disease and 10 with ulcerative colitis  the results were negative in all cases  this study does not support a role for m paratuberculosis in crohn s disease  
class1	brucellar and tuberculous spondylitis  a comparative study of their clinical features  the clinical data from 19 patients with brucellar spondylitis and 15 with tuberculous spondylitis were compared  the former disease affects males whose occupations expose them to brucella  the lumbar spine is usually involved and there are other symptoms of brucellosis  tuberculous spondylitis is not usually accompanied by general symptoms  the dorsal spine is more frequently affected and may exhibit vertebral collapse and paraspinal abscesses  these differences permit a presumptive aetiological diagnosis  but the definitive diagnosis depends upon bacteriological tests  
class1	spinal instability secondary to metastatic cancer  fifty five patients with severe pain from spinal instability secondary to metastatic cancer were referred to hope hospital  none being judged to be in a terminal condition  one patient had too extensive disease for surgery so 54 were treated by 55 spinal stabilisations  49 obtained complete relief of pain and two had partial relief  there were three failures  twenty eight of the patients had clinical evidence of spinal cord or cauda equina compression and were decompressed at the time of stabilisation  of these  20 had major recovery of neurological function  patients with pre operative evidence of extradural tumour had  prophylactic  decompression at the time of stabilisation  none of these patients later developed signs of cord or cauda equina compression  the results suggest that alleviation of pain and restoration of mobility are best achieved by segmental spinal stabilisation  a few patients require a combined anterior and posterior stabilisation  postoperative radiotherapy should be given whenever possible  and the causative tumour should be treated by endocrine or chemotherapy  as indicated  
class1	transarticular fixation for severely displaced supracondylar fractures in children  we have reviewed 34 children who had been treated by open reduction through a medial incision and transarticular pinning for a severely displaced supracondylar fracture of the humerus  follow up ranging from nine months to 20 years showed that 27 of 34 elbows  79   had excellent or good results  with satisfactory resolution of neurovascular problems and no complications due to the method of treatment  
class1	early complications in the operative treatment of ankle fractures  influence of delay before operation  we have reviewed the early complications of 121 surgically treated closed ankle fractures  the complication rate was 30   with 14 major and 22 minor complications  fractures with skin blisters or abrasions had more than double the overall complication rate  fracture dislocations had three times as many major complications as simple fractures  and those not fixed within 24 hours had a 44  major complication rate compared to 5 3  in those operated upon as emergencies  patients transferred from another medical facility had high complication rates  especially if they had fracture dislocations  we conclude that operative treatment of ankle fractures must be delivered in a timely fashion  especially in severe fractures  we would caution against the practice of transferring patients with serious ankle fractures before completion of definitive care  
class1	the use of a tourniquet when plating tibial fractures  sixty closed fractures of the tibia were treated by open reduction and internal fixation with plates and screws  half the operations were performed with a thigh tourniquet and half without  in the tourniquet group  there were six cases with erythema and induration of the wound  in the other group there were no such complications  despite negative bacterial cultures  superficial infection of the inflamed wounds was suspected  it is suggested that a tourniquet may predispose tissues to infection  and its use is not recommended during operations for internal fixation of the tibia  
class1	ureaplasma urealyticum chronic osteomyelitis in a patient with hypogammaglobulinemia  mycoplasma species are recognized as important pathogens in patients with hypogammaglobulinemia  in this article we describe  for the first time  a patient with hypogammaglobulinemia who developed osteomyelitis of the hip caused by ureaplasma urealyticum  this article emphasizes the need for considering infection with mycoplasma species in patients with antibody deficiency  
class1	urinary nitrate excretion in relation to murine macrophage activation  influence of dietary l arginine and oral ng monomethyl l arginine  murine macrophage oxidation of l arginine guanidino nitrogen to nitrite nitrate yields an intermediate effector  possibly nitric oxide  with antimicrobial activity  total body nitrogen oxidation metabolism  nom  was measured in vivo by determining the urinary nitrate excretion of mice ingesting a chemically defined nitrite nitrate free diet  as reported previously  mycobacterial infection with bacillus calmette guerin led to a large increase in urinary nitrate excretion  this increase was temporally related to macrophage activation in vivo  the substrate for macrophage nitrogen oxidation metabolism in vitro  l arginine  was deleted from the diet without ameliorating the urinary nitrate excretion response induced by bcg  this suggested that l arginine was synthesized endogenously because there are no other known natural substrates for nom  a competitive inhibitor of nom  the l arginine analog  ng monomethyl l arginine was fed to mice in their drinking water  ng monomethyl l arginine ingestion blocked both basal and bacillus calmette guerin induced urinary nitrate excretion over a 2 4 week time span  these experimental conditions should prove useful for further investigation on the role of macrophage nom in host defense against intracellular microorganisms  
class1	septic shock and death due to occult sinusitis  we report a case of septicaemia and death due to occult sinusitis in an otherwise healthy adult  septicaemia was diagnosed on clinical grounds and blood culture grew streptococcus pneumoniae  maxillary sinusitis was discovered incidentally on a ct scan four days after the onset of symptoms  a sinus wash out revealed pus which on culture was positive for streptococcus pneumoniae  the patient deteriorated gradually and died despite appropriate therapy  we conclude that sinusitis should be suspected in any case of septicaemia where the primary focus is not known and the patient does not respond quickly to treatment  
class1	a cross sectional study of a program for hiv infection control among public house workers  we report results of a cross sectional study of a program for human immunodeficiency virus  hiv  infection control among public house workers in dar es salaam  forty percent of the 605 workers sampled had been part of this program  which included behavioral counseling and provision of condoms  for 1 year  the remaining 60  were new recruits  program participation was associated with both enhanced condom use  p less than 0 001  and behavioral modification  p less than 0 001   females  and specifically barmaids  were more likely to be condom users but were less likely to have changed their behavior in other respects  seropositivity to both hiv and treponema pallidum tended to be higher among females  especially the barmaids  since barmaids and waitresses in public houses in dar es salaam often engage in prostitution  it is felt that to effect a reduction of numbers of their sexual partners  there is a need to address the social and economic factors underlying high risk sexual behavior  
class1	nosocomial pseudomonas pickettii bacteremias traced to narcotic tampering  a case for selective drug screening of health care personnel three patients in a university hospital developed nosocomial infusion related pseudomonas pickettii bacteremia  investigation identified six additional patients who had received intravenous fluid contaminated by p pickettii but did not become ill  all nine patients had had surgery  and each of these patients but only nine of 19 operated on control patients had received intravenous fentanyl citrate in the operating room  the mean dose given to the nine case patients was far greater than that given to control patients  fentanyl in 20  40   of 50 predrawn 30 ml syringes was shown to be contaminated by p pickettii  contamination was caused by theft of fentanyl from predrawn synringes and replacement by distilled water contaminated by p pickettii  narcotic theft by health care personnel may cause patients to suffer pain needlessly and can also result in dire unanticipated consequences  such as nosocomial bacteremia  whereas drug testing in the workplace is highly controversial  we believe that testing of health care personnel is indicated when drug abuse or theft is suspected  
class1	protective efficacy of haemophilus influenzae type b polysaccharide and conjugate vaccines in children 18 months of age and older  to evaluate the protective efficacy of polyribosylribitol phosphate  prp  and polyribosylribitol phosphate diphtheria toxoid  prp d  vaccines in children 18 to 59 months of age  we conducted a case control study in los angeles  calif  county between july 1  1988  and july 31  1989  seventy nine children with invasive haemophilus influenzae type b disease 18 to 59 months of age were identified  and 212 controls were selected by random digit telephone dialing methods  cases and controls were stratified by age and month of disease onset of the case  seventeen prp vaccine failures and two prp d vaccine failures occurred more than 2 weeks after vaccination  the prp vaccine was shown not to be effective  point estimate  47   95  confidence interval   307  to 47    but the prp d vaccine was 88  protective  95  confidence interval  42  to 97    adjustment of the efficacy estimates for potential confounding variables did not change the results significantly  the prp d vaccine provided significantly better protection than the prp vaccine against invasive h influenzae type b disease in this population  
class1	tick borne borreliosis in west africa  reported cases of tick borne relapsing fever due to the spirochaete borrelia crocidurae are rare in west africa  and few epidemiological data are available  to see how common relapsing fever is in senegal thick blood smears from cases of fever of unknown origin and from randomly selected clinic outpatients from a rural dispensary were examined for borrelia  the prevalence of borrelia infections in small mammals was also assessed  borrelia was seen in smears of 12  0 9   of 1340 children  all children who tested positive had complained of acute fever  prevalence was 0   0 496   0 5   2 417   1 6   5 308   and 4 2   5 119  at ages 0 1  2 4  5 9  and 10 14  respectively  26 other instances of borreliosis were seen in patients from different regions of senegal  blood samples from 7 of these patients were inoculated intraperitoneally into white mice  serious infection developed in all mice  borrelia was seen in thick smears from 65 of 461 wild rodents or insectivores  six rodents species were infected  from a sample of 93 rodents  33 3  were infected  as judged by intraperitoneal inoculation of white mice  compared with 14 1  by direct smear examination  the findings suggest that borreliosis has a wide distribution and a high incidence in senegal  this disease may be a major cause of morbidity in rural areas throughout much of west africa  
class1	aerobic and anaerobic microbiology of acute suppurative parotitis  aspirates of pus from acute suppurative parotitis were studied for aerobic and anaerobic bacteria  bacterial growth was present in 23 specimens  a total of 36 bacterial isolates  20 anaerobic and 16 aerobic and facultative  were recovered  accounting for 1 6 isolates per specimen  0 9 anaerobic and 0 7 aerobic and facultative   anaerobic bacteria only were present in 10  43   patients  aerobic and facultatives in 10  43    and mixed aerobic and anaerobic flora in 3  13    single bacterial isolates were recovered in 9 infections  6 of which were staphylococcus aureus and 3 were anaerobic bacteria  the predominant bacterial isolates were s  aureus  8 isolates   bacteroides sp   6 isolates  including 4 bacteroides melaninogenicus group   and peptostreptococcus sp   5   beta lactamase producing organisms were recovered from 11  73   of the 15 specimens tested  this study highlights the polymicrobial nature and importance of anaerobic bacteria in acute suppurative parotitis  
class1	a placebo controlled trial of maintenance therapy with fluconazole after treatment of cryptococcal meningitis in the acquired immunodeficiency syndrome  california collaborative treatment group  background and methods  in patients with the acquired immunodeficiency syndrome  aids   the rate of relapse after primary treatment for cryptococcal meningitis remains high  we conducted a controlled  double blind trial to evaluate the efficacy of maintenance therapy with fluconazole  at entry into the study  all participants had sterile cultures of cerebrospinal fluid  blood  and urine after following a standardized course of therapy for culture proved cryptococcal meningitis  the patients were randomly assigned to take either fluconazole or placebo as maintenance therapy  the dose of fluconazole was 100 mg daily in the first phase of study and 200 mg daily in the second phase  results  of 84 patients initially enrolled  16  19 percent  were found to have silent  persistent infection on the basis of cultures that became positive after entry into the study  7 other patients were lost to follow up shortly after entry  of the remaining 61 patients  10 of 27 assigned to placebo  37 percent  and 1 of 34 assigned to fluconazole  3 percent  had a recurrence of cryptococcal infection at any site  difference in risk  34 percent  95 percent confidence interval  15 to 53   of the 11 recurrent infections  7 were detected in urine obtained after prostatic massage  there were four recurrent meningeal infections in the patients taking placebo  but none in those taking fluconazole  mean duration of follow up  164 days   p   0 03   in multivariate analyses  the best predictors of recurrence free survival were fluconazole treatment  p   0 02  relative hazard  13 2   a lower serum cryptococcal antigen titer  p   0 05  relative hazard  1 2   and more prolonged primary therapy with flucytosine  p   0 09  relative hazard  1 1   survival and toxicity were similar in the two maintenance treatment groups  conclusions  in patients with aids  silent persistent infection is common after clinically successful treatment for cryptococcal meningitis  maintenance therapy with fluconazole is highly effective in preventing recurrent cryptococcal infection  
class1	syphilitic meningomyelitis  a 28 year old nonimmunocompromised man developed secondary syphilis confirmed by serum and csf findings  his course was complicated by chorioretinitis  extensive skin lesions  and spastic paraparesis secondary to syphilitic meningomyelitis  mri of the spinal cord was strikingly abnormal  
class1	amoxicillin treatment of bacterial vaginosis during pregnancy  the purpose of this investigation was to evaluate the efficacy of amoxicillin for treatment of bacterial vaginosis during pregnancy  the diagnosis of bacterial vaginosis was established by clinical examination and microscopic examination of a gram stain and saline preparation of vaginal secretions  in a double blind  randomized manner  108 patients at 15 25 weeks  gestation were assigned to treatment with oral amoxicillin  500 mg three times daily for 14 days  or placebo  patients were evaluated 2 weeks after treatment  at 34 36 weeks  gestation  and at delivery  there were no significant differences between the two groups with respect to any clinical or microbiologic measure of treatment outcome  there were also no significant differences in the frequency of obstetric complications  we conclude that amoxicillin is not effective therapy for bacterial vaginosis in pregnant women  
class1	clue cells in predicting infections after abdominal hysterectomy  seventy women scheduled for abdominal hysterectomy were examined for the presence of clue cells in the vaginal discharge in an attempt to identify a possible risk group for development of postoperative infection  seven of 20 women  35   with clue cells developed vaginal cuff infections or wound infections  compared with four of 50 women  8   without clue cells  p less than  01   women with bacterial vaginosis  diagnosed by air dried vaginal smears  are therefore at risk for postoperative infection  
class1	recombinant fusion protein identified by lepromatous sera mimics native mycobacterium leprae in t cell responses across the leprosy spectrum  pooled polyvalent sera from lepromatous leprosy patients were used to screen a lambda gt11 recombinant dna expression library of mycobacterium leprae in order to identify the relevant antigens recognized by the human immune response  of the 300 000 phages screened  4 clones were identified that coded for fusion proteins of the same molecular mass  the fusion protein from clone lsr2 was tested for immunoreactivity in assays using peripheral blood cells and sera from 11 laboratory personnel and 105 patients across the leprosy spectrum  lsr2 protein appears to be predominantly a t cell antigen  it evokes similar lymphoproliferative responses as the native bacillus both at the individual level and in the leprosy spectrum as a whole  though only 50  of patient sera with anti m  leprae antibodies reacted with the fusion protein  the pattern of reactivity in the antibody responses was also similar for the various clinical types  the coding regions of clones lsr1 and lsr2 are identical  they show no homology with sequences stored in data banks and encode a protein of 89 amino acids with a calculated molecular mass of approximately 10 kda  
class1	pyogenic spinal sepsis in adults  twenty adult patients presented with bacteriologically and histologically proven nontuberculous spinal sepsis  thirteen patients presented with varying degrees of neurologic impairment  all patients underwent spinal decompression  in 11 this was combined with an anterior fusion using autogenous tricortical iliac grafts  all patients have recovered and are ambulatory  and no patient s disorder was made worse by surgery  twenty three separate organisms were cultured  only five of which were staphylococcus  the antibiotic courses were shorter and pain relief more rapid with anterior fusion  all anterior bone grafts incorporated rapidly  and there was no progression of kyphosis or sequestration of grafts  regardless of organisms or level  the rational treatment of adult spinal sepsis necessitates the securing of tissue from the spine for histologic and bacteriologic examination  pain relief  stabilization  and neural decompression can best be achieved with anterior decompression and fusion  autogenous iliac crest grafts incorporate in the presence of sepsis  
class1	hepatomuscular failure in septic catabolism  altered muscular response to plasma proteolytic factor in decreased hepatic mitochondrial redox potential  to estimate the contribution of muscle protein in whole body protein catabolism  the muscular contribution index  mci  urine 3 methylhistidine urine total nitrogen  was determined in 49 cases of elective laparotomy  together with the arterial blood ketone body ratio  kbr  acetoacetate beta hydroxybutyrate   which reflects hepatic mitochondrial redox potential  mci increased after operation and the occurrence of severe infection  provided kbr was maintained above 0 7  in patients with sepsis  however  mci decreased dependently with kbr  n   33  p less than 0 01   in these patients  plasma proteolysis inducing activity determined by in vitro bioassay increased in inverse proportion to kbr  n   20  p less than 0 01   moreover  plasma concentrations of not only aromatic but also branched chain amino acids markedly increased when kbr decreased to below 0 4  n   23  p less than 0 05   thus the role of muscle protein in septic catabolism is diminished under reduced hepatic mitochondrial redox potential  despite the rapid increase of proteolysis inducing activity  this finally leads to the failure of amino acid uptake by muscles  as well as liver  these results suggest that the deteriorated substrate exchange may form the metabolic background for multiple systems organ failure  which is often preceded by reduced kbr  
class1	initial results with slightly modified kock pouch  my initial experience with 20 patients undergoing kock pouch continent urinary diversion is reviewed  the procedure has been slightly modified from that described by kock and skinner  all patients have been followed for at least four months  median  33 months   there have been no early complications related to the pouch  the most significant problem  incontinence  has occurred in 2 patients  10   at three and four months  respectively  after surgery  only 1 of these patients required temporary use of an external appliance  leakage was due  in both cases  to a patulous efferent nipple valve  both were repaired by plication of the nipple  and no new efferent limbs were constructed  in 1 patient  5   prolapse of the afferent limb associated with reflux and pyelonephritis developed one year post surgery  stones have developed in 3 patients  15    all patients are currently continent and stone free  and all are pleased with the result  
class1	group b streptococcus  an unusual cause of severe peritonitis in young children treated with continuous ambulatory peritoneal dialysis  peritonitis in continuous ambulatory peritoneal dialysis  capd  patients is only rarely caused by beta hemolytical streptococci species  we describe two young children  aged 15 months and 5 years  respectively  who presented an unusually severe course of peritonitis due to group b beta hemolytical streptococci  this course of the disease showed a strong similarity with neonatal streptococcal septicemia  in neonates  igg2 deficiency is thought to be partly responsible for the severity of this condition  this may also be true for young children treated with capd  since igg2 deficiency has been established for children  
class1	mechanisms of hemolysis and anemia associated with acute antepartum pyelonephritis  anemia develops in about a fourth of women whose pregnancy is complicated by pyelonephritis  although its exact mechanism has not been defined clearly  in this study of 18 women with antepartum pyelonephritis  although only a third had anemia  hematocrit less than 30 vol dl   there was evidence for hemolysis in all 18  specifically there was a mean decrease in hematocrit of 5 vol dl from admission to discharge  with scanning electron microscopy  we compared erythrocyte morphologic aberrations that were found in women with renal infection with those of normally pregnant women  and the former had significantly increased proportions of echinocytes in particular  but schistocytes and spherocytes were increased also  total 10 3  vs 1 4   p less than 0 0001   these changes  especially echinocytosis  have been induced in vitro by lipopolysaccharide  and they are known to lead to premature red blood cell destruction in vivo  we conclude that hemolysis with subsequent anemia in pregnant women with pyelonephritis is caused by lipopolysaccharide induced red blood cell membrane damage  
class1	phospholipase c activity in microorganisms associated with reproductive tract infection  phospholipase c  lecithinase or phosphatidylcholine phosphorylase  catalyzes the hydrolysis of lecithin into phosphorylcholine and 1 2 diglyceride  bacterial production of phospholipase c may damage reproductive tract tissues by both direct and indirect mechanisms  use of the synthetic substrate p nitrophenylphosphorylcholine phospholipase c activity was determined in 204 isolates representative of those found in female genital tract  multiple aerobic  28   and anaerobic  28   reproductive tract microorganisms showed phospholipase c activity  phospholipase c producing isolates included strains of bacteroides fragilis  b  bivius  b  thetaiotaomicron  gardnerella vaginalis  and group b streptococcus  phospholipase c activity was heterogenous  not all isolates that belong to a particular species showed activity  phospholipase c production may be a possible virulence factor produced by a number of microflora commonly implicated in various reproductive tract infections or conditions  as well as in some instances of preterm birth  
class1	delayed onset pseudophakic endophthalmitis  we reviewed 19 cases of delayed onset pseudophakic endophthalmitis in which diagnostic cultures were performed at one month or more after cataract extraction with posterior chamber intraocular lens implantation  we isolated four different organisms in these 19 cases  12 propionibacterium species  63    three candida parapsilosis  16    three staphylococcus epidermidis  16    and one corynebacterium species  5    because of the unusual delayed onset features of these cases and the retrospective nature of this study  a variety of treatment regimens were used  twelve patients had recurrence of marked inflammation despite an apparent initial cure  and ten of these patients had positive culture results on repeat examination of intraocular fluids  nine patients continued to be treated with topical corticosteroids postoperatively to suppress low grade inflammation  of the 19 patients  16 had final visual acuity of 20 400 or better  delayed onset pseudophakic endophthalmitis had a more favorable visual prognosis  compared to acute onset endophthalmitis  
class1	immunoreactivity of anti streptococcal monoclonal antibodies to human heart valves  evidence for multiple cross reactive epitopes  association of group a streptococci with acute rheumatic fever and valvular heart disease is well established  however the basis of valve injury remains unclear  in this study  anti streptococcal monoclonal antibodies  mabs  cross reactive with myocardium were reacted with sections from 22 rheumatic valves  nine normal  five endocarditic  one  floppy   and one marfan valve  in immunohistochemical studies  mab reactivity was observed with cardiac myocytes  smooth muscle cells  cell surface and cytoplasm of endothelial cells lining valves  and valvular interstitial cells  endothelial basement membrane and elastin fibrils reacted with the mabs  whereas collagen was unreactive  similar reactivity was seen with sera from acute rheumatic fever patients  the anti streptococcal mabs reacted with intravalvular myosin and vimentin in western blots  and purified elastin competitively inhibited the binding of the anti streptococcal mabs to whole group a streptococci  the data show that human heart valves have numerous sites of immunoreactivity with anti streptococcal mabs and acute rheumatic fever sera of potential importance in the pathogenesis of rheumatic valvular injury  
class1	bacterial phagocytosis in obstructive jaundice  a microbiologic and electron microscopic analysis  reticuloendothelial system dysfunction has been suggested as an explanation for the increased susceptibility to infection in patients with obstructive jaundice  in the present study  the response of cholestatic rats to a bacterial challenge was investigated and the uptake of bacteria by their kupffer cells was examined with the electron microscope  rats underwent bile duct ligation  bdl  n   8  of sham celiotomy  sc  n   8  and were allowed to recover for 10 days  they were then injected with 10 9  staphylococcus aureus iv and killed at intervals of 15  30  60  and 180 minutes after injection  two from each group were killed at each interval  quantitative blood cultures were performed  and specimens of liver and lung were obtained for quantitative bacterial culture and processed for electron microscopy  bacteria were rapidly cleared from the bloodstream of sc animals but persisted in bdl rats  electron microscopy consistently demonstrated bacteria within kupffer cell phagocytic vesicles of both sc and bdl animals at each interval selected  there was no morphologic difference in these vesicles between the two groups  bacteremia persists in bdl rats subjected to a bacterial challenge despite rapid uptake of bacteria in apparently normal phagocytic vesicles  this study suggests a defect in intracellular killing of bacteria  an impairment of delivery of bacteria to re cells  or a combination of these factors  
class1	evaluation of three techniques for documenting staphylococcus epidermidis vascular prosthetic graft infections  staphylococcus epidermidis  s  epidermidis  vascular prosthetic graft infections are notoriously hard to detect  three different techniques of determining whether vascular prosthetic grafts were infected using a dog model were evaluated  aortic angiograms were compared with nuclear magnetic resonance  nmr  imaging and systemic norepinephrine  ne  kinetics to determine if either newer technique would be more reliable than standard angiograms  twelve dogs were randomized to control  n   6  or infected groups  n   6   all dogs had a 5 cm section of their infrarenal aorta replaced with knitted dacron vascular prosthetic graft  the grafts in the infected group were contaminated by soaking them in a broth containing s  epidermidis  ne production and clearance rates were calculated for all animals after an infusion of 3h ne using the steady state radionuclide tracer methodology  one week following graft insertion  dogs were reanesthetized  and the 3h ne infusion and measurements were repeated  standard angiograms and nmr imaging were also performed  once all tests were performed  the prosthetic grafts were removed for cultures  comparisons between the initial and final norepinephrine measurements for each group were made using the nonparametric wilcoxon two sample test  while comparisons between the groups were made by chi square or the student s t test  angiogram results were similar for control and infected animals  angiograms missed disruption of the proximal anastomosis found in three of the six infected dogs at graft removal  none of the six control animals  while five of the six infected animals  had localized areas of high signal intensity on nmr imaging  p less than 0 01  suggesting abscess formation  
class1	effect of oxygen free radical scavengers on survival in sepsis  sepsis remains a leading cause of death in the surgical intensive care unit  sicu  patient following major surgery or trauma  recent work has demonstrated that oxygen free radicals  ofr  generated during sepsis contribute to the pathogenesis of this syndrome  the purpose of this study was to evaluate the effect of various new free radical scavengers on survival in sepsis  a total of 85 male sprague dawley rats were placed into one of the following treatment groups  control  cecal ligation and puncture  clp   pre at  pretreatment with alpha tocopherol  at  10 mg 100 gm sc x 3 days  and 5 mg 100 gm iv prior to clp  at  20 mg 100 gm at time of clp and 4 hours following clp  u74006f   21 aminosteroid which inhibits lipid peroxidation  3 mg kg iv at the time of and 4 hours following clp  u78517f   alpha tocopherol analogue  3 mg kg at the time of and 4 hours following clp  survival was determined at various time points up to 72 hours  pretreatment with at resulted in improved survival  whereas the novel ofr scavengers u78517f and u74006f significantly improved survival and were efficacious without pretreatment  it was concluded that ofr scavengers can improve survival in sepsis  
class1	transtracheal delivery of oxygen  efficacy and safety for long term continuous therapy  transtracheal  tt  oxygen delivery involves administration of oxygen percutaneously through a catheter inserted in the suprasternal trachea  transtracheal oxygen delivery has been proposed as a means of overcoming the high visibility  inconvenience  and discomfort associated with nasal cannula use  this report describes our experience using tt delivery in 40 patients with chronic obstructive pulmonary disease  n   32  and other types of lung disease  n   8   overall acceptance of tt catheter use was high and only 5 subjects elected to discontinue use  we believe the tt route is a relatively safe approach for oxygen administration and a promising method of improving patient compliance  it also offers the potential of more adequately oxygenating patients with refractory hypoxemia  
class1	clinical outcome of seriously ill surgical patients with intra abdominal infection depends on both physiologic  apache ii score  and immunologic  dth score  alterations  the delayed type hypersensitivity  dth  response and the apache ii score in 118 patients with surgical infections were measured prospectively and related to outcome  logistic regression analysis generated the equation   formula  see text   the risk assessment as calculated by this model was compared to that using the apache ii system alone in a separate group of 354 patients  there was an improvement in the predictive capacity of the apache ii   dth equation compared to apache ii alone  as shown by a better fit of expected and observed deaths  an improved goodman kruskal g statistic  and a larger area under the receiver operating characteristic curve  it is concluded that the dth response  a broad marker of immunocompetence  is an independent prognostic factor in surgical patients and can be used in combination with the apache ii score  a measure of acute physiology  to estimate better the outcome of surgical patients  
class1	diets enriched with n 3 fatty acids ameliorate lactic acidosis by improving endotoxin induced tissue hypoperfusion in guinea pigs  the effect of 6 weeks dietary lipid manipulation on the acute physiologic response to 7 hour continuous endotoxin infusion in guinea pigs was examined  one diet was enriched with n 3 fatty acids  whereas the other contained n 6 fatty acids  primarily linoleic acid  animals fed n 6 fatty acids developed significant lactic acidemia  microvascular muscle hypoperfusion  and pulmonary infiltrates in response to endotoxin infusion  n 3 fatty acid fed animals demonstrated improved lactate levels  microvascular muscle perfusion  and lung morphology compared to n 6 fatty acid fed animals after endotoxin infusion  there was no significant change in cardiac output  pao2  or mean arterial blood pressure at the end of the endotoxin infusion in either group  pretreatment with indomethacin  or bm 13505  a specific thromboxane a2 receptor blocker  ameliorated the development of metabolic acidosis in n 6 fatty acid fed animals  demonstrating a role for prostanoids in the sequelae of endotoxemia  the ability of dietary pretreatment with n 3 fatty acids to influence favorably the physiologic response to endotoxin represents a novel nutrient metabolic interaction with potential therapeutic implications  
class1	adult overwhelming meningococcal purpura  a study of 35 cases  1977 1989  the study objective was to describe the clinical  biologic  and hemodynamic features of adult overwhelming meningococcal purpura and to examine the prognostic factors by multivariate analysis at the time of admission to the intensive care unit  thirty five patients  greater than or equal to 13 years of age  with meningococcal infection  circulatory shock  and generalized purpuric lesions of abrupt onset were recorded in eight intensive care units from 1977 to 1989  the patients were young  mean age  26 6 years  range  13 to 68 years  and had been previously healthy  the female to male ratio was 3 1  mortality was 54 3   with most deaths occurring within the first 48 hours  usually secondary to irreversible shock with multiple organ failure  ischemic complications  eight cases   prolonged heart failure  seven cases   and secondary septicemia  five cases  were the chief complications among survivors  initial hemodynamic study after volume loading showed low stroke volume index  mean     sd  29 4     13 ml m2  and tachycardia  mean     sd  138     16 beats per minute   a profile suggesting a greater myocardial depression than usually observed in gram negative bacillary septic shock  univariate prognostic analysis showed that four variables at the time of admission were associated with fatal outcome  a plasma fibrinogen level of 1 5 g l or less  a factor v concentration of 0 20 or less  a platelet count lower than 80 x 10 9  l  and a cerebrospinal fluid leukocyte count of 20 x 10 6  l or less  stepwise regression analysis showed that low fibrinogen level  less than or equal to 1 5 g l  was the sole adverse prognostic variable  odds ratio   2  95  confidence interval  1 5 to 2 7   adult overwhelming meningococcal purpura is still associated with high mortality and morbidity  low fibrinogen level at time of admission may permit early recognition of the most severely ill patients  
class1	humoral immunity in surgical patients with and without trauma  we measured antitetanus toxoid antibody responses after blunt  n   24  and penetrating  n   7  trauma and compared them with responses in patients without trauma  n   55   patients were defined as anergic or reactive on the basis of delayed type hypersensitivity response  the response to tetanus toxoid vaccination on admission of patients surviving trauma for over 2 weeks was defined as the ratio of day 14 to day 0 serum igg antitetanus toxoid levels  antitetanus toxoid responses were normal after both blunt and penetrating trauma  when stratified according to delayed type hypersensitivity responses  patients with trauma showed better antibody responses than patients without trauma  major infection rates were similar between trauma groups  three of 24 with blunt trauma vs two of seven with penetrating trauma  and independent of delayed type hypersensitivity  two of 20 reactive patients vs three of 11 anergic patients   in contrast to patients without trauma  one of 19 reactive patients vs 15 of 36 anergic patients   we conclude that decreased delayed type hypersensitivity after moderate trauma is temporary  and that this transient immunodeficiency is not as strongly associated with reduced antibody responses and increased risk of infection as anergy in surgical patients without trauma  
class1	clinical spectrum of fungal infections after orthotopic liver transplantation  during a 50 month period  we identified 91 episodes of fungal infection in 72 liver transplant recipients  23 8    candida species accounted for 83 5  of cases  clinical patterns of fungal infections included disseminated infection  19   peritonitis  17   pneumonitis  15   multiple sites of colonization  13   fungemia  11   and other sites  16   the diagnosis of fungal infection was usually made in the first 2 months  84 7  of cases   at a mean time of 16 days after transplantation  risk factors for fungal infections included retransplantation  risk score  intraoperative transfusion requirement  urgent status  roux limb biliary reconstruction  in adults   steroid dose  bacterial infections and antibiotic therapy  and vascular complications  fungal infections were successfully treated with amphotericin b in 63 cases  74 1   but were associated with diminished patient survival  50  vs 83 5    fungal infection is a frequent source of early morbidity and can be related to well defined risk factors  suggesting the need for effective prophylaxis  
class1	transient and distant infections alter later intraperitoneal abscess formation  transient nosocomial infections  such as line sepsis and pneumonia  are common in today s critical care patient population  although generally well treated  the effect of these transient antigen exposures on the immune system is unclear  we have previously shown that prior intraperitoneal inoculation with live bacteria leads to increased numbers of intraperitoneal abscesses  data presented here demonstrate in a murine model that two immunizations with live escherichia coli  bacteroides fragilis  or both  administered systemically via intracardiac injection or at a focal distant site in subcutaneous tissue  significantly increased the number of mixed e coli b fragilis intraperitoneal abscesses when induced 1 week later  further  immunization with e coli  either alone or in combination with b fragilis  increased the total number of anaerobes recovered per mouse  transient or focal sublethal infections can significantly alter an animal s immune response to later infectious insults  particularly the formation of intraperitoneal abscesses  
class1	pneumonia complicating abdominal sepsis  an independent risk factor for mortality  nosocomial pneumonia  np  is associated with a significant mortality  66  in a previous retrospective study of np complicating intra abdominal sepsis  ias   we prospectively compared the outcome of np complicating ias with that of recurrent ias  r ias  in the absence of np  data were collected prospectively on 300 patients with ias  34 patients who presented with pneumonia were excluded from the analysis  44  mortality   one hundred seventy one patients with no np and no r ias  group 1  had a hospital mortality of 20   34 patients   36 without np in whom r ias developed  group 2  had a 17  mortality  six patients   and 47 with np but no r ias  group 3  had a 53  mortality  25 patients   finally  12 patients who had both np and r ias suffered a 75  mortality  nine patients   we examined the relationships among the following putative risk factors and mortality  apache  acute physiology and chronic health evaluation  ii score  at initial presentation with ias   the need for mechanical ventilatory assistance following initial treatment for peritonitis  steroid requirement  generalized peritonitis vs abscess  and the need for surgical as opposed to percutaneous treatment  using mortality as the dependent variable  group 2 vs 3 as the explanatory variable  and the risk factors as confounders  logistic regression analysis indicated that the group difference was significant after controlling for confounders  we conclude that np complicating ias is an independent risk factor associated with a significant mortality compared with r ias  these data challenge the notion that death in ias is usually due to recurrent or persistent intra abdominal infection  
class1	effect of dietary fish oil on plasma thromboxane b2 and 6 keto prostaglandin f1 alpha levels in septic rats  increased mortality from sepsis is associated with high levels of thromboxane b2  txb2  and 6 keto prostaglandin f1 alpha  pgf1 alpha   linoleic acid  an n 6 essential fatty acid  is the usual precursor of txb2 and pgf1 alpha  while fish oil is rich in n 3 essential fatty acid  the precursor of less active moieties  rats were fed chow  an essential fatty acid deficient diet  or an essential fatty acid deficient diet supplemented with linoleic acid or fish oil for 2 weeks  the animals then underwent a sham operation or cecal ligation and puncture to induce sepsis  six hours later  blood was obtained for analysis  the chow and linoleic acid diets produced significant  twofold to fivefold  increases in levels of both txb2 and pgf1 alpha after sepsis  the essential fatty acid deficient diet and fish oil diet protected against increases in levels of txb2 or pgf1 alpha during sepsis  dietary restriction of linoleic acid or fish oil supplementation may play an important role in altering the inflammatory mediator response to sepsis  
class1	diagnosis and treatment of cytomegalovirus disease in transplant patients based on gastrointestinal tract manifestations  infection due to cytomegalovirus is a substantial cause of morbidity and mortality in immunocompromised patients  in particular  cytomegalovirus infection has been associated with a significant detrimental effect on patient and allograft survival after solid organ transplantation  we are evaluating a new antiviral agent  ganciclovir 9  1 3 dihydroxy 2 2 propoxymethyl  guanine  dhpg   used in solid organ transplant recipients who developed life threatening cytomegalovirus infections  between march 1  1987  and june 30  1989  we treated 93 solid organ transplant patients who developed tissue invasive cytomegalovirus disease  from this group of patients we have identified 14 patients with primary gastrointestinal cytomegalovirus disease who received treatment with dhpg  tissue diagnosis was made by endoscopy of the upper gastrointestinal tract  11 patients  or colonoscopy  three patients   invasive cytomegalovirus disease was identified prior to severe complications of the gastrointestinal tract in all but one patient  who suffered colonic perforation prior to treatment with dhpg and subsequently died of bacterial sepsis  while 13 of the 14 patients improved after treatment with dhpg  four patients required additional treatments for recurrent cytomegalovirus disease and recovered  no dhpg toxicity was observed  we believe treatment with dhpg is indicated in this patient population  but that further studies are indicated to fully define the impact of this recommendation on both patient and allograft survival after solid organ transplantation  
class1	hepatic extraction of indocyanine green is depressed early in sepsis despite increased hepatic blood flow and cardiac output  although active hepatocellular function is depressed during sepsis  it is not known whether this occurs in the very early stages of sepsis and whether it is due to depressed cardiac output or hepatic blood flow  to study this  rats were subjected to sepsis by cecal ligation and puncture and hepatocellular function was determined at various intervals thereafter by assessing the ability of the liver to clear different doses of indocyanine green  the indocyanine green concentration was continuously measured in vivo with a fiberoptic catheter and an in vivo hemoreflectometer  maximal velocity and kinetic constant of the clearance of indocyanine green  hepatic blood flow  and cardiac output were determined in experimental and sham operated rats  the results demonstrate that hepatic blood flow and cardiac output increased 2 to 10 hours after cecal ligation and puncture  while hepatocellular function  maximum velocity and kinetic constant  was decreased even 2 hours following cecal ligation and puncture  no linear correlation between hepatocellular function and hepatic blood flow or cardiac output was found under such conditions  the extremely early depression in active hepatocellular function  despite the increased hepatic blood flow and cardiac output  may form the basis for cellular dysfunctions leading to multiple organ failure during sepsis  
class1	effects of high dose igg on survival of surgical patients with sepsis scores of 20 or greater  sixty two consecutive septic surgical patients receiving standard multimodal intensive care unit treatment who developed a sepsis score of 20 or greater  day 0  were randomized to receive 0 4 g kg of either intravenous igg  29 patients  or human albumin  controls  33 patients   repeated on days  1 and  5  in a prospective  double blind  multicenter study  the two groups were similar in age  initial sepsis scores  and acute physiology and chronic health evaluation ii score  a significantly lower mortality was recorded in the igg treated group  38   than in controls  67    septic shock was the cause of death in 7  of igg treated patients and in 33  of controls  the results of this study indicate that high dose igg improves survival and decreases death from septic shock in surgical patients with a sepsis score of 20 or greater  
class1	clostridium difficile disease in a department of surgery  the significance of prophylactic antibiotics  a clustering of clostridium difficile associated disease in a department of surgery prompted a program of infection control and the evaluation of contributing factors  fifty patients had diarrhea and positive assays for c difficile cytotoxin during the study period  twenty one of the 36 cases that developed among patients admitted to the surgical services occurred on two adjacent general surgery wards that shared attending surgeons and house staff  perioperative prophylactic antibiotics predated c difficile associated disease in 20 patients  12 of whom had short courses  less than 24 hours   symptoms were typically nonspecific and early diagnosis may be difficult  incidence remained high  despite infection control measures  until the coincidental closure of two surgical wards  clostridium difficile associated disease is a nosocomial infection that can be associated with short courses of prophylactic antibiotics  recommendations regarding the use of perioperative prophylaxis should recognize c difficile associated disease as a significant potential complication  
class1	macrophage antigen presentation and interleukin 1 production after cecal ligation and puncture in c3h hen and c3h hej mice  following cecal ligation and puncture with a 25 gauge needle  endotoxin sensitive c3h hen mice have a 45  mortality compared with no mortality in endotoxin resistant c2h hej mice  macrophage production of interleukin 1 and antigen presentation were studied in these two strains of mice following cecal ligation and puncture at 2  4  8  16  and 24 hours and at 2  4  6  and 8 days  splenic macrophages were cultured with a t helper cell clone  d10 g4 1   and antigen presentation and interleukin 1 production were measured by d10 g4 1 proliferation  macrophage antigen presentation by c2h hej mice was markedly increased compared with that in c3h hen mice at all times after cecal ligation and puncture  most strikingly at 2 days  185m740 cpm for c3h hej mice vs 30 300 for c2h hen mice   macrophage interleukin 1 production was significantly increased in c3h hej mice vs c3h hen mice at all times after cecal ligation and puncture  except at 2 days  and was maximal at 8 days  25 000 cpm for c3h hej mice vs 5190 for c3h hen mice   these data suggest that the differences in mortality after cecal ligation and puncture between these two strains of mice may relate to a supranormal response of macrophages of c3h hej mice or to an inadequate response of macrophages of c3h hen mice  
class1	infection with hiv as a risk factor for adverse obstetrical outcome  we carried out a case control study to investigate the role of sexually transmitted diseases  stds   including infection with hiv  as risk factors for adverse outcome of pregnancy  overall  1507 women were enrolled within 24 h of delivery  cases  n   796  were mothers of low birthweight infants  less than 2500 g  or of stillborns  low birthweight infants were divided into preterms  n   373  and neonates small for gestational age  n   234   stillborns were separated into intrauterine fetal deaths  n   120   and intrapartum fetal deaths  n   69   controls were selected from mothers delivering a live baby of greater than or equal to 2500 g  n   711   the maternal hiv seroprevalence in the control group was 3 1   prematurity was associated with maternal hiv antibody  8 6  seropositive  adjusted odds ratio  or  2 1  95  confidence interval  ci  1 1 4 0   as was being born small for gestational age  7 7  seropositive  adjusted or 2 3  95  ci 1 2 4 2   in mothers who delivered a stillborn baby  both intrauterine fetal death  11 7  seropositive  adjusted or 2 7  95  ci 1 3 5 5  and intrapartum fetal death  11 6  seropositive  adjusted or 2 9  95  ci 1 3 6 5  were independently associated with hiv seropositivity in the mother  maternal syphilis was confirmed as an important risk factor for intrauterine fetal death  14 3  positive  adjusted or 4 8  95  ci 2 4 9 5   no significant association was found between other stds  including gonococcal and chlamydial infection  and adverse obstetrical outcome  these results suggest an association between maternal hiv infection and adverse obstetrical outcome  defined as low birthweight and stillbirth  
class1	six year follow up of infants with bacteriuria on screening  objective  to determine the value of screening for bacteriuria in infants with special emphasis on the natural course of untreated asymptomatic bacteriuria  renal growth  and renal damage  design  prospective six year follow up of infants with bacteriuria on screening in an unselected infant population  setting  paediatric outpatient clinic  patients  50 infants  14 girls  36 boys  with bacteriuria on screening verified by suprapubic aspiration from an unselected population of 3581 infants in a defined area of gothenburg  interventions  children with asymptomatic bacteriuria and normal findings on initial urography were untreated  although other infections were treated  main outcome measures  culture of urine and determination of c reactive protein concentration every six weeks for the first six months after diagnosis  every three months from six months to two years  and every six months between two and three years  thereafter yearly urine culture  evaluation of renal concentrating capacity with a desmopressin test  radiological examination  including first and follow up urography and micturition cystourethrography without antibiotic cover  and measurement of renal parenchymal thickness and renal surface area  results  of the original 50 infants  37  12 girls  25 boys  were followed up for at least six years  two infants developed pyelonephritis within two weeks after bacteriuria was diagnosed  the others remained free of symptoms  45 infants were untreated  the bacteriuria cleared spontaneously in 36 and in response to antibiotics given for infections in the respiratory tract in eight  recurrences of bacteriuria were observed in 10 of the 50 children  of whom one had pyelonephritis  no child had more than one recurrence  at follow up urography in 36 of the 50 children  9 girls  27 boys  after a median of 32 months no child had developed renal damage  first samples tested for renal concentrating capacity showed significantly higher values than those from a reference population  mean sd score 0 50  95  confidence interval 0 21 to 0 79  p less than 0 001   but the last samples showed no significant difference  mean sd score 0 08   0 24 to 0 40  p greater than 0 05   conclusions  mass screening for bacteriuria in infancy results primarily in detection of innocent bacteriuric episodes and is not recommended  
class1	urodynamic morbidity and dysuria prophylaxis  a group of 324 patients received prophylactic treatment with either sodium bicarbonate  potassium citrate or a glucose placebo following urodynamic studies  urine was screened for infection both before and after testing and the incidence of dysuria assessed by postal questionnaire  63  of patients experienced some degree of dysuria and this was severe and prolonged in 6 3   the majority of whom were male  neither sodium bicarbonate nor potassium citrate was any more effective in preventing dysuria than placebo  the presence of severe prolonged dysuria was not associated with a urinary tract infection or with any particular urodynamic diagnosis  
class1	local antibiotic delivery in the treatment of bone and joint infections  antibiotics can be delivered locally via an implantable pump to treat bone and joint infections  this is a completely closed system  and the pump is refilled percutaneously at intervals based on its flow rate  the use of this method is described in three specific clinical situations   1  resistant osteomyelitis  patients with persistent infections despite previous therapy    2  acutely infected arthroplasties  symptomatic for less than six weeks   and  3  chronically infected arthroplasties  patients infected more than six weeks   in all three clinical situations  hospitalization time was shortened  and high local and low systemic levels of antibiotic were obtained  there was only one incident of side effects to the antibiotic used  this method has been successful in obtaining long term suppression of infection in 30 of 42 patients with resistant osteomyelitis  30 of 37 patients with acutely infected arthroplasties  and seven of ten patients with chronically infected arthroplasties  the complication unique to this method of therapy is pump site and catheter site infections  this occurred in three patients with recalcitrant osteomyelitis and three patients with acutely infected arthroplasties  
class1	a comparison between single and double dose intravenous timentin for the prophylaxis of wound infection in elective colorectal surgery  a prospective  randomized  single blind  controlled clinical trial was undertaken to determine whether two doses of systemic timentin provided superior prophylaxis against postoperative sepsis in elective colorectal surgery compared with a single dose of the same antibiotic  timentin  a combination of ticarcillin and clavulanic acid was administered intravenously  3 1 g  at the commencement of operation to all patients  and this was repeated after 2 hours in those patients randomized to receive a second dose  the wound infection rate was 11 percent in the 143 patients completing follow up and receiving a single dose  and 13 percent in the 128 patients receiving two doses of timentin  p greater than 0 05   the rates of postoperative septicemia 3 vs  4 percent and intra abdominal abscess 5 vs  8 percent were similar  multivariate analysis of the factors likely to affect postoperative would infection rate demonstrated an association with the type of hospital  public or private  wound infection rate 16 and 6 percent  respectively  p less than 0 01   and the surgeon group defined by the number of patients contributed greater than 25 or less than 25  wound infection rate 6 and 18 percent  respectively  p less than 0 05   we concluded that a single dose of intravenous timentin was as effective as two doses for prophylaxis against surgical infection and that the surgeon group and the hospital in which the operation took place were statistically significant predictors of postoperative wound infection  
class1	colonic histoplasmosis in acquired immunodeficiency syndrome  report of two cases  colonic histoplasmosis is a rare entity  there have been four previous reported cases within the population of patients with human immunodeficiency virus  hiv  infection  because of the increasing incidence of hiv infection within regions where histoplasmosis is endemic  this condition may become more common  gastrointestinal histoplasmosis has protean clinical manifestations  and symptoms are often nonspecific  any patient with hiv infection who has unexplained gi symptoms should undergo evaluation for possible histoplasmosis  aggressive long term amphotericin b therapy has been effective in hiv patients with histoplasmosis  resection or diversion of symptomatic colonic strictures caused by histoplasmosis may be necessary in addition to medical therapy  
class1	a rare cause of colitis  brucella melitensis  report of a case  documentation of gastrointestinal lesions in brucella infections is sparse  a case of brucella melitensis type 3 infection accompanied by erosive lesions of the colon  observed by endoscopy and histopathologic examination  is reported  such gastrointestinal lesions have not been described since 1934  before 1934 only postmortem observations are recorded  
class1	high protein ascites in patients with the acquired immunodeficiency syndrome  diseases of the liver or peritoneum resulting in ascites have been infrequently reported in patients with the acquired immunodeficiency syndrome  since 1985  eight noncirrhotic patients with the acquired immunodeficiency syndrome presenting with new onset high protein ascites have been evaluated  all but one patient had nondiagnostic paracentesis studies  laparoscopy with biopsy of identified abnormalities or percutaneous omental biopsy were diagnostic in four patients  non hodgkin s lymphoma was the cause in three patients  and disseminated cryptococcosis occurred in one patient  in the four other patients  chronic nonspecific peritonitis was found at laparoscopy  follow up of these latter patients  including exploratory laparotomy in one patient and autopsy in two patients  disclosed no specific cause  patients with the acquired immunodeficiency syndrome and high protein ascites of uncertain etiology should undergo directed peritoneal evaluation as a potentially treatable disorder may be found  however  despite extensive evaluation  a subset of patients in whom no specific cause can be identified still remains  
class1	reconstruction of the chronically insufficient anterior cruciate ligament with the central third of the patellar ligament  the results of reconstruction of the anterior cruciate ligament with the central third of the patellar ligament as a free  autogenous  non vascularized graft were retrospectively reviewed at our institution  eighty reconstructions in seventy nine patients were evaluated after a minimum of two years  in forty eight  60 per cent  of the knees  the reconstruction was augmented with an extra articular lateral sling of iliotibial band  the patients were evaluated with a physical examination  a kt 1000 arthrometer  radiographs  a subjective questionnaire  and a revision of the scale of the hospital for special surgery for rating ligaments  postoperatively  seventy six  95 per cent  of the eighty knees no longer gave way  and the pivot shift test was negative in sixty seven  84 per cent  of the knees  the average score on the ligament rating scale was 93 points  all of the patients who had clinical instability at the time of the most recent follow up had associated ligamentous instability that had not been appreciated or addressed at the time of reconstruction  arthrometric evaluation revealed that the laxity differed by three millimeters or less from that of the untreated knee in sixty  76 per cent  of the treated knees  in the patient who had bilateral reconstruction  the laxity was the same in both knees  seventeen patients  who had more than three millimeters of translation  also had additional related ligamentous instability  most commonly posterolateral instability and insufficiency of the medial collateral ligament  we think that major associated ligamentous instability predisposes the reconstruction to failure and should be corrected in conjunction with the reconstruction  
class1	prosthetic arthroplasty of the knee after resection of a sarcoma in the proximal end of the tibia  a report of sixteen cases  the results of a specific type of prosthetic reconstruction of the knee  total replacement arthroplasty  after resection of a sarcoma of the proximal part of the tibia in sixteen patients were retrospectively reviewed  the diagnosis was stage iib osteogenic sarcoma in nine patients  stage iib malignant fibrous histiocytoma in three patients  and stage ib sarcoma of various types in four patients  the length of tibial resection ranged from 100 to 257 millimeters  of the eleven patients who were available for functional examination  mean duration of follow up  sixty three months   three patients had an excellent result  seven had a good result  and one had a fair result  of the five patients who were not available for functional testing  one who was doing well was lost to follow up at eighty months  one had died of metastases at sixteen months  and three had had a secondary amputation for infection or for loosening of the prosthesis  
class1	clinical and immunologic responses to haemophilus influenzae type b tetanus toxoid conjugate vaccine in infants injected at 3  5  7  and 18 months of age  the safety and immunogenicity of haemophilus influenzae type b tetanus toxoid conjugate vaccine  hib tt  were evaluated in 77 healthy infants receiving injections at 3  5  7  and 18 months of age  no serious local or systemic reactions were noted  after the first injection the geometric mean hib antibody level rose to 0 55 micrograms ml  and each subsequent injection elicited a statistically significant rise in the geometric mean  the percentage of vaccinees with hib antibody levels greater than 0 15 micrograms ml serum was 75 5  after the first  97 4  after the second  and 100  after the third hib tt injection  this percentage fell to 90 9  at 18 months of age but rose again to 100  after the fourth injection  control infants  n   10  injected with diphtheria tetanus toxoid pertussis vaccine only had nondetectable levels after the second injection  hib tt elicited increases of hib antibody in all isotypes  igg greater than igm greater than iga  among igg subclasses the highest increases were of igg1  all vaccinated subjects had greater than 0 01 u ml of tt antibody  estimated protective level  throughout the study  we conclude that hib tt  injected at 3  5  7  and 18 months  is safe and induces protective levels of antibodies during the age of highest incidence of meningitis caused by hib  
class1	testpack chlamydia for chlamydial detection in physicians  offices  chlamydia trachomatis is widely recognized as the most prevalent sexually transmitted disease  it is often asymptomatic and can lead to serious sequelae  including infertility and ectopic pregnancy  for this reason  testing of patients at risk is a necessary health care measure  this study compared testpack chlamydia to chlamydiazyme for the direct detection of chlamydial antigen in endocervical specimens  one thousand three hundred seventy six patients seen in 47 private practice offices of obstetrician gynecologists and family practitioners were screened  testpack chlamydia  a 25 minute enzyme immunoassay  had a specificity of 98 6  and sensitivity of 90  when compared with chlamydiazyme  a four hour laboratory test  the overall prevalence of chlamydial infection in this population was 3 6   the prevalence among patients less than or equal to 24 years of age was 7 6  higher among subgroups with symptoms and other identified risk factors  the positive predictive value of testpack chlamydia  83 7   makes it an accurate assay for testing women at risk for chlamydial infections  
class1	ibuprofen prevents deterioration in static transpulmonary compliance and transalveolar protein flux in septic porcine acute lung injury  the effects of intravenous ibuprofen on measurements of pulmonary function and alveolar capillary membrane permeability to protein in sepsis induced porcine acute lung injury  ali  were studied  young swine  15 25 kg  were anesthetized  cannulated  and ventilated  5 cm h2o peep  0 5 fio2  and 15 cc kg tidal volume   three groups were studied  septic animals  ps  n   10  received pseudomonas aeruginosa for 1 hr iv  controls  c  n   9  received 0 9  nacl  and ibuprofen treated septic animals  ps   ibu  n   7  received ibuprofen 12 5 mg kg at 0 and 120 min post ps  systemic  sap  and pulmonary  pap  arterial pressures  pao2  cardiac index  ci   static lung compliance  cl   evlw  thermal cardiogreen   and peripheral white blood cell counts  wbc  were measured  bronchoalveolar lavage  bal  was performed for protein and   neutrophil   pmn  content  results  ps produced significant  p less than 0 05  decreases in cl  pao2  sap  ci  and peripheral wbc and increases in pap  evlw  bal protein  and  pmn s vs  controls  ibu prevented the early increase in pap and attenuated the late increase in pap and evlw  ibu also maintained pao2  cl  bal protein  and  pmn s in bal at control levels  but exhibited no significant effect on peripheral leukopenia  these data strongly suggest that ibuprofen administered before and at 120 min after onset of pseudomonas infusion improves lung compliance and affects neutrophil function sufficiently to significantly ameliorate many of the physiologic derangements in acute sepsis  
class1	splenectomy does not influence outcome of pneumococcal septicemia in a porcine model  the existence of the overwhelming postsplenectomy infection syndrome in adults after traumatic splenectomy is controversial  due to the similarity of the porcine immune system to man we chose the pig to study subsets of peripheral mononuclear cells after splenectomy and resistance to experimental pneumococcal infection after splenic surgery and specific immunization  female miniature pigs were assigned to four operative groups  sham operation  splenectomy  splenic resection  and heterotopic splenic autotransplantation  hematologic and flow cytometric analysis of mononuclear cells and their subsets revealed a marked leukocytosis following splenectomy and autotransplantation but no significant shift in monocyte and b cell numbers  response of leukocytes to septicemia  bacterial elimination from peripheral blood  and mortality were not affected by splenectomy or spleen preserving operations  mortality of splenectomized animals was 18   compared to 42  in sham operated controls  difference not significant   immunization protected animals from development of leukopenia  and led to an enhanced bacterial elimination  and a significantly decreased mortality of 5   compared to 48  in nonimmune animals  thus our data do not show significant effects of splenectomy on subsets of porcine mononuclear cells or on resistance to experimental pneumococcal septicemia  
class1	intracranial bullet migration  a sign of brain abscess  case report  an unusual case of migration of an intracranial bullet fragment within a brain abscess is reported  movement of the bullet was first detected on skull films  and the significance of this finding on plain radiographs is emphasized  
class1	pulmonary aspergillosis in the acquired immunodeficiency syndrome background and methods  symptomatic pulmonary aspergillosis has rarely been reported in patients with the acquired immunodeficiency syndrome  aids   we describe the predisposing factors  the clinical and radiologic features  and the therapeutic outcomes in 13 patients with pulmonary aspergillosis  all of whom had human immunodeficiency virus  hiv  infection and 12 of whom had aids  results  pulmonary aspergillosis was detected a median of 25 months after the diagnosis of aids  usually following corticosteroid use  neutropenia  pneumonia due to other pathogens  marijuana smoking  or the use of broad spectrum antibiotics  two major patterns of disease were observed  invasive aspergillosis  in 10 patients  and obstructing bronchial aspergillosis  in 3   cough and fever  the most common symptoms  tended to be insidious in onset in patients with invasive disease  median duration  1 3 months before diagnosis   breathlessness  cough  and chest pain predominated in the three patients with obstructing bronchial aspergillosis  who coughed up fungal casts  radiologic patterns included upper lobe cavitary disease  sometimes mistaken for tuberculosis   nodules  pleural based lesions  and diffuse infiltrates  usually of the lower lobe  transbronchial biopsies were usually negative  but positive cultures were obtained from bronchoalveolar lavage fluid or percutaneous aspirates  dissemination to other organs occurred in at least two patients  and direct invasion of extrapulmonary sites was seen in two others  the results of treatment with amphotericin b  itraconazole  or both were variable  ten of the patients died a median of 3 months after the diagnosis  range  0 to 12 months   conclusions  pulmonary aspergillosis is a possible late complication of aids  if diagnosed early  it may be treated successfully  
class1	abscess of the sphenoid sinus after transsphenoidal surgery  a case of a bacterial abscess developing in the sphenoid sinus 2 weeks after transsphenoidal surgery is presented  although abscesses within the sella turcica have been reported as rare complications of transsphenoidal surgery  this is the first reported case of the postoperative formation of an abscess of the sphenoid sinus  the patient sought treatment for severe headaches  nausea and vomiting  and marked temperature elevation  a computed tomographic scan demonstrated soft tissue and air within the sphenoid sinus  a regimen of stress doses of hydrocortisone and antibiotics was prescribed  and the patient underwent transsphenoidal drainage of the sphenoid sinus  the sella turcica was not involved  anaerobic cultures were positive for fusobacterium necrophorum  
class1	epidural tuberculoma of the spine  case report epidural tuberculomas of the spine have been reported only rarely during the past few decades  a case of a surgically treated epidural tuberculoma of the thoracic spine in a 76 year old women is presented  
class1	oral hairy leukoplakia in hiv infection  a diagnostic pitfall  twenty nine human immunodeficiency virus  hiv  infected patients with white  nonremovable lesions on the lateral border of the tongue  clinically suggestive of oral hairy leukoplakia  hl   were studied  in particular  the value of local antifungal therapy in establishing the diagnosis of hl was investigated  in 15 patients  52   the lesions could be ultimately attributed to a candidal infection of the tongue  in 10 of the remaining 14 patients  a biopsy was obtained from lesions persisting after local antifungal treatment  in all biopsy specimens  the diagnosis of hl was confirmed by histopathologic examination and the demonstration of epstein barr virus dna by polymerase chain reaction  southern blot hybridization  and dna in situ hybridization  the present data confirm that the diagnosis of hl in hiv infected patients cannot be reliably made on clinical criteria alone  but requires histopathologic confirmation including the demonstration of epstein barr virus dna  preferably by dna in situ hybridization  however  with regard to the differential diagnosis of white  nonremovable lesions on the lateral border of the tongue in hiv infected patients  the present study suggests that persistence of lesions after local antifungal therapy is highly suggestive of hl  
class1	hiv infection  clinical features and treatment of thirty three homosexual men with kaposi s sarcoma  the clinical findings of patients with oral kaposi s sarcoma are reviewed  these oral findings commonly included candidiasis  hairy leukoplakia  gingivitis associated with human immunodeficiency virus  hiv   periodontitis  and other symptoms  including xerostomia  the other common symptoms of hiv disease that may be of importance in leading to a diagnosis are reviewed in this patient group  treatment by local radiotherapy or by intralesional vinblastine of these oral kaposi s sarcomas resulted in successful palliation  with more than 50  regression of the lesions in 80  of the patients treated  
class1	treatment of refractory oral candidiasis with fluconazole  a case report  we describe a patient with the acquired immunodeficiency syndrome who had persistent oral esophageal pseudomembranous candidiasis clinically refractory to nystatin  clotrimazole  and ketoconazole  in vitro resistance to clotrimazole was demonstrated as well  the patient received temporary relief with intravenous amphotericin b therapy  but this was associated with serious adverse effects  including transfusion requiring anemia  azotemia  and severe thrombophlebitis  despite two courses of intravenous amphotericin b therapy  the patient s highly symptomatic  recurrent oral and esophageal candidiasis continued  the patient was then treated with fluconazole and obtained immediate relief without associated adverse effects  
class1	hiv infection in healthcare workers  how great is the risk  what can be done before and after exposure  healthcare workers know that there is a risk of hiv infection through exposure to aids patients  in both hospital and office settings  physicians have the opportunity to set standards and promote education about the degree of risk  effective precautions  and postexposure testing  prophylaxis  and treatment  drs henry and thurn share the latest findings and offer policy recommendations based on their own experience  
class1	fungal pulmonary infections after bone marrow transplantation  evaluation with radiography and ct  the authors reviewed 55 pairs of chest radiographs and computed tomographic  ct  studies obtained in 33 febrile bone marrow transplant  bmt  recipients  the images were read separately  without knowledge of the clinical diagnosis  twenty one episodes of fungal infection were documented  one chest radiograph showed a pneumonia like opacity  and 17 showed nodular opacities  five with cavitation  in 20 of 21 episodes  ct showed nodules with cavitation  n   7   halo  n   4   hazy margin  n   5   air bronchogram  n   2   cluster of fluffy nodules  n   1   or sharp margin  n   1   in none of the nine bacteremic episodes  however  were there opacities on chest radiographs or ct studies  ct studies demonstrating complicated nodules in febrile bmt patients strongly suggest a fungal infection  whereas negative ct studies suggest bacteremia or non filamentous fungal infection of nonpulmonary origin  ct appears to add useful information to radiographic analysis during the assessment of febrile episodes in bmt patients  especially when invasive diagnostic procedures pose a high risk  
class1	mycetoma  comparison of mr imaging with ct  magnetic resonance  mr  images obtained in 18 patients with pathologically confirmed mycetoma in the body  n   4  or lower extremity  n   14  were retrospectively reviewed and compared with computed tomographic  ct  scans in 15 patients and surgical findings in 10  t1 weighted images showed an infiltrating mass  same signal intensity as muscle  involving skin  subcutaneous fat  muscles  tendons  and other tissues  on t2 weighted images  the mass and affected structures showed moderately increased signal intensity  bone marrow involvement was detected in seven patients and was best visualized on t1 weighted images  ct showed moderate enhancement of the infiltrative process in all patients  bone changes  seen in nine  included coarse trabeculation  periosteal reaction  endosteal proliferation  and patchy destruction  mr imaging and ct were comparable and correlated well with surgery in showing the extent of soft tissue involvement  early bone changes  important for therapy planning for pedal mycetoma  were seen only at ct  the study showed that mr imaging is sensitive for assessing the extent of mycetoma in the soft tissues  ct should be the method of choice for staging pedal lesions because it can be used to detect early bone involvement  
class1	bull horn injuries  bull horn injury is not uncommon  and during a 12 year period from 1977 to 1988  101 patients required inpatient treatment at the christian medical college hospital  a teaching hospital at vellore in south india  the ages of these patients ranged from two years to 90 years and the male to female ratio was 4 1  sixty one per cent of the injuries occurred either to the perineum or abdomen and wounds were directed obliquely upward  thirty five per cent required extensive surgical intervention  the over all wound infection rate was 12 9 per cent  of wounds that were primarily closed  42 9 per cent had wound infection  while only 6 3 per cent that were secondarily closed developed infection  two patients died as a consequence of the injury  based on the results of this study  we recommend that a careful evaluation of the injury and timely and appropriate management of each patient must be done to reduce morbidity and mortality  primary closure of wounds must be avoided even when surgical intervention is possible soon after injury  
class1	late cholangitis after successful surgical repair of biliary atresia  bacterial cholangitis is a frequent complication of successful surgical repair of biliary atresia  occurring in 93  of patients before the age of 1 year  but thought to be rare after 2 years of age  among 76 children free of jaundice more than 5 years after operation  four presented with late cholangitis  7 to 13 5 years old   consisting of fever  jaundice  and abdominal pain with biochemical features of an inflammatory process and cholestasis  liver biopsy specimens consistently demonstrated histological features of cholangitis  growth of microorganism  or both  cholangitis subsided spontaneously in one patient or in response to intravenous administration of antibiotics  cholangiography consistently demonstrated biliary abnormalities but no definite obstruction to the bilioenteric anastomosis  all the children had good hepatic function 3 weeks to 4 years after the episode of cholangitis  these results suggest that cholangitis may occur several years after surgery but does not seem to alter prognosis  
class1	factors affecting outcome in meningococcal infections  a prognostic score for evaluating meningococcal infections in patients consists of the following five features that indicate a poor prognosis  onset of petechiae within 12 hours of presentation  shock  normal or low peripheral leukocyte count  normal or low erythrocyte sedimentation rate  and absence of meningitis  based on our experience and some published data  we suspected that the score may no longer be reliable  we reviewed the charts of 73 children with meningococcal infection from december 19  1979 to december 19  1987 and applied the prognostic score mentioned previously  our findings indicate that although a low score is generally associated with a good outcome  a higher score is less predictive of poor outcome than previously suggested  a rash with petechiae or purpura  the presence of shock  and a normal or low peripheral leukocyte count continue to be predictors of poor outcome  erythrocyte sedimentation rate was not evaluated owing to a limited amount of data  the absence of meningitis did not correlate with a worse outcome in our patients  most patients who died had evidence of meningeal involvement at the time of presentation  instead  altered mental status at presentation  particularly obtundation or coma  was an ominous sign  we conclude that absence of meningitis is not a good predictor of outcome  as was previously thought  altered mental status at the time of presentation may prove to be a stronger indicator of poor outcome  
class1	antibody responses to four haemophilus influenzae type b conjugate vaccines  serum antibody responses to four haemophilus influenzae type b capsular polysaccharide protein conjugate vaccines  prp d  hboc  c7p  and prp t  were studied and compared in 175 infants  85 adults and 140 2 year old children  antibodies to the h influenzae type b polysaccharide vaccines were determined with a farr type radioimmunoassay  the infants received two doses of vaccine at the ages of 4 and 6 months  after the first dose of vaccine  the geometric mean antibody concentration measured at the age of 6 months was 0 09 to 0 10 mg l  only marginally higher than that measured before immunization in all infants who had received prp d  hboc  or c7p but increased to 0 82 mg l in those who had received prp t  one month after the second dose  the geometric mean antibody concentration was increased in all vaccine groups  no significant differences were noted between recipients of hboc  c7p  or prp t  geometric mean antibody concentrations  4 32  3 10  and 6 10 mg l  respectively   whereas the prp d recipients had a significantly lower geometric mean antibody concentration  0 63 mg l   in contrast  prp d  hboc  c7p  and prp t were all highly immunogenic in adults  with no differences noted among them  the 2 year old children also responded to one dose of these vaccines with a high antibody concentration  
class1	lyme disease  recommendations for diagnosis and treatment the incidence and the endemic range of lyme disease in the united states have increased steadily since the disease was originally recognized in lyme  connecticut  in 1975  because of the varied clinical manifestations of this illness and the use of unstandardized serologic testing methods  diagnosis is often uncertain and treatment outcomes are often difficult to evaluate  the antibiotic regimens that are commonly used in clinical practice have changed rapidly  they show much regional variation with little critical comparison of treatment results  the clinical diagnosis and the literature on the treatment of the various stages of lyme disease are reviewed  the reported data are supplemented with recommendations based on 15 years of clinical experience with this illness  
class1	diagnosis of lyme disease based on dermatologic manifestations  lyme disease  or lyme borreliosis  is an infection caused by the spirochete borrelia burgdorferi  which is most commonly transmitted to humans by a tick bite  characterized by early and late phases  lyme disease is a multisystem illness involving the skin  heart  joints  and nervous system  diagnosis is based predominantly on clinical manifestations  the most specific being dermatologic  thus  recognizing the dermatologic manifestations of lyme disease is important for diagnosis and institution of appropriate  effective therapy  approximately 75  of patients with lyme disease present with the pathognomonic skin lesion erythema migrans  an expanding erythematous lesion  during early infection  secondary erythema migrans lesions or borrelia lymphocytoma may occur  borrelia lymphocytoma commonly presents as an erythematous nodule on the ear lobe or nipple  during late infection  acrodermatitis chronica atrophicans  an erythematous  atrophic plaque unique to lyme disease may appear  it has been described in about 10  of patients with lyme disease in europe  fibrotic nodules associated with acrodermatitis chronica atrophicans as well as other sclerotic and atrophic lesions  such as morphea  lichen sclerosus et atrophicus  anetoderma  and atrophoderma of pasini and pierini  have been seen late in the course of lyme disease  in a few cases  other sclerodermatous lesions  such as eosinophilic fasciitis and progressive facial hemiatrophy  have been linked to b  burgdorferi infection  we review the cutaneous lesions associated with lyme disease  
class1	cerebrospinal fluid immune complexes in patients exposed to borrelia burgdorferi  detection of borrelia specific and  nonspecific complexes  we analyzed cerebrospinal fluid  csf  from 32 patients with neurological symptoms and evidence of borrelia burgdorferi infection  29 were seropositive as determined by enzyme linked immunosorbent assay  2 were cell mediated immune positive  and 1 had been seropositive as shown by enzyme linked immunosorbent assay 9 months previously   csf immune complexes were found in 22  69   of 32 patients  in 18  there was sufficient sample to isolate immune complexes  by enzyme linked immunosorbent assay  isolated immune complexes from 10 of these 18 patients contained antibody specific for b  burgdorferi antigens  the isotypes were igg  n   8   igm  n   3   and iga  n   2   by immunoblot  these antibodies were directed against b  burgdorferi 41 kda antigen and occasionally against the 33  and 17 kda antigens  anti b  burgdorferi igm was present in patients with acute neurological symptoms  was predominantly complexed rather than free  and decreased with clinical recovery in the one serial study  three patients were nonreactive for free csf antibodies  but had complexed antibodies to the organism  the preliminary finding of specific b  burgdorferi components in immune complexes in csf suggests an active process triggered by the organism  even in the absence of other csf abnormalities  
class1	effect of rifabutin on disseminated mycobacterium avium infections in thymectomized  cd4 t cell deficient mice  disseminated mycobacterium avium infection is the major cause of bacteremia in patients with acquired immunodeficiency syndrome  we present here a new animal model of this disease  thymectomized c57bl 6 mice that were intravenously infused with monoclonal antibody to selectively deplete cd4  t cells  the increased susceptibility of such animals to m  avium infection is comparable to that of c57bl 6 beige mice and thus may provide a viable alternative to the latter model  further  using representative strains of acquired immunodeficiency syndrome associated m  avium  serotypes 1  4  and 8 and a rough isolate   we show that the course of such infections in thymectomized  cd4 deficient mice can be markedly restrained and in some cases the infections can be sterilized by treatment over a 120 day period with a regimen containing 40 mg of the new antimycobacterial agent rifabutin per kg  body weight   
class1	efficacy of short courses of oral novobiocin rifampin in eradicating carrier state of methicillin resistant staphylococcus aureus and in vitro killing studies of clinical isolates  methicillin resistant staphylococcus aureus  mrsa  is an important nosocomial infection problem  colonization appears to be more common than invasive disease is  eradication of colonization or the carrier state could limit the spread of mrsa  thus reducing the potential for mortality and morbidity in other patients  the detection of patients with mrsa infection in a rehabilitation ward led to a study of the combination of novobiocin rifampin in vivo and in vitro  we found that 300 mg of rifampin plus 500 mg of novobiocin orally twice daily for 5 days  in 18 courses of treatment given to 12 patients  resulted in the clearing of mrsa in 79  of the evaluable courses and 81  of the evaluable sites  a second course cleared mrsa from one of the patients with a treatment failure  side effects were not noted  all 18 pretherapy isolates were susceptible to either drug in vitro  but 1 of 2 posttherapy isolates was rifampin resistant  timed kill studies demonstrated that the rate of killing was the same with either drug alone or both drugs together  pretherapy isolates from treatment successes or failure were killed at the same rate by the drug combination  however  with the rifampin resistant isolate killing ceased after 48 h  results of this study suggest that previously untreated patients are likely to have isolates that are susceptible to the combination of drugs and that the combination is commonly effective in eradicating mrsa carriage  since the regimen is orally administered  and thus convenient  in conjunction with other measures it has the promise of reducing the spread of mrsa in hospitals  
class1	therapy of pulmonary nocardiosis in immunocompromised mice  we compared the bactericidal efficacies of various antimicrobial agents and combinations thereof in experimentally induced nocardia asteroides pneumonia in immunocompromised mice  cortisone acetate treatment  which produced impaired cell mediated immune function  was followed by nasal inoculation of 5 x 10 4  cfu of n  asteroides into each mouse  therapy was begun 24 h after inoculation and continued for the next 96 h  dosages of antimicrobial agents resulted in concentrations approximating levels in human serum  animals from each of nine treatment groups were sacrificed every 24 h  the pulmonary tissue obtained was homogenized and quantitatively cultured  results were calculated to indicate the number of cfu per gram of lung tissue  amikacin and imipenem were the two most effective single agents studied  sulfadiazine and ciprofloxacin were ineffective  and ceftriaxone reduced bacterial counts modestly  combination therapy did not enhance the bactericidal activities of the agents tested  we conclude that amikacin and imipenem  as well as select broad spectrum cephalosporins  represent therapy superior to the sulfonamides in this experimental model and may represent alternative treatment for patients who cannot tolerate sulfa agents  e g   human immunodeficiency virus infected patients  or who fail primary treatment  
class1	ampicillin resistant enterococcal species in an acute care hospital  a prospective review of all enterococcal isolates for 13 months showed that 9 0  were resistant to ampicillin  mic  greater than or equal to 16 micrograms ml  zone diameter  less than 15 mm   as determined by the vitek system  disk diffusion  microdilution mic testing  and macrodilution mic testing  all were beta lactamase negative  a total of 19 and 3 resistant isolates were from urine and intravascular sites  respectively  ampicillin resistant enterococci appear to be a growing clinical problem  
class1	endogenous colonization by gentamicin resistant gram negative bacilli elaborating aminoglycoside  3  5 acetyltransferase  members of the family enterobacteriaceae that elaborate aminoglycoside 3 5 acetyltransferase  aac 3  5  caused a nosocomial outbreak at the vanderbilt university medical center and have persisted  to see whether the gene for aac 3  5 was present in the community  stool cultures of newly admitted patients and ambulatory persons were examined with a specific gene probe  aac 3  5 positive strains were present in the intestinal flora examined  
class1	increasing resistance of staphylococcus aureus to ciprofloxacin  we demonstrated the marked emergence of resistance to ciprofloxacin among staphylococcus arueus strains isolated at the ann arbor veterans administration medical center  all s  aureus isolates tested from 1984 to 1985 were susceptible  whereas 55 1  of methicillin resistant and 2 5  of methicillin susceptible strains from 1989 had high level resistance to ciprofloxacin  
class1	audit of results of operations for infantile pyloric stenosis in a district general hospital because of the proposal that infants with hypertrophic pyloric stenosis should only be treated by surgeons with an interest in paediatric surgery  we carried out a retrospective study to audit our experience in a district general hospital  forty six infants over a five year period underwent pyloromyotomy  there were no deaths  and 36 infants  78   made uneventful recoveries  perforation of the duodenal mucosa occurred during the operation in 11 patients  and eight complications developed in six of these infants  there were seven wound infections  and two patients had vomiting that lasted four days or longer after their operations  there were no long term feeding problems  the results of this study show that such patients can be successfully treated in district general hospitals  and three areas merit special attention  meticulous surgical technique  the use of prophylactic antibiotics  and early graduated feeding  
class1	local infectious complications following large joint replacement in rheumatoid arthritis patients treated with methotrexate versus those not treated with methotrexate  we performed a 10 year retrospective analysis of the frequency of local postoperative infectious complications in methotrexate  mtx  treated rheumatoid arthritis patients who underwent total joint arthroplasty  sixty patients  who had a total of 92 joint arthroplasties  were receiving mtx  a comparison group of 61 patients with a combined total of 110 total joint arthroplasties were not receiving mtx  the 2 groups were compared for the occurrence of local postoperative infectious complications and poor wound healing  eight patients in the mtx group experienced a total of 8 complications  8 7  of procedures   in comparison  5 patients in the non mtx group experienced a total of 6 complications  5 5  of procedures   a difference that was not statistically significant  chi 2   0 816  p   0 366   statistical analysis of many other variables revealed none that could be identified as risk factors for postoperative complications  these results suggest that treatment in the perioperative period with weekly low dose pulse mtx does not increase the risk of local postoperative infectious complications or poor wound healing in rheumatoid arthritis patients who undergo total joint arthroplasty  
class1	cerebral circulation and metabolism in patients with septic encephalopathy  cerebral circulation and metabolism in septic encephalopathy have not been well documented  the authors measured cerebral blood flow  cbf  and metabolic rate for oxygen  cmro2  in six patients with septic encephalopathy associated with multiple organ failure  three to five organs   they found that cbf and cmro2 were significantly lower than awake control values of 46     2 to 28     3 ml 100g min  mean     sem  and 3 1     0 2 to 1 2     0 2 ml 100g min  respectively  cerebral vascular resistance  cvr  and cerebral circulatory index  cci cbf cmro2  were significantly higher than the control values of 2 0     0 1 to 3 0     0 4 mm hg ml 100g min and 15 1     0 8 to 24 2     3 3  respectively  at the time of cerebral circulatory and metabolic measurements  their consciousness varied between 4 and 10 as evaluated by the glasgow coma scale  the electroencephalogram showed diffuse slow wave activity and the latency of the auditory brain stem evoked response was prolonged in four of six patients  computed brain tomography showed either no abnormality or mild atrophy  it is concluded that cbf and cmro2 are disproportionally decreased during septic encephalopathy in association with dysfunction of the cns and decreased electrical activity  
class1	choroidal lesions in patients with aids  seven cases of bilateral  scattered  yellow white choroidal lesions have been seen in aids patients since january 1988  one resulted from presumed extension of cryptococcal meningitis into the optic nerve and choroid  all the remaining six patients had pneumocystis pneumonia at some time during the course of the disease and were receiving aerosolised pentamidine therapy  none died quickly of disseminated pneumocystis carinii infection  unlike previously reported patients  mycobacterial infection was also present in five of these six patients  the differential diagnosis of this entity in aids patients is discussed  
class1	corneal sensitivity and correlations between decreased sensitivity and anterior segment pathology in ocular leprosy  leprosy is one of the leading causes of corneal hyposensitivity  in this article the corneal sensitivity of 143 leprosy patients was examined  and correlations between corneal hyposensitivity and anterior segment pathology were detected  twenty four healthy volunteers were examined as controls  various degrees of corneal loss of sensitivity were found in 46 2  of leprosy patients  lagophthalmos  chronic lepromatous granulomatous uveitis  iris atrophy  and social blindness were found 4 5 16 6 times more frequently in eyes which developed severe corneal hyposensitivity  
class1	influence of untreated chronic plastic iridocyclitis on intraocular pressure in leprosy patients  the intraocular pressures of a total of 286 eyes of patients with lepromatous and borderline lepromatous leprosy who never had regular ophthalmological care or local eye treatment were measured  the patients were categorised according to the type of leprosy they had  and the eyes were categorised as without or with chronic plastic iridocyclitis  in patients with lepromatous and borderline lepromatous types of leprosy the intraocular pressure was significantly lower in eyes with chronic plastic iridocylitis 10 1  3 6  mmhg than in both unaffected eyes 11 0  3 2  mmhg and control eyes 13 5  2 5  mmhg  it has been shown that chronic plastic iridocyclitis which remains untreated for years results in a lower intraocular pressure than normal  
class1	prevalence of chlamydia trachomatis infection in women having cervical smear tests objective  to determine the prevalence of sexually transmitted diseases in patients with normal and abnormal cervical smears  design  a prospective study of asymptomatic women with normal cervical smears attending their general practitioner and newly referred patients with abnormal smears attending a colposcopy clinic  setting  a hospital based colposcopy clinic and an urban general practice  list size 5500  in north west glasgow  subjects  197 asymptomatic women attending their general practitioner for cervical smear tests and 101 randomly selected patients attending the colposcopy clinic for investigation of abnormal smears  main outcome measures  presence of various sexually transmitted infections as determined by culture and serological tests  results  of the 101 women with cytological abnormalities  six had current chlamydial infection proved by culture and none had gonococcal infection  of the 197 women with normal smears  24  12   had a chlamydial infection and two had gonorrhoea  serological studies for chlamydia trachomatis specific antibody also indicated that a large proportion of patients had been exposed to this agent in both groups  there was no significant difference between the groups in the prevalence of any sexually transmitted disease studied  conclusion  a high prevalence of chlamydial infection is present in women in north west glasgow irrespective of their cervical cytological state  
class1	diagnosis of disease caused by mycobacterium avium complex  isolation of mycobacterium avium complex from sputum specimens in association with the appearance of a new cavitary  or infiltrative  lesion was studied in 299 patients from whom the organism was isolated one or more times  of the patients studied  114 showed only single isolation  of these 114  only two patients  2 percent  had association with appearance of a cavitary lesion  of 29 patients who showed two isolations  26  90 percent  had the association  of 40 patients who showed three isolations  39  98 percent  had the association  all 116 patients who showed four or more isolations had the association with appearance of a cavitary lesion  accordingly  of a total of 185 patients who showed two or more isolations  181  98 percent  had the association  of these 181  176  97 percent  showed two or more isolations in the sputum examinations made in the initial three days  therefore  the sputum examination in the first three days after onset of disease is most important for the diagnosis of disease caused by mycobacterium avium complex  since the probability that casual isolation of the organism occurs twice is extremely low  we can make the diagnosis of pulmonary infection caused by this organism by evidence of two or more isolations of the organism in the first few days after the onset of disease  which is associated with appearance of a new cavitary  or infiltrative  lesion  moreover  theoretical consideration made in this study has led us to conclude that patients who have had a single isolation of the organism together with a new cavitary lesion should be regarded as having an infection  
class1	reversible decrease of oxygen consumption by hyperoxia  the hemodynamic and metabolic effects of 90 minutes normobaric hyperoxia were studied in 20 critically ill patients  11 septic  9 nonseptic  requiring mechanical ventilation with inspired o2 fraction  fio2  less than 0 40  thirty minutes after increasing the fio2 to 1 0  arterial po2 had increased from about 100 to about 400 mm hg  and whole body oxygen uptake  vo2  was decreased 10 percent  p less than 0 05  due to an 18 percent decrease in o2 extraction ratio  during the subsequent 60 minutes of hyperoxia  there was no further significant change in vo2  cardiac index did not change in hyperoxia  but it increased 10 percent  p less than 0 05  in recovery as systemic vascular resistance decreased  vo2 returned to baseline after 30 minutes recovery at original fio2 due to increased o2 extraction as well as the increased cardiac output  the decrease in vo2 without a decrease in o2 delivery may reflect maldistribution of blood flow and functional o2 shunting to protect tissue from unphysiologically high po2  while brief oxygenation is advisable before periods of hypoventilation  the present data suggest that hyperoxic ventilation in these patients with already adequate o2 delivery was counterproductive  
class1	miliary tuberculosis presenting as hepatic and renal failure  a 67 year old man developed hepatic and renal failure over a six day period  despite full supportive measures  he died on his 11th day of hospitalization with fulminant dic and hepatic  renal  and respiratory failure  postmortem examination revealed acid fast bacilli in virtually all organ systems  miliary tuberculosis should be considered as a potentially treatable cause of hepatic failure  
class1	left atrial bacterial mural endocarditis  an unusual case of staphylococcus aureus endocarditis confined to the mural left atrium is presented  echocardiographic studies revealed a 1 5 x 2 0 cm vegetation mimicking a myxoma situated in the path of a mitral regurgitant jet on a color doppler test  emboli to upper and lower extremities and brain complicated the patient s preoperative course  surgical excision and pathologic examination confirmed this rare occurrence  
class1	pleural pneumocystis carinii infection  extrapulmonary pneumocystis carinii infection is a rare occurrence in patients with aids  pleural involvement has been demonstrated in only one case  and this occurred after pneumothorax  this is a case report of pleural pneumocystosis in a patient with aids who did not have a pneumothorax  
class1	esophageal candidiasis in aids  successful therapy with clotrimazole vaginal tablets taken by mouth  in this paper we describe the results of oral therapy of esophageal candidiasis with clotrimazole vaginal tablets in 25 homosexual men with aids  of whom 19 had oral candidiasis and 16 had esophageal symptoms  therapy with clotrimazole vaginal tablets  100 mg  taken by mouth cleared the esophageal symptoms  oral candidiasis  and esophageal lesions completely in all 25 men  clotrimazole vaginal tablets are a useful alternative to other antifungal agents for the treatment of esophageal candidiasis in aids patients  
class1	hageman factor dependent kinin activation in burns and its theoretical relationship to postburn immunosuppression syndrome and infection  burn injury and intradermal injection of bradykinin or histamine cause permeability changes visualized as dye release lesions in the skin of guinea pigs injected intravenously with evans blue dye  antihistamine pretreatment ablates the histamine but not the effect of thermal injury or bradykinin  bradykinin is generated via activation of hageman factor in a two step reaction  steps 1 and 2 can be inhibited by corn trypsin inhibitor and soy bean trypsin inhibitors  respectively  dye release lesions were reduced from thermal injury and bradykinin injections when these substances were injected into the skin first  angiotensin converting enzyme deactivates bradykinin by degrading it  angiotensin converting enzyme inhibitor neutralizes angiotensin converting enzyme  dye release lesions from both thermal injury and bradykinin injection were enhanced because of continued bradykinin build up when these treatments were preceded by subcutaneous injections of angiotensin converting enzyme inhibitor  thus bradykinin is generated in thermal injury via the hageman factor dependent pathway  hageman factor sits at the apex of a series of interrelated cascade systems  all of which impinge on the animal s immune status  uncontrolled hagemen factor activation in thermal injury may be the link among all the events collectively known as the  post thermal injury immunosuppression syndrome    
class1	infection control in a burn center  no consensus has been reached on the ideal isolation technique to prevent hospital acquired infection in the patient with burns  this study reports four 2 month consecutive periods of microbial surveillance in a burn center intensive care unit  phase i  the first period of surveillance  demonstrated a unit acquired colonization rate of 63   with the marker organisms appearing at 4 to 8 days  direct observation of isolation technique showed a 51  error rate  a mandatory educational session reviewing the high colonization rates  observed breaks in isolation technique  and principles of infection control failed to decrease the colonization rates as measured in phase ii  a simplified isolation technique was adopted  which led to a decrease in unit acquired colonization  from 63  to 33  in phase iii from phase i values  p   0 0514   and to a significant delay in inception  from 7 8 to 21 days  in those colonized with pseudomonas aeruginosa  p less than 0 05   the simplified isolation technique decreased isolation costs over a 6 month period from  53 000 to  30 000  to confirm the decrease colonization rates from phase i to phase iii  a fourth 2 month surveillance period was undertaken 6 months later  phase iv demonstrated similar results to those of phase iii  
class1	diffuse adhering escherichia coli  daec  as a putative cause of diarrhea in mayan children in mexico  diarrhea is a major cause of infantile morbidity and mortality in developing countries  a community based  case control study was conducted in a southern mexican mayan village for 3 weeks during the peak diarrhea period to prospectively identify the infectious agents associated with childhood diarrheal disease  several enteropathogens were isolated from stools of 34 of 58 cases  although none was significantly associated with diarrhea  for the 24 cases from which no enteropathogens were isolated  diffuse adhering escherichia coli  daec  strains were significantly associated with diarrheal disease  p less than  02  odds ratio   6  95  confidence limit  1 08 99 0   daec were highly heterogeneous with respect to plasmid content and serotype  three dna probes designed to differentiate e  coli exhibiting localized  diffuse  or aggregative adherence were compared with results from a standard hela cell binding assay to assess the utility of these probes in the field  this study provides evidence for the potential pathogenic capacity of daec and underscores the variety of diarrheal agents operating within a community  
class1	beta lactam resistance mechanisms of methicillin resistant staphylococcus aureus  in vitro and in vivo activity of amoxicillin and penicillin g alone or combined with a penicillinase inhibitor  clavulanate  were tested against five isogenic pairs of methicillin resistant staphylococcus aureus  mrsa  producing or not producing penicillinase  loss of the penicillinase plasmid caused an eight times or greater reduction in the mics of amoxicillin and penicillin g  from greater than or equal to 64 to 8 micrograms ml   but not of the penicillinase resistant drugs methicillin and cloxacillin  greater than or equal to 64 micrograms ml   this difference in antibacterial effectiveness correlated with a more than 10 times greater penicillin binding protein 2a affinity of amoxicillin and penicillin g than of methicillin and a greater than or equal to 90  successful amoxicillin treatment of experimental endocarditis due to penicillinase negative mrsa compared with cloxacillin  which was totally ineffective  p less than  001   amoxicillin was also effective against penicillinase producing parent mrsa  provided it was combined with clavulanate  penicillinase sensitive beta lactam antibiotics plus penicillinase inhibitors might offer a rational alternative treatment for mrsa infections  
class1	diagnosing staphylococcus aureus endocarditis by detecting antibodies against s  aureus capsular polysaccharide types 5 and 8  consecutive serum samples from patients with staphylococcus aureus endocarditis or septicemia or non s  aureus endocarditis and febrile nonsepticemic controls were tested for antibodies against s  aureus capsular polysaccharide  cp  types 5 and 8 by elisa  the upper normal antibody levels were defined as the upper 99 5  confidence limits of the values from the febrile controls  all available patient isolates were tested for the presence of cp type 5 or 8  85  of the isolates expressed either serotype   and all five patients with s  aureus endocarditis had positive antibody levels against the corresponding serotype within the first 10 days of infection  three other endocarditis patients lacked isolates for cp testing but two of these were positive  positive antibody levels were found in 0 of 28 septicemia patients  in 1 of 12 non s  aureus endocarditis patients  and in 3 of 37 febrile controls  thus  testing for anti cp 5 or 8 antibodies  especially together with cp serotyping of the patient s isolate  seems to provide important information in the differential diagnosis of endocarditis in patients with s  aureus septicemia  
class1	extremely high incidence of antibiotic resistance in clinical isolates of streptococcus pneumoniae in hungary  an epidemiologic survey of antibiotic resistance among pneumococcal isolates collected during 1988 and 1989 in hungary indicated that as many as 58  of all isolates and 70  of isolates from children were resistant to penicillin  these figures surpass even the highest values reported thus far for spain and south africa for the same period  almost or more than 70  of the penicillin resistant isolates were also resistant to tetracycline  erythromycin  and cotrimoxazole and approximately 30  to chloramphenicol  intravenous administration of ampicillin  30 mg kg  did not interfere with the growth in the cerebrospinal fluid of three resistant strains introduced into the rabbit model of experimental meningitis  no resistant strain showed beta lactamase activity  a representative highly resistant strain contained altered penicillin binding proteins  low penicillin affinities and abnormal molecular sizes  and was also resistant to the lytic and killing effects of penicillin  
class1	serologic diagnosis of human ehrlichiosis using two ehrlichia canis isolates  ehrlichia canis or a closely related rickettsial organism has been implicated serologically and morphologically as the causative agent of human ehrlichiosis in the united states  although e  canis has been serially propagated in primary canine monocytes  only a limited quantity of antigen is obtained by this method  a continuous canine macrophage cell line  dh82  supports the growth of a new isolate of e  canis established from the whole blood of a carrier dog in oklahoma  serologic comparison of the oklahoma isolate in the continuous canine cell line with a florida isolate in commercial antigen slides revealed 100  specificity and 87 5  sensitivity  
class1	recombinant murine granulocyte macrophage colony stimulating factor augments neutrophil recovery and enhances resistance to infections in myelosuppressed mice  the ability of recombinant murine granulocyte macrophage colony stimulating factor  rmgm csf  to protect myelosuppressed mice against lethal infections was evaluated  in mice myelosuppressed by cyclophosphamide  subcutaneously administered rmgm csf was a potent stimulus of granulopoiesis by increasing the number of gm csf responsive precursor cells in bone marrow followed by a profound neutrophilia  neutrophil recovery was augmented by rmgm csf in a dose dependent manner at daily doses of 0 6 5 0 micrograms mouse  in addition  rmgm csf increased the functional activity of circulating neutrophils at similar doses  when rmgm csf was administered to neutropenic mice before experimentally induced pseudomonas aeruginosa  staphylococcus aureus  or candida albicans infections  it protected against these lethal infections  resulting in increased numbers of survivors  these data suggest that rmgm csf protects neutropenic mice from lethal infections  probably by augmenting neutrophil recovery after myelosuppression and activation of mature cells  
class1	clinical disease  drug susceptibility  and biochemical patterns of the unnamed third biovariant complex of mycobacterium fortuitum  previous studies of mycobacterium fortuitum identified isolates that did not fit its two recognized biovariants  eighty five clinical isolates of this group  the  third biovariant complex   were evaluated  they represented 16  of 410 isolates of m  fortuitum submitted to a texas laboratory and 22  of 45 isolates in queensland  australia  most infections  76   involved skin  soft tissue  or bone and occurred after metal puncture wounds or open fractures  isolates differed from biovar fortuitum in resistance to pipemidic acid and use of mannitol and inositol as carbon sources  two subgroups were present  and examples were deposited in the american type culture collection  isolates were resistant to doxycycline and one third were resistant to cefoxitin  all were susceptible to amikacin  ciprofloxacin  sulfamethoxazole  and imipenem  surgical debridement combined with drug therapy based on in vitro susceptibilities resulted in cures of cutaneous disease or osteomyelitis  dna homology studies are needed to determine the taxonomic status of these organisms  
class1	susceptibility to invasive haemophilus influenzae type b disease and the immunoglobulin g2m n  allotype  there has been considerable controversy about the role of the immunoglobulin g2m n  allotype and risk of invasive haemophilus influenzae type b  hib  disease  this allotype was studied in a large cohort of finnish children  178  with invasive hib disease  the g2m n  allotype distribution was similar to that in the normal white finnish population  no increased risk of hib disease could be associated with the n  n  genotype  i e   lack of g2m n  allotype   thus  the g2m n  allotype does not seem to be a major determinant of susceptibility to hib infection among white populations in industrialized countries  
class1	role of tolerance in cloxacillin treatment of experimental staphylococcus aureus endocarditis  the role of staphylococcus aureus tolerance was investigated in endocarditis in rats  the efficacies of cloxacillin  gentamicin  and a combination of the two were compared for animals infected with a tolerant strain  its kill sensitive variant  or a nonisogenic nontolerant strain of s  aureus  cloxacillin was significantly less effective for treating the tolerant than for the nontolerant strains  the addition of gentamicin to cloxacillin reduced bacterial numbers in endocardial vegetations for the tolerant strain comparable to the reduction by cloxacillin alone for the nontolerant strains  but had no additional effect for the nontolerant strains  isolates from animals infected with the tolerant or nontolerant strains during antibiotic treatment remained tolerant or nontolerant  these results show that the in vitro phenomenon of tolerance is relevant in vivo  
class1	serotypes of respiratory isolates of streptococcus pneumoniae compared with the capsular types included in the current pneumococcal vaccine  the serotypes of 474 clinically significant streptococcus pneumoniae respiratory isolates collected during a national surveillance study in 1987 1988 were compared to the capsular types included in the 23 valent pneumococcal polysaccharide vaccine licensed for use in the united states  overall  355 isolates  74 9   belonged to types included in the current vaccine  while another 65  13 7   were types serologically related to vaccine types and likely to be protective by virtue of cross reactivity  relatively few isolates  9 1   belonged to nonvaccine serotypes  and only 2 3  were nontypable  the mucoid serotype 3 was most frequent  13 1  of total   followed by 19f  9 3    23f  7 4    6b and 14  5 7  each   and 4 and 6a  5 5  each   the most frequent type not included in the vaccine was type 16  2 1  of all isolates   thus  nearly 89  of respiratory isolates included in this study were encompassed within the antigenic spectrum of the currently marketed pneumococcal vaccine  
class1	effect of indomethacin on the pathophysiology of experimental meningitis in rabbits  the effects of indomethacin on central nervous system abnormalities in rabbits with experimental pneumococcal meningitis were studied  as expected  prostaglandin e2 levels in cerebrospinal fluid were significantly lower in the indomethacin treated group  indicating that the drug effectively reduced prostaglandin synthesis  brain edema was markedly attenuated in the indomethacin treated group  however  cerebrospinal fluid white blood cell counts  lactate and protein concentrations  and intracisternal pressure were not significantly different between groups  it seems that indomethacin  while effective in reducing brain edema  does not significantly affect other important pathophysiologic alterations in experimental pneumococcal meningitis  
class1	urinary phenolic glycolipid 1 in the diagnosis and management of leprosy  a simplified assay to measure the phenolic glycolipid 1  pgl 1  of mycobacterium leprae in the urine was applied to the diagnosis of leprosy and the monitoring of antileprosy chemotherapy  one hundred seventy nine previously untreated patients and 25 normal controls were tested  the specificity of the assay was 100   there were no false positive results  the sensitivity of the assay varied with the type of leprosy from 92  for lepromatous leprosy to 56  for borderline lepromatous and 18  for borderline tuberculoid patients  after the onset of chemotherapy in lepromatous leprosy patients  there was often a transient increase of urinary pgl 1  followed by a steady decline  within 3 months of multiple drug therapy  urinary pgl 1 levels were reduced by 90  99  and were often undetectable  this assay appears to have considerable potential for monitoring chemotherapy and detecting treatment failure and relapse in patients with hansen s disease  
class1	yersinia enterocolitica o 3  an emerging cause of pediatric gastroenteritis in the united states  the yersinia enterocolitica collaborative study group  after an outbreak of yersinia enterocolitica infections among black children in atlanta  a seven hospital study was conducted to determine the importance of this pathogen in other communities with large black populations  of 4841 stool specimens from patients with gastroenteritis examined between november 1989 and january 1990  y  enterocolitica  shigella  campylobacter  and salmonella were identified in 38  49  60  and 98 specimens  respectively  34  92   of 37 y  enterocolitica isolates were serotype o 3  of the 38 patients with yersiniosis  37  97   were children  illnesses were clustered around the holidays  and 20  62   of 32 patients had been exposed to raw pork intestines in the 2 weeks before onset  exposure was significantly associated with illness in a case control study of eight patients identified at one hospital  p    004   infants less than or equal to 6 months old with yersiniosis were more likely to have immature to total neutrophil ratios greater than 0 50 than were infants of comparable age with salmonellosis  p    02   infrequently isolated in the past  y  enterocolitica o 3 is emerging as an important enteric pathogen in this country  particularly among black children  
class1	preexposure of the peritoneum to live bacteria increases later mixed intraabdominal abscess formation and delays mortality  intraabdominal infections are a major source of morbidity and mortality for the trauma and postoperative patient  transient peritoneal contamination with bacteria after either intentional or unintentional violation of the gut are common  the effect of this intermittent antigen exposure upon later formation of intraabdominal abscesses is unclear  previous experiments by others have demonstrated that repeated exposure to bacteroides fragilis capsular polysaccharide can induce a t lymphocyte mediated immunity to subsequent induction of pure b  fragilis abscess formation  in a murine mixed intraabdominal abscess model  preexposure to live escherichia coli  b  fragilis  or both increased the number of later abscesses and in some cases their bacterial composition  further  immunization with e  coli alone increased late mortality without altering overall mortality  these data suggest that the alterations of immune function produced by live  transient bacteria upon subsequent mixed intraabdominal abscess induction result in fundamentally different consequences from those observed after specific polysaccharide antigen exposure and subsequent monomicrobial abscess induction  
class1	nosocomial legionnaires  disease and use of medication nebulizers  guidelines for the prevention of nosocomial pneumonia specify that only sterile fluids should be used for aerosol therapy  however  this recommendation may not be uniformly followed  thirteen patients with nosocomial pneumonia due to legionella pneumophila serogroup 3  lp3  were identified at a community hospital in the period from 1984 through 1988  12 patients  92   had chronic obstructive pulmonary disease  and 9 patients  69   died  an epidemiologic investigation suggested that the use of nebulizers to deliver medication was associated with acquiring legionnaires  disease  the hospital potable water system was contaminated with lp3  and a survey indicated that tap water was commonly used to wash medication nebulizers  lp3 in respirable size droplets was isolated from aerosols generated by a nebulizer containing lp3 at one tenth the concentration found in the hospital potable water  these findings support the recommendation that only sterile fluids be used for filling or cleaning respiratory care equipment and suggest that this guideline is not universally followed  
class1	serum erythropoietin levels in the anaemia of chronic disorders  serum erythropoietin  s epo  levels were measured in 50 patients with anaemia of chronic disorders  acd   classified into three groups according to their aetiology  inflammatory  n   20   infectious  n   15  and neoplastic  n   15   the inflammatory group showed a higher mean s epo level  mean value     sem  69     11 mu ml 1  than the neoplastic  43     5 mu ml 1  p less than 0 05  and infectious groups  27     4 mu ml 1  p less than 0 01   the s epo level in the inflammatory group also differed from that of 32 healthy controls  36     3 mu ml 1  p less than 0 05   fourteen patients with added iron deficiency  12 subjects from the inflammatory group  showed the highest s epo concentration  72     17 mu ml 1   conversely  s epo levels were lower in febrile subjects  12 patients with infection and five with malignancy  than in non febrile patients  28     4 mu ml 1 vs  55     7 mu ml 1  p less than 0 01   in the infectious group  the logarithm of s epo correlated directly with the haemoglobin and haematocrit values  we conclude that differences in s epo concentration in acd may be further related to the patient s iron stores and temperature  a decrease in epo production may contribute to the pathogenesis of acd secondary to infection  
class1	lag screw fixation of mandibular angle fractures  this article presents a technique of applying lag screws for treating fractures of the mandibular angle  a review of 30 patients who had lag screws placed to treat such fractures showed that it is an extremely useful  but technique sensitive  method of providing rigid internal fixation  the advantages and complications of this technique over bone plate fixation are discussed  
class1	virola  a promising genus for ethnopharmacological investigation  data are now available on the antifungal use of virola from four countries and some 14 different tribes of indians in these countries who employ the virola exudate for the same or similar purposes  three of the five methods of ethnobotanical investigation proposed by schultes and swain in 1976 have been employed in this ethnobotanical research  furthermore  both of the present authors have successfully employed this antifungal treatment themselves  given that deep fungal infections of the skin are often considered incurable with medications currently in use  further laboratory analysis of virola resin should be undertaken as soon as possible  
class1	definitions  classification  and clinical presentation of urinary tract infections  urinary tract infections encompass a spectrum of clinical and pathologic conditions involving various parts of the urinary tract  each syndrome has its own unique epidemiology  natural history  and clinical manifestations  basic terminology used in describing urinary tract infections is defined in this article  a classification of these infections and their clinical features is presented  
class1	bacterial etiologic agents in the pathogenesis of urinary tract infection  most of the information available concerning virulence factors of uropathogens is based on studies of escherichia coli  the commonest cause of urinary tract infections  earlier studies revealed several phenotypic escherichia coli virulence factors that influenced both the anatomic level and severity of urinary tract infection  virulence factors included o antigen serotype  presence and quantity of k capsular polysaccharide  adherence to uroepithelial cells  resistance to serum bactericidal activity  hemolysin  and aerobactin production  the introduction of dna hybridization methodology has provided a valuable tool for reevaluation of the epidemiology of escherichia coli infection as well as an alternative to the conventional phenotypic approach for studying the genotypic basis for virulence  
class1	host defense mechanisms in the pathogenesis of urinary tract infection  certain microorganisms have a propensity for causing urinary tract infection  and the route  either ascending or hematogenous  by which microorganisms contaminate the urinary tract from external sources is frequently characteristic of the microorganism  there are local defense mechanisms both in the urine and at each anatomic site in the urinary tract  urethra  bladder  ureter  and kidney   the defense mechanisms at one site may have opposing effects on microbial growth at other sites in the urinary tract  the outcome following entrance of microorganisms into the urinary tract is a result of competing forces  which consist of these local urinary defense mechanisms  the initial numbers of microorganisms contaminating the urinary tract  and microbial virulence factors  
class1	epidemiology and natural history of urinary tract infections in children  recent retrospective surveys have supported previous investigations in demonstrating the incidence of uti during infancy  0 3  to 1 2  of infants develop symptomatic uti during the first year of life  boys are more commonly infected during the first 3 months of life  after the first year  symptomatic uti is much more frequent among girls  similarly  asymptomatic bacteriuria is more frequently detected in boys than in girls during the first 12 months of life  thereafter  the incidence decreases markedly in boys but increases in girls  recent investigations indicate that lack of circumcision is a risk factor for uti among male infants  recurrent uti is common and frequently asymptomatic  the most important microbiologic factor that is associated with e  coli causing acute pyelonephritis is adherence mediated by p fimbriae  other factors  such as capsule  lipopolysaccharide  aerobactin production  and serum resistance  also determine the invasiveness of e  coli  vesicoureteral reflux appears to be an important host factor predisposing to uti  microbiologic and host factors that are determinants of renal scarring are under investigation  
class1	the natural history of urinary infection in adults  the vast majority of otherwise healthy adults with anatomically and functionally normal urinary tracts experience few untoward long term consequences from symptomatic or asymptomatic utis  effective early treatment of symptomatic infection rapidly curtails bacterial invasion and the resulting inflammatory response  rarely  uncomplicated acute pyelonephritis causes suppuration and renal scarring  urinary infections in patients with renal calculi  obstructed urinary tract  neurogenic bladder  or diabetes are frequently much more destructive and have ongoing sequelae  strategies to treat both the infection and the complications are often necessary to alter this outcome  
class1	laboratory in the diagnosis and management of urinary tract infections  the laboratory is essential in the diagnosis and management of utis  the presence of pyuria and bacteriuria  the two most important indicators of utis  are most accurately determined by standard techniques  in quantitating pyuria  the finding of greater than or equal to 10 leukocytes mm3 of urine by either hemocytometry or direct microscopy correlates highly with symptomatic  culture proven utis  the determination of bacteriuria by direct microscopy is inaccurate  particularly at lower levels of bacteriuria  thus  quantitative urine cultures remain the most accurate measure of bacteriuria  significant bacteriuria  previously defined as greater than or equal to 10 5  cfu ml of urine  has been redefined with the observation that as few as 10 2  cfu ml can be associated with significant pyuria and symptoms suggestive of cystitis  the need for routine and posttreatment urine cultures in nonpregnant women with acute dysuria remains controversial  but current data suggest that they are usually unnecessary  rapid diagnostic tests for detection of pyuria and bacteriuria are designed to increase efficiency and decrease cost in the diagnosis of uti  unfortunately  none of these techniques can quantitate pyuria or bacteriuria as accurately as the standard methods  but the level of accuracy offered by the standard methods is not always necessary in the care of patients with uncomplicated utis  these tests are particularly well suited for screening asymptomatic high risk populations  noninvasive localization techniques continue to be explored as possible alternatives to invasive localization procedures  but they remain largely research tools that are not readily available to the practicing clinician  understanding the applicability and appropriate use of newer technologies in the evaluation of patients with utis and how these technologies complement the standard diagnostic techniques will lead to better  more efficient  and less costly patient care  
class1	management of urinary tract infections in children  urinary tract infection is common in children  the presentation varies with age  younger children exhibit protean signs  diagnosis is dependent on the demonstration of significant bacteriuria in a properly collected and handled urine sample  the approach to treatment depends on the degree of illness at presentation  the presence of structural urinary tract abnormalities  and the age of the patient  pathophysiology of urinary tract infection is dependent on interactive factors of the host and of the invading microorganism  urinary tract abnormalities have significant impact on the management of children with urinary tract infections  both medically and surgically  of particular importance is the observation that renal damage usually occurs within the first 5 years of life  and treatment delay in some young patients may have significant consequences  the overall prognosis in children with urinary tract infection is favorable  
class1	management of acute uncomplicated urinary tract infection in adults  acute uncomplicated uti is one of the most common problems for which young women seek medical attention  and it accounts for considerable morbidity and health care costs  acute cystitis is a superficial infection of the bladder mucosa  whereas pyelonephritis involves tissue invasion of the upper urinary tract  localization tests suggest that as many as one third of episodes of acute cystitis are associated with silent upper tract involvement  acute cystitis or pyelonephritis in the adult patient should be considered uncomplicated if the patient is not pregnant or elderly  if there has been no recent instrumentation or antimicrobial treatment  and if there are no known functional or anatomic abnormalities of the genitourinary tract  most of these infections are caused by e  coli  which are susceptible to many oral antimicrobials  because of the superficial nature of cystitis  single dose and 3 day regimens have gained wide acceptance as the preferred methods of treatment  review of the published data suggests that a 3 day regimen is more effective than a single dose regimen for all antimicrobials tested  regimens with trimethoprim sulfamethoxazole appear to be more effective than those with beta lactams  regardless of the duration  acute pyelonephritis does not necessarily imply a complicated infection  upper tract infection with highly virulent uropathogens in an otherwise healthy woman may be considered an uncomplicated infection  the optimal treatment duration for acute uncomplicated pyelonephritis has not been established  and 14 day regimens are often used  we prefer to use antimicrobials that attain high renal tissue levels  such as trimethoprim sulfamethoxazole or quinolones  for pyelonephritis  women with frequently recurring infections can be successfully managed by continuous prophylaxis  either daily or thrice weekly  by postcoital prophylaxis  or  in compliant patients  by early self administration of single dose or 3 day therapy as soon as typical symptoms are noted  our drug of choice for all these regimens is trimethoprim sulfamethoxazole  acute uncomplicated cystitis in adult men is very uncommon  but it is occasionally noted in homosexual men who practice insertive and intercourse or in heterosexual men whose partners have vaginal colonization with e  coli  
class1	epidemiology  natural history  and management of urinary tract infections in pregnancy  the urinary tract undergoes profound physiologic and anatomic changes during pregnancy that facilitate the development of symptomatic utis in women with bacteriuria  although the adverse effects of asymptomatic bacteriuria on maternal and fetal health continue to be debated  it is clear that asymptomatic bacteriuria is the major risk factor for developing symptomatic uti and that symptomatic infections are associated with significant maternal and fetal risks  because the majority of symptomatic utis develop in women with bacteriuria earlier in pregnancy  treatment of bacteriuria is undertaken to prevent symptomatic infections  all women should be screened at the first antenatal visit  which is reliably and inexpensively done with a dipstick culture  short course therapy is as effective as prolonged therapy and should be followed with a repeat culture to document clearing of the bacteriuria  failure to eliminate bacteriuria with repeated therapy or recurrence with the same organism is indicative of renal parenchymal infection or a structural abnormality  all women with persistent bacteriuria or recurrent infection should have follow up cultures and a complete urologic evaluation after delivery  
class1	special problems of urinary tract infection in the elderly  bacteriuria is much more common among elderly than among younger populations  and is most often asymptomatic  asymptomatic bacteriuria in the elderly is a benign condition in the vast majority of cases and does not require therapy  when symptomatic lower uti occurs  short course  3 day  therapy with any of several agents is indicated  and is usually effective  women with frequently recurrent symptomatic uti may benefit from estrogen therapy  fourteen days of therapy is indicated in patients with upper uti  the typical signs and symptoms of pyelonephritis may be altered or absent in elderly patients  
class1	urinary tract infection in the impaired host  in general  defects in phagocytosis and in humoral or cellular immunity do not appear to predispose to the acquisition of uti but do influence the clinical manifestations and the severity  microbiology  and complications of infection once it is established  the incidence of uti in immunosuppressed patients other than diabetics or renal transplant recipients is not higher than the incidence in nonimmunosuppressed individuals  the higher frequencies of infection seen in diabetics and in renal transplant recipients correlate best with the duration of bladder instrumentation rather than with glycosuria or immunosuppressive regimen  neutropenia blunts the clinical manifestations of uti and predisposes to bacteremia  use of broad spectrum antibiotics results in alterations in indigenous flora  promotes urinary infections with resistant nosocomial pathogens  and predisposes to fungemia with hematogenous seeding of the urinary tract  routine screening for detection of asymptomatic bacteriuria and prompt institution of antimicrobial therapy is indicated only in renal transplant recipients within 3 months of their surgery and not in any of the other diseases discussed  
class1	prostatitis  several distinct types of prostatitis  or prostatitis syndromes  are now recognized  the most common forms include acute and chronic bacterial prostatitis  nonbacterial prostatitis  and prostatodynia  bacterial prostatitis  caused mainly by coliform bacteria  pseudomonas  and enterococcus faecalis  is often difficult to cure and usually requires extended therapy  4 16 weeks  with an appropriate antimicrobial agent that achieves therapeutic levels in the prostatic secretory system  about 90  of men with prostatitis have nonbacterial prostatitis or prostatodynia  nonbacterial prostatitis is an inflammation of the prostate of unknown cause  patients with prostatodynia typically have sterile cultures and normal prostatic secretions but demonstrate an acquired voiding dysfunction on videourodynamic testing  because nonbacterial types of prostatitis have no recognized infectious cause  treatment using antimicrobial agents is ineffective and unwarranted  
class1	radiology of renal infection  radiology plays a key role in the diagnosis and treatment of renal inflammatory diseases  the efficacious use of the various imaging modalities in evaluating renal inflammatory disease requires knowledge of their attributes as well as their weaknesses  we review the available studies and use of contrast agents  and illustrate radiologic findings in specific inflammatory disease processes  
class1	the role of the urologist in urinary tract infection  the urologist s role in urinary tract infections will vary according to the situation  urologists do give primary care  consult  define anatomic abnormalities  surgically correct abnormalities  and do basic research in the field of urinary tract infections  urologists are essential in diagnosing and managing cases with infections behind obstructions and working out the differential diagnoses of chronic prostatitis  
class1	the catheter and urinary tract infection  catheter associated bacteriuria is the most common infection acquired in hospitals and nursing homes  this infection would be even more common but for the use of the closed catheter system  most modifications have not improved upon the closed catheter itself  however  even with meticulous care  this system will not prevent bacteriuria forever  after bacteriuria develops  our ability to limit its complications is minimal  additionally  the catheterized urinary tract becomes a reservoir of bacteria that can be transferred to other patients  once a catheter is put in place  one must keep two important concepts in mind   1  keep the catheter system closed in order to postpone the onset of bacteriuria  and  2  remove the catheter as soon as possible  if the catheter can be removed before bacteriuria develops  postponement becomes prevention  however  the best prevention is not to use a urethral catheter at all  non device alternatives to urethral catheterization should be used whenever possible  if these are not useful or successful  then other devices might be considered  for incontinent men  a condom catheter is a useful alternative  for patients with urinary retention  intermittent or suprapubic catheterization may be options for both short term and long term needs  the roles of these alternatives to urethral catheters must be defined by controlled trials  
class1	urinary tract infection  economic considerations  urinary tract infection results in significant morbidity and mortality while consuming large amounts of national resources  the prevention  diagnosis  and treatment of urinary tract infection produce both costs and benefits  and economic analysis provides a rational framework for looking at these effects  the goals and methods of economic analysis in medicine are summarized  and strategies to address uncomplicated cystitis  nosocomial urinary tract infection  and pyelonephritis are reviewed  with an emphasis on the economic trade offs faced by decision makers  
class1	sexual transmission of human t cell leukemia virus type i associated with the presence of anti tax antibody  the tax gene product  tax protein  of human t cell leukemia virus type i  htlv i  is a specific transcriptional activator of the viral long terminal repeat sequence and is essential for the replication cycle of the virus  to elucidate the relationship between the presence of anti tax antibody and the transmission of the viral infection  annual consecutive serum samples from married couples serologically discordant or concordant for htlv i were examined  these included 5 individuals whose spouses seroconverted during this 5 year follow up study period  the samples were tested by a western blot assay using a recombinant tax protein as the antigen  the results showed that 24 of 32  75   men in the concordant couples  both husband and wife were htlv i carriers  had anti tax antibody  while only 5 of 18  27 8   men in the discordant couples  husband was carrier and wife was seronegative to htlv i  were positive for anti tax antibody  p   0 0012   furthermore  all spouses of the 5 seroconverters  4 women and 1 man  had anti tax antibody  while only 23 of 46  50   age matched randomly selected htlv i carriers from the discordant couple group had anti tax antibody  when the data were analyzed by gender  all husbands of the female seroconverters had anti tax antibodies  which was significantly higher than the prevalence of anti tax antibodies in men who did not transmit the virus to their spouses during the follow up period  p   0 017   in addition  antibody reactivity to other htlv i antigens  including env gp46  transmembrane protein gp21  and gag p19 and p24  were examined  the results indicated no significant differences between the prevalence of antibody reactivity to any of the antigens in the spouses of the seroconverters and the reference group  we conclude that the presence of anti tax antibody in men may indicate a high risk of viral transmission to their wives via heterosexual routes  
class1	relationship of transfusion and infectious complications after gastric carcinoma operations  to determine the effect of transfusion on the incidence of postoperative infection  a retrospective cohort study of 196 patients who underwent surgery for gastric carcinoma in the period from 1985 through 1989 was carried out  seventy one patients  36 2   developed postoperative septic complications  they had received an average of 4 2 blood units  as compared with 2 7 units received by patients not affected  p less than 0 0053   the hypothesis of dose response relationship is supported by the mantel haenszel test  as applied to the overall results  p less than 0 01  and the results grouped by duration of operation  p less than 0 02   furthermore  logistic regression analysis shows transfusion to be an independent risk factor in the incidence of infection  p less than 0 01   as are antibiotic prophylaxis  p less than 0 015   urinary tract catheterization  p less than 0 002   and the duration of surgery  p less than 0 027   this significance is attained after adjustment for age  gender  period of evolution of symptoms  preoperative infection s   number of white cells  hemoglobin level and total proteins on diagnosis  location of tumor  tumor  nodes  and metastasis staging  operative technique  drainage of the area of operation  enteral nutrition  and the histologic studies and macroscopic appearance of the tumor  this study is further evidence that transfusion may cause an increased incidence of postoperative infection  
class1	mycobacteremia in acquired immune deficiency syndrome  rapid diagnosis based on inclusions in the peripheral blood smear  in 16 cases of human immunodeficiency virus associated mycobacterium avium intracellulare complex  mac  infection  7 were diagnosed after finding intracytoplasmic negatively staining linear inclusions within histiocytes using romanowsky stained bone marrow aspirate smears  four patients had inclusions within monocytes and neutrophils in the peripheral blood smear  the authors believe these cases represent the first reported examples of mac inclusions observed within leukocytes in wright s stained peripheral blood smears  inclusions usually were found in the setting of prominent toxic changes in leukocytes such as large dohle bodies  marked granulation  and vacuolation  these inclusions are characteristic of mycobacteria and can be confirmed by acid fast stains and mycobacteriologic culture  the authors present the clinical and laboratory setting in which identification of inclusions in peripheral blood smears may be a rapid  minimally invasive  and cost effective method of diagnosing mycobacterial infection  
class1	issues in cerebrospinal fluid management  csf venereal disease research laboratory testing  three policies for decreasing unnecessary cerebrospinal fluid  csf  management venereal disease research laboratory  vdrl  tests were compared  the first policy attempted to educate physicians about the use of serologic tests for diagnosing neurosyphilis but allowed the csf vdrl to be performed either as a screening test or as a retrospective test  the second policy required that the csf vdrl be performed as a retrospective test without regard to the patient s serologic status  the third policy required that a patient be seropositive by either rapid plasma reagin  rpr  or fluorescent treponemal antibody absorbance  fta abs  before a csf vdrl could be performed  before these policies were instituted  vdrl testing was performed on 18 2  of all csf samples  the optional and required retrospective policies decreased the csf vdrl rate to 13 0  and 8 5   respectively  but the percentages of seropositive patients for whom these procedures were performed were only 7 3  and 12 9   the third policy decreased the csf vdrl test rate to 1 8   p less than 0 001  with seropositivity improving to 90   to assure serologic tests are obtained in the evaluation of neurosyphilis  requirement for seropositivity must be implemented with the use of retrospective csf vdrl testing  
class1	issues in cerebrospinal fluid management  acid fast bacillus smear and culture  meningeal tuberculosis is an uncommon disease in the united states with an annual incidence of fewer than 200 cases  this study evaluates three approaches to improving the use of the cerebrospinal  csf  acid fast bacillus  afb  smear and culture procedure   1  education alone   2  optional screening by which physicians can select to have the afb analysis stopped if the initial csf findings are unremarkable  and  3  mandatory screening before the performance of all csf afb analyses  with education alone  the csf afb culture rate decreased from 20 6  of all csf acquisitions to 15 7   p less than 0 001   however  the effect may have been related to a decrease in all types of afb testing  optional screening had no impact on the afb testing rate  mandatory screening significantly decreased the csf afb rate to 6 7   p less than 0 001   unrelated to changes in other types of afb testing  laboratories that employ mandatory screening should report the screening results immediately and have a mechanism whereby physicians can bypass the screen  providing csf afb analysis on unremarkable fluid from high risk patients  
class1	plasma terminal complement complexes in acute poststreptococcal glomerulonephritis  in most instances of acute poststreptococcal glomerulonephritis  apsgn   activation of the complement system occurs  as reflected by decreased levels of the complement proteins c3  c5  and properdin  p   recent studies implicate terminal complement complexes  tcc  in the pathogenesis of glomerular injury  the fluid phase tcc  sc5b 9  reflects the formation of membrane bound c5b 9 and has been used as a clinical marker in various diseases  plasma concentrations of sc5b 9 were measured with an enzyme immunoassay using a monoclonal antibody to a neoantigen expressed on the sc5b 9 complex in 13 children who presented with clinical and pathologic features of apsgn  sc5b 9 was significantly elevated in all plasmas obtained within 30 days after onset of clinical glomerulonephritis  concentrations of sc5b 9 in acute plasmas were significantly higher than those of paired convalescent samples  for individual patients  as sc5b 9 concentration returned to normal there was a coincident decrease in serum creatinine concentration and urinary protein excretion  signifying clinical improvement in glomerulonephritis  thus  tcc generation commonly occurs in the early stages of apsgn and may be of importance in the pathogenesis of the condition  
class1	acute glomerulonephritis in a patient with rocky mountain spotted fever  it is generally assumed that acute tubular necrosis is the etiology of renal failure that can occur during the course of rocky mountain spotted fever  rmsf   however  histologic examination of kidneys has been mainly limited to autopsy cases of fulminant infections  acute glomerulonephritis due to glomerular immune complex deposition has not been reported in rmsf  we describe a case of acute oliguric renal failure that developed more than 2 weeks following the onset of rmsf  renal biopsy showed acute glomerulonephritis with inflammatory cell infiltration and subendothelial immune deposits  thus  acute glomerulonephritis should be in the differential diagnosis of acute renal failure that occurs in rmsf  
class1	results of bronchoscopically obtained lower airway cultures from adult sickle cell disease patients with the acute chest syndrome  purpose  the purpose of this study was to determine the frequency of bacterial pneumonia as a cause of the acute chest syndrome in adult patients with sickle cell disease based on bronchoscopically obtained lower airway cultures and to describe the clinical  laboratory  and roentgenographic features of the acute chest syndrome in a series composed entirely of adult patients with sickle cell disease  patients and methods  we reviewed the hospital records from 19 episodes  18 patients  of acute chest syndrome in adult patients with sickle cell disease  greater than or equal to 19 years of age  who had undergone flexible bronchoscopy to obtain lower airway cultures between january 1979 and july 1987  we also recorded patients  clinical  laboratory  and roentgenographic characteristics  results  pneumonia was diagnosed in four of 19 episodes  21   of acute chest syndrome based on quantitative cultures obtained at bronchoscopy  the pneumonia was caused by streptococcus pneumoniae in two patients and mixed aerobic and anaerobic organisms in the other two patients  forty four of 45 blood cultures were negative  and one grew staphylococcus epidermidis  which was considered a contaminant  chest roentgenograms revealed lower lobe involvement in 17 episodes  90   and bilateral infiltrates in six  32    pleural effusions occurred in seven episodes  37    and pleural fluid samples obtained from five of these revealed sterile exudates  conclusion  the results of this retrospective study suggest that bacterial pneumonia is an uncommon cause of acute chest syndrome in adult patients with sickle cell disease  these results are consistent with previous retrospective studies using noninvasive techniques to diagnose pneumonia  nevertheless  there appeared to be no reliable noninvasive variables that could accurately differentiate between patients with and without pneumonia and  consequently  we recommend empiric antibiotic therapy in addition to usual supportive care of these patients  
class1	idiopathic neutropenia  antineutrophil antibodies and clinical correlations  purpose  the present study was done to evaluate the clinical characteristics of a large series of adult patients with chronic idiopathic neutropenia  and correlate the presence of antineutrophil antibodies  their class  igg or igm   and their ability to fix complement with clinical parameters  including other hemocytopenias  splenomegaly  and infections  patients and methods  one hundred twenty one adult patients with chronic idiopathic neutropenia were studied  serum neutrophil binding antibodies were measured using paraformaldehyde fixed granulocytes  pfgs  from normal volunteers as target cells  125i labeled staphylococcal protein a was used to detect igg antibodies while igm antibodies were detected by using 125i labeled mouse monoclonal anti igm antibody  sera containing antineutrophil antibodies were tested for their ability to fix complement on donor pfgs by using 125i labeled monoclonal antibody to the third component of complement  results  of the 121 patients with chronic idiopathic neutropenia  71 patients had isolated neutropenia  while 50 had neutropenia combined with either anemia and or thrombocytopenia  among the 71 patients with isolated neutropenia  there were 51 females  72    compared with 28 females  56   among the 50 patients with combined hemocytopenias  p   0 083   patients with multiple hemocytopenias were significantly older  p less than 0 01   were more likely to demonstrate splenomegaly  p   0 001   and may have had more infectious complications  from all the patients  36  of sera were shown to have antineutrophil antibodies  with a non significant trend for these to be found more frequently in patients with multiple hemocytopenias  sera with mixed igg igm antineutrophil antibodies were significantly more likely to fix complement than those with isolated igg or igm antibodies  and among the patients with antineutrophil antibodies  complement fixing antibodies were significantly associated with multiple hemocytopenias  splenomegaly was significantly associated both with antineutrophil antibodies  p   0 008  and with infections  p   0 007   antineutrophil antibodies were not associated with infections  conclusions  approximately one third of adult patients with idiopathic neutropenia have igg and or igm antineutrophil antibodies demonstrable in their serum  there is a subset of patients with idiopathic neutropenia with multiple hemocytopenias who tend to be older  less likely to show female predominance  more likely to have splenomegaly and infections  and more likely to have antineutrophil antibodies  especially mixed igg igm and complement fixing antibodies  
class1	hosts on which nymphal ixodes ricinus most abundantly feed  to identify hosts that may serve as european reservoirs for the agent of lyme disease  borrelia burgdorferi  we determined whether nymphal ixodes ricinus feed mainly on particular mice  apodemus flavicollis or a  agrarius   voles  clethrionomys glareolus  or on sand lizards  lacerta agilis  and whether the abundance of these hosts corresponds to the seasonal activity of the subadult stages of the vector tick  in all sites  the mice appeared most heavily infested by larvae  at least seven parasitized each mouse  about three per vole and four per lizard  many fewer nymphal i  ricinus parasitized a  flavicollis and c  glareolus than did larvae  although more than 30 times as many larval than nymphal ticks parasitized the two most abundant hosts  c  glareolus and a  flavicollis   about 15 times as many fed on a  agrarius and twice as many on lizards  nymphal and larval ticks fed on rodents at about the same time  lizards were most abundantly parasitized by nymphs somewhat earlier than by larvae  early in the season of transmission of lyme disease  virtually all a  agrarius as well as lizards were potentially exposed to spirochetes borne by nymphal i  ricinus  we concluded that larval and nymphal i  ricinus differentially parasitize different hosts  because so many of these nymphs feed on them  a  agrarius may more effectively serve as reservoirs for the agent of lyme disease than do other putative reservoir hosts  the presence of lizards may inhibit transmission  
class1	postpartum amaurosis  blindness is a rare but dramatic complication of pregnancy and delivery  we present the case of a patient who developed toxemia at the time of delivery that with ineffective treatment resulted in cortical blindness without seizure activity  the pathogenesis as well as the diagnostic workup and treatment of this unusual complication are discussed  
class1	closed suction drainage following knee arthroplasty  effectiveness and risks  a prospective investigation was performed to determine when to remove a suction drain following total knee arthroplasty  tka   forty one tkas were randomly allocated to closed suction drainage for either 24 or 48 hours  the drain was removed and the tip was cut off and processed by a method giving quantitative cultures  in the 48 hour group  85  of the total volume was drained during the first 24 hours  during the following 24 hour period  a mean volume of only 50 ml was drained  no organism was isolated from cultures of drain tips sampled at 24 hours  however  at 48 hours  25  of the drain tips yielded light growths of coagulase negative staphylococci  four drain tips  and staphylococcus aureus  one drain tip   clinical evaluations of wound healing were comparable in the two groups  clearly  nothing is to be gained by continuing drainage beyond 24 hours  if drainage is maintained for longer periods  there is an increased risk of contamination by bacteria  
class1	prevalence of antibody to borrelia burgdorferi in children with juvenile rheumatoid arthritis  lyme arthritis and juvenile rheumatoid arthritis  jra  share a number of clinical features  our study was performed in order to determine the prevalence of antibody to borrelia burgdorferi in 50 children with jra who reside in a nonendemic area  three patients were weakly reactive and one patient was reactive when tested using an enzyme immunoassay to detect serum antibody to b  burgdorferi  no patient  however  had definitive serologic evidence of b  burgdorferi infection by western blot analysis  we conclude that the prevalence of antibody to b  burgdorferi is very low in children with jra who reside in a nonendemic area  
class1	septic arthritis due to group c streptococcus  report and review of the literature  a case of polyarticular septic arthritis due to lancefield group c streptococcus is described and the clinical details of 9 reported cases of septic arthritis due to group c streptococcus reviewed  several features of the presentation and course of these patients  including polyarticular involvement  4 10   bacteremia  5 10   clinically important dysfunction in other systems  4 10 patients  cardiac  3  cns  2  pneumonia  1  gastrointestinal  1   fatal outcome  3 10 patients  2 during the course of active infection  and poor functional outcome in affected joints  4 7 surviving patients   serve to place group c streptococcus septic arthritis as a syndrome distinct from that usually expected with streptococcal septic arthritis  specific features of the bacteriology of group c streptococcus are reviewed  including confusion with group a streptococcus when analyzed using nonserologic methods  occasional zoonotic source  and frequency of tolerance to penicillin  in order to emphasize the importance of both the specific identification of this particular streptococcal strain and the initiation of aggressive antibiotic therapy when group c streptococcus is identified as the causative agent in a case of septic arthritis  
class1	purulent pericarditis and cardiac tamponade caused by nocardia asteroides in mixed connective tissue disease  pericardial nocardiosis is extremely rare  but may affect especially immunocompromised hosts  we describe the first reported case of purulent pericarditis with cardiac tamponade as the initial presentation of systemic nocardiosis in a patient with mixed connective tissue disease  our case emphasizes the importance of identifying infectious causes of pericarditis in patients with connective tissue diseases  longterm survival was achieved with a combined medical and surgical approach  
class1	spermatic cord for onlay coverage of urethral defect  segmental urethral necrosis may accompany scrotoperineal gangrene  and primary closure of the urethral defect may unacceptably reduce urethral dimensions  this dilemma has been managed successfully in 5 patients by application of the intact spermatic cord to the urethral defect and approximation to its margins  a representative case is described  
class1	improvement in the diagnosis of abscesses associated with endocarditis by transesophageal echocardiography background  echocardiography is recognized as the method of choice for the noninvasive detection of valvular vegetations in patients with infective endocarditis  with transesophageal echocardiography being more accurate than transthoracic echocardiography  the diagnosis of associated abscesses by transthoracic echocardiography is difficult or even impossible in many cases  however  and it is not known whether transesophageal echocardiography is any better  methods  to determine the value of transesophageal echocardiography in the detection of abscesses associated with endocarditis  we studied prospectively by two dimensional transthoracic and transesophageal echocardiography 118 consecutive patients with infective endocarditis of 137 native or prosthetic valves that was documented during surgery or at autopsy  results  during surgery or at autopsy  44 patients  37 3 percent  had a total of 46 definite regions of abscess  abscesses were more frequent in aortic valve endocarditis than in infections of other valves  and the infecting organism was more often staphylococcus  52 3 percent of cases  in patients with abscesses than in those without abscesses  16 2 percent   the hospital mortality rate was 22 7 percent in patients with abscesses  as compared with 13 5 percent in patients without abscesses  whereas transthoracic echocardiography identified only 13 of the 46 areas of abscess  the transesophageal approach allowed the detection of 40 regions  p less than 0 001   sensitivity and specificity for the detection of abscesses associated with endocarditis were 28 3 and 98 6 percent  respectively  for transthoracic echocardiography and 87 0 and 94 6 percent for transesophageal echocardiography  positive and negative predictive values were 92 9 and 68 9 percent  respectively  for the transthoracic approach and 90 9 and 92 1 percent for the transesophageal approach  variation between observers was 3 4 percent for transthoracic and 4 2 percent for transesophageal echocardiography  conclusions  the data indicate that transesophageal echocardiography leads to a significant improvement in the diagnosis of abscesses associated with endocarditis  the technique facilitates the identification of patients with endocarditis who have an increased risk of death and permits earlier treatment  
class1	candidal infection in oral lichen planus  the prevalence of candidal infection in lichen planus  lp  and its possible association with ulceration were independently examined in two archived series of 108 and 77 cases derived from two separate populations  to ensure that similar material was being compared  each case was histopathologically reassessed and confirmed as lp or reclassified as nonspecific lichenoid stomatitis  nsls   lichenoid dysplasia  ld   or other  o   three further sections  cut at 25 microns intervals  were stained with periodic acid schiff reagent for the identification of intraepithelial candidal pseudohyphae  as control specimens  61 normal and 59 hyperkeratotic mucosal samples were similarly processed and examined  candidal infection was found in 17 4  and 16 4  of ulcerated and nonulcerated lp cases  respectively  and in 40 0  and 16 7  of ulcerated and nonulcerated nsls cases  respectively  one case of ld was infected  each control series contained one infected case  the results indicate that candidal infection occurs more readily in lp and nsls  with no apparent association with ulceration in lp  the comparatively marked increase in the infection prevalence of ulcerated nsls cannot be statistically confirmed  and its significance remains uncertain  
class1	the office laboratory  few areas of medicine are experiencing such tremendous growth as the office based laboratory  recent advances in technology and changes in reimbursement practices have greatly expanded the potential of this segment of patient care  in the 1990s the physician has opportunity to introduce many testing procedures to the office laboratory that were not available 20 years ago  requirements in the areas of quality assurance and quality control are constantly changing  these regulations vary from state to state and each laboratory should know what is required by their respective certifying agency  in today s market  the physician must choose between the referral laboratory or the resources in the office and consider which option provides the best in care and cost to the patient  
class1	antibiotics and infectious diseases  selection of antibiotics in clinical practice has become increasingly complex because more patients have underlying predispositions to infection  a greater variety of microorganisms with varying antibiotic resistance patterns cause these infections  and more antibiotics are available to treat these pathogens  a practical approach to antibiotic decision making involves comparing the advantages and disadvantages of each group of antibiotics available while remembering the patient population being treated and the common pathogens encountered in one s practice  it is helpful to study the penicillin derivatives in approximately chronologic order of development and the cephalosporins in terms of generations because this puts the use of each individual agent in perspective  familiarity with commonly encountered adverse antibiotic reactions  dosage guidelines  and special situations  pregnancy  pediatric patients  will help avoid problems associated with antibiotic use  finally  having one or more useful references at hand will aid in resolving questions about antibiotic use  
class1	sexually transmitted diseases  over the past two decades the incidence of stds has dramatically increased in the united states  most patients with these infections present first to primary care physicians  all physicians must be familiar with the common std syndromes and the indications for specific diagnostic tests in order to provide a comprehensive treatment plan  primary prevention strategies based on patient education and secondary prevention through judicious use of screening tests in appropriate settings can also limit the morbidity associated with stds  
class1	infectious skin diseases  descriptions of individual diseases  including impetigo  scarlet fever  and toxic shock syndrome  are presented in the context of the specific organisms that cause them  pictures are used to show some of the diseases  testing and treatment information for these diseases are included  
class1	antibiotics for common infections in the elderly  a decline in host defense mechanisms and concurrent diseases combine to make the elderly patient particularly susceptible to common infections  the bacterial cause and antimicrobial sensitivity patterns may also be different in the elderly  the appropriate selection and dosing of antibiotics for elderly patients with such common infections as pneumonia  bronchitis  urinary tract infections  and skin and soft tissue infections will optimize the patient s response while minimizing adverse consequences  
class1	incidence  causes and mechanism of hypercalcaemia in a hospital population in hong kong  to determine the incidence and causes of hypercalcaemia in a hospital population in hong kong  all 29 107 samples received in the laboratory in one year were analysed for plasma calcium and albumin  and samples with a plasma calcium concentration adjusted for albumin greater than 2 55 mmol l were investigated  plasma calcium greater than 2 55 mmol l was found in 462 patients  repeat samples were received from 302 of these and hypercalcaemia was confirmed in 183  the main causes of hypercalcaemia were malignancy  72 1 per cent   tuberculosis  6 0 per cent   and primary hyperparathyroidism  5 5 per cent   in the malignant hypercalcaemia group  carcinoma of lung was the most common  31 8 per cent  and carcinoma of breast was uncommon  3 0 per cent   secondary deposits in bone were detected in 35 of the 122 solid tumours  in order to identify the mechanism of hypercalcaemia the contributions of renal tubular reabsorption and increased bone resorption to the plasma calcium concentration were calculated  increased tubular reabsorption was the main contributor to hypercalcaemia in primary hyperparathyroidism and carcinoma of liver  none of whom had bony metastases  and it contributed significantly to hypercalcaemia in carcinoma of lung without bony metastases and carcinoma of oesophagus  we conclude that in hong kong  a  primary hyperparathyroidism is uncommon   b  tuberculosis is an important cause and  c  humoral factors may be responsible for a relatively high proportion of cases of malignant hypercalcaemia  
class1	enhancement of hiv 1 cytocidal effects in cd4  lymphocytes by the aids associated mycoplasma  coinfection with mycoplasma fermentans  incognitus strain  enhances the ability of human immunodeficiency virus type 1  hiv 1  to induce cytopathic effects on human t lymphocytes in vitro  syncytium formation of hiv infected t cells was essentially eliminated in the presence of m  fermentans  incognitus strain   despite prominent cell death  however  replication and production of hiv 1 particles continued during the coinfection  furthermore  the supernatant from cultures coinfected with hiv 1 and the mycoplasma contained a factor that inhibited the standard reverse transcriptase enzyme assay  the modification of the biological properties of hiv 1 by coinfection with mycoplasma may be involved in the pathogenesis of acquired immunodeficiency syndrome  aids   
class1	use of plasmid profiles in the investigation of a patient with helicobacter pylori infection and peptic ulcer disease  plasmids may effect bacterial virulence and antibiotic resistance  and serve as epidemiologic markers  in this study  plasmid dna profiles of serial isolates of helicobacter pylori showed persistence of an identical strain of this organism in a patient with duodenal ulcer disease  three control strains of h  pylori isolated from other patients contained plasmids different from each other and from that of the original patient  two of these strains had two plasmids each  these data have important implications for further study of the epidemiology and pathogenesis of h  pylori related diseases  
class1	peritoneal blastomycosis  blastomycosis is a systemic fungal infection caused by blastomyces dermatitidis  involvement of the peritoneum is unusual  with only two previously reported cases that occurred in association with disseminated disease  a single case of histopathologically proven blastomycosis involving the peritoneum is presented  as well as a short overview of previously published cases on gastrointestinal and peritoneal blastomycosis  the case is unique in that chronic peritonitis was the only manifestation of disease  the diagnosis was made by laparoscopy  
class1	antistaphylococcal activities of teicoplanin and vancomycin in vitro and in an experimental infection  the efficacies of vancomycin and teicoplanin in an experimental staphylococcus aureus infection in granulocytopenic mice were related to their activities in vitro and their pharmacokinetic profiles  in vitro teicoplanin had a higher intrinsic activity than vancomycin did  and it also had a more favorable pharmacokinetic profile  resulting in higher peak concentrations in plasma  a longer elimination half life  and a larger area under the concentration time curve than those of vancomycin  to predict the antibacterial efficacies of the drugs in vivo on the basis of their activities in vitro and pharmacokinetics  a mathematical model was applied  in the model the in vitro effect was expressed as the difference in growth rate between control cultures and those in the presence of the antibiotic  er   and the in vivo effect was expressed as the difference between numbers of cfu in control and antibiotic treated animals  en   the integral of er against time  ert  was calculated by using the concentrations found in vivo  a significant linear relationship was found between en and ert for different dosages at the same times  4 h  after drug administration as well as for the same doses at consecutive times  although at the lowest doses of teicoplanin the observed effect was less than the predicted effect  
class1	pharmacokinetics and tissue penetration of a single dose of ornidazole  1 000 milligrams intravenously  for antibiotic prophylaxis in colorectal surgery  levels in serum and tissue penetration of ornidazole were studied after a single intravenous injection of 1 000 mg given to 14 patients for prophylaxis of surgical infection  they were scheduled for elective colorectal surgery  adequate levels in blood  greater than or equal to mic for 90  of bacteroides fragilis strains tested  were found in all patients throughout the procedure and up to hour 24  mean maximal  15 min  and last determined  24 h  ornidazole levels in serum were 24     5 2 and 6 3     1 4 mg liter  respectively  beta phase elimination half life was 14 1     2 7 h  and clearance and apparent volume of distribution were 47     12 ml min and 0 9     0 13 liters kg  respectively  in all patient  adequate levels in tissue were found in the abdominal wall and the epiploic fat at time of incision and in the colonic wall at time of anastomosis  at time of closure  all but one patient had adequate levels in tissue in the abdominal wall and the epiploic fat  no anaerobic nor aerobic infection occurred in the study patients  
class1	comparative study of the effects of four cephalosporins against escherichia coli in vitro and in vivo  a thigh muscle infection induced with escherichia coli in irradiated mice was used as a model to compare the in vivo pharmacodynamics of the antibacterial effect of four cephalosporins  i e   cefepime  ceftriaxone  ceftazidime  and cefoperazone  with the in vitro antibacterial pharmacodynamics of these drugs  the following in vitro pharmacodynamic parameters were determined  the maximum effect as a measure for efficacy  the 50  effective concentration as a parameter for potency  and the slope of the concentration effect relationship  for analysis of the in vivo antibacterial pharmacodynamics  the same parameters were applied for the dose instead of the concentration  for the detection of a relationship between concentration and antibacterial effect in vivo  we determined the pharmacokinetics of the four cephalosporins in the plasma of mice  the results showed that  in general  there is a direct relationship between the in vivo and in vitro pharmacodynamics of these cephalosporins  the maximum effects of cefepime  ceftazidime  and cefoperazone were approximately similar in vivo and in vitro  the sequence of potency of these drugs was  in descending order  cefepime  ceftazidime  and cefoperazone  ceftriaxone differed from the other three cephalosporins in that it displayed unexpected in vivo pharmacodynamics  ceftriaxone was just as efficacious as the other three in vitro  but its maximum effect in vivo was much lower  this relatively low maximum effect of ceftriaxone in vivo was not explained by the pharmacokinetic characteristics of the drug  from the present results it can be concluded that the in vitro efficacy of cephalosporins does not necessarily have a predictive value for the in vivo efficacy  
class1	nasal midline masses in infants and children  dermoids  encephaloceles  and gliomas  nasal dermoids  gliomas  and encephaloceles are uncommon congenital lesions that result from aberrant embryologic development  we have treated 46 children with these nasal lesions  in view of the potential intracranial connection  patients are at risk for intracranial infection  and early surgical correction is thus imperative  neuroimaging studies may help to predict intracranial involvement  
class1	cytomegalovirus diaper dermatitis  cytomegalovirus inclusions have been reported in perineal ulcers from immunosuppressed adults  the importance of this finding is unknown  we report the first pediatric case of cutaneous cytomegalovirus infection in an infant with congenital human immunodeficiency virus infection  presenting as a diaper dermatitis  cytomegalovirus was cultured from the skin biopsy specimen  and characteristic inclusions were seen on hematoxylin eosin stained sections  results of this biopsy specimen analysis prompted further investigation revealing disseminated cytomegalovirus infection  including retinitis  aggressive pursuit of a pathogen in common conditions such as diaper dermatitis is strongly recommended in immunosuppressed pediatric patients  
class1	the peritoneal environment during infection  the effect of monomicrobial and polymicrobial bacteria on po2 and ph  intraperitoneal  ip  abscesses frequently are composed of aerobes and anaerobes  and  in experimental models  a particulate adjuvant  the environmental changes effected by these components  either singularly or in combination  have not been well defined  the ip po2  ph  and recoverable bacteria from the peritoneum of rats were quantified over 6 hours during simple aerobic and anaerobic infections and during mixed peritonitis with and without a sterile feces barium sulfate adjuvant  sfa   fourteen groups were studied  receiving intraperitoneally  at time of oxygen probe placement  1 ml normal saline  control   escherichia coli  ec   bacteroides fragilis  bf   sfa alone  or a mixture of ec and bf  ec and sfa  bf and sfa  or ec  bf  and sfa  control animals exhibited a stable ip po2 and ph during 6 hours  in monomicrobial ec peritonitis  inocula well below the ld50 produced an increased ip po2 and reduced arterial peritoneal gradient  apg   with a stable ip ph  by 6 hours lethal doses of ec produced a dramatic decline in ip po2  with no change in arterial po2 as well as acidic ip and arterial phs  simple bf peritonitis caused no or minor elevations in ip and arterial po2 with no change in ph  during mixed infections a significant decline in the ip po2 and ph at 6 hours in those groups infected with both sfa and ec of a moderate  normally sublethal inoculation was observed  while arterial po2 was unchanged and arterial ph was decreased only slightly  concomitantly there was a significant increased number of aerobic bacteria in those groups with sfa as adjuvant compared to similar inocula without sfa  this study demonstrates the complex interactions of bacteria  sterile particulate adjuvant  sfa   and the host peritoneum  it suggests that the combination of sfa and aerobic bacteria alter the peritoneal environment to one permitting anaerobic growth and promoting abscess formation  
class1	elevated plasma endothelin 1 concentrations are associated with the severity of illness in patients with sepsis  plasma immunoreactive endothelin 1 concentrations were determined by radioimmunoassay in 11 septic patients during the first 24 hours after the development of the sepsis syndrome in 15 nonseptic postoperative patients studied 24 hours after open heart surgery and in 14 healthy volunteers  mean endothelin 1 plasma concentrations were significantly  p less than 0 001  increased in septic patients  19 9     2 2 pg ml  mean     standard error  compared to concentrations found in postoperative cardiac patients  11 9     0 7 pg ml  or in healthy volunteers  6 1     0 3 pg ml   in septic patients elevated plasma concentrations of endothelin 1 were inversely correlated with cardiac index  r    0 80  p less than 0 005  and positively correlated the severity of illness as documented by apache ii score  r   0 74  p less than 0 01  and plasma creatinine levels  r   0 80  p less than 0 005   no such correlations were found in postoperative cardiac patients  these results indicate that endothelin 1 concentrations are correlated with the severity of illness and depression of cardiac output in patients with sepsis  
class1	hemodynamic effects of lobar pulmonary artery occlusion in a porcine sepsis model  we induced severe pulmonary hypertension and acute lung injury in 6 pigs by pseudomonas aeruginosa infusion  we studied the effect of pulmonary artery catheter inflation of a pulmonary artery catheter balloon in the left lower lobar pulmonary artery was accompanied by a significant  p less than 0 05  paired t test  increase in pulmonary artery pressure  a decrease in left atrial pressure  a decrease in cardiac output  and a decrease in mean arterial pressure  no significant changes occurred when the catheter was advanced into the wedged position without balloon inflation  balloon inflation had no significant effect on these variables before bacterial infusion  we conclude that with sufficiently severe pulmonary hypertension in association with diffuse lung injury  lobar pulmonary artery occlusion may cause alterations in cardiac output and left atrial pressure  this may confuse interpretation of pulmonary artery catheter measurements  
class1	thoracoscopic debridement and pleural irrigation in the management of empyema thoracis  as a sequel to a paper reporting good results obtained in 12 patients with empyema thoracis treated by thoracoscopic debridement and irrigation in our department  subsequent experience with a further 18 patients is reported  drainage of pus and irrigation resulted in resolution of pyrexia with improvement in general condition in all patients  overall  complete resolution was obtained by this technique alone in 60   18 30   of the 12 patients in whom complete resolution was not obtained  secondary surgical measures resulted in resolution of empyema in 8  four patients died  all were elderly and severely debilitated  3 with advanced malignancy  their deaths were not related to the technique  which was well tolerated in all cases  thoracoscopic debridement and irrigation used routinely as a first line measure in empyema thoracis is a safe and relatively atraumatic procedure  does not exclude the use of any subsequent surgical measure  and provides valuable time to improve the condition of debilitated patients so that they may tolerate more aggressive surgical procedures  
class1	an unusual complication of cardiac transplantation  infected aortic pseudoaneurysm  infections after cardiac transplantation are a frequent cause of early morbidity and mortality  an unusual site for such a complication is at the aortic anastomotic suture line  we report a case of an infected aortic pseudoaneurysm  seen as recurrent septicemia  during the first 6 months after cardiac transplantation  
class1	candida pyelonephritis complicating traumatic c5 quadriplegia  diagnosis and management  we present the first reported case of candida pyelonephritis in a spinal cord injured patient  in addition to multiple courses of empiric antibiotics  the neurogenic bladder and alteration in cell mediated immunity found in spinal cord injured patients may have increased this patient s susceptibility to fungal disease  a 50 year old patient with c5 motor functional quadriplegia developed candid albicans pyelonephritis while undergoing rehabilitation  the patient had several surgical procedures and multiple courses of antibiotic therapy during acute hospitalization  he continued to have a hectic fever curve  leukocytosis with increased band forms  lethargy  and progressive uremia during rehabilitation  successful investigation of the patient s condition included assessment of serologic tests for candida precipitin antigen  multiple blood and urine cultures  exclusion of other causes of hectic fever  abdominal computerized tomogram  which revealed a left kidney hypodensity with irregular margins  and a retrograde pyelogram  which demonstrated multiple renal pelvic filling defects  cystoscopically placed ureteral stents  which relieved the genitourinary obstruction  drained gross pus from which candida albicans was cultured  the patient was treated with amphotericin b and showed clinical improvement  pathogenesis  presentation  diagnosis  and treatment of candida pyelonephritis are reviewed  
class1	effect of splenectomy on morbidity and survival following curative gastrectomy for carcinoma  we performed a retrospective analysis of 392 patients who underwent curative resection of gastric adenocarcinoma to evaluate the impact of splenectomy on survival from gastric cancer and postoperative morbidity  twelve factors  including splenectomy  were associated with a poor prognosis by univariate analysis  multivariate analysis identified six of these factors  but not splenectomy  as independently predictive of death due to gastric cancer  the apparent adverse effect of splenectomy was due to its association with other significant risk factors  postoperative complications occurred more commonly in patients who underwent splenectomy than in those who did not  45  vs 21    patients in the splenectomy group also had a higher percentage of infectious complications than those in the nonsplenectomy group  75  vs 47    we conclude that splenectomy has no direct influence on survival  but that it increases the morbidity of curative gastrectomy and should be avoided unless the spleen is close to or invaded by the tumor  
class1	cytologic diagnosis of aspergillosis in cardiac transplantation  fine needle aspiration of the lung is now widely utilized to diagnose pulmonary neoplasms  but often serologic techniques or open lung biopsy is relied on for the diagnosis of infectious pulmonary processes  we report a series of four patients in whom the fine needle aspiration technique was used to make the rapid cytologic diagnosis of pulmonary aspergillosis  culture confirmation was also obtained on the aspirated material  a discussion of the available techniques for the laboratory diagnosis of pulmonary aspergillosis is presented and the advantages of fine needle aspiration cytology are stressed  our favorable results support expanded use of fine needle aspiration cytology in the evaluation of lung nodules appearing in immunosuppressed populations  
class1	nosocomial outbreak of cryptosporidiosis in aids patients  objective  to describe a nosocomial outbreak of cryptosporidiosis during four months after june 1989  setting  a department of infectious diseases in copenhagen  seeing about half the patients with aids in denmark  subjects  73 hiv antibody negative subjects and 60 antibody positive subjects admitted as inpatients during the transmission period of the outbreak  20 june 14 august   of whom 18  17 with aids  one with aids related complex   developed cryptosporidiosis  two further hiv negative subjects  one departmental secretary  one visiting relative  developed cryptosporidiosis  main outcome measures  cryptosporidia in stool samples  clinical symptoms  cd4 cell count  hiv antigen concentration  chemotherapeutic treatment  results  the source of the outbreak was identified as ice from an ice machine in the ward  contaminated by an incontinent  psychotic patient with cryptosporidiosis picking out ice for cold drinks  the mean incubation time was at least 13 days that is  twice that in hiv negative patients  of the 18 patients with aids who developed cryptosporidiosis  five recovered  two were symptomless carriers  three died of unrelated causes  and eight died after prolonged diarrhoea  among the 57 exposed hiv antibody positive inpatients  excluding two patients and the index case with cryptosporidiosis diagnosed elsewhere   significantly more of those who developed symptomatic cryptosporidiosis received oral sulphonamides than those who did not  91   10 11 v 48   21 44  p less than 0 05   conclusions  the clinical and epidemiological findings indicate that infection was the consequence of very small inocula  increased sensitivity to cryptosporidiosis may be an unrecognised side effect of oral sulphonamide treatment in patients with aids  
class1	hemodialysis for acute renal failure in patients with hematologic malignancies  objective  to assess the prognosis of patients with hematologic malignancies in acute renal failure who require hemodialysis  design  retrospective study  setting  icu  patients  forty three consecutive patients  methods  prognostic analysis using both univariate and multivariate  stepwise regression  methods  results  fifteen  35   patients recovered from acute renal failure and 12  28   were discharged from the icu  the prognosis of patients with acute renal failure linked to sepsis is poorer than the prognosis of the patients with acute renal failure from other etiologies  only one patient survived in the former group  n   26  and 11 in the latter group  n   17   p less than  0001 in multivariate analysis  when accompanied by associated respiratory failure  mortality rate was higher  93  vs  33   p less than  0001   the simplified acute physiology score  saps  calculated within the first 24 hr of admission was significantly  p less than  001  related to mortality when the saps was greater than or equal to 13  the presence of neutropenia and the type of hematologic malignancy were not related to a worse prognosis  tolerance to hemodialysis appeared good  and complications were rare  
class1	pulmonary artery occlusion left atrial pressure gradient  an important factor in determining pulmonary venous vascular resistance in acute pulmonary failure  objective  to determine whether pulmonary artery occlusion pressure  paop  accurately reflects left atrial pressure  lap  in acute pulmonary failure  design  sham controlled laboratory investigation on goettingen minipigs  interventions  induction of acute respiratory failure by a 4 hr infusion of live escherichia coli bacteria in 11 animals  two animals served as the control group  anesthesia was obtained with methohexital piritramide and pancuronium bromide  measurements and main results  cardiac output and pressures were measured by means of femoral artery  pulmonary artery  and left atrial catheters  arterial alveolar po2 ratio was calculated to evaluate pulmonary function  measurements were obtained before and after 1 and 2 hr of the e  coli infusion  statistical significance was tested with analysis of variance  e  coli infusion caused the hypodynamic shock and respiratory failure  the paop lap gradient was  0 3     1 6 mm hg before bacteremia and increased significantly  p less than  001  to 2 9     1 8 and 3 4     2 0 mm hg after 1 and 2 hr of bacteremia  respectively  no significant changes occurred in the sham group  conclusions  a paop lap gradient may develop during acute respiratory failure  therefore  pulmonary venous vascular resistance may be underestimated if its determination is based on paop  an increase in bronchial to pulmonary blood flow and pulmonary venoconstriction are discussed as hypothetical causes of a paop lap gradient during acute respiratory failure  
class1	postoperative irrigation suction drainage after pelvic colonic surgery  a prospective randomized trial  a 2 year randomized prospective clinical trial was undertaken to determine whether postoperative irrigation of the pelvis would result in a decreased incidence of local septic complications  two hundred consecutive patients undergoing low pelvic procedures with rectal resection and entry of the presacral space by a single surgeon  were randomized  in the irrigation group  two of four presacral sump drains were placed to low intermittent suction and the remaining sumps infused continuously with saline until the effluent was clear  in the drainage alone group  all four presacral sump drains were placed to suction  drains were removed when drainage was less than 50 ml 24 hours  perioperative antibiotics and bowel preparation were identical  postoperative complications included pelvic abscess  n   7   anastomotic leak cuff sinus  n   11   abdominal wound infection  n   19   and perineal wound infection  n   5   postoperative irrigation of the pelvis did not result in a reduction in the overall rate of local pelvic septic complications  positive intraoperative presacral cultures  the presence of anaerobes in the presacral space  and duration of pelvic drainage had no effect on the development of pelvic sepsis  
class1	clostridium difficile  a common and costly colitis  clostridium difficile infection manifests as a self limiting diarrhea  protracted colitis  or toxic pseudomembranous colitis  the incidence of c  difficile in a 514 bed community hospital was studied retrospectively  155 patients of a total 18 262 admitted during 1988 were identified with c  difficile as an admitting or subsequent diagnosis  the method of diagnosis  mode of therapy  and related costs were analyzed  we have determined that education  with an emphasis on pathogenesis and prevention  is necessary to reduce the incidence in the hospital and the cost to the patient  
class1	vaccination with legionella pneumophila membranes induces cell mediated and protective immunity in a guinea pig model of legionnaires  disease  protective immunity independent of the major secretory protein of legionella pneumophila  we have examined the capacity of legionella pneumophila membranes to induce cell mediated immune responses and protective immunity in a guinea pig model of legionnaires  disease  guinea pigs immunized by aerosol with l  pneumophila membranes developed strong cell mediated immune responses to l  pneumophila membranes as demonstrated by cutaneous delayed type hypersensitivity and in vitro splenic lymphocyte proliferation  guinea pigs immunized by aerosol or by subcutaneous inoculation with l  pneumophila membranes developed strong protective immunity against lethal aerosol challenge with l  pneumophila  overall  in six independent experiments  39 of 49  80   guinea pigs immunized with l  pneumophila membranes survived challenge compared with 2 of 40  5   sham immunized controls  p   2 x 10  13   in contrast  guinea pigs immunized by aerosol with formalin killed l  pneumophila did not develop either a strong cell mediated immune response to l  pneumophila antigens or protective immunity to lethal aerosol challenge  the capacity of l  pneumophila membranes to induce protective immunity was independent of the major secretory protein of l  pneumophila  which we previously demonstrated is an immunoprotective molecule  purified l  pneumophila membranes did not contain detectable major secretory protein  msp  on immunoblots  immunization of guinea pigs with l  pneumophila membranes did not induce anti msp antibody  and guinea pigs developed comparable protective immunity after immunization with membranes from either an l  pneumophila strain that secretes the major secretory protein or an isogenic mutant that does not  this study demonstrates that  a  immunization with l  pneumophila membranes but not formalin killed l  pneumophila induces strong cell mediated immune responses and protective immunity   b  l  pneumophila membranes contain immunoprotective molecules distinct from the major secretory protein of l  pneumophila  and  c  l  pneumophila membranes have potential as a vaccine against legionnaires  disease  
class1	mycoplasma pulmonis infections cause long lasting potentiation of neurogenic inflammation in the respiratory tract of the rat  these experiments were done to learn whether mycoplasma pulmonis infections of the respiratory tract of rats can potentiate  neurogenic inflammation  and whether this potentiation is amplified by factors that exacerbate the infections  pathogen free f344 rats were inoculated intranasally with m  pulmonis or with sterile culture medium and then lived for 4 wk in an ammonia free atmosphere or in air containing ammonia  100 parts per million   neurogenic inflammation was evoked by an intravenous injection of capsaicin  and 5 min later the magnitude of the response was quantified by measuring the amount of extravasation of two tracers  monastral blue pigment and evans blue dye  we found that vascular permeability in the tracheas of all rats was normal in the absence of capsaicin  however  a 75 micrograms kg dose of capsaicin  which caused almost no extravasation of evans blue in the tracheas of pathogen free controls  17     3 ng mg  mean     se   produced extensive extravasation in the infected rats  135     18 ng mg  p less than 0 001   similarly  this dose of capsaicin produced 30 times as much monastral blue extravasation in the infected rats  area density   47     8  of surface area  as it did in the pathogen free rats  1 6     0 5   p less than 0 001   a difference that resulted from increases in the number of monastral blue labeled postcapillary venules and in the amount of labeling per venule  exposure of the infected rats to ammonia exacerbated the infections  further increased the number of monastral blue labeled vessels and the amount of labeling per vessel  and made the rats so sensitive to capsaicin that a normally tolerable dose of 150 micrograms kg i v  caused fatal apnea  ammonia did not have these effects in pathogen free rats  we conclude that m  pulmonis infections of the airway mucosa cause a potent  long lasting potentiation of neurogenic inflammation  which results in part from an increase in the number and responsiveness of mediator sensitive postcapillary venules  these changes can be amplified by environmental factors such as ammonia which exacerbate the infections  
class1	rhodococcus infection of the skin with lymphadenitis in a nonimmunocompromised girl  a 7 year old girl had a 4 x 3 x 3 cm nodule on the left wrist with axillary lymphadenopathy  acid fast bacilli were seen on a smear from a biopsy specimen of this granulomatous skin lesion  a rhodococcus species grew on culture  skin infections caused by rhodococcus may be more common than the few prior case reports suggest  
class1	successful treatment of disseminated cutaneous cytomegalic inclusion disease associated with hodgkin s disease  a case of disseminated cutaneous cytomegalic inclusion disease associated with hodgkin s disease is described  the patient had a diffuse eruption of pruritic  erosive erythematous nodules  histologically  many inclusion bodies were observed in perivascular areas of the skin lesions  immunohistologically  the inclusion bodies positively stained with both anticytomegalovirus antibody and anti factor viii related antibody  on electron microscopy many virus particles and dense bodies were found in the area where inclusion bodies were observed  treatment with high dose intravenous acyclovir and a large amount of immunoglobulin resulted in prompt healing of the skin lesions  subsequently  the patient s hodgkin s disease was well controlled on chemotherapy  the patient steadily improved without relapse of skin lesions 1 year after antiviral therapy was administered  
class1	group a streptococcal cellulitis adenitis in a patient with acquired immunodeficiency syndrome  a rapidly enlarging left inguinal adenitis  with positive groove sign  and fever  chills  malaise  hypotension  headache  scarlatiniform rash  choleroid diarrhea  and proteinuria developed in an homosexual man who was positive for human immunodeficiency virus  the needle aspiration of the inguinal mass showed group a beta hemolytic streptococci and the blood cultures were negative  suggesting group a streptococcal cellulitis adenitis with toxic strep syndrome  treatment with penicillin and surgical drainage was successful  bacterial infections associated with defective humoral immunity appear to be common in patients with acquired immunodeficiency syndrome  aids   and some of these infections have a remarkable extensive and lethal evolution  therefore streptococcal adenitis should be considered in any patient with aids or aids related syndrome in whom rapidly enlarging inguinal nodes develop  
class1	patrick watson williams and the concept of focal sepsis in the sinuses  an historical caveat for functional endoscopic sinus surgery  from 1900 to 1940 the theory of focal sepsis was invoked to justify a number of dubious surgical procedures  surgeons believed they were acting rationally  patrick watson williams advocated suction exploration of the paranasal sinuses for mental patients  claiming to cure criminal insanity by sphenoidotomy  favourable contemporary reviews showed international approval  the rational basis of treatment was emphasised  but there was little systematic evaluation of outcome  current enthusiasm for functional endoscopic sinus surgery is also based on a rational approach  logical deductions from pathophysiological  facts   outcome has still not been evaluated scientifically  we should learn from history  treatment should not be based too readily on what seems to be rational now  ideas of physiology and pathology change  what seems logical today may appear ridiculous tomorrow  careful analysis of outcome  preferably by controlled clinical trials  is needed as a rational treatment requires empirical validation just as much as any other  
class1	apparent increase in the incidence of invasive group a beta hemolytic streptococcal disease in children  recently  among adults  an increase in the incidence of invasive disease caused by group a beta hemolytic streptococci  gabs  has been noted  as has the appearance of a severe illness called  toxic shock like syndrome   also caused by gabs  we now report an apparent increase beginning in 1987 in the incidence of invasive disease caused by gabs in children  among these patients the manifestations were varied  one child had signs and symptoms compatible with the streptococcal toxic shock like syndrome  among the gabs isolates from our patients  8  80   of 10 evaluated for m protein antigens were nontypeable  further studies will be necessary to determine the relationship between serotypes and virulence of gabs  physicians should be aware of the possibility of an increasing incidence of invasive gabs disease in children  as well as its manifestations  which may include toxic shock like syndrome  
class1	changes in cardiac function during extracorporeal membrane oxygenation for persistent pulmonary hypertension in the newborn infant  the effects of extracorporeal membrane oxygenation  ecmo  on cardiac function and its determinants  preload  afterload  contractility  and heart rate  are largely unknown  although some evidence exists that function may decrease  to determine whether cardiac function decreases and what changes in the determinants take place during and after ecmo  we observed 26 newborn infants with persistent pulmonary hypertension  serial echocardiograms were performed before ecmo  during maximum cardiopulmonary bypass  and after ecmo  cardiac function was assessed by using standard echographic ejection phase indices  shortening fraction and cardiac output   heart rate  preload  left ventricular end diastolic dimension and area   afterload  left ventricular end systolic wall stress   and contractility  relationship between velocity of circumferential fiber shortening and wall stress  were also measured  ejection phase indices significantly decreased during ecmo  shortening fraction 33  to 25   cardiac output 205 to 113 ml kg min  p less than 0 05  and returned to normal after ecmo  shortening fraction 26  to 34   cardiac output 107 to 240 ml kg per minute  p less than 0 05   heart rate also significantly decreased during ecmo  158 to 118 beats min  p less than 0 05   preload significantly increased after ecmo  left ventricular end diastolic dimension 1 4 to 1 6 cm  left ventricular end diastolic area 1 9 to 2 2 cm2  p less than 0 05   there were no significant changes in contractility and afterload during any study period  we conclude that  although left ventricular ejection phase indices and heart rate decreased during ecmo  these changes were transient and resolved when bypass was terminated  contractility and afterload did not appear affected by bypass  
class1	discriminate use of electrocautery on the median sternotomy incision  a 0 16  wound infection rate  between june 1978 and june 1989  superficial or deep mediastinitis  or both  developed in only five  0 16   of 3118 consecutive patients  all patients studied underwent cardiac procedures through a median sternotomy and survived more than 7 postoperative days  the surgical team disciplined itself to divide presternal soft tissues with a scalpel and used electrocautery for pinpoint hemostasis only  this 0 16  infection rate was statistically significantly lower than those in 28 previously published studies  pearson s chi 2 test  p less than 0 05   twenty four predisposing factors were evaluated by fisher s exact test  among these only an operating time longer than 3 hours is related to sternotomy infections  p   0 0208   and this effect was not a strong one  statistical evidence strongly suggests that discriminate use of electrocautery is a major reason for the lowest median sternotomy infection rate reported to date  
class1	cortisol response to corticotropin and survival in septic shock corticotropin stimulation tests were used to assess adrenocortical function in 32 patients with septic shock  13 patients had a poor cortisol response  rise less than 250 nmol l  to corticotropin  all of whom died  however  there were only 6 deaths among the 19 patients with adequate responses  p less than 0 001   these results suggest that some patients with septic shock may have relative adrenocortical insufficiency  
class1	severity of cystic fibrosis in patients homozygous and heterozygous for delta f508 mutation  to assess the relation between genotype and severity of disease in cystic fibrosis  cf  the frequencies and extent of several features of its phenotypic expression were investigated in the 235 patients who attend the danish cf centre  14 patients who attend irregularly and 3 who do not carry the delta f508 mutation at all were excluded  the case reports of the remaining 218 patients  aged 4 months to 41 years  were carefully evaluated  and they were all analysed for the delta f508 mutation  172  79   were homozygous for delta f508 and 46  20   were heterozygous  the mutation therefore occurs on 89  of the chromosomes analysed  there were no significant differences between the homozygous and heterozygous groups in the proportions with meconium ileus at birth  liver involvement  or chronic pseudomonas aeruginosa infection  however  significantly more of the homozygous patients had onset of symptoms before the age of 6 months  p less than 0 025   they were significantly younger at diagnosis  p   0 013  and centre referral  p   0 006   they required greater pancreatic enzyme substitution  p   0 0002  and had poorer lung function  and the calculated yearly incidence of chronic ps aeruginosa infection and yearly mortality rates were greater than in heterozygous patients  p   0 0001   
class1	intracranial complications of paranasal sinusitis  a combined institutional review  intracranial complications of paranasal sinusitis constitute true surgical and medical emergencies  the charts of all patients  n   649  admitted for acute or chronic sinusitis to the university of minnesota hospital and to the university of michigan medical center during a 13 year period  1975 to 1988  were retrospectively reviewed to determine the incidence of complications  the clinical presentation  bacteriology  involved sinuses  influencing host factors  white blood cell count on presentation  length of hospitalization  and postinterventional complications are presented  twenty four patients with intracranial complications from paranasal sinusitis are studied for an incidence of 3 7   aggressive medical and semi emergent surgical intervention are required to prevent excessive morbidity and or mortality  intracranial complications included subdural empyema  frontal lobe abscesses  intrahemispheric abscesses  cavernous and superior sagittal sinus thrombosis  and osteomyelitis  
class1	managing skin infections in children  because neonates and very young children have little or no immunity to common streptococci and staphylococci  skin infections caused by these organisms must be regarded warily  prompt and proper treatment may be critical in preventing progression of the lesions and averting systemic complications  
class1	screening for sexually transmitted diseases by primary care physicians  the acquired immunodeficiency syndrome epidemic has drawn attention to screening for sexually transmitted diseases by primary care physicians  a telephone survey of primary care physicians in an area with a high incidence of stds  washington  dc  to ascertain the determinants and the extent of screening and counseling for stds was completed in 1987  ninety nine physicians  33 internists  38 obstetrician gynecologists  and 28 family general practitioners   representing 61  of those eligible  completed the interview  one third  39 4   were screening for gonorrhea  more than one half  57 5   for syphilis  and almost all  94   had tested at least one individual for human immunodeficiency virus infection  analysis suggested that concomitant screening for hepatitis b was significantly and positively associated with screening for gonorrhea and syphilis  less than half  45 9   of the physicians asked new patients about their sexual practices  physicians should take histories of sexual practices and do more preventive counseling  
class1	community acquired pulmonary infections in a public municipal hospital in the 1980s  the relative and absolute incidences of community acquired bacterial and tuberculous pulmonary infections  in patients admitted to a public municipal hospital  and the clinical and radiographic characteristics of these infections were retrospectively determined for the first time in 20 years  the data were compared to those previously reported in the literature  such data were also specifically determined for alcoholics and compared to those found in nonalcoholics  the absolute numbers of infections due to pneumococci and anaerobes  and to tuberculosis  were not dissimilar to those reported in the literature  even though relatively few hemophilus infections were documented  the lack of klebsiella sp infections was remarkable but not unexpected  alcoholic patients had significantly higher rates of tuberculosis  cavitary disease  lung disease presumably due to anaerobes  and blood culture positive pneumonia  the relative concordance of our results for bacterial and tuberculous infections with those predicted from the published literature was striking  the high frequency of tuberculosis in our patients was particularly striking at a time when the incidence of tuberculosis nationwide  in patients without acquired immunodeficiency syndrome  has declined significantly  
class1	false positive results in serologic tests for rocky mountain spotted fever during pregnancy  the data from this study demonstrate that false positive results from tests for rocky mountain spotted fever increase with the duration of pregnancy  the sera of 4 0   2 50  of women in their first trimester of pregnancy  10 9   5 46  in their second trimester  and 12 1   12 99  in their third trimester yielded false positive results from latex agglutination assays for rickettsia rickettsii infections  the cause of these false positive results was not determined by this study  these false positive titers were not associated with clinical findings or other laboratory abnormalities  even though these sera did not contain antibodies to r rickettsii detectable by indirect fluorescent antibody testing  such false positive results from serologic tests for rocky mountain spotted fever can obscure the patient s correct diagnosis  this may lead to the unnecessary use of potentially toxic antibodies and prevent initiation of appropriate therapy  
class1	postanginal sepsis with dysphagia  we have described a 10 year old girl who had dysphagia followed abruptly by arthritis  streptococcus pyogenes was identified as the pathogen by fasciotomy with bone biopsy  and a tonsillar fluid collection confirmed the diagnosis of postanginal sepsis  the patient was cured by a 6 week course of parenteral antibiotics  
class1	profound papilledema due to cryptococcal meningitis in acquired immunodeficiency syndrome  successful treatment with fluconazole  although cryptococcal meningitis is a frequent infection in patients with aids  papilledema is rarely reported  we have reported a case of profound papilledema associated with cryptococcal meningitis in a patient with aids  after treatment failure with amphotericin b  the patient was successfully treated with fluconazole  and the papilledema resolved  
class1	a case of neonatal tetanus  the morbidity and mortality from neonatal tetanus are preventable  it is largely a disease of developing countries  this single case of neonatal tetanus in southern florida must serve as an indicator for the need for health care professionals to evaluate the degree of utilization of maternal health services and the impact of immunization programs for those women at risk  in this case  women who have migrated from developing countries  
class1	focal hepatic tuberculosis in a patient with acquired immunodeficiency syndrome  patients infected with hiv are known to have unusual manifestations of a variety of infections  we have described the third reported case of a patient with aids having an apparent pyogenic liver abscess subsequently diagnosed as focal hepatic tuberculosis  this case emphasizes the need for aggressive diagnostic procedures for evaluation of focal liver abnormalities in these patients  
class1	stomatococcus mucilaginosus catheter related infection in an adolescent with osteosarcoma  ours is apparently the first reported pediatric case of stomatococcus mucilaginosus bacteremia  it is the second reported case of s mucilaginosus catheter associated infection  but the first case successfully treated without removing the central venous catheter  this unusual organism should be added to the list of opportunistic pathogens that can be isolated from immunocompromised pediatric patients  
class1	bacterial translocation from the gut impairs systemic immunity  the goal of this study was to determine the influence of bacterial translocation on systemic immunity  since bacteria and their products play a major role in the development and maintenance of the host s immune system  to test this hypothesis  we measured the blastogenic response of mononuclear cells harvested from the blood  spleen  peyer s patches  and mesenteric lymph nodes of control and escherichia coli c25 monoassociated mice to a battery of mitogens  the e  coli c25 monoassociation model was used because this bacterial translocation model is not associated with experimental manipulations that are likely to affect the systemic immune system  the mitogenic response of lymphocytes isolated from the e  coli c25 monoassociated mice was significantly depressed compared to the control groups  p less than 0 01   since the biologic significance of depressed in vitro mitogen responsiveness is difficult to determine  we assessed the ability of the mice to control a bacterial challenge using an in vivo staphylococcus aureus abscess model  it appears that the observed changes in mitogen responsiveness may be of biologic significance  since the ability of the e  coli c25 monoassociated mice to control the injected s  aureus was impaired  p less than 0 01   these results suggest that an association exists between bacterial translocation and decreased systemic immune responsiveness  
class1	bilateral emphysematous pyelonephritis  emphysematous pyelonephritis is an uncommon and serious infection associated with gas forming coliform bacteria  bilateral involvement is rare with only 10 reported cases in the english literature  prompt and aggressive management is required to salvage these patients  preservation of renal function using broad spectrum antibiotics and surgical drainage provide the greatest benefit to these patients  three new cases are presented with a brief review of the results of management in the reported cases  
class1	cephalosporins  rationale for clinical use  cephalosporins  the most widely used class of antibiotics  are more resistant than penicillins to inactivation by beta lactamases  based on their spectrum of activity against gram negative bacteria  cephalosporins are classified into three generations  the generation classification  however  does not correlate with activity against gram positive bacteria or anaerobes  first generation cephalosporins have a narrow gram negative spectrum but are most active against gram positive bacteria  particularly staphylococcus aureus  third generation compounds have excellent activity against gram negative bacteria  the cephamycins  a second generation subgroup that includes cefoxitin  cefotetan and cefmetazole  have the best activity against anaerobes  
class1	extraction of implanted transvenous pacing leads  a review of a persistent clinical problem  within a few months of implantation  permanent pacemaker leads become ensheathed in fibrocollagenous tissue  this tissue may anchor the lead so that it is difficult  dangerous  or impossible to remove it  leads with bulbous or finned tips are particularly resistant to extraction  the risks of applying traction to an entrapped lead include induction of bradycardia or ventricular tachycardia and fibrillation  invagination of the right ventricle  avulsion of the right ventricular myocardium or tricuspid valve  hemopericardium  and cardiac tamponade  forceful traction may result in uncoiling of the conductor  disruption of the insulation  or complete fracture  leaving an intravascular remnant that may embolize or be a source for thrombosis  although fixation and abandonment of an inactive chronically implanted lead is frequently appropriate and is known to pose little long term risk  the retained inactive lead may interact adversely with a new active lead and then increase the risk of venous thrombosis  serve as a potential nidus for infection  or produce spurious electrical sensing signals that may be sensed by the pulse generator  absolute indications for lead removal are those in which there would be a life threatening situation if the lead were to remain in situ  in the absence of an absolute indication  the decision to proceed with extraction must be made by weighing the potential for serious morbidity or mortality against risks of the extraction technique  techniques for lead removal include traction and open cardiotomy operations  when a portion of the lead is intravascular  forceps  snares  baskets  countertraction  or lead transection devices may be used to retrieve the fragment  
class1	empiric antibiotic selection by physicians  evaluation of reasoning strategies  the objectives of the study were to evaluate the appropriateness of empiric antibiotic selection by housestaff treating medical patients with bacteremia  the design was a prospective  observational study at a university affiliated hospital  seventy eight patients with bacteremia were evaluated  a clinical grade of acceptable or not acceptable was assigned to each antibiotic prescription by a consensus panel  the consensus panel found that 34 6  of antibiotic prescriptions were unacceptable  clinical grade   at least one flaw in the chain of reasoning was found in 56 4  of the 78 cases evaluated  assessment of the clinical setting was correct in 94 9  of the cases  the portal of entry was identified in 91   adequate knowledge of the bacterial flora at the suspected site of infection was found in 69   the diagnostic workup was appropriate in 81   and the correct antibiotic susceptibility patterns were given in 72   a correct chain of reasoning was more likely to result in an acceptable clinical grade than flawed reasoning  p less than 0 005   however  an appropriate antibiotic selection was made by some physicians despite flawed reasoning  and inappropriate antibiotic selection occurred in a few cases despite fautless reasoning  in 3 8  of cases  unexpected organisms appeared in blood culture  prescription of broad spectrum antibiotics may then be learned response  if so  educational efforts that emphasize narrow  rather than broad spectrum prescribing may be inadequate to change physician prescribing habits  
class1	gonococcal endocarditis  twenty five year experience  gonococcal endocarditis is a devastating albeit rare complication of disseminated gonorrhea  it virtually disappeared as a disease entity with the advent of antibiotic therapy  recently  it has reappeared with surprisingly high frequency for unclear reasons  since 1983  the authors have observed six episodes of this disease in five patients  the largest series reported to date  it is predominantly a disease of young people without underlying valvular heart disease  characteristic clinical features include a high frequency of congestive heart failure and nephritis and a proclivity for aortic valve involvement  commonly with associated ring abscess  and large vegetations  genitourinary symptoms  arthralgias  and rash are uncommon  previously undescribed features include involvement of all four valves simultaneously  recurrence on an aortic valve prosthesis  and a high frequency of terminal complement deficiencies  precipitous hemodynamic deterioration despite appropriate therapy is not uncommon  and overall mortality rate remains an alarming 19   
class2	varicella with delayed hemiplegia  we report 4 children who developed acute hemiplegia 7 weeks to 4 months after varicella infection  in 2 patients  carotid angiography demonstrated segmental narrowing and occlusion of the middle cerebral artery  their clinical and angiographic features were similar to those associated with contralateral hemiplegia after herpes zoster ophthalmicus  the pathogenesis of which comprises cerebral angiitis due to varicella zoster viral infection  we believe that our patients had the same pathogenesis  in a survey of infectious diseases in our region  the frequency of varicella with delayed hemiparesis was roughly 1 6 500 varicella patients  
class2	prevalence of hiv antibody and pregnancy in tayside  1984 9  background to screening  objective  to determine age specific prevalence of hiv antibody  incidence of pregnancy  and likelihood of detection and correct assignment to risk category by antenatal screening of women known to be positive for hiv antibody  from 1984 to 1989  design  retrospective analysis of reproductive history and risk behaviour of women positive for hiv antibody and prediction of detection by screening on the basis of blood group samples  guthrie tests  and rubella tests  setting  city of dundee  where the prevalence of hiv is high  since the appearance of hiv in 1984  predominantly among heterosexual intravenous drug users  patients  all  61  women known to be positive for hiv antibody who had had clinically indicated tests  for whom case notes were available for 60  main outcome measures  risk assessment according to case notes and reported to the laboratory  incidence of infection  geographical location  age  date of positive test result  and reproductive history  results  with 61 infected women the overall minimum prevalence among women within the city of dundee was 0 67 1000 and 2 9 1000 among women in their third decade  of the 60 women whose reproductive history was available  35 had 57 pregnancies  36 of which occurred after seroconversion was known to have taken place  representing 8 7  of the total number of affected pregnancies reported for the united kingdom  if antenatal screening for hiv had been performed between 1984 and 1989 it could not have detected positivity for hiv antibody in 25  42   women who had no pregnancies during this time  among the remaining 35 women  screening samples taken for blood grouping could have identified a maximum of 34  57    samples taken to check rubella susceptibility a maximum of 22  37    and blood spots on guthrie cards a maximum of 19  32    retesting would have occurred in 14 women 33 times with samples taken for blood grouping  but three and four women would have been tested twice using samples taken for rubella testing and guthrie cards respectively  anonymous screening would have been unable to determine risk category as a history of intravenous drug use was known in 47  79   women before testing but this was increased by a further 5  8   who admitted to it after the test result was known  conclusion  interpreting the results of antenatal screening programmes will be complex and will underestimate overall prevalence of hiv antibody among women  this will be exaggerated by strategies based on anonymous testing with guthrie cards or on samples taken for rubella testing  which do not include women who have had an earlier loss of pregnancy  only open testing with consent will permit satisfactory attribution to  
class2	gastrointestinal function and structure in hiv positive patients  we examined 19 patients  17 men  with human immunodeficiency virus  hiv  infection and gastrointestinal symptoms to determine whether those symptoms were due to either a gastrointestinal tract infection or a defect in mucosal absorption because of an enteropathy  the erythrocyte folate and serum vitamin b12 levels were within normal limits in all of the patients  the serum ferritin level was elevated in 12  the xylose absorption test results were abnormal in 8 of the 13 patients able to complete the study  none of the duodenal aspirates yielded a pathogen  light microscopy revealed nonspecific lymphocytic inflammation without infection in the stomach  in seven patients   the esophagus  in five   the duodenum  in two  and the rectum  in two   however  biopsy specimens were positive for candida albicans in the esophagus  four patients   cytomegalovirus in the esophagus  one  and the rectum  two   helicobacter pylori in the antrum  two   treponema infection in the rectum  two  and mycobacterium avium intracellulare in the small intestine  one   only three patients had a normal series of biopsy specimens  all of the patients had similar ultrastructural changes at the epithelial stromal junction of the antral glands and in the intestinal crypts  we conclude that abnormal biochemical and endoscopic findings are common in hiv positive patients with gastrointestinal symptoms  defects in carbohydrate absorption and ultrastructural changes may be responsible for some aspects of hiv enteropathy  
class2	resistance to infection by hiv 1 of peripheral blood mononuclear cells from hiv 1 infected patients is probably mediated by neutralizing antibodies  we have investigated whether pbmc of hiv 1 seropositive subjects are as susceptible to in vitro infection by hiv 1 as are pbmc from seronegative controls  accordingly  stimulated pbmc from 19 hiv 1 infected subjects were inoculated with four different variants of hiv 1  none of these cultures produced either detectable quantities of viral reverse transcriptase activity or p24 ag following inoculation with hiv 1  in contrast  in five of six cases in which these pbmc were depleted of b cells by antibody plus complement prior to viral inoculation  the presence of viral reverse transcriptase and p24 ag was detected  the presence of normal levels of cd4 ag at the surface of the cd4  cells in these populations was established by flow cytometry  analysis by an immunoblot assay revealed that anti hiv antibodies were present in the sera obtained from these infected donors  in addition  7 of 10 culture fluids derived from the nondepleted pbmc were shown to contain virus neutralizing antibodies  cultures which were depleted of b cells did not contain detectable levels of antiviral antibodies  confirmation that the virus produced by the pbmc which had been depleted of b cells was of the strain used to infect the cultures  rather than that which initially caused patient infection  was provided on the basis of differential susceptibility to antibody neutralization  these results suggest that antibodies produced by b cells in cultures of pbmc from seropositive donors may restrict infection by hiv 1 of such cultures under laboratory conditions  
class2	endemic kaposi s sarcoma in human immunodeficiency virus type 1 seronegative persons  demonstration of retrovirus like particles in cutaneous lesions  in 1984  greek physicians reported on the clustering of cases of kaposi s sarcoma  ks  on the peloponnesus peninsula  to gain more insight into its pathogenesis  we studied the seroepidemiologic and clinicopathologic characteristics of 12 greek ks patients  eight male four female  five of whom were residents of an endemic area on the peloponnesus  these patients were in good general health with ages ranging from 48 to 80 years  had no clinical signs of immunodeficiency  and combined the features of both classic and epidemic ks in that they displayed not only involvement of acral areas but also widespread mucocutaneous lesions  routine laboratory data were within normal limits  no patient had htlv 1 and hiv 1 2 antibodies  but all patients had antibodies to several herpesviruses  the histopathology was characteristic of ks with the peculiar feature of a dense infiltrate composed predominantly of cd4  t lymphocytes  immunoenzymatic morphologic studies of the ks cells were consistent with their origin from lymphatic endothelium  outstanding ultrastructural findings were tubuloreticular structures and cylindrical confronting cisternae  structures that are indicative of an ongoing viral infection  indeed  extensive electronmicroscopic studies resulted in the detection of retrovirus like particles in close association to ks cells in five of 12 patients  this in situ observation opens the possibility that this retro virus contributes to ks development  
class2	assessment of platelet antibody by flow cytometric and elisa techniques  a comparison study  two different methods for evaluating platelet antibody were used to study 12 normal subjects and 24 patients consisting primarily of intravenous drug users  ivdus  who were positive for human immunodeficiency virus  hiv   total platelet associated immunoglobulin g  igg  and immunoglobulin m  igm  were measured by enzyme lined immunosorbent assay on platelet lysate  and platelet surface associated igg and igm were measured by semiquantitative flow cytometry  igg and igm values showed significant correlations between the two measurement methods  mean platelet surface igg and total igg were 3 6 and 4 3 times greater  respectively  in ivdus than in controls  and platelet igm was also significantly higher in ivdus than in controls as measured by both techniques  although mean platelet immunoglobulin levels were higher in the ivdus with thrombocytopenia than in ivdus with normal platelet counts  these differences did not achieve significance  these data show that platelet igg and igm levels are increased in ivdu associated hiv infection and suggest that these increases are not confined to patients manifesting thrombocytopenia  the herein described platelet surface antibody and total platelet antibody measurements appear to be equally useful in studying this patient population  specific details for generating platelet associated immunofluorescence units are discussed  
class2	use of ct and mr imaging to distinguish intracranial lesions and to define the need for biopsy in aids patients to explore the potential usefulness of imaging studies in the diagnosis of focal central nervous system  cns  lesions associated with acquired immunodeficiency syndrome  aids   the authors retrospectively examined the radiographic studies of 149 aids patients who presented with signs and symptoms of the three most common focal cns lesions  of these patients  74  50   had toxoplasma abscesses  45  30   had primary cns lymphoma  and 30 patients  20   had progressive multifocal leukoencephalopathy  pml   magnetic resonance  mr  imaging was more sensitive than computerized tomography  ct  in detecting lesions  especially in cases of pml  whereas ct was unable to distinguish mass lesions caused by toxoplasmosis from those caused by lymphoma  71  of the solitary lesions seen on mr images were lymphomas  these results indicate that empirical treatment for toxoplasmosis  the most common initial treatment for aids patients with neurological symptoms stemming from mass lesions  is not likely to be successful for patients with solitary lesions on mr images  rather  early biopsy is advisable  if the presence of lymphoma is confirmed  the rapid initiation of treatment can allow prolonged high quality survival  
class2	disturbances in the cerebral perfusion of human immune deficiency virus 1 seropositive asymptomatic subjects  a quantitative tomography study of 18 cases  quantitative measurements of cerebral blood flow  cbf  by xenon 133  133xe  tomography  together with magnetic resonance imaging  mri   electroencephalography  eeg   psychometric tests  and laboratory analyses were performed on 18 human immunodeficiency virus 1  hiv 1  seropositive asymptomatic subjects  abnormalities of cerebral perfusion were observed in 16 cases  88    these abnormalities were particularly frequent in the frontal regions  77  of cases   mri demonstrated leucoencephalopathy in only two cases  eeg showed only induced diffuse abnormalities in two cases  psychometric tests showed restricted moderate disturbances in 55  of patients  these disturbances mostly concerned those sectors involved in cognitive functions and memorization  these results indicate that quantitative measurements of cbf by 133xe spect is capable of detecting abnormalities of cerebral perfusion at a very early stage  phase ii  of hiv 1 infection  these abnormalities are indications of disturbances resulting from unidentified metabolic or vascular lesions  this technique appears to be superior to mri at this stage of the disease s development  it could provide objective information leading to earlier treatment  and prove useful in evaluating potential antiviral chemotherapy  
class2	nebulized albuterol in acute bronchiolitis  in a double blind  placebo controlled trial  40 infants between 6 weeks and 24 months of age who had a first episode of wheezing and other signs and symptoms of bronchiolitis were randomly assigned to receive either nebulized albuterol  0 15 mg kg dose  or placebo  saline solution  for two administrations 1 hour apart  the albuterol therapy resulted in a significantly greater improvement in the accessory muscle score  decreases 0 70 vs decreases 0 30  p   0 03   oxygen saturation  increases 0 71  vs decreases 0 47   p   0 01  after one dose  and in the accessory muscle score  decreases 0 86 vs decreases 0 37  p   0 02   respiratory rate  decreases 19 6  vs decreases 8 0   p   0 016   and oxygen saturation  increases 0 76  vs decreases 0 79   p   0 015  after two doses of the drug  the response to therapy was similar in infants younger and those older than 6 months of age  the heart rate rose slightly more in the albuterol group  increases 7 76 from baseline  versus the placebo group  decreases 6 79   there were no other side effects of the treatment  of the 34 children from whom nasal specimens were obtained by swab for viral identification  24 had positive test results  21 for respiratory syncytial virus  1 for parainfluenza  1 for paramyxovirus  and 1 for influenza a   we conclude that nebulized albuterol constitutes a safe and effective treatment of infants with bronchiolitis  
class2	immunologic and pathologic manifestations of the infection of rhesus monkeys with simian immunodeficiency virus of macaques  the striking similarities between simian immunodeficiency virus  siv  induced disease in macaque monkeys and hiv induced disease in humans make the siv induced macaque monkey an extraordinarily important model for the study of aids  the most significant difference between these lentivirus induced syndromes is the more rapid progression of disease in siv infected monkeys  the immunologic and pathologic manifestations of siv infections in rhesus monkeys are described  
class2	a report of eight hiv seropositive patients with major depression responding to fluoxetine  this pilot study examined the effectiveness of fluoxetine in depressed human immunodeficiency virus  hiv  seropositive asymptomatic patients  eight patients  participating in an azt trial who met criteria for major depression syndrome  dsm iii r   were treated with fluoxetine  20 or 40 mg day  for 4 weeks  initially  mean hamilton depression scores were 23 8  range of 17 31   and improved to 6 4  range of 3 10   all subjects maintained their remission over a 2 month follow up  fluoxetine treatment may be effective in treating major depression in hiv seropositive asymptomatic patients  
class2	relationship between aids latency period and aids survival time in homosexual and bisexual men  we identified 277 homosexual and bisexual men diagnosed with acquired immune deficiency syndrome  aids  whose estimated human immunodeficiency virus  hiv  seroconversion dates  ranging from 1977 85  could be well approximated  these men were from a cohort of 6 705 homosexual and bisexual men originally recruited for studies of sexually transmitted hepatitis b in san francisco in 1978 80  we compared the time from hiv seroconversion to the initial disease diagnostic of aids  aids latency period  with the time from first aids diagnosis to death  aids survival time  and found no significant overall correlation between latency period and survival time  both kaplan meier and cox proportional hazard stepwise analyses found the initial aids diagnosis to be significantly associated with latency period  with individuals first diagnosed with kaposi s sarcoma  ks  having a shorter latency but longer survival than those first diagnosed with pneumocystis carinii pneumonia  pcp  or other aids diagnoses  individuals with ks tended to be diagnosed earlier in the epidemic compared to those with pcp and other non ks diagnoses  the aids survival time was significantly associated with the initial aids diagnosis but not with the estimated year of seroconversion  the year of first aids diagnosis  age at seroconversion  or racial ethnic group  the information presented here on the relationship between the aids latency period and survival times suggests a model for the pathogenesis of hiv infection in which there is continual deterioration of the immune system  the wider use of antiviral and prophylactic therapies both preceding and following a diagnosis of aids may change this model as both latency and survival times are improved  
class2	the risk of development of htlv i associated myelopathy tropical spastic paraparesis among persons infected with htlv i  using data obtained in national surveys of human t lymphotropic virus type i  htlv i  associated myelopathy tropical spastic paraparesis  ham tsp  conducted in japan in 1987 and 1988  we estimated the yearly and lifetime risk that ham tsp will develop in an htlv i infected person   definite  ham tsp was defined as slowly progressive myelopathy with antibodies to htlv i in both serum and cerebrospinal fluid  estimates of htlv i infection rates in eight endemic prefectures  by age group and sex  were obtained from serologic studies of blood donors  population figures  by age group  sex  and prefecture  were obtained from the census  of 589 definite cases of ham tsp reported nationally  397 occurred in residents of the eight endemic prefectures  of these  170 reported onset of illness during the years 1982 1988  average incidence  24 3 cases year   using the estimated htlv i infection rates and the 1985 census figures  we estimated the number of htlv i infected persons in the eight prefectures in 1985 at 794 800  we therefore estimated the incidence of ham tsp among htlv i infected persons at 3 1 x 10  5  cases year  assuming a lifetime of 75 years  the lifetime incidence is approximately one quarter of 1   this estimate is important in counseling persons such as blood donors found to be infected with htlv i  
class2	a study of htlv i and its associated risk factors in trinidad and tobago  seroprevalence of human t lymphotropic virus type 1  htlv i  among a sample of persons selected from a government register of businesses in trinidad was 3 2  in 1 025 persons of african descent compared to 0 2  among 487 persons of asian descent and 0  among 46 persons of european descent  in tobago  from a coastal village  among persons of african ancestry ascertained as part of a cardiovascular survey  the rate was 11 4   which was significantly higher when corrected for age and race than the rate in trinidad  the seroprevalence rate of antibodies to hepatitis a and b was also significantly elevated in tobago compared to trinidad  htlv i seroprevalence rates were higher in females than males while hepatitis a and b rates were not significantly different in the two sexes  for males  age was a significant determinant of htlv i seropositivity  while for females  age  markers of poor sanitation  and hepatitis b were each independently linked to htlv i seropositivity  the frequent occurrence of multiple infectious exposures in persons of lower socioeconomic circumstances in this tropical environment may result in immune activation that heightens susceptibility to htlv i infection  
class2	acute central nervous system symptoms caused by ibuprofen in connective tissue disease  we describe 2 cases of acute encephalopathy in patients with connective tissue disease caused by small doses of ibuprofen  in addition to aseptic meningitis  both patients had altered mental status and focal neurologic signs  ophthalmoplegia in one and hemiparesis in the other  the spectrum of neurologic manifestations of ibuprofen hypersensitivity is reviewed  
class2	transmission of hiv 1 infections from mothers to infants in haiti  impact on childhood mortality and malnutrition  the cds jhu aids project team  of 4588 pregnant women in a high risk haitian population  443  9 7   were serologically positive for the human immunodeficiency virus type 1  hiv 1   infants born to women who were hiv 1 seropositive were more likely to be premature  of low birth weight  and malnourished at 3 and 6 months of age than were infants born to women who were hiv 1 seronegative  increased mortality was observed in infants born to women who were hiv 1 seropositive by 3 months of age  at 12 months of age  23 4  of the infants born to women who were hiv 1 seropositive had died compared with 10 8  of the infants born to women who were hiv 1 seronegative  at 24 months of age  the mortality rates were 31 3  and 14 2   respectively  maternal hiv 1 infections resulted in an 11 7  increase in the overall infant mortality rate in this population  the estimated mother to infant hiv 1 transmission rate in these breast fed infants was 25   similar to the rates reported for non breast fed populations in the united states and europe  
class2	acute sensorineural deafness in lassa fever a prospective audiometric evaluation of 69 hospitalized febrile patients in sierra leone  west africa  revealed a sensorineural hearing deficit  snhd  in 14  29   of 49 confirmed cases of lassa fever and in 0 of 20 febrile controls  an snhd was present in nine  17 6   of 51 people who had evidence of previous lassa virus infection  twenty six of 32 local residents who had previously sustained a sudden deafness had antibody titers to lassa virus of 16 or greater  compared with six of 32 matched controls  lassa fever is associated with an incidence of snhd  which considerably exceeds that previously reported with any other postnatally acquired infection  and accounts for a prevalence of virus related hearing impairment in the eastern province of sierra leone that is greater than that reported from anywhere else in the world  
class2	antibody persistence in gambian children after high dose edmonston zagreb measles vaccine  measles antibody concentrations in gambian children immunised at 4 months of age with a high dose edmonston zagreb  ez  measles vaccine or at 9 months with conventional schwarz vaccine were measured 5 months after vaccination  and at 18 and 36 months of age  schwarz vaccinees produced  on average  a 2 4 fold higher concentration of measles haemagglutinin inhibiting  hai  antibody than ez vaccinees  but at 36 months of age 82 of 93  88   ez vaccinees and 83 of 87  95   schwarz vaccinees had measles plaque neutralising antibody concentrations above the assumed protective level of 200 miu ml  p greater than 0 1   hai antibody concentrations 5 months after vaccination were inversely related to the presence of maternal antibody at vaccination  but above protective levels  at 18 and 36 months of age there was no relation to antibody concentration at vaccination  and decay of hai antibody between 18 and 36 months of age was similar for ez and schwarz vaccinees  
class2	congenital syphilis presenting in infants after the newborn period background and methods  there has been a recent  dramatic increase in the incidence of congenital syphilis  particularly in urban areas  we describe seven infants seen during one year who were first given a diagnosis of congenital syphilis at 3 to 14 weeks of age  when symptoms developed  we reviewed these infants  charts in order to ascertain the reasons for the failure to diagnose syphilis at birth and to identify the signs and symptoms of congenital syphilis in this group of infants  results  at delivery  four of the infants and their mothers had negative qualitative rapid plasma reagin tests for syphilis  the other three mothers had been seronegative during the pregnancy and were therefore not tested at delivery  two of their infants were seronegative at birth  and one was not tested  when the infants became symptomatic between 3 and 14 weeks of age and were admitted to the hospital  all seven infants and the five mothers available for testing were found to be seropositive for syphilis  four infants presented with a characteristic diffuse rash  the other three presented with fever and were found on admission to have aseptic meningitis  all these infants had multisystem disease  as evidenced by hepatomegaly  increased aminotransferase and alkaline phosphatase levels  anemia  and monocytosis  in all the infants syphilis responded to parenteral penicillin  conclusions  congenital syphilis may be missed if serologic tests are not performed for both the mother and her infant at the time of delivery  even when these tests are performed  some infants are not identified as having syphilis  probably because the infection is very recent and there has been insufficient time for an antibody response to develop  some infants with congenital syphilis of later onset do not present with a typical rash  therefore  at least in areas where the disease is prevalent  serologic tests for syphilis should be included in the evaluation of all febrile infants  even those with negative results on serologic testing at birth  
class2	colposcopic survey of papanicolaou test negative cases with hyperkeratosis or parakeratosis  a colposcopic survey was performed in 269 consecutive women with negative cytology showing hyperkeratosis or parakeratosis  a colposcopy guided biopsy specimen of cervical abnormalities was taken in 88 cases  and human papillomavirus infection  hpv  was detected histologically in 25 cases  no cervical intraepithelial neoplasia  cin  was detected  the detection rate of hpv was not significantly different from that observed in a consecutive series of 1073 papanicolaou test negative subjects self referred for colposcopy  colposcopic screening of subjects showing hyperkeratosis or parakeratosis with otherwise negative smears is not recommended because it does not allow detection of cytologically false negative cin  
class2	oral and pharyngeal herpes simplex virus infection after allogeneic bone marrow transplantation  analysis of factors associated with infection  this study analyzed factors associated with acute oropharyngeal herpes simplex virus  hsv  infection in 627 patients who had undergone allogeneic bone marrow transplantation for leukemia  lymphoma  or aplastic anemia  hsv infection developed in 233  37   of the patients  all but two were seropositive for hsv before transplant  sixty two percent of the seropositive patients had at least one episode of hsv reactivation during the first 100 days after transplant  other factors that placed patients at increased risk for hsv infection were a pretransplant diagnosis of leukemia  being in remission at the time of transplant  and or having been conditioned for transplant with chemoradiotherapy  recognition of factors that may predispose patients to hsv infection helps determine those transplant recipients who might benefit most from antiviral prophylaxis or other approaches to prevention of hsv reactivation  
class2	infectious diarrhea  managing a misery that is still worldwide  infectious diarrhea is the largest single cause of morbidity and mortality in the world  bacteria  viruses  and protozoan parasites are the most common causative agents  treatment in most cases of bacterial and viral diseases consists of correcting fluid loss and electrolyte imbalance by oral or parenteral rehydration  antimicrobial therapy is reserved for very ill patients only  with the exception of cryptosporidium  for which no effective agent is yet available  all protozoan infections are treatable with metronidazole  
class2	productive human immunodeficiency virus infection levels correlate with aids related manifestations in the patient  mononuclear cells were obtained from 71 human immunodeficiency virus type 1  hiv 1  seropositive subjects presenting and first visit either as asymptomatic or with minor symptoms and with cd4 lymphocytes greater than 550 per mm3  group a  35 patients  or as patients with aids  aids related illnesses  or cd4 lymphocytes less than 400 per mm3  group b  36 patients   after 1 5 years of follow up  13 patients of group a had essentially retained their initial status  asymptomatics   the 22 others had suffered clinical or immunological deterioration  progressors   frozen cells were thawed and submitted to lethal gamma irradiation in vitro  4500 rads  1 rad   0 01 gy  before they were cultured with normal phytohemagglutinin stimulated lymphocytes to determine radiation resistant hiv expression ex vivo  r hev   hiv antigenemia correlated with r hev values in 142 samples  r   0 92  p less than 0 001  but was a less sensitive predictor of disease than r hev  r hev was detected in all specimens from patients with major aids related illnesses or hiv associated cd4 lymphopenia  in 77  of the progressors from group a  r hev detection preceded the onset of aids associated disease or cd4 lymphopenia by 1 year  average   conversely  r hev was low or was not detected in 36 sequential specimens from the 13 patients who remained asymptomatic over the following 2 5 years  thus  persistently low hiv expression in vivo predicted a nondiseased state  whereas higher hiv expression levels seemed necessary for disease to occur  these data indicate that r hev is related to productive hiv infection in vivo  the latter acting as a determinant of aids related illnesses  in view of this  measurement of hiv expression levels in the patient should be useful in antiviral efficacy trials  
class2	polymerase chain reaction evidence for human immunodeficiency virus 1 neutralization by passive immunization in patients with aids and aids related complex  we tried to assess the long term safety and potential efficacy of passive immunization in aids related complex  arc  and aids patients  we also wanted to establish whether hyperimmune plasma from healthy human immunodeficiency virus 1  hiv 1  infected individuals clears the cell free virus from circulation  using the polymerase chain reaction  pcr   we were able to provide conclusive evidence that hyperimmune plasma is effective and maintains long term neutralization of viremia  using the cell test  we found that in most patients the total antibody level was maintained  in one of the arc patients  it actually increased 8 fold and has remained at that level for nearly 2 years  the cd4  cell count decreased in the aids patients but was stable in the arc patient  clinically  there was an initial improvement in all patients  but five of six of the advanced terminal aids patients had died by month 17  our studies suggest that passive immunization may be safe in arc and aids patients  it reduces hiv 1 viremia to levels undetectable even by pcr  to advanced terminal patients  the benefit is of limited duration  while to arc patients it may be long term  therefore  passive immunization should start early in the disease  
class2	evidence for susceptibility of intrathymic t cell precursors and their progeny carrying t cell antigen receptor phenotypes tcr alpha beta   and tcr gamma delta   to human immunodeficiency virus infection  a mechanism for cd4   t4  lymphocyte depletion  individuals infected by the human immunodeficiency virus type 1  hiv 1  demonstrate progressive depletion and qualitative dysfunction of the helper t4  cd4   cell population  mechanisms proposed for attrition of cd4  t cells include direct cytopathicity of these mature cells following infection as well as infection of early t lymphocyte progenitors  the latter mechanism could lead to failure to regenerate mature functioning cd4  t cells  the present study determines the susceptibility of thymocytes at various stages of maturity to infection with hiv 1  various normal thymocyte populations were inoculated with hiv 1  including unfractionated  uf   cd3  cd4  cd8    triple negative   tn    cd4  cd8    double positive   dp   thymocytes  and thymocyte populations obtained by limited dilution cloning  cultures were studied for the presence of hiv 1 dna by polymerase chain reaction in addition to examination for reverse transcriptase activity  we determined that transformed t cell and thymocyte cell lines completely lacking cd4 were not susceptible to infection by hiv 1  whereas all of the following lines were  uf thymocytes  70 90  cd4hi    dp thymocytes  99  cd4hi    tn thymocytes  0  cd4hi    and tcr alpha beta    tcr gamma delta    or cd16  cd3   natural killer  thymocyte clones expressing variable levels of cd4 and representing the progeny of tn thymocytes   tcr alpha beta   and tcr gamma delta   refer to the chains of the t cell antigen receptor  tcr   and cd4hi refers to a strong rightward shift  greater than 30 linear channels  of the cd4 curve on flow cytometric analysis compared with control   monoclonal antibodies  mabs  to cd4  t4a epitope  but not to cd3  t3  were capable of blocking infection of mature and immature cd4hi  thymocytes  moreover  anti cd4 t4a  mabs also inhibited infection of cd4hi  tn thymocytes  indicating that these t cell precursors  despite their apparent  triple negativity   cd3  cd4hi  cd8    expressed sufficient cd4 molecules to become infected  cell sorter analysis with a panel of cd4 mabs demonstrated a mean shift of the mean fluorescence channel  mfc  with cd4 mabs on tn thymocytes of 6     4 mfc units  thus  intrathymic t cell precursors and their progeny representing many stages of t cell ontogeny are susceptible to infection by hiv 1  including early tn thymocytes  which express very low levels of cd4  infection of multiple stages and multiple subsets of the t cell lineage in man  mediated via the cd4 molecule  may explain the inability of the t cell pool to regenerate in the setting of progressive hiv infection  
class2	oral findings in hiv infected patients attending a department of internal medicine  the contribution of intraoral examination towards the clinical management of hiv disease the occurrence of oral mucosal lesions was studied in 70 consecutive human immunodeficiency virus  hiv  infected patients  including 35 patients with aids  who had been admitted to a department of internal medicine  lesions of the oral mucosa were observed in 52 patients  74 per cent   oral candidiasis  50 per cent   hairy leukoplakia  14 per cent   periodontal disease  13 per cent   and oral kaposi s sarcoma  4 per cent  were the most common lesions  oral mucosal lesions suggestive of hiv infection were present in ten of 12 patients of unknown hiv status in whom pneumocystis carinii pneumonia was suspected  close cooperation between the medical and dental professions is recommended since accurate intraoral examination can make a valuable contribution towards the clinical management of hiv infected patients and may influence the cdc classification of this disease  
class2	subacute sclerosing panencephalitis in black children  a review of 18 cases  despite the fact that measles is severe and presents in very young black children in natal  south africa  no case of subacute sclerosing panencephalitis was reported from this region prior to 1982  a retrospective study was therefore made over the six year period 1982 1987 of 18 patients who presented to the king edward viii teaching hospital  durban  with clinical and laboratory features of subacute sclerosing panencephalitis  the majority of patients  66 per cent  were between 8 and 12 years of age  the mean age of onset was 9 3 years  the youngest patient being four years nine months and the oldest 14 years  the male to female ratio was 1 25 1  a previous history of primary measles infection was obtained in 44 4 per cent of cases  62 5 per cent occurred before the second birthday  the commonest mode of presentation was personality  intellectual and behaviour disorders  83 per cent  followed by myoclonic seizures  61 per cent  and choreiform movements  28 per cent   measles antibody was present in the csf in all cases  the eeg was abnormal in all recorded cases with pathognomonic periodic complexes being found in 56 2 per cent  confirmation of the diagnosis was provided by brain biopsy in two cases and by necropsy in one case  the findings of this study suggest that subacute sclerosing panencephalitis may not be as uncommon in black children as has hitherto been thought  
class2	preliminary report  protection of cynomolgus macaques against simian immunodeficiency virus by fixed infected cell vaccine cynomolgus macaques were vaccinated with inactivated simian immunodeficiency virus infected cells and  quil a  as adjuvant at 0  4  8  and 36 weeks or at 0  4  8  and 16 weeks  2 weeks later these animals  together with a similar unvaccinated group  were challenged with 10 mid50  50  monkey infectious doses  of a pool of sivmac251 previously titrated in vivo  virus was repeatedly isolated from unvaccinated animals on at least five separate occasions and proviral dna was detected in circulating lymphocytes by polymerase chain reaction amplification  by contrast  virus and proviral dna were not found in any of the vaccinated animals  however  the same vaccination regimen used after live virus challenge did not eliminate virus from previously infected macaques  
class2	asymptomatic and neurologically symptomatic hiv seropositive individuals  prospective evaluation with cranial mr imaging  as part of a prospective multidisciplinary study of individuals seropositive for the human immunodeficiency virus  hiv   cranial magnetic resonance  mr  imaging was performed on 119 hiv seropositive subjects  95 asymptomatic  24 symptomatic  and the results were correlated with clinical data  mr images regarded as positive included those showing atrophy and or white matter lesions  on the basis of these criteria  96 subjects had normal mr images and 23 had abnormal images  results of chi 2 analysis revealed a statistically significant difference between the asymptomatic group  12 of 95  13   with abnormal scans  and the symptomatic group  11 of 24  46   with abnormal scans   p    001   in the asymptomatic group  positive mr images showed fewer  smaller  and or less extensive abnormalities  the researchers conclude that  a  mr imaging can show indirect evidence of hiv infection early in the disease  but abnormalities will be minor and seen only in a small minority of neurologically asymptomatic subjects   b  the appearance of clinically recognizable neurologic disease correlates with the mr imaging findings of increasingly severe brain atrophy and white matter lesions  and  c  in some hiv seropositive subjects  despite neurologic disease  mr images can remain normal  results indicate that routine screening with cranial mr imaging of neurologically asymptomatic hiv seropositive individuals would likely result in a low yield of positive findings  
class2	the safety and immunogenicity of a human immunodeficiency virus type 1  hiv 1  recombinant gp160 candidate vaccine in humans  niaid aids vaccine clinical trials network  objective  to evaluate the safety and immunogenicity of a human immunodeficiency virus type 1  hiv 1  recombinant envelope glycoprotein  rgp 160  candidate vaccine in humans  subjects  healthy adults  72  who were seronegative for hiv 1 were randomly assigned to one of four groups  interventions  the subjects were randomly assigned to receive 40 or 80 micrograms of rgp 160  10 micrograms of hepatitis b vaccine  or placebo in three doses  on days 0  30  and 180   with an elective  nonblinded administration of a fourth dose on day 540  measurements and main results  neither clinical nor laboratory toxicity was encountered during a follow up period exceeding 21 months  no effect of immunization was noted on lymphocyte counts  mitogenic responses  or delayed type hypersensitivity  serum antibody responses to hiv envelope proteins detected by western blot were seen in 30 of 33 subjects  91   95  ci  71  to 97   receiving either 40  or 80 micrograms doses of rgp160 and were most commonly of weakly reactive intensity  responses were first noted by western blot after the second dose  they markedly increased in frequency after the third dose and declined over the next 12 to 18 months  the administration of a fourth dose resulted in homologous neutralizing activity in sera from 5 to 24 subjects  21   ci  7  to 37   as well as in complement mediated antibody dependent enhancement in sera from 6 of 24 subjects  25   ci  10  to 42    antibody responses were detected by enzyme linked immunosorbent assay  elisa  less frequently than by western blot  and these responses persisted for a shorter time  conclusions  the administration of rgp160 was well tolerated and safe  resulted in a high rate of antibody response by western blot after the administration of the third and fourth doses  and generated serum neutralizing activity and complement mediated antibody dependent enhancement in some subjects after the fourth dose  
class2	abnormal function of cd4  helper inducer t lymphocytes in a patient with widespread human papillomavirus type 3 related infection  human papillomavirus induced infections may be associated with cellular immunodeficiency  however  very little is known about the dysfunctional interactions among t lymphocytes  b lymphocytes  and antigen presenting cells  a 30 year old heterosexual man with a 10 year history of persistent multiple refractory flat wart lesions containing human papillomavirus type 3 related dna sequence was studied  the patient had a severe depletion of cd4  t lymphocytes and a compensatory increase in the number of cd8  t lymphocytes  impaired t lymphocyte response to various stimuli was found  depletion of the increased number of cd8  t lymphocytes  which suppressed immunoglobulin production in vitro  did not restore the impaired t lymphocyte response  immobilized anti cd3 beads that stimulate the t lymphocyte antigen complex in the absence of antigen presenting cells indicated a t lymphocyte defect  rather than a decreased antigen presenting cell function  thus  the pronounced cellular immunodeficiency was due to abnormal function of the cd4  helper inducer t lymphocytes  
class2	induction of interleukin 6 during human immunodeficiency virus infection  interleukin 6  il 6   a multifunctional cytokine produced in monocytes  fibroblasts  and other cell types  is induced by a variety of stimuli  including bacteria  viruses  and other cytokines  when normal monocyte cultures were exposed to a monocytotropic strain of human immunodeficiency virus  hiv   htlv iiiba l  significant levels of il 6 bioactivity were detected in the culture supernatants after 12 to 43 days of incubation  at a time when there was associated evidence of hiv production  similarly  when normal monocyte cultures were cocultured with peripheral blood mononuclear cells from hiv infected individuals  hiv replication in these cultures was associated with production of il 6  in further studies  we determined that mean serum levels of il 6 bioactivity were abnormally elevated in hiv seropositive individuals with stage 1 2 infection  25 2 x divided by 1 8 u ml  and stage 3 4 infection  46 1 x divided by 1 7 u ml  when compared with normals  1 6 x divided by 1 2 u ml   in contrast mean serum il 6 levels were not different from normal in stage 5 6 infection  2 7 x divided by 1 6 u ml   a selected group of 12 hiv seropositive individuals  stages 1  2  and 3  who harbored hiv capable of replicating in t cells but not in monocyte cultures had a mean serum il 6 level of 5 3 u ml  x divided by 1 5   a value significantly lower  p less than  004  than that measured in control hiv seropositive individuals infected with monocytropic hiv  39 x divided by 1 9 u ml   in addition  serum il 6 levels in hiv seropositive individuals  stages 1 through 6  correlated directly with serum immunoglobulin g  igg  levels  r    74  p less than  001   monocytes but not t cells are capable of a high level il 6 production in vitro  and monocyte derived il 6 stimulates ig production in activated b cells  thus  hiv seropositive individuals who often are infected with monocytotropic hiv and often display abnormally elevated serum igg levels may exhibit these abnormalities as a consequence of abnormally elevated il 6 levels induced by hiv  
class2	antibody dependent cellular cytotoxicity against hiv coated target cells by peripheral blood monocytes from hiv seropositive asymptomatic patients  cytotoxic effector cells like cytotoxic t cells  nk cells  monocytes macrophages  and neutrophils can lyse directly hiv infected or hiv coated cells in the absence or presence of anti hiv antibodies  therefore  these cytotoxic mechanisms can be invoked either in the control of hiv infection at early stages of the disease or in the generalized immunosuppression observed at later stages of the disease  the relationship between anti hiv effector mechanisms and disease  however  remains elusive  the present study investigates in hiv  seropositive asymptomatic patients peripheral blood monocytes  pbm  mediated antibody dependent cellular cytotoxicity  adcc  against hiv coated target cells in the presence of heterologous or autologous anti hiv serum  to test for specific adcc against hiv ag  a t4  cem tr line resistant to tnf and macrophage mediated cytotoxicity was selected in vitro  adcc was performed in an 18 h 51cr release assay using cem tr cells coated with inactivated hiv  unlike pbm from normal controls  significant adcc was observed by pbm from hiv  seropositive patients in the presence of pooled hiv  antiserum  the adcc activity was specific for hiv and was dependent on the e t ratio and the antiserum dilution used  upon activation of pbm with rifn gamma  both normal and hiv  pbm mediated adcc against hiv coated cem tr  furthermore  adcc activity by pbm from hiv  seropositive patients in the presence of their autologous serum was examined  significant adcc activity was observed and was dependent on the e t ratio and serum dilution used  the findings demonstrating anti hiv adcc activity by pbm from hiv  seropositive individuals and their autologous sera support the notion that monocyte mediated adcc may be operative in vivo  
class2	interferon as an agent against herpes simplex virus  the effectiveness and limitations of interferon as an antiviral agent in man is exemplified by its actions against herpes simplex types 1 and 2  given in adequate doses parenterally before or shortly after infection  interferon can ameliorate or reduce clinical manifestations or reduce the virus yield  it usually cannot completely prevent disease and may be particularly problematical if used late after infection in an acute disease  it is ineffective against the state of latent infection in ganglia  interferon may have more potential in slower virus diseases and diseases in which other pathogenetic mechanisms affected by interferon s pleiotropic actions are operative  
class2	long term combined rifn alpha 2a and zidovudine therapy for hiv associated kaposi s sarcoma  clinical consequences and side effects  interferon alpha  ifn alpha  has been shown to be effective in treating hiv associated ks in at least 30  of patients  and zidovudine has proved beneficial for aids patients  moreover  both drugs have demonstrated an inhibitory effect on hiv replication  based on the above  we combined ifn alpha and zidovudine for treatment of hiv associated ks in order to evaluate tolerance and clinical efficacy  twenty one homosexual men with histologically proved hiv associated ks were treated in an open trial with rifn alpha 2a 18 x 10 6  iu every second day and zidovudine 800 1200 mg d  treatment was discontinued within the first month in six patients  three of them developed subjective intolerance  and three others contracted severe opportunistic infections or hiv cachexia  fifteen evaluable patients received combination treatment over a period of 2 20 months  average 10 months   the dosage was reduced as required based on drug induced cytotoxicity  complete remission was observed in four patients  partial remission in three  stable disease in two  and progression in six  resulting in an overall response rate of 46   negative p24 expression prior to treatment was a positive predictor  although extracutaneous involvement had a negative influence on tumor remission  even patients with a mean initial t helper cell count below 100 mm3 responded positively  in conclusion  combination therapy of rifn alpha 2a with azt may effectively control hiv related kaposi s sarcoma in more than 40  of patients  in contrast to monotherapy with ifn alpha  patients with severely reduced immune systems will also benefit from combined treatment  
class2	biologic effects of interferons  if one were to review articles on ifn published between 1957 and 1967 it would become apparent that virtually none of the tenets held then are still valid today  whereas ifn was long considered to be a specific antiviral substance without any effect on normal cellular metabolism  we accept today that it affects normal cell division and many specialized cellular functions  in this respect it is not unique  ifn is a prototype of a family of similar substances now called cytokines that all appear to function as regulatory molecules  it was held that the production of ifn constituted a specific response to a viral infection  today we believe that ifn is an integral part of a cytokine network and that they and other cytokines may be produced constitutively at low levels  these substances exert multiple effects on virtually all cells  they play an important role in host defense against viral and parasitic infections  and in the resistance to experimental tumors  ifn can be shown to exert effects on the immune system and on lymphocyte circulation  lastly  because of the multiplicity of their biologic effects  they may even contribute to the pathogenesis of certain diseases  thus  when large amounts of ifn are administered or induced in newborn mice they can cause liver  kidney  and pulmonary disease  the field of ifn and cytokine research continues to expand and there is an increasing number of therapeutic applications  twenty years from now  scientists and clinicians may be surprised that we understood so little of how ifn act and how inadequately we used them to treat disease  
class2	mucosal immunity induced by enhance potency inactivated and oral polio vaccines  oral polio vaccine  opv  is recommended for routine immunization in the united states in part because of its ability to induce intestinal and pharyngeal immunity to reinfection  mucosal immunity produced by opv and enhanced potency inactivated polio vaccine  e ipv  was compared by challenging vaccines with type 1 opv  fewer opv  25   than e ipv  63   vaccinees excreted opv virus in stool after challenge  the mean stool virus titer was higher and the duration of shedding longer among e ipv excreters  only one e ipv and three opv vaccinees shed virus in the pharynx after challenge  prechallenge serum neutralizing antibody levels were not statistically different among e ipv vaccinees who did and did not shed virus  these levels were much higher than those of opv vaccinees  poliovirus specific iga levels in stool did not correlate with viral excretion  e ipv was less effective than opv in preventing and limiting intestinal infection  even though it induced higher postvaccination serum antibody levels  
class2	measles among the amish  a comparative study of measles severity in primary and secondary cases in households  an outbreak of measles among a predominantly unvaccinated and susceptible amish population in lebanon county  pennsylvania  offered the opportunity to test the hypothesis that secondary cases in households are more severe than primary cases because the former have more intense exposure and receive a greater virus inoculum  of 130 measles cases reported between april and june 1988  119  92   constituted a study of disease severity  severity was assessed by determining frequency and duration of symptoms  length of any hospitalization  and number of days in bed  in a univariate analysis  fewer secondary cases had conjunctivitis  relative risk  rr   0 67  95  confidence interval  ci   0 48 0 96  and headache  rr  0 37  ci  0 15 0 86   but more had earache  rr  9 69  ci  1 8 202 9  compared with primary cases  secondary cases had a shorter mean duration of coryza  4 0 vs  5 0 days  student s t test  p    08   however  a logistic regression model that matched by family and controlled for age and sex indicated that there were no significant differences in measles severity among primary and secondary cases in households  
class2	use of brain biopsy for diagnostic evaluation of patients with suspected herpes simplex encephalitis  a statistical model and its clinical implications  niaid collaborative antiviral study group  using the decision analysis technique and multivariate regression methods  a statistical model was established to define the utility of brain biopsy for diagnostic evaluation of patients with suspected herpes simplex encephalitis  hse   two strategies were compared  strategy i  brain biopsy with acyclovir  acv  treatment for 10 days in biopsy positive patients  and strategy ii  acv therapy without brain biopsy  strategy i resulted in a greater 6 month survival rate when the likelihood of patients having hse was less than 70   based on the current estimated prevalence of hse  for patients with suspected hse  of 35   strategy i showed a slight advantage of a 3 2  increase in 6 month survival rate  an individual patient s chance of a positive brain biopsy can be predicted using a mathematical equation based on several important clinical assessments  this equation in conjunction with the decision analysis is a useful guide for the clinical management of patients with regard to brain biopsy  
class2	characterization of herpes simplex virus type 2 latency associated transcription in human sacral ganglia and in cell culture  the ability of herpes simplex virus type 2  hsv 2  to establish latency in and reactivate from sacral dorsal root sensory ganglia is the basis for recurrent genital herpes  the expression of hsv 2 genes in latently infected human sacral ganglia was investigated by in situ hybridization  hybridizations with a probe from the long repeat region of hsv 2 revealed strong nuclear signals overlying neurons in sacral ganglia from five of nine individuals  the rna detected overlaps with the transcript for infected cell protein o but in the opposite  or  anti sense   orientation  these observations mimic those made previously with hsv 1 in human trigeminal ganglia and confirm the recent findings during latency in hsv 2 infected mice and guinea pigs  northern hybridization of rna from infected vero cells showed that an hsv 2 latency associated transcript was similar in size to the larger  1 85 kb  latency transcript of hsv 1  thus  hsv 1 and hsv 2 latency in human sensory ganglia are similar  if not identical  in terms of their cellular localization and pattern of transcription  
class2	exacerbation of bacterial toxicity to infant ferrets by influenza virus  possible role in sudden infant death syndrome  published erratum appears in j infect dis 1991 jul 164 1  232  of several toxins examined  only staphylococcal alpha and gamma toxin  endotoxin  and diphtheria toxins were lethal for 5 day old ferrets  their toxicities were enhanced in animals infected at 1 day old with influenza virus  from 3 fold with staphylococcal gamma toxin through 14 fold for staphylococcal alpha toxin  84 fold for endotoxin  and 219 fold for diphtheria toxin  no increased viral replication occurred in any tissue  thus the effects of the toxins were exacerbated by the infection  not vice versa  neonates died suddenly without clinical symptoms as in human babies dying from the sudden infant death syndrome  sids   pathologic examination showed inflammation in the upper respiratory tract  lung edema and collapse  and early bronchopneumonia in the toxin  and influenza virus treated animals but not in those treated with toxin or virus alone  thus  bacterial toxins could play a role in sids  this being more likely with a concomitant influenza virus infection  
class2	serologic discrimination of human t cell lymphotropic virus infection by using a synthetic peptide based enzyme immunoassay  synthetic peptides corresponding with unique regions of the envelope glycoproteins  gp46  of human t cell lymphotropic viruses  htlvs  were used in an enzyme immunoassay to determine if htlv i and  ii infections could be discriminated  two synthetic htlv i sequence derived peptides  env 1  amino acids 191 215  and env 5  amino acids 242 257   reacted with 92  and 100  of the serum specimens  n   52  from htlv i infected persons  respectively  although a small percentage  8 6   of serum specimens from persons infected with htlv ii cross reacted with env 1  none of these specimens reacted with env 5  peptide env 2 encoded by the envelope region of htlv ii  amino acids 187 210  reacted with serum specimens from both htlv i  94    and htlv ii  74   infected patients  whereas env 6  another htlv ii peptide  amino acids 238 254   reacted with less than 6  of the specimens  therefore  the env 5 peptide with amino acid sequence serproasnvalservalproserserserserthrproleuleutyr represents an immunodominant domain of htlv i that is recognized by serum antibodies from all htlv i infected persons  moreover  the env 5 based elisa allows a categorical distinction between the closely related htlv i and  ii infections  
class2	the role of secretory immunity in hepatitis a virus infection  because the role of intestinal immunity remains uncertain in hepatitis a  samples of feces and saliva from infected primates and humans were tested for virus neutralizing activity  only two of eight owl monkeys infected by the intragastric route developed neutralizing antibody detectable in extracts of feces collected up to 88 days after viral challenge  although serum neutralizing antibody was present in all monkeys by day 33  similarly  neutralizing antibody was detected in fecal extracts from none of three experimentally infected human volunteers and only 1 of 15 naturally infected humans  the single positive human specimen contained occult blood  only 2 of 19 saliva samples from naturally infected humans had significant viral neutralizing activity  in contrast  neutralizing antibody to type 2 poliovirus was present in most human fecal or saliva specimens tested  these data suggest that intestinal immunity does not play a significant role in protection against hepatitis a  
class2	molecular pathologic study of human papillomavirus infection in inverted papilloma and squamous cell carcinoma of the nasal cavities and paranasal sinuses  nasal inverted papilloma is a rare benign tumor occasionally associated with squamous cell carcinoma  to determine the etiological role of human papillomavirus in inverted papilloma  and to clarify the relationship between human papillomavirus and malignant transformation of this benign tumor  we retrospectively analyzed inverted papillomas from 26 patients  7 of whom had squamous cell carcinoma  we used an immunohistochemical method and molecular pathologic techniques  or dot blot hybridization of dna extracted from paraffin embedded tissues  in situ hybridization  and polymerase chain reaction  human papillomavirus was detected in 5 of 26 patients  19    3 patients with human papillomavirus 11 and 2 patients with human papillomavirus 16  the latter 2 patients had inverted papillomas associated with squamous cell carcinoma  we speculate that human papillomavirus may be related to the malignant transformation of inverted papillomas  
class2	headache and acquired immunodeficiency syndrome  because the acquired immunodeficiency syndrome  aids  virus is neurotropic  physicians will continue to see a rise in the number of neurologic complications of this syndrome  much of this increase will be accompanied by headache  not only as a primary symptom of hiv infection or opportunistic disease but also as a result of diagnostic tests and therapeutic efforts  complete understanding of the ramifications of headache in aids will be important in the 1990s as we continue to treat a younger population  usually affected by benign vascular and muscle contraction type headache  
class2	bismuth subsalicylate in the treatment of acute diarrhea in children  a clinical study  bismuth subsalicylate  bss  and placebo were evaluated in a double blind  placebo controlled study as adjunct to rehydration therapy in 123 children  aged 4 to 28 months  hospitalized with acute diarrhea  the dosing regimen was 20 mg kg five times daily for 5 days  significant benefits were noted in the bss group compared with placebo as manifested by decreases in stool frequency and stool weights and an improvement in stool consistency  significant improvement in clinical well being  and shortening of the disease duration  patients treated with bss had a significant reduction in duration of hospital stay  6 9 days  compared with placebo treated patients  8 5 days   also  intravenous fluid requirements decreased significantly more rapidly and to a greater degree in the bss treated group  bismuth subsalicylate was associated with clearance of pathogenic escherichia coli from the stools in 100  of cases but was not different from placebo in rotavirus elimination  bismuth subsalicylate was well tolerated with no reported adverse effects  blood bismuth and serum salicylate levels were well below levels considered toxic  in this study  bss provided effective adjunctive therapy for acute diarrhea  allowing children to get well sooner with less demand on the nursing and hospital staff  
class2	risk of respiratory illness associated with day care attendance  a nationwide study  the risk of respiratory and other illnesses in children  age groups  6 weeks through 17 months  18 through 35 months  and 36 through 59 months  in various types of day care facilities was studied  children considered exposed to day care were those who were enrolled in day care with at least one unrelated child for at least 10 hours per week in each of the 4 weeks before the interview  unexposed children were not enrolled in any regular child care with unrelated children and did not have siblings younger than 5 years of age receiving regular care with unrelated children  although an increased risk of respiratory illness was associated with attending day care for children in all three age groups  this risk was statistically significant only for children 6 weeks through 17 months of age  odds ratio   1 6  95  confidence interval   1 1 to 2 4  and children 18 through 35 months of age who had no older siblings  odds ratio   3 4  95  confidence interval   2 0 to 6 0   in contrast  day care attendance was not associated with an increased risk of respiratory illness in children 18 through 35 months of age with older siblings  odds ratio   1 0   for children aged 6 weeks through 17 months  the exposure to older siblings was associated with an increased risk of respiratory illness  however  for children aged 36 through 59 months  older siblings were protective against respiratory illness  in addition  for the children in each age group currently in day care  increased duration of past exposure to day care was associated with a decreased risk of respiratory illness  
class2	pediatric emergency room visits  a risk factor for acquiring measles  in recent years  measles outbreaks have occurred among unimmunized children in inner cities in the united states  from may 1988 through june 1989  1214 measles cases were reported in los angeles  and from october 1988 through june 1989  1730 cases were reported in houston  more than half of cases were in children younger than 5 years of age  most of whom were unvaccinated  of cases of measles in preschool aged children  nearly one fourth in los angeles and more than one third in houston were reported by one inner city emergency room  to evaluate whether emergency room visits were a risk factor for acquiring measles  in los angeles  35 measles patients and 109 control patients with illnesses other than measles  and in houston  49 measles patients and 128 control patients  who visited these emergency rooms  were enrolled in case control studies  control patients were matched to case patients for ethnicity  age  and week of visit  records were reviewed to determine whether case patients had visited the emergency room during the period of potential measles exposure  which was defined as 10 to 18 days before rash onset  and whether control patients had visited 10 to 18 days before their enrollment visit  in los angeles  23  of case patients and 5  of control patients  odds ratio   5 2  95  confidence interval   1 7  15 9  p less than  01   and in houston  41  of case patients and 6  of control patients  odds ratio   8 4  95  confidence interval   3 3  21 2  p less than  01   visited the emergency room during these periods  
class2	malignant lymphomas in cynomolgus monkeys infected with simian immunodeficiency virus  malignant lymphomas were observed in 38   9 of 24  of simian immunodeficiency virus  siv  infected cynomolgus monkeys  macaca fascicularis  5 to 15 months after inoculation with siv strain smm3  lymphomagenesis in the siv infected monkeys was not related directly to the siv infectious dose given  all siv infected animals developed severe immunodeficiency  no significant difference in immunodeficiency was observed between tumor bearing and non tumor bearing animals  in contrast  no lymphomas were observed in a comparable group of hiv 2 infected monkeys  which did not develop immunodeficiency  nor did the noninfected control monkeys  all 9 siv related tumors were high grade b cell lymphoblastic or pleomorphic lymphomas with extranodal  disseminated growth  most tumors showed marked infiltration by monocytes and cd8  t lymphocytes  occasional tumor infiltrating cells showed immunohistochemical reaction for siv  the cells of two tumors were established in vitro and shown to be of b cell phenotype  the tumor cell cultures showed no reverse transcriptase activity and no evidence of virus infection by electron microscopy  our observations indicate that siv induced immunodeficiency in cynomolgus monkeys also mimics hiv infection and aids in humans with regard to increased lymphomagenesis and type of lymphomas  
class2	hiv associated myocarditis  pathology and immunopathology  autopsy studies of aids  acquired immune deficiency syndrome  patients showed a high incidence of myocarditis  to attain a better understanding of the pathogenesis  the pathology and immunopathology of nine endomyocardial biopsies with active myocarditis from 18 human immunodeficiency virus  hiv  positive patients were systematically characterized  these were compared with 17 biopsies with active myocarditis from patients without aids risk factors  in both groups  the myocarditis consisted of either multifocal or interstitial infiltrates of small lymphocytes and isolated myocyte necrosis  the lymphocytes consisted of t cells  cd2   cd3   and cells not identified by the usual markers  b cells  monocytes  cd4  cells  and natural killer  nk  cells were only rarely observed  all of the hiv positive patients but only 7 of 17 non hiv patients had cd8  lymphocytes in the infiltrates  p less than 0 01   the arteriolar endothelium demonstrated induced class i  hla a  b  c  and ii  hla dr  antigens in both groups  in situ hybridization for hiv 1 failed to identify the virus in the specimens  the immunopathology is consistent with a cell mediated injury to the myocytes in hiv positive patients and is similar to a subgroup of myocarditis in the non hiv group  
class2	the relationship between viral rna  myelin specific mrnas  and demyelination in central nervous system disease during theiler s virus infection  the da strain of theiler s murine encephalomyelitis virus  dav  causes a chronic demyelinating disease in susceptible mouse strains  to elucidate the pathogenesis of dav induced demyelination  the authors investigated the spatial and chronologic relationship between virus  antigen and rna   myelin specific mrnas  and demyelination in dav infected mice using immunohistochemistry  in situ hybridization  and slot blot hybridization analyses  in spinal cord white matter  viral rna was detected easily in ventral root entry zones 1 to 2 weeks after infection  viral rna increased to maximum levels by 4 weeks after infection  which was associated with inflammation and mild demyelination  at 8 to 12 weeks after infection  when demyelination became most extensive  viral rna was significantly decreased  demyelination did not chronologically or spatially parallel the presence of viral rna within the spinal cord  decrease of myelin specific mrnas  including myelin basic protein and proteolipid protein mrnas  was observed within the demyelinating lesions with or without detectable viral rna  these results indicate that a viral infection of white matter in the early phase of the infection initiates spinal cord disease leading to demyelination  but later an ongoing immunopathologic process contributes to the presence of extensive demyelination  
class2	glucocorticoid level and neuropsychiatric symptoms in homosexual men with hiv infection  objective  there is a controversial literature suggesting that stress  anxiety  and depression are harmful to the immune system and therefore to health  preclinical studies indicate that activation of the hypothalamic pituitary adrenal  hpa  axis by stress may be responsible for immunocompromise  the goal of this study was to assess this phenomenon in human immunodeficiency virus  hiv  infection  method  homosexual men in the community who did not meet modified centers for disease control criteria for acquired immune deficiency syndrome  aids  were recruited for the study  113 of the men were hiv positive and 77 were hiv negative  very few of the men studied suffered from depression or anxiety disorder at the time of the first assessment  twenty four hour urinary free cortisol levels were obtained from the 112 hiv positive and 75 hiv negative men whose 24 hour urine volumes were 500 ml or more  cortisol levels were correlated with measures of medical  immunological  neurological  and psychiatric status  results  small but significant correlations between 24 hour urinary free cortisol and medical status  level of depression  and level of anxiety were found in the hiv positive group  there was no relationship between cortisol level and the number of cd4  or cd8  t lymphocytes or the cd4 cd8 ratio  conclusions  although hpa activation may be associated with stress in cases of hiv infection  it does not seem to be associated with further loss of cd4  t lymphocytes  subjects with hiv infection with the most evidence of medical complications may also be the most anxious and depressed  
class2	human cytomegalovirus viraemia in hiv 1 seropositive patients at various clinical stages of infection  eighty two hiv 1 seropositive subjects were examined for the presence and quantification of human cytomegalovirus  hcmv  in peripheral blood polymorphonuclear leukocytes  pmnl  by polymerase chain reaction  culture and immunofluorescence in order to investigate the relationship between viraemia and immunosuppression  patients were divided into three groups   1  asymptomatic subjects with greater than 400 x 10 6  l cd4 lymphocytes  n   30    2  asymptomatic subjects with less than 400 x 10 6  l of cd4 lymphocytes and zidovudine  n   20   and  3  aids related complex  arc  aids patients on zidovudine  n   32   evidence of hcmv infection in circulating pmnl was found in 15 out of 29 arc aids patients examined  51 7    whereas no infection was detected among the 50 asymptomatic hiv 1 seropositive subjects  hcmv related symptoms were found only where the number of infected pmnl was greater than 50 per 2 x 10 5  cells  
class2	extrapulmonary and disseminated tuberculosis in hiv 1 seropositive patients presenting to the acute medical services in nairobi  we studied 506 consecutive adult acute medical admissions to hospital in nairobi  95  18 8   were seropositive for hiv 1  and 43 new cases of active tuberculosis  tb  were identified  tb was clearly associated with hiv infection  occurring in 17 9  of seropositive patients compared with 6 3  of seronegatives  odds ratio  or  3 2  95  confidence limits  cl  1 6 6 5   extrapulmonary disease was more common in seropositive than seronegative tb patients  nine out of 17 versus five out of 26  or 4 7  95  cl 1 01 23 6   this accounted for most of the excess cases of tb seen in seropositive patients  mycobacteraemia was demonstrated in two of eight seropositive tb patients but in none of 11 seronegative tb patients  no atypical mycobacteria were isolated  the world health organization  who  clinical case definition for african aids did not discriminate well between seropositive and seronegative tb cases  five out of seven seropositive women with active tuberculosis had delivered children in the preceding 6 months and were lactating  compared with only one out of eight seronegative tuberculous women  an association between recent childbirth  hiv immunosuppression and the development of tb is suggested  
class2	neuropsychometric performance of asymptomatic hiv infected subjects  the objective of this study was to determine whether there are measurable differences in neuropsychometric performances between hiv positive asymptomatic subjects and high risk hiv negative individuals  we carried out concurrent neuropsychological testing of hiv positive subjects screened for drug treatment protocols at a clinical research center and hiv negative subjects seeking confidential testing  fifty hiv negative and 33 hiv positive subjects who did not admit to use of central nervous system  cns  active drugs  more than one drink of alcohol per day  or drug use comprised the final group for analysis  a neuropsychological test battery designed to evaluate verbal memory  motor function  orientation and attention was administered to all subjects  in addition  affective state was assessed with the beck depression inventory  multivariate analysis of variance indicated no difference in the performance of the two groups  only one subtest  the wechsler adult intelligence scale digit span  forward  reached a level of significant difference  p less than 0 05  by univariate analysis  we conclude that neuropsychometric performance of asymptomatic hiv positive subjects cannot be distinguished from that of high risk hiv negative subjects by a battery of traditional neuropsychological tests  
class2	infection of cynomolgus monkeys with hiv 2 protects against pathogenic consequences of a subsequent simian immunodeficiency virus infection  simian immunodeficiency virus  siv  infection in cynomolgus macaques leads to severe immunodeficiency with a fatal outcome  in contrast  hiv 2 infects these primates without apparently causing any immunological abnormalities  in this study three cynomolgus monkeys were experimentally infected with hiv 2 strain sbl k135 and 168 days later challenged with 10 100 animal infectious doses of the closely related siv strain sm to study protective immunity  at the time of siv challenge the hiv 2 infected monkeys had neutralizing antibodies against hiv 2  but virus could no longer be recovered from their peripheral blood mononuclear cells  pbmcs  and no clinical symptoms or decrease in cd4  lymphocytes were observed  follow up for 9 months after challenge with siv showed that the hiv 2 infected monkeys were protected against siv induced immunodeficiency  no decrease of cd4  lymphocytes  and lymphadenopathy  however  they were not resistant to siv infection since virus could be recovered from their pbmcs and they developed anamnestic antibody responses  four naive control monkeys which were inoculated with the same dose of siv became persistently infected and developed a decrease of the absolute numbers of cd4  cells and showed a marked lymphadenopathy  two out of four control animals died 58 265 days postinfection with an immunosuppressive disease  immunohistochemical examination showed abundant viral antigen in lymph node biopsies from the siv infected control monkeys but absence of siv or hiv 2 antigens in the biopsies from the three hiv 2 preinfected and siv superinfected monkeys  the present study demonstrates possibilities for induction of immunity against immunodeficiency induced by a primate lentivirus  a concept with application also to hiv infection and aids in man  
class2	enhancement of erythrocytic adenosine deaminase following treatment of aids related complex aids patients with zidovudine  the levels of adenosine deaminase  ada  were determined in the erythrocytes of 10 patients with sexually transmitted hiv 1 infection  five cases with aids related complex  arc  and five with aids  before and after therapy with zidovudine  azidothymidine  azt   a linear increase in ada activity was observed during the second and third months of zidovudine treatment  with a final increase of about threefold after 3 months of drug administration  the concentration of adenosine triphosphate  atp  was significantly lower in the erythrocytes of the same group of patients with respect to healthy controls  and a further decrease was noted after 3 months of zidovudine treatment  the results obtained indicate that treatment of arc aids subjects with zidovudine induces metabolic changes which could be responsible for the development of anaemia  an adverse effect frequently associated with zidovudine therapy  
class2	poverty and hiv seropositivity  the poor are more likely to be infected  we analyzed demographic and behavioral risk factors for hiv seropositivity using data from 3601 clients of the main hiv counseling and testing clinic for high risk people in seattle  washington  usa  clients with lower income were found to be more likely to be hiv seropositive  before and after controlling for other demographic and risk factors with logistic regression  this result supports the hypothesis that the impoverished are at increased risk for hiv infection due to the physical and social circumstances in which their poverty places them  these may include poor access to risk reduction information and less support for implementation of risk reduction strategies  
class2	delayed detection of congenital hearing loss in high risk infants objective  to examine the methods used to investigate children at high risk of congenital hearing impairment  and to see whether the introduction of evoked response audiometry has reduced the mean age at which hearing loss is identified  design  clinicians who notified children to the national congenital rubella surveillance programme were asked retrospectively to complete a questionnaire examining the methods used to identify hearing impairment and the age at testing in two consecutive five year cohorts  the presence or absence of hearing loss was confirmed by obtaining the results of audiometric evaluations and  whenever possible  a recent pure tone audiogram  setting  the united kingdom  patients  children notified to the national congenital rubella surveillance programme and born in 1978 87 in whom igm specific for rubella was detected shortly after birth  main outcome measures  the age at which hearing loss was identified and the degree of loss in decibels at 250  500  1000  2000  and 4000 hz measured by pure tone audiometry  results  61  52   of 117 children born in 1978 82 had a hearing impairment of 40 db or greater in both ears  the mean loss was 93 db  in the following five years 75  47   of 159 children had impaired hearing  their mean loss being 96 db  the age at which the hearing loss was confirmed decreased from 11 6 to 9 8 months as a result of earlier auditory evoked response testing  nevertheless  only eight  13   of the children with hearing impairment born in 1978 82 and 16  21   of those born in 1983 7 had these tests performed in the first six months of life  conclusions  unacceptable delays in identifying hearing loss occurred in this high risk group because of failure to arrange auditory evoked response testing in early infancy  evoked response audiometry is sensitive and specific and should be undertaken within the first few months of life for all infants known to be at risk of sensorineural hearing loss  
class2	course of hiv i infection in a cohort of homosexual and bisexual men  an 11 year follow up study  objective  to characterise the natural history of sexually transmitted hiv i infection in homosexual and bisexual men  design  cohort study  setting  san francisco municipal sexually transmitted disease clinic  patients  cohort included 6705 homosexual and bisexual men originally recruited from 1978 to 1980 for studies of sexually transmitted hepatitis b  this analysis is of 489 cohort members who were either hiv i seropositive on entry into the cohort  n   312  or seroconverted during the study period and had less than or equal to 24 months between the dates of their last seronegative and first seropositive specimens  n   177   a subset of 442 of these men was examined in 1988 or 1989 or had been reported to have developed aids  main outcome measures  development of clinical signs and symptoms of hiv i infection  including aids  aids related complex  asymptomatic generalised lymphadenopathy  and no signs or symptoms of infection  measurements and main results  of the 422 men examined in 1988 or 1989 or reported as having aids  341 had been infected from 1977 to 1980  49   167  of these men had died of aids  10   34  were alive with aids  19   65  had aids related complex  3   10  had asymptomatic generalised lymphadenopathy  and 19   34  had no clinical signs or symptoms of hiv i infection  cumulative risk of aids by duration of hiv i infection was analysed for all 489 men by the kaplan meier method  of these 489 men  226  46   had been diagnosed as having aids  we estimated that 13  of cohort members will have developed aids within five years of seroconversion  51  within 10 years  and 54  within 11 1 years  conclusion  our analysis confirming the importance of duration of infection to clinical state and the high risk of aids after infection underscores the importance of continuing efforts both to prevent transmission of hiv i and to develop further treatments to slow or stall the progression of hiv i infection to aids  
class2	the chest roentgenogram in pulmonary tuberculosis patients seropositive for human immunodeficiency virus type 1  to determine the impact that co infection with hiv has on the radiographic presentation of pulmonary tuberculosis  we examined the chest roentgenograms obtained before treatment in 225 hiv tested adult haitians with bacillary  smear or culture or both  positive pulmonary tuberculosis  there were 67 hiv seropositive and 158 hiv seronegative patients  intrathoracic adenopathy alone was more common and parenchymal infiltrates less common in hiv seropositive patients  p less than 0 05   although a parenchymal infiltrate was less likely to be cavitating in the hiv seropositive group  p less than 0 05  when cavitary parenchymal disease was present  hiv seropositivity did not affect the number of cavities  single or multiple  or the size of the largest cavity  patients with aids were significantly more likely to have a chest radiographic pattern consistent with primary tuberculosis  80 percent  than hiv seropositive patients without aids  30 percent   and the latter were significantly more likely to have such a pattern than hiv seronegative patients  11 percent   p less than 0 05   the hiv seropositive patients were equally infectious  regardless of the pattern of disease  primary vs postprimary   even though pulmonary tuberculosis in an hiv seropositive adult probably results from reactivation of dormant foci or reinfection  the pattern on the chest roentgenogram often suggests primary disease  especially if the patient has aids  
class2	pneumocystis carinii pneumonia  rare cause of hemoptysis  pneumocystis carinii pneumonia is a frequent manifestation of the acquired immunodeficiency syndrome  aids   it commonly presents with nonproductive cough  fever  and dyspnea  we report this case of p carinii pneumonia presenting with hemoptysis  since to the best of our knowledge  hemoptysis has not been reported to be a presenting manifestation of p carinii pneumonia  autopsy revealed multiple lung cavities  
class2	latent hiv 1 infection in enriched populations of blood monocytes and t cells from seropositive patients  the extent of latent hiv 1 infection in blood t cells and monocytes of 23 seropositive individuals was examined using dna amplification  pcr  of hiv 1 sequences  amplified dna was found in at least one cell type in all seropositives tested  including 13 asymptomatic  5 arc  and 5 aids patients  amplification with two or more primer sets from the gag  env  ltr occurred in 21  91   patients  t cells and 17  74   patients  monocytes  however  amplification with the ltr primers in monocytes was uncommon  among four patients tested  amplified dna continued to be detected after a greater than one thousand fold dilution  less than 500 cells  of both t cell and monocyte lysates  repeat analysis after 7 9 mo in five seropositives yielded similar findings in t cells and monocytes  but some variation in the efficacy of amplification with individual primers occurred  there was no difference in those 10 patients who were taking azt  compared to those who were untreated  our results indicate that a fraction  less than 1   of both t cells and monocytes in blood carry a latent infection in all stages of hiv 1 disease and can serve as reservoirs throughout azt therapy  
class2	elevated serum concentrations of ige antibodies to environmental antigens in hiv seropositive male homosexuals  forty five homosexual male subjects with human immunodeficiency virus  hiv  infection  who received care during a 4 month period in an ambulatory center for acquired immunodeficiency syndrome  aids   were classified according to their principal presentation with characteristic secondary infections  cdc group iv c  n   28   cancers  iv d  n   10   or limited or no symptoms  groups ii  iii  iv a  or iv b  n   7   the incidence of allergic rhinitis and conjunctivitis increased after hiv seroconversion by approximately twofold in patients of groups iv c and iv d  the mean serum concentration of ige was significantly higher for group iv c than for the other hiv seropositive groups and for a control group of 45 hiv seronegative homosexual male subjects from the same community who were studied concurrently  more patients in groups iv c and iv d had positive rasts for a panel of environmental antigens than patients in the other hiv seropositive groups and the hiv seronegative control group  patients with aids presenting with typical secondary infections thus have a high frequency of some clinical and laboratory manifestations of allergic diseases  
class2	swine influenza virus infections  transmission from ill pigs to humans at a wisconsin agricultural fair and subsequent probable person to person transmission  in september 1988  a previously healthy 32 year old pregnant woman was hospitalized for pneumonia and died 8 days later  the only pathogen detected was an influenza virus antigenically related to the swine influenza virus  siv   four days before illness onset  the patient visited a county fair swine exhibition where there was widespread influenzalike illness among the swine  to detect other persons who were possibly infected by contact with the ill swine  we measured serum siv hemagglutination inhibition antibody titer in 25 swine exhibitors who were 9 to 19 years old  nineteen  76   had siv hemagglutination inhibition titers of 20 or greater  antibody was undetectable in serum samples from 25 swine exhibitors from a neighboring county  additional studies suggest that one to three health care personnel who had contact with the patient developed influenzalike illnesses with laboratory evidence of siv infection  an outbreak of apparent siv infection in swine resulted in multiple human infections  and  although no recognized community outbreak resulted  there was evidence of virus transmission from the patient to health care personnel  
class2	evaluation of enzyme immunoassays for antibody to human t lymphotropic viruses type i ii  to evaluate the sensitivity and specificity of htlv i ii assays  serum from 1100 pregnant haitian women was tested with seven commercially available htlv i ii assays  serum that was found to be reactive in any assay was analysed by western blot and all indeterminate samples were further characterised by radioimmunoprecipitation assays  ripa   59  5 4   samples were htlv i ii antibody positive by western blot and or ripa  the sensitivity of these seven assays ranged from 93 2  to 100   with the  recombinant htlv i   cambridge bioscience  and  serodia htlv i   fujirebio  assays having the highest sensitivity  100    the specificity of these assays ranged from 98 4  to 100   with the abbott assay having the highest specificity  99 5   100   according to two different methods of evaluation  whether the antigens used in any assay were whole disrupted virus or recombinant gene products made no difference  the low positive predictive values of some of these assays  71 8 91 7    even in a high prevalence population  and the need for ripa to test indeterminate sera  indicate that for routine screening of blood donors there is still room for improvement both in screening and confirmatory assays for htlv i ii  
class2	unexplained rabies in three immigrants in the united states  a virologic investigation background  extensive investigation of three patients who died of rabies in the united states failed to reveal any source of exposure to the disease  the three patients had immigrated to the united states from areas in laos  the philippines  and mexico where rabies is endemic  methods  we studied rabies viruses isolated from the three patients  other patients with a known source of exposure  and animals in the united states  thailand  as a proxy for laos   the philippines  and mexico  the viruses were characterized by indirect immunofluorescence and neutralization tests according to their reactions to panels of monoclonal antibodies  transcribed complementary dna from these isolates was amplified by the polymerase chain reaction  the dna product was then analyzed by differential digestion with restriction enzymes  results  the viral isolate from each of the three patients was a rabies variant with distinctive antigenic or genetic characteristics  for each of the three isolates  identical variants were found in specimens from rabid animals obtained from or near the country in which the patient lived before immigrating to the united states  none of these variants were found among the isolates collected from rabid animals in the united states  conclusions  rabies infection in these three patients did not originate in the united states but resulted from exposures in laos  the philippines  and mexico  since the three patients had lived in the united states for 4 years  6 years  and 11 months  our findings suggest that the onset of the clinical manifestations of rabies occurred after long incubation periods  
class2	tropical spastic paraparesis like illness occurring in a patient dually infected with hiv 1 and htlv ii  we describe a 34 year old man from southern florida with a history of intravenous drug use  dually infected with human immunodeficiency virus type 1  hiv 1  and human t lymphotropic virus type ii  htlv ii   who developed a myelopathy clinically indistinguishable from htlv i associated myelopathy tropical spastic paraparesis  ham tsp   this myelopathy was characterized by spastic lower extremity weakness  distal paresthesias  sensory loss with a discrete thoracic level to pinprick  back pain  impotence  and sphincter disturbances  nerve conduction studies revealed an associated mixed axonal and demyelinative neuropathy  despite a lack of response to 10 months of zidovudine therapy  the myeloneuropathy improved dramatically 2 years after its onset in the absence of any therapeutic intervention  
class2	human papillomaviruses  pediatric perspectives on a family of multifaceted tumorigenic pathogens as summarized here human papillomaviruses are associated with a wide spectrum of epithelial lesions  ranging from benign warts to invasive carcinomas  they have been difficult to study in part because they have not yet been propagated in tissue culture  fortunately advances in molecular biology have allowed characterization of hpv genomes and identification of some hpv gene functions  in addition to their clinical importance hpvs represent an important tool for exploring virus cell interactions  gene expression  cellular differentiation and cancer  hpv infections are not only common but also difficult to treat and prevent  depending on the hpv type and location  the modes of hpv transmission may involve casual physical contact  sexual contact and perinatal vertical transmission  hpv dna genomes replicate at a low copy number in basal cells and  as most clinicians know  are difficult to eradicate  there is often a long latent period and subclinical infections  and hpv dna can be found in normal tissue adjacent to lesions  hpvs can cause widely disseminated lesions  especially in the immunocompromised host and in epidermodysplasia verruciformis  aside from the rare carcinomas  the most serious life threatening hpv induced illness in children is recurrent respiratory papillomatosis  somewhat surprisingly in malignant lesions hpv dna is also found as fragments incorporated into the cellular genome  unlike retroviruses such as human immunodeficiency virus which integrate into the cellular genome as part of their life cycle  hpv integration is a terminal event for viral replication  such integration may be critical  however  for viral induced abnormal cell growth  perhaps the most important implication of the finding that some anogenital cancers are in part sexually transmitted infectious diseases is that they may be preventable  the data overwhelmingly suggest that avoidance of exposure to hpv via abstinence or monogamy in both partners markedly reduces the risk of cervical cancer  a more realistic goal  however is prevention of hpv transmission by the use of barrier method contraceptives  which may be protective against development of cervical carcinoma  the america association of pediatrics committee on adolescents has outlined the obligation of pediatricians to be actively involved in adolescent education on sexually transmitted diseases  certainly a fundamental knowledge of hpv epidemiology  the risks of hpv related sequelae and prevention of hpv infection are important considerations for adolescent sexuality  although helpful  such awareness alone falls far short of making an impact on sexual behaviors  a significant reduction in hpv infection rates could be achieved only by inundating adolescents at an early age with a highly visible society wide campaign directed at these issues  
class2	herpes zoster ophthalmicus and iris cysts  herpes zoster ophthalmicus has been associated with numerous complications such as neuropathy  keratitis  anterior uveitis  and neuralgia  to my knowledge  there have been no reports of secondary iris cyst formation  i hereby report the case of a patient who developed an iris cyst during a herpes zoster ophthalmicus infection  
class2	childhood blindness in peru  a survey of childhood blindness in peruvian children was done  although most causes of blindness were due to congenital and hereditary conditions  measles accounted for almost 10  of blindness  with widespread measles immunization  this preventable cause of blindness in children can be eliminated or dramatically reduced  
class2	neuromuscular function in polio survivors at one year follow up  published erratum appears in arch phys med rehabil 1991 mar 72 3  213  many polio survivors complain of progressive loss of strength  work capacity  endurance  and ability to recover from fatiguing activity  these variables were measured initially and one year later in the quadriceps muscles of 28 symptomatic and 16 asymptomatic persons who had polio and 38 control individuals  peak knee extension torque was measured isokinetically and isometrically  endurance  or the amount of time the subject could maintain isometric torque at 40  of maximal torque  was measured  work capacity was determined as the product of isometric torque and endurance time  recovery of strength was measured at regular intervals for ten minutes after the endurance test  statistical analysis was done by repeated measures anova  although the initial measures showed significant deficits in mean peak torque  work capacity  and recovery of strength in symptomatic postpolio subjects  no significant changes were found one year later in any of the variables  we conclude that symptomatic postpolio subjects do not lose significant neuromuscular function in one year  
class2	cat scratch disease  an unusual cause of combative behavior  acute encephalitis is an unusual manifestation of cat scratch disease  the authors present the case of a 27 year old man who exhibited the acute onset of encephalitis manifested by violent behavior and confusion  the diagnosis of drug abuse was presumed initially  but a careful examination revealed the true cause to be cat scratch disease  emergency physicians are frequently faced with the challenging task of evaluating confused and combative patients  this case demonstrates the importance of a complete physical examination and a thorough laboratory evaluation  
class2	antibodies to hiv 1 nef p27   prevalence  significance  and relationship to seroconversion  a sensitive and specific enzyme linked immunoassay for antibodies to the human immunodeficiency virus type 1  hiv 1  nef gene product  p27  has been developed using recombinant escherichia coli derived protein from the lav 1 bru sequence  of 92 hiv 1 infected hemophiliacs  72  78   produced anti nef antibodies in this assay  the early appearance of anti nef prior to full seroconversion was a rare event in this population  occurring in only one subject  approximately 1    anti nef antibodies were not detected in any of 500 sera from 98 repeatedly hiv seronegative subjects who had been exposed to sexually transmitted modes of hiv infection  45 subjects  or through blood products  53 subjects   there was no significant association of titer or anti nef antibody with protection from disease in hiv infection  p   0 1   although the nef protein is relatively immunogenic in natural infection  this study cannot confirm the previously reported high prevalence of anti nef antibodies prior to seroconversion  nor the finding of anti nef antibodies in hiv seronegative but exposed subjects  
class2	rapid diagnosis of herpes simplex encephalitis by nested polymerase chain reaction assay of cerebrospinal fluid  with the aim of improving early diagnosis of herpes simplex encephalitis a polymerase chain reaction  pcr  assay with two  nested  primer pairs was developed for the amplification of herpes simplex virus dna in cerebrospinal fluid  csf   southern blotting was used to confirm the specificity of the amplification  the assay was applied to 151 csf samples from 43 consecutive patients with herpes simplex encephalitis verified by the finding of herpes simplex virus viral antigen in a brain biopsy sample or at necropsy  13  and or intrathecal production of igg antibody to the virus  40   as controls  87 csf samples from 60 patients with acute febrile focal encephalopathy  initially suspected to be herpes simplex encephalitis but excluded by the absence of intrathecal antibody synthesis  were tested  pcr detected herpes simplex virus dna in 42 of the 43 patients with proven herpes simplex encephalitis  all but 1 were positive in the first csf sample taken  the 1 pcr negative patient had been treated with acyclovir from 20 h after the onset of symptoms  all the control subjects were pcr negative  as were 270 internal contamination controls  the pcr result remained positive in samples drawn up to 27 days after the onset of neurological symptoms  this method is a rapid and non invasive means to diagnose herpes simplex encephalitis  it is highly sensitive and specific  
class2	mycobacterial infection after renal transplantation  report of 14 cases and review of the literature  during a nine year period  14 cases of mycobacterial infection  tuberculosis  developed in 403 renal transplant recipients at the king faisal specialist hospital and research centre in riyadh  saudi arabia  an incidence of 3 5 per cent  the annual incidence of tuberculosis was about 50 times higher than that in the general population  infection was disseminated in nine  64 3 per cent   pulmonary in four  28 6 per cent   and genitourinary in 1  7 1 per cent   in one patient tuberculosis was transmitted by the donor s kidney  the clinical manifestations were often ill defined and not different from that in the normal host  cultures from all patients grew mycobacterium tuberculosis  concomitant infection with other organisms was present in five patients  35 7 per cent   two of 18 patients  group 1  with positive pretransplant tuberculin skin test developed tuberculosis after transplantation  11 per cent   and neither received isoniazid prophylaxis  three of 70 patients  group 2  with negative skin tests developed tuberculosis after transplantation  4 3 per cent   the difference between the two groups was not statistically significant  review of all published cases of mycobacterial infections in renal transplant recipients revealed 130 cases  tuberculosis was disseminated in 38 7 per cent  pulmonary in 40 2 per cent  cutaneous in 12 per cent  and miscellaneous in 9 4 per cent  atypical mycobacteria were responsible for 29 per cent of disseminated infections  8 per cent of pulmonary infections and all cases of cutaneous and articular tuberculosis  invasive procedures were needed to establish the diagnosis in 21 of 33 disseminated cases but in only three of 47 cases of pulmonary tuberculosis  p less than 0 0001   the mortality rate from disseminated disease was 37 per cent and from all other forms of tuberculosis was 11 per cent  p less than 0 005   these findings  1  confirm the higher incidence of tuberculosis in renal transplant recipients  compared to the general population   2  suggest that pretransplant skin testing probably has little value in identifying patients at risk   3  show that disseminated tuberculosis is common after renal transplantation and requires invasive procedures for diagnosis   4  confirm that the donor kidney may be an important source of infection  and  5  indicate that concomitant infection with other organisms is common  
class2	persistent rectal ulcer associated with human papillomavirus type 33 in a patient with aids  successful treatment with isotretinoin  rectal dysplasia and carcinoma associated with human papillomavirus infection are increasing in prevalence among homosexual men  particularly those infected with the human immunodeficiency virus  we report a case involving a 39 year old homosexual man with aids who developed a persistent rectal ulcer  a biopsy of the ulcer revealed severe squamous dysplasia  and human papillomavirus type 33 was detected in rectal tissue with use of in situ dna hybridization  this genotype of virus has not been previously associated with anal or rectal dysplasia in homosexual men  including those infected with the human immunodeficiency virus  the rectal ulcer resolved after 2 months of oral therapy with 60 mg d of isotretinoin  a retinoid  
class2	inpatients with aids and aids related complex  economic inpact on hospitals in north carolina  to determine the economic impact of acquired immunodeficiency syndrome  aids  or aids related complex  arc  cases on north carolina hospitals  we collected inpatient data from all north carolina hospitals on charges and number of patients discharged with these diagnoses  more than 97  of the state s hospitals responded to the survey for the study year  1987 1988   there were 540 aids arc discharges from 58 north carolina general hospitals and 125 aids arc discharges from 13 other types of hospitals  for a statewide total of 665 patients  the total general hospital charges for aids arc inpatients in north carolina were approximately  7 7 million per year  and almost  2 million of these charges were uncompensated by any insurance  the greatest burden of cost for this care was borne disproportionately by 15 of the 58 general hospitals  accounting for 82  of the discharges  
class2	perinatal transmission of human papillomavirus  human papillomavirus infection is probably the most prevalent sexually transmitted disease in the united states  in adults  it is associated with condylomata acuminata and with neoplastic changes ranging from dysplasia to carcinoma  infected mothers may transmit human papillomavirus during the perinatal period  affected children face prolonged  difficult treatment for respiratory papillomatosis  prevention of infection remains the best approach  since diagnostic and therapeutic methods are suboptimal  
class2	antiviral drug therapy  major advances in molecular virology have led to the development of new antiviral compounds  these drugs include ribavirin  used in the treatment of severe respiratory syncytial virus infection in children  amantadine  used in the prophylaxis and treatment of influenza a infection  acyclovir  used in a variety of herpesvirus infections  including primary gingivostomatitis  genital herpes and herpes zoster  ganciclovir  used in the treatment of retinitis due to cytomegalovirus  and zidovudine  used in the prophylaxis and treatment of human immunodeficiency virus infection  
class2	hepatobiliary manifestations of the acquired immune deficiency syndrome  patients with the acquired immune deficiency syndrome  aids  frequently develop hepatic dysfunction  although hepatic injury may indirectly result from malnutrition  hypotension  administered medications  sepsis  or other conditions  the hepatic injury is frequently due to opportunistic hepatic infection  directly related to aids  infection with mycobacterium avium intracellulare typically occurs in patients with advanced immunocompromise and with systemic symptoms due to widely disseminated infection  in contrast  hepatic tuberculosis often occurs with less advanced immunocompromise  cytomegaloviral infection may produce a hepatitis  cytomegaloviral and cryptosporidial infections have been implicated as causes of acalculous cholecystitis and of a secondary sclerosing cholangitis  about 10 20  of patients with aids have chronic hepatitis b infection  these patients tend to develop minimal hepatic inflammation and necrosis  the clinical findings in patients with hepatic cryptococcal infection are usually due to concomitant extrahepatic infection  hepatic histoplasmosis usually develops as part of a widely disseminated infection with systemic symptoms  hepatic involvement by kaposi s sarcoma is rarely documented ante mortem because an unguided liver biopsy is an insensitive diagnostic procedure  patients with non hodgkin s lymphoma of the liver typically have lymphadenopathy  hepatomegaly  and systemic symptoms  as a pragmatic approach  patients with liver dysfunction and hiv related disease should have a sonographic or computerized tomographic examination of the liver  patients with dilated bile ducts should undergo endoscopic retrograde cholangiopancreatography because opportunistic infection may produce biliary obstruction  patients with a focal hepatic lesion should be considered for a guided liver biopsy  patients with a significantly elevated serum alkaline phosphatase level should be considered for a percutaneous liver biopsy  when performed for these indications  liver biopsy will demonstrate a significant disease involving the liver in about 50  of patients with aids and in about 25  of patients who are hiv seropositive but who are not known to have aids  the clinical impact of a diagnostic biopsy is blunted by a lack of efficacious therapy for many opportunistic infections  
class2	upper gastrointestinal bleeding in dengue fever  twenty six virologically and serologically confirmed dengue patients with signs of upper gastrointestinal tract bleeding  13 1   were studied during the 1987 outbreak in southern taiwan  within a 1 yr period from 1987 to 1988 in kaohsiung chang gung memorial hospital  there were 198 patients with dengue fever confirmed  viral isolation and serological studies indicated that type i dengue was the cause  there was no evidence of sequential secondary infection among them  the 26 patients were evaluated gastroduodenoscopically  most of the dengue patients who developed upper gastrointestinal bleeding had gastric ulcers or duodenal ulcers  superficial and hemorrhagic gastritis are the other relevant endoscopic findings  thirteen patients  50   had a past history of peptic ulcer symptoms  whereas the other 13 did not  dengue infection is a precipitating factor in inducing peptic ulcer bleeding because of hemostatic derangements  supportive therapy and blood transfusions alone were adequate treatment  except for one patient who required surgery due to massive bleeding of a duodenal ulcer  no mortality was observed in this study  
class2	whipple s disease can mimic chronic aids enteropathy  previous case reports have demonstrated that the intestinal pathology of mycobacterium avium intracellulare  mai  infection in the acquired immune deficiency syndrome  aids  has a light microscopic appearance similar to whipple s disease  this case report describes a 52 yr old male patient with a clinical picture suggestive of aids  including diarrhea  weight loss  oral thrush  and intestinal cryptosporidiosis  the intestinal biopsy showed light microscopic features compatible with either mai or whipple s disease  but electron microscopy confirmed the presence of the whipple bacillus  markers of human immunodeficiency virus  hiv  infection were absent  although immune abnormalities have been reported in whipple s disease  this is the first report of opportunistic infections complicating this condition  a useful clinical pearl emerges from this and other cases  aids can mimic whipple s disease  whipple s disease can mimic aids  
class2	therapy of persistent human papillomavirus disease with two different interferon species  consensus interferon and interferon alfa 2a were used to treat patients with persistent human papillomavirus disease  thirty one patients were treated with either consensus interferon or a placebo  25 received active drug and 6 received placebo   and 24 patients were treated with interferon alfa 2a  of the 25 patients who received consensus interferon  19  76   showed either complete or partial clearing of condyloma 10 and 16 weeks after initiation of therapy  in 22 of the 24 patients  91   who received interferon alfa 2a  clearing was demonstrated after a similar time period  thirty of 34 patients who had no response or a partial response requested additional therapy  and 20 of these patients treated with adjunctive therapy had a complete response  the results of this study support the efficacy of both interferons in the treatment of overt condyloma acuminatum and suggest that interferon enhances subsequent adjunctive therapy  
class2	human immunodeficiency virus induced immunosuppression  a risk factor for human papillomavirus infection  in a group of 92 women with genital condylomata  15  16 3   human immunodeficiency virus positive patients were found  whereas no case was detected in a control group of 100 women  the relative risk was greater than 19 28  human immunodeficiency positive status was associated with other parameters  lower age and parity  major frequency of induced abortions  and sexually transmitted diseases  thus although human immunodeficiency positive status seems to be a true risk factor in relation to the altered immunologic state  an indirect association cannot be discarded  such patients should be screened closely for human papillomavirus infection and cervical cancer  among human immunodeficiency positive women  a more resistant behavior of human papillomavirus associated lesions was detected  recurrence persistence of 41 7  versus 12    a fact that might also be in relation to the immunodepressed status  
class2	the influence of human immunodeficiency virus infection on tuberculosis in kampala  uganda  the clinical  radiographic  and microbiologic features of 59 patients with pulmonary tuberculosis in kampala  uganda were studied and correlated with the serologic reactivity to the human immunodeficiency virus  hiv  of these patients  two thirds of the patients with tuberculosis were hiv seropositive  histories of fever and weight loss were more prominent in hiv seropositive patients  and perihilar and basilar infiltrative diseases were more frequently seen in hiv seropositive patients  although all patients responded similarly to drug therapy  cutaneous drug reactions were seen in nearly one third of hiv seropositive patients receiving thiacetazone  
class2	comparison of hiv detection by virus isolation in lymphocyte cultures and molecular amplification of hiv dna and rna by pcr in offspring of seropositive mothers  an early and accurate diagnosis of hiv infection is needed in the offspring of seropositive mothers  to this end  we have used two techniques for the direct detection of hiv in 12 newborns tested within 2 weeks after birth and 12 children  hiv isolation was carried out in lymphocyte cocultures and compared with detection of dna and rna sequences by molecular amplification using the polymerase chain reaction  pcr   in lymphocyte cocultures  hiv was isolated in 8 of 24 cases  33    including 3 newborns  3 symptomatic children  and 2 asymptomatic ones  hiv dna was detected by pcr in twice as many cases  i e   in 16 24 cases  66    including 7 12 newborns  4 4 symptomatic children  and 5 8 asymptomatic ones  2 of whom became seronegative  hiv rna was detected in 10 of 16 cases  60   with detectable hiv dna  including all of the cases who had a positive hiv isolation  only children with clinical or biological signs of hiv infection were positive for hiv rna  furthermore  signs of hiv infection appeared within 6 months in three of the four newborns who were positive for hiv rna at birth  these results indicate that hiv dna detection by pcr is far more sensitive than hiv isolation in culture for the early diagnosis of hiv infection in offspring of seropositive mothers  hiv rna detection appears to be a useful prognostic marker since it does correlate with disease progression and may serve as a clue for hiv replication in vivo  
class2	polypharmacy among patients attending an aids clinic  utilization of prescribed  unorthodox  and investigational treatments  the objective of this study was to describe the utilization and characteristics associated with the use of prescribed  over the counter  investigational  and unorthodox treatments among aids clinic patients  this report is derived from cross sectional data obtained using structured telephone surveys  study participants  n   197  were recruited from the university of california  san francisco  medical center aids clinic  one hundred eighty nine participants  96   received 1 24 prescription medications during the 3 months prior to interview  those with an aids diagnosis received a relatively greater number of prescription drugs  p   0 0001   an average of 5 6 prescribed medications were used by aids patients versus 4 8 among aids related complex and 2 3 among asymptomatic patients  thirty one percent participated in drug trials during the 3 months before interview  including 18  who were in multiple studies  twenty nine percent used unorthodox treatments  seventy five  40   received prescription medication from a provider other than their primary provider  a more advanced stage of illness was associated with the use of unorthodox treatments  p   0 003   users of these treatments had a greater educational attainment than nonusers  p   0 03  and were significantly less likely to report that their primary provider was aware of all the treatments they used  odds ratio   2 1  p less than 0 03   we conclude that use of polypharmacy among some aids clinic patients is common  could create an increased risk for adverse drug reactions  and may affect clinical drug trials  despite having decided to obtain care at a university based clinic  many of the participants of this study also chose to receive unorthodox therapies and care from nonprimary medical providers  
class2	survival differences in patients with aids  published erratum appears in j acquir immune defic syndr 1991 4 7  737  to define the clinical  demographic  and behavioral variables that may influence survival in patients with aids  we studied 526 patients with aids diagnosed through september 1987 who were cared for at a single medical center  a diversity of racial and ethnic backgrounds  ages  both men and women  and all risk behaviors except hemophilia were well represented  the initial aids defining diagnosis was the most powerful predictor of survival  the median survival was 12 8 months for patients presenting with kaposi s sarcoma  p less than 0 001   10 9 months for patients presenting with pneumocystis carinii pneumonia  p less than 0 001   and 4 8 months for patients presenting with other infections or neoplasms  p less than 0 02   for the entire series  male sex and younger age were associated with more favorable survival  p less than 0 025   for those presenting with pneumocystis carinii pneumonia  in addition to younger age  p less than 0 025   black race  p less than 0 025  and the combination of male sex and intravenous drug use  p less than 0 005  were associated with a more favorable survival  within a setting of comparable clinical care  survival from the point of diagnosis of aids is associated most strongly with the initial aids diagnosis  but differences in age  gender  race  and risk behavior also exert an influence on survival  
class2	detection of salivary hiv 1 specific igg antibodies in high risk populations in zaire  saliva and blood samples were tested for human immunodeficiency virus 1  hiv 1  antibodies in two high risk populations in kinshasa  zaire  in a seroprevalence study of 458 sexually transmitted disease  std  clinic attendees  142 of 145 seropositive individuals had enzyme linked immunosorbent assay  elisa  positive saliva samples  97 9  sensitivity   all saliva samples from seronegative patients were elisa negative  100  specificity   of the 142 elisa positive saliva specimens  137 were also western blot positive  94 5  sensitivity   in a subsequent seroincidence study of 315 initially seronegative female prostitutes followed during 183 woman years of observation  9 of 14 women who seroconverted  7 7  seroincidence  had elisa positive saliva samples at the time seroconversion was detected  only three of these saliva specimens could be confirmed by western blot  although salivary testing for hiv 1 antibodies using conventional assays was not sensitive in detecting recent seroconversions  screening of salivary samples for hiv 1 antibody provides a convenient alternative method for conducting seroprevalence surveys in populations in whom venipuncture is not possible or convenient  
class2	medical care of the hiv infected child  familiarity with the demographics of pediatric hiv disease and recognition of common and uncommon presentations of infection are keys to diagnosing the hiv infected child  subsequent management entails preventative care  including immunizations and nutritional support  as well as management of hiv related complications  
class2	pneumocystis carinii infections in hiv infected children  since 1981  1200 children with acquired immunodeficiency syndrome have been reported to the centers for disease control  among these children  pneumocystis carinii has been the leading cause of serious morbidity and mortality  this review discusses the epidemiology  diagnosis  and treatment of p  carinii  
class2	lymphocytic interstitial pneumonia  lymphocytic interstitial pneumonia is at present a pathologic diagnosis  in the setting of a chronic interstitial pneumonia in a child with lymphocytosis  hyperglobulinemia  and lymphadenopathy or parotid enlargement  the diagnosis is often clinically presumed  at present the diagnosis can be established firmly only by lung biopsy  models of pathogenesis include nonspecific stimulation of the immune system  hiv specific stimulation  or synergy between ebv and hiv  treatment includes oxygen and bronchodilators as needed  the role of zidovudine and of steroids in the management of lip remains to be determined  
class2	pathology of childhood aids  pathologic lesions in children with acquired immunodeficiency syndrome  aids  can be classified into three broad categories   1  primary lesions related directly to infection by human immunodeficiency virus  hiv   e g   in the lymphoreticular system and brain    2  associated lesions related to direct or indirect sequelae of hiv infection  e g   opportunistic infections  lymphoid interstitial pneumonitis  and so forth   and  3  lesions of undetermined pathogenesis  e g   cardiomyopathy  nephropathy  and so forth   the pathologic features of the various lesions in these three categories are described  clinical relevance of the pathologic study of aids is discussed  data on perinatal pathology of aids is reviewed  
class2	upper respiratory tract infections in young children  duration of and frequency of complications  this study was performed to determine the usual duration of community acquired viral upper respiratory tract infections and the incidence of complications  otitis media sinusitis  of these respiratory tract infections in infancy and early childhood  children in various forms of child care arrangements  home care  group care  and day care  were enrolled at birth and observed for 3 years  families were telephoned every 2 weeks to record on a standardized form the type and severity of illnesses experienced during the previous interval  only children remaining in their original child care group for the entire study period were compared  the mean duration of an upper respiratory tract infection varied between 6 6 days  for 1  to 2 year old children in home care  and 8 9 days  for children younger than 1 year in day care   the percentage of apparently simple upper respiratory tract infections that lasted more than 15 days ranged from 6 5   for 1  to 3 year old children in home care  to 13 1   for 2  to 3 year old children in day care   children in day care were more likely than children in home care to have protracted respiratory symptoms  of 2741 respiratory tract infections recorded for the 3 year period  801  29 2   were complicated by otitis media  during the first 2 years of life  children in any type of day care were more likely than children in home care to have otitis media as a complication of upper respiratory tract infection  in year 3  the risk of otitis media was similar in all types of child care  
class2	clinical manifestations of primary herpes simplex virus type 1 infection in a closed community  the clinical features and the molecular epidemiology of primary herpes simplex virus type 1  hsv 1  infection among children younger than 3 years of age were investigated in day care nursery  serial sera were assayed for anti hsv 1 glycoprotein b antibody by enzyme linked immunosorbent assay  serologic examinations revealed 55 cases of primary hsv infection during the observation period  fifty one of them  93   had typical herpetic gingivostomatitis  showing a high rate of clinically overt infection  four outbreaks of herpetic gingivostomatitis were observed during the observation period  forty one children were infected with hsv 1 in the outbreaks  the rates of infection in the susceptible children were 81   73   78   and 100   respectively  in the four outbreaks  restriction endonuclease analysis of dna of isolated hsv revealed that only one strain of hsv 1 had been transmitted among children for a long period  
class2	lack of transmission of the live attenuated varicella vaccine virus to immunocompromised children after immunization of their siblings  the safety of administering the live attenuated oka merck varicella vaccine to the well siblings of children with malignancy was evaluated as a strategy for reducing the risk of household exposure to varicella among immunocompromised children  susceptible well children were eligible for vaccination if the child with malignancy had leukemia  lymphoma  or solid tumor in remission for 3 months or longer  no evidence of vaccine virus transmission was found among 30 children with malignancy whose 37 healthy susceptible siblings were immunized with varicella vaccine  varicella zoster virus was not isolated from the oropharyngeal secretions taken from 17 vaccinees or their 14 immunocompromised siblings  none of the 30 immunocompromised children had vaccine related rashes or showed immunologic evidence of subclinical varicella zoster virus infection based on testing for varicella zoster virus igg antibodies and t lymphocyte proliferation to varicella zoster virus  four healthy vaccinees eventually had mild breakthrough cases of varicella  with transmission to the high risk sibling in 3 cases  however  even in these families  the immunocompromised children had been protected from household exposure varicella for at least 20 months early in the course of their immunosuppressive treatment  
class2	infection in utero  us findings in 19 cases  the results of antenatal sonographic studies of 19 fetuses with congenital infections were retrospectively reviewed by the authors  recognizing the significance of these antenatal sonographic findings is important because in utero infections can have devastating effects on the developing fetus  an infectious viral agent was isolated in laboratory tests at birth in 11 patients  and the effects of a viral agent were proved clinically in eight  antenatal sonography demonstrated abnormalities in 18 fetuses  multiple organ systems were affected in 47   intracranial abnormalities  cardiac abnormalities  and parenchymal calcifications occurred in 42   37   and 32   respectively  large placentas were seen in 32   and the volume of amniotic fluid was decreased in 37  and increased in 37   sixty three percent of fetuses were either aborted or died at birth  the 37  that lived were all developmentally impaired  on the basis of these sonographic  laboratory  and clinical findings  the authors conclude that when multiple organ system abnormalities are found at antenatal ultrasound  the presence of an in utero infection should be considered  the parents should be informed that there is a poor prognosis for any fetus demonstrating such abnormalities  
class2	clinicopathologic studies of children who die of acute lower respiratory tract infections  mechanisms of death  clinicopathologic correlations for 71 cases of fatal pneumonia in children were determined  the mechanism of death for these patients was multifactorial  severe pneumonia alone accounted for 11 deaths  15 5    pneumonia associated with sepsis occurred in 42 children  59 2    heart failure  8 5    hypovolemia  4 2    and nosocomial infection  12 6   were also seen in children with fatal acute lower respiratory tract infection  extensive consolidation  squamous metaplasia  and hyaline membranes were present in the lungs of these children  patients with severe disease must receive  in addition to antibiotics for acute episodes  individualized intensive respiratory and supportive care  since these types of care are not available in poor communities  vaccination against measles and vitamin a supplementation for malnourished children may ameliorate the conditions that appear to predispose these children to severe or fatal disease  
class2	etiologic  clinical  and pathologic analysis of 31 fatal cases of acute respiratory tract infection in argentinian children under 5 years of age  during a 3 year survey of 805 children with acute lower respiratory tract infection  alri  who were admitted to three hospitals in buenos aires  31 fatal cases were recorded  a fatality rate of 3 8   of the 31 children who died  77  were less than 1 year of age  48  were boys  58  were malnourished  29  had previous respiratory disease  and 22  had previous congenital disease  all children who died had clinical diagnoses of pneumonia  71   or bronchiolitis  29    autopsies were performed in 14 of the cases  viral etiology was determined by both cell culture and indirect immunofluorescence  iif  assay of either nasopharyngeal aspirates  npa  or lung tissue and bacterial etiology was determined by isolation of organisms from blood  lung tissue  and or pleural fluid  npa was examined for bordetella pertussis by iif  pathogens were identified in 65  of fatal cases  seven cases were bacterial  seven cases were viral  and six cases resulted from mixed infections  lung tissue yielded positive etiologic results in 10 of 13 cases  histopathologic examination performed on specimens from the 14 autopsied children revealed necrotizing bronchiolitis with intranuclear inclusions  n   5  and multifocal pneumonia  n   9   
class2	etiologic and clinical evaluation of acute lower respiratory tract infections in young argentinian children  an overview  this paper summarizes the first study on clinical  etiologic  and epidemiologic features of acute lower respiratory tract infection  alri  in children in argentina  a total of 1 003 children less than 5 years of age  805 inpatients and 198 outpatients  presenting with alri were studied during a 40 month period  nasopharyngeal aspirate  npa   blood  urine  and throat swab samples were collected when each child was first seen for care  virologic studies were performed on the npa by means of indirect immunofluorescence and isolation of virus in cell culture  bacteriologic studies primarily were done by means of culture of blood or pleural fluid  when available   bordetella pertussis and mycoplasma pneumoniae  however  were searched for by the use of immunofluorescence and complement fixation testing  respectively  in paired sera  respiratory syncytial virus was the most commonly isolated virus  followed by adenovirus  parainfluenza virus  and influenza virus  streptococcus pneumoniae was the most frequently isolated bacterium  followed by b  pertussis and haemophilus influenzae type b  overall  the patient fatality rate was 3 8  among inpatients with pneumonia or bronchiolitis  
class2	acute lower respiratory tract infections in hospitalized patients with diarrhea in dhaka  bangladesh  this study focused on 401 children less than 5 years old who were hospitalized with acute lower respiratory tract infection  alri  and diarrhea in dhaka  bangladesh  and who were investigated for the presence of both bacterial and viral respiratory tract pathogens as well as for selected diarrheal pathogens  the most common manifestations of alri were pneumonia  374 cases   bronchiolitis  12 cases   and tracheobronchitis  11 cases   the majority  77   of the illnesses were in children less than 2 years of age  and 88  of the children were malnourished  a respiratory tract pathogen was identified in 30  of the patients  and a diarrheal pathogen was identified in 34   the overall case fatality rate in children with alri and diarrhea was 8   the case fatality rate was 14  in children with bacterial pneumonia and diarrhea  3  in those with viral pneumonia and diarrhea  and 14  in malnourished children with shigellosis and alri  the most common respiratory tract pathogens were respiratory syncytial virus  streptococcus pneumoniae  influenza viruses  and haemophilus influenzae type b  
class2	diagnoses of acute lower respiratory tract infections in children in rawalpindi and islamabad  pakistan  a hospital based inpatient and outpatient study of 1 492 cases of acute lower respiratory tract infection  alri  was conducted from november 1986 to march 1988 in two hospitals in rawalpindi and islamabad  pakistan  specimens of nasopharyngeal aspirate were processed for viral studies in all cases  blood cultures were performed in 1 331 cases  and urine was obtained for detection of bacterial antigen in 378 cases  but 227 of these samples had bacterial contamination and were discarded  respiratory syncytial virus was identified in 33  of cases  and haemophilus influenzae and streptococcus pneumoniae were identified in 9 6  and 9 9  of cases  respectively  nonencapsulated h  influenzae accounted for 32  of the haemophilus isolates  and type b was the only encapsulated h  influenzae strain identified  of the s  pneumoniae serotypes isolated  31  are not included in the currently available polyvalent pneumococcal vaccine  no clinical characteristic was demonstrated to be a reliable indicator for bacterial alri  
class2	etiology of acute lower respiratory tract infection in children from alabang  metro manila  the etiology of acute lower respiratory tract infection  alri  was identified in 235  43 8   of 537 hospitalized children less than 5 years of age  clinical evidence of measles was found in 258  48 0   patients  of whom 59 had a second viral infection  a viral agent was identified in an additional 121 patients  so that a total of 379  70 6   had viral infections  after measles  respiratory syncytial virus was the most common respiratory virus  bacteremia was noted in 72 children  13 4    occurring as frequently in children with measles  14 8   as in those without  12 1    haemophilus influenzae and salmonella typhi were predominant in the former  and h  influenzae  staphylococcus aureus  and streptococcus pneumoniae were prominent in the latter  the presence of bacterial antigen in urine was not helpful in identifying bacterial infection  extrapulmonary and intrapleural complications  concomitant measles  complicated alri  female gender  and malnutrition were associated with increased mortality among children with alri  the importance of measles immunization  vitamin a supplementation for alleviation of defects associated with malnutrition  and timely antimicrobial therapy is emphasized  
class2	acute respiratory tract infections among a birth cohort of children from cali  colombia  who were studied through 17 months of age  for this study  340 children less than 18 months old from a low income  urban neighborhood in cali  colombia  were observed from birth by means of weekly home visits to detect cases of acute respiratory tract infection  all suspected cases were confirmed by trained doctors in a special clinic  information on symptoms  signs  and potential risk factors was documented prospectively  etiologic agents were identified in cases of lower respiratory tract infection  lri   the overall incidence of acute respiratory tract infection was 6 6 cases per child year at risk  the incidence of upper respiratory tract infection was 4 9 cases per child year at risk and that of lri was 1 7 cases per child year at risk  crowding in the home was found to be significantly associated with an increased incidence of lri  respiratory syncytial virus was the viral agent most frequently isolated from cultures of nasopharyngeal aspirates of children with lri  staphylococcus aureus was the bacterial agent most frequently isolated from the blood of patients with lri  
class2	isolation and identification of viral agents in argentinian children with acute lower respiratory tract infection  from a total population of 1 002 children with acute lower respiratory infection  alri   identification of virus was achieved in 304 cases  in this survey  1 000 nasopharyngeal aspirate and 13 lung tissue samples were tested in four cell lines  hep 2  mrc 5  mdck  and llc mk2  and by indirect immunofluorescence  iif   while 242 paired sera were studied by complement fixation  respiratory syncytial virus  rsv  was the most frequently detected agent  n   183   followed by adenovirus  n   28   parainfluenza  n   5  and 3  n   16  viruses  and influenza a  n   10  and b  n   4  viruses  the sensitivity and specificity of iif identification vs  isolation in cell culture were high for rsv  91 5  and 94 9   respectively   however  iif proved poorly sensitive for detection of adenovirus  sensitivity  23 8   specificity  100    the complement fixation test proved the least effective  with a sensitivity of only 41 5   therefore  on the basis of our experience  it appears that the yield for positive diagnosis of virus is increased if both isolation in multiple cell lines and identification by means of iif are used  our survey provides for the first time reliable data on the viral etiology of alri in argentina  as determined by three different methods  
class2	acute lower respiratory tract infection due to virus among hospitalized children in dhaka  bangladesh  the nature of acute lower respiratory tract infection  alri  in hospitalized children and of the associated viral agents was assessed in a study of 601 children less than 5 years old over a 24 month period  of these children  80  were less than 24 months of age and the ratio of boys to girls was 1 7 1  pneumonia  86 5  of cases  was the most frequently observed clinical manifestation  shedding of virus was detected in 21 1  of the children  the highest rate occurred in infants 0 5 months old  27   as compared with a rate of only 12 5  in children 25 60 months old  virus was detected in 33 3   32 8   21 2   and 20  of the cases of tracheobronchitis  bronchiolitis  pneumonia  and croup  respectively  among the viruses detected  78  were respiratory syncytial virus  rsv   91  of infections with this virus occurred in children less than 2 years old  and 14 4  were influenza virus types a and b  of the rsv infections  61  occurred in infants less than 1 year old  the case fatality rate was 6 8  overall and was 4 8  in virus associated cases  no consistent pattern of seasonal occurrence of viral infections was discerned  rsv was detected throughout the year  with increased prevalence from january to april  
class2	a hospital based study of acute viral infections of the respiratory tract in thai children  with emphasis on laboratory diagnosis  the hospital based study described here examined the viruses found in 738 children less than 5 years old who presented at ramathibodi hospital  bangkok  thailand  from january 1986 to december 1987 with acute respiratory tract infections  three methods for detection of viral infection are compared  direct examination of epithelial cells of the respiratory tract with the use of fluorescent antibody staining  isolation of virus  and measurement of antibody in acute  and convalescent phase sera  viral infections were found in 44 7  of the study population  diagnosis by the examination of epithelial cells with the fluorescent antibody staining procedure was found to have several deficiencies  however  this technique was the most sensitive for diagnosis of infection due to respiratory syncytial virus  isolation of virus was the best method for identification of adenoviruses  parainfluenza 1 and 3 viruses  and influenza b virus  problems associated with serodiagnosis included failure to obtain specimens of convalescent phase blood in 24 5  of cases and insensitivity of serodiagnosis for young children except for the identification of antibody to influenza a virus  the combination of all three tests yielded the best rate of detection of virus  
class2	vaccination for disease  recombinant virus vaccines that express a limited number of epitopes are currently being developed to prevent disease by changing the relative balance between viral spread and the immune response  some circumstances  however  were found in infections with a noncytopathic virus in which vaccination caused disease  sensitive parameters included the genetic background of the host  the time or dose of infection  and the constituents of the vaccine  thus  immunopathologic damage by t cells may be an unwanted consequence of vaccination with the new types of peptide or recombinant vaccines that are being investigated for the human immunodeficiency viruses and other pathogens  
class2	the effect of anti neoplastic drugs on murine acquired immunodeficiency syndrome  the murine acquired immunodeficiency syndrome  maids  is associated with proliferation of target cells that have been infected by a defective retrovirus  to control the growth of this primary neoplasia  virus inoculated mice were treated with anti neoplastic drugs  paradoxically  cyclophosphamide  which is also immunosuppressive  was very effective in preventing the appearance and progression of the disease  in restoring a normal t cell function  and in depleting the number of infected target cells  this result suggests that the proliferating infected target cells were responsible for the immunodeficiency  
class2	htlv i associated myelopathy  ham  after blood transfusion in a patient with cd2  hairy cell leukemia  hairy cell leukemia complicating hemolytic anemia developed in a 46 year old woman  morphologically and cytochemically typical hairy cells were found to express both cd20 and cd2 antigens  expression of surface igg of kappa chain type and the rearrangement of ig but not t cell receptor beta genes confirmed a b cell origin of the leukemia  blood transfusion was followed by disappearance of the hemolysis and a marked improvement of the leukemia  however  the patient developed progressive spastic spinal paraplegia about seven months after transfusion and was diagnosed as having htlv i associated myelopathy  ham  by the demonstration of htlv i antibodies in serum and cerebrospinal fluid  htlv i infection via the transfusion may have been involved in the hematologic improvement seen in this patient  autopsy showed demyelination  vacuolar degeneration  gliosis  and perivascular cuffing in the white matter of spinal cord without evidence of leukemic infiltration  
class2	occurrence of multiple types of human papillomavirus in genital tract lesions  analysis by in situ hybridization and the polymerase chain reaction  more than 22 types of human papillomavirus  hpv  have been detected in genital tract squamous cell intraepithelial lesions  seven of two hundred eighty six  2 4   genital tract tissues in which hpv dna was detected by in situ hybridization contained two or more different hpv types  when analyzed by site  5 of 204  2 4   of cervical intraepithelial lesions were infected by more than one type  compared with 2 of 82  2 4   of vulvar lesions  the rate for low grade lesions was similar  5 218  2 3   to that for high grade lesions  2 68  2 9    in contrast  two different hpv types were detected in 6 33  18   of tissues by the polymerase chain reaction  pcr  using type specific primers for eight hpv types  it is concluded that infection by one hpv type is rarely associated with concurrent  active  infection by a second hpv type  even though dna of a different viral type can be detected by pcr in about one fifth of such cases  further study is required to determine if an existing hpv infection can inhibit replication by a different hpv type  
class2	olfactory identification deficits in hiv infection  objective  impaired odor identification is described in a number of cns disorders  and human immunodeficiency virus  hiv  infects the cns in a large percentage of patients  to evaluate whether impaired olfaction may indicate cns disease  the authors measured odor identification in patient groups defined along a continuum of progressive immunodeficiency and in a comparison group  method  most of the 42 hiv infected patients in the study were outpatients in a clinic specializing in treatment of hiv infected individuals  the comparison subjects were 37 healthy age  and sex matched individuals who were recruited from hospital and medical school personnel  ten of the patients were hiv seropositive but had no symptoms  24 had clinical evidence of immunocompromise  and eight had hiv dementia  all subjects were given the university of pennsylvania smell identification test  which presents common odorants and requires the subject to identify the odor from a four item word list  the data were analyzed by using analysis of variance after arc sine transformation and scheffe post hoc analysis  results  all patients scored significantly lower on the smell identification test than did the comparison subjects  the patients with hiv dementia had significantly lower scores than did the other two groups of patients  conclusions  clinically  impaired olfaction might serve as a marker of early cns hiv involvement  future studies should attempt to match comparison and experimental populations for socioeconomic status and hiv risk behavior  
class2	roseola infantum and other syndromes associated with acute hhv6 infection  eight cases of acute human herpesvirus type 6  hhv6  infection in infants were diagnosed serologically by the demonstration of igm anti hhv6  8 8  and a significant change in total anti hhv6 antibody titre  6 8   four infants were sufficiently ill to require admission to hospital and further investigations  one with encephalitis and three with gross hepatosplenomegaly  two of whom had evidence of simultaneous infection with another herpes virus  the remaining four infants had an illness compatible with roseola infantum  although this diagnosis had not been made clinically  sera from two of those infants with rash had been sent for analysis to exclude rubella because the infants  mothers were pregnant  the other two had received antibiotics when febrile  and the subsequent appearance of the roseola rash had raised the possibility of antibiotic allergy  the data suggest that there are clinical syndromes in addition to roseola infantum associated with the presence of igm anti hhv6  in which serological screening for evidence of acute hhv6 infection may be useful  
class2	amebic meningoencephalitis in a patient with aids caused by a newly recognized opportunistic pathogen  leptomyxid ameba  a fatal case of meningoencephalitis due to a leptomyxid ameba in a patient with the acquired immunodeficiency syndrome is presented  this opportunistic organism has not been previously recognized as a human pathogen  a 36 year old male intravenous drug abuser died after an 18 day hospital course heralded by fever and headache and followed by nuchal rigidity and hemiparesis  computed tomography of the head showed multiple hypodense lesions  neuropathologic examination showed that in addition to human immunodeficiency virus encephalomyelitis  there was multifocal meningoencephalitis with trophozoites and cysts morphologically indistinguishable from those of acanthamoeba  these organisms were also found in the kidneys and adrenal glands  by immunofluorescence  the parasites showed antigenic identity with a free living leptomyxid ameba and failed to react with any of a spectrum of antiacanthamoeba antisera  this emphasizes the importance of immunofluorescence identification of morphologically indistinguishable ameba species  
class2	seborrheic dermatitis and hiv infection  qualitative analysis of skin surface lipids in men seropositive and seronegative for hiv  we measured skin surface lipids  cholesterol  free fatty acids  triglycerides  wax esters  and squalene  in patients seropositive for human immunodeficiency virus  hiv  and those seronegative for hiv with and without seborrheic dermatitis  cholesterol and wax ester fractions were similar in all four groups but triglycerides and squalene were significantly increased and free fatty acids significantly decreased in hiv positive patients  regardless of the presence of seborrheic dermatitis  in addition  a strong negative correlation was found between free fatty acid and triglyceride levels  we conclude that abnormalities of skin surface lipids are not associated with the development of seborrheic dermatitis in hiv positive persons but are associated with hiv infection itself  
class2	the evolution of lymphadenopathy and hypergammaglobulinemia are evidence for early and sustained polyclonal b lymphocyte activation during human immunodeficiency virus infection  to examine whether polyclonal activation of b lymphocytes as measured by hypergammaglobulinemia contributes to lymphadenopathy in human immunodeficiency virus  hiv  infection  correlates of adenopathy were examined in 240 homosexual men  lymph node size was measured in 12 sites semiannually over 4 years  both adenopathy and hyperglobulinemia developed within 1 year after seroconversion and persisted at high levels  adenopathy declined near diagnosis of aids whereas serum igg decreased 8 16 months after diagnosis  adenopathy attributable to hiv occurred in all palpable node groups  by logistic regression  hiv positive men were best discriminated from hiv negative men by size of posterior cervical nodes and the number of sites with enlarged nodes  in a repeated measures model of covariance  adenopathy in hiv positive men was associated with more cd4  cells  p less than  002   elevated serum globulins  p less than  01   and lower platelet counts  p less than  05   adenopathy declined over time  p less than  001  and with diagnosis of aids or aids related complex  p less than  03   thus  adenopathy and hypergammaglobulinemia are correlated and follow a similar course through various stages of hiv infection  suggesting that both are caused by polyclonal b cell activation  
class2	human t lymphotropic virus type ii  htlv ii  infection in a cohort of new york intravenous drug users  an old infection  to identify risk factors for human t lymphotropic virus type ii  htlv ii  infection in intravenous drug users  ivdus   participants in a longitudinal study of human immunodeficiency virus  hiv  infection in a new york methadone maintenance program were studied  of 270 participants tested for htlv i ii  21  8   were seropositive  of those  15  71   had htlv ii specific sequences by polymerase chain reaction  pcr  and 1  5   had both htlv i  and  ii specific sequences  3 persons with indeterminate serologic results were also pcr positive for htlv ii  htlv ii infection was significantly associated with older age but was not predicted by sex  race  socioeconomic status  transfusion history  or hiv infection status  behavioral factors since 1978  such as duration and frequency of intravenous drug use  needle sharing  visits to shooting galleries  or number of sex partners  were also not associated with htlv ii infection  these findings are in contrast with the association of these risk factors with hiv in this group and suggest that  among ivdus  htlv ii is an older endemic infection that is less efficiently transmitted than hiv  
class2	protection against zosteriform spread of herpes simplex virus by monoclonal antibodies  the in vivo protective role of herpes simplex virus  hsv 1  specific antibody was analyzed using monoclonal antibodies  mabs  reactive with discrete antigenic sites on glycoproteins b  c  and d  gb  gc  gd  in the murine zosteriform spread model of hsv 1  all of the anti gc and anti gd mabs  and one of four anti gb mabs  b6  were protective  the in vitro abilities of the mabs to neutralize hsv 1 and mediate antibody dependent cellular cytotoxicity  adcc  against hsv 1 infected cells were examined as potential mechanistic correlates to in vivo protection  all animals given mabs at high adcc unit doses were protected  some but not all mice given mabs at high adcc unit doses were protected  these studies designate specific epitopes recognized by protective antibodies and indicate that protection from the neurologic spread of hsv may be related to neutralization  adcc  or both  the actual contribution of adcc and neutralization to in vivo antibody mediated protection remains unclear  
class2	epidemiologic patterns of wild type hepatitis a virus determined by genetic variation  hepatitis a virus  hav  isolates from different parts of the world are a single serotype  however  genetic analysis of the vp1 genome region of published hav sequences suggested that distinct genotypes of hav could be defined based upon the geographic source of the original isolates  to circumvent the process of cell culture adaptation or animal passage  a 247 bp segment within the vp1 genome region of wild type hav was amplified by reverse transcription followed by polymerase chain reaction amplification in the presence of negative  and positive sense primers  from the sequences obtained from 22 epidemiologically distinct hav isolates  three genetic groups of hav could be delineated  two of the groups differed by 10   while the third group differed from other isolates by approximately 20   these investigations indicate that hav isolates from different parts of the world can be differentiated genetically  which will facilitate studies of epidemiologic transmission  
class2	genome analysis of adenovirus type 31 strains from immunocompromised and immunocompetent patients  adenovirus type 31  ad31  was isolated from 15 immunocompromised patients in 12 of whom seroconversion was also recorded  ad31 infection has a substantial clinical relevance since 8 of 10 with lower respiratory tract infection and 4 of 4 with hepatitis died  therefore  ad31 isolates from immunocompetent and immunodeficient hosts were compared by restriction endonuclease analysis  nine genome types were identified among the 79 ad31 isolates  pairwise comparison of comigrating restriction fragments indicated that the genome types could be divided into three genomic clusters  several ad31 genome types were isolated from immunocompromised patients  but no highly virulent genome type could be found  a genome type was identified in a child with severe combined immunodeficiency who originally was infected with another genome type  this observation is suggested to have evolutionary implications  
class2	comparison of heterotypic protection against influenza a taiwan 86  h1n1  by attenuated and inactivated vaccines to a chile 83 like viruses  children  n   192  aged 3 19 years from 98 families completed this double blind  placebo controlled study comparing the efficacy of a bivalent attenuated  cr  vaccine with trivalent inactivated  ti  vaccine  both vaccines contained a chile 83  h1n1  like antigens  after vaccination the geometric mean titer to a taiwan 86  h1n1  was 1 36 in the cr group  1 92 in the ti group  and 1 5 in the placebo group  during the influenza a taiwan 86  h1n1  epidemic  21 4  of cr recipients  16 7  of ti recipients  and 43 9  of placebo recipients were infected with influenza a taiwan  ti vaccine provided better heterotypic protection than did cr vaccine for children aged 10 18 years  infection rate  0 vs  24   respectively  p less than  025   in contrast  in the younger children  3 9 years   cr vaccine tended to be more protective  19  vs  26  for ti   
class2	recovery of human immunodeficiency virus type 1 from semen  minimal impact of stage of infection and current antiviral chemotherapy  because exposure to semen is important for the sexual transmission of human immunodeficiency virus type 1  hiv   the relationship of stage of infection and antiviral chemotherapy to isolation of hiv from semen was investigated  whereas hiv was isolated from peripheral blood mononuclear cells of all seropositive persons tested  it was isolated from semen in only 11  32   of 34 men  including 3 of 6 who were studied sequentially over time  hiv was isolated from 6  32   of 19 semen specimens from 14 asymptomatic persons  centers for disease control  cdc  class ii or iii  and from 10  28   of 36 semen specimens from 20 symptomatic patients  cdc class iv   isolation of hiv from semen did not correlate with cd4  or cd8  t lymphocytes counts or zidovudine therapy  seropositive men may shed hiv in semen early in the course of infection  and zidovudine therapy seems to have no effect on the recovery of hiv and  thus  on the potential for sexual transmission of hiv  
class2	antiidiotypic responses to immunization with anti leu 3a in human immunodeficiency virus seropositive individuals  anti idiotypic antibodies to anti cd4 monoclonal antibodies  mabs  have been reported to bind to the human immunodeficiency virus  hiv  envelope glycoprotein gp120  to establish whether hiv infected patients can mount an anti idiotypic response to murine mab  four individuals with symptoms of aids related complex  arc  were immunized over 10 weeks with six intramuscular injections of anti leu 3a  1 mg   despite their immunocompromised state  all patients made anti constant region and anti idiotypic antibodies  although the amplitude of the responses varied between individuals  no significant toxic or allergic reactions were seen  and there were no changes in clinical status during the 6 months after immunization  no increase in serum hiv neutralization titers was seen  and purified anti idiotypic antibodies did not bind gp120  
class2	comparative virologic studies of condylomata acuminata reveal a lack of dual infections with human papillomaviruses  condylomata acuminata are epithelial proliferations caused by infection of the anogenital squamous epithelium with human papillomavirus  hpv   dna dna hybridization techniques and the extremely sensitive polymerase chain reaction  pcr  were used to analyze biopsies from patients with clinically diagnosed condyloma acuminatum for the presence of hpv dna  pcr analyses using primers and oligonucleotide probes specific for the e6 e7 region of hpv 6   11  or  16 showed that 31  93 9   of 33 tissue biopsies contained hpv dna  22 contained type 6 dna  6 contained type 11 dna  and 3 contained type 16 dna  eleven biopsies positive by pcr were southern hybridization negative or were considered inadequate for southern analysis  in all 11  the presence of hpv dna was corroborated by the observation of histopathologic evidence suggestive of hpv infection or by in situ hybridization  no evidence of multiple infections with hpv 6 or  11 and hpv 16 was seen  
class2	encephalitogenicity for rats of myelin basic protein without the aid of water in oil emulsions  the induction of experimental allergic encephalomyelitis  eae  with purified myelin basic protein  mbp  has  heretofore  required its incorporation in a water in oil emulsion or adsorption on particulate adjuvants  in the present work  the absorption of a saline solution of mbp from the peritoneal cavity into the mediastinal lymph nodes was increased by giving repeated inoculations or by pretreating rats with a peritoneal irritant  under these conditions  the only adjuvant needed for production of eae was aqueous pertussis vaccine which was injected separately a few hours or one day after the mbp  pertussis vaccine was also necessary for production of eae with intradermal injection of aqueous mbp  by injecting the aqueous mbp directly into pre enlarged popliteal lymph nodes  it was possible to produce eae without the pertussis vaccine  thus  eae can be induced in rats using mbp without the addition of freund s adjuvant or pertussis vaccine  
class2	dietary intake in patients with acquired immunodeficiency syndrome  aids   patients with aids related complex  and serologically positive human immunodeficiency virus patients  correlations with nutritional status  one of the major clinical manifestations of the acquired immunodeficiency syndrome  aids  and aids related complex  arc  is the development of cachexia  this most likely results from a multifactorial interplay of poor diet  malabsorption  and altered metabolism  to assess the potential role of nutrient intake in the development or persistence of malnutrition  a detailed analysis was performed of a 72 hr diet record in clinically stable patients with aids  n   18   arc  n   12  and in human immunodeficiency virus  hiv  seropositive controls without significant manifestations of disease  n   13   total calorie intake was 39 1     13 2 kcal kg day in aids patients vs 34 6     7 8 kcal kg day in arc patients or 31 9     17 7 kcal kg day in hiv seropositive cases  all p   ns   likewise  mean protein intakes were similar among the groups and exceeded recommended daily dietary allowance  rda  guidelines  the mean body weight changes from the inception of illness were  11     1  in aids   6     7  in arc  vs  3     2  in hiv seropositive only cases  p less than 0 05 vs aids and arc   dietary vitamin and mineral analysis revealed that 88  of aids  88  of hiv seropositive  and 89  of arc patients were ingesting less than 50  rda for at least one nutrient  the mean number of deficiencies per patient was 1 8     1 3 in aids  3 8     3 5 in arc  and 2 9     2 5 in hiv seropositive only cases  p less than 0 05 aids vs arc   there were no significant correlations between specific anthropometric measurements and dietary intakes of protein or fat  
class2	children born to women with hiv 1 infection  natural history and risk of transmission  european collaborative study  600 children born to hiv infected mothers by june 15  1990  in ten european centres were followed to study the natural history of hiv infection and the vertical transmission rate  they were seen at birth  every 3 months up to 18 months of age  and every 6 months thereafter  at last follow up  64 children were judged to be hiv infected and 343 had lost antibody and were presumed uninfected  the initial clinical feature in infected children was usually a combination of persistent lymphadenopathy  splenomegaly  and hepatomegaly  though 30  of children presented with aids  or with oral candidosis followed rapidly by aids  an estimated 83  of infected children show laboratory or clinical features of hiv infection by 6 months of age  by 12 months  26  have aids and 17  die of hiv related disease  subsequently  the disease progresses more slowly and most children remain stable or even improve during the second year  the vertical transmission rate  based on results in 372 children born at least 18 months before the analysis  was 12 9   95  cl 9 5 16 3    virus has been repeatedly isolated in an additional small proportion of children  2 5   95  cl 0 7 6 3   who lost maternal antibody and have remained clinically and immunologically normal  without a definitive virological diagnosis  the monitoring of immunoglobulins  cd4 cd8 ratio  and clinical signs could identify hiv infection in 48  of infected children by 6 months  with a specificity of more than 99   
class2	a controlled trial comparing vidarabine with acyclovir in neonatal herpes simplex virus infection  infectious diseases collaborative antiviral study group  background  despite the use of vidarabine  herpes simplex virus  hsv  infection in neonates continues to be a disease of high morbidity and mortality  we undertook a controlled trial comparing vidarabine with acyclovir for the treatment of neonatal hsv infection  methods  babies less than one month of age with virologically confirmed hsv infection were randomly and blindly assigned to receive either intravenous vidarabine  30 mg per kilogram of body weight per day  n   95  or acyclovir  30 mg per kilogram per day  n   107  for 10 days  actuarial rates of mortality and morbidity among the survivors after one year were compared overall and according to the extent of the disease at entry into the study  infection confined to the skin  eyes  or mouth  encephalitis  or disseminated disease   results  after adjustment for differences between groups in the extent of disease  there was no difference between vidarabine and acyclovir in either morbidity  p   0 83  or mortality  p   0 27   none of the 85 babies with disease confined to the skin  eyes  or mouth died  of the 31 babies in this group who were treated with vidarabine and followed for a year  88 percent  22 of 25  were judged to be developing normally after one year  as compared with 98 percent  45 of 46  of the 54 treated with acyclovir  95 percent confidence interval for the difference   4 to 24   for the 71 babies with encephalitis  mortality was 14 percent with vidarabine  5 of 36  and with acyclovir  5 of 35   of the survivors  43 percent  13 of 30  and 29 percent  8 of 28   respectively  were developing normally after one year  95 percent confidence interval for the difference   11 to 39   for the 46 babies with disseminated disease  mortality was 50 percent  14 of 28  with vidarabine and 61 percent  11 of 18  with acyclovir  95 percent confidence interval for the difference   20 to 40   of the survivors  58 percent  7 of 12  and 60 percent  3 of 5   respectively  were judged to be developing normally after one year  95 percent confidence interval for the difference   40 to 50   both medications were without serious toxic effects  conclusions  in this multicenter  randomized  blinded study there were no differences in outcome between vidarabine and acyclovir in the treatment of neonatal hsv infection  the study lacked statistical power to determine whether there were sizable differences within the subgroups of those with localized hsv  encephalitis  or disseminated disease  
class2	predictors of morbidity and mortality in neonates with herpes simplex virus infections  the national institute of allergy and infectious diseases collaborative antiviral study group  background  in a controlled trial comparing acyclovir with vidarabine in the treatment of neonatal herpes simplex virus  hsv  infection  we found no significant difference between the treatments in adjusted mortality and morbidity  hence  we sought to define for the entire cohort  n   202  the clinical characteristics that best predicted the eventual outcome in these neonates  methods  data were gathered prospectively at 27 centers between 1981 and 1988 in infants less than one month of age who had virologically confirmed hsv infection  we examined the outcomes by multivariate analyses of 24 variables  disease was classified in one of three categories based on the extent of the involvement at entry into the trial  infection confined to skin  eyes  or mouth  encephalitis  or disseminated infection  results and conclusions  there were no deaths among the 85 infants with localized hsv infection  the mortality rate was significantly higher in the 46 neonates with disseminated infection  57 percent  than in the 71 with encephalitis  15 percent   in addition  the risk of death was increased in neonates who were in or near coma at entry  relative risk  5 2   had disseminated intravascular coagulopathy  relative risk  3 8   or were premature  relative risk  3 7   in babies with disseminated disease  hsv pneumonitis was also associated with greater mortality  relative risk  3 6   in the survivors  morbidity was most frequent in infants with encephalitis  relative risk  4 4   disseminated infection  relative risk  2 1   seizures  relative risk  3 0   or infection with hsv type 2  relative risk  4 9   with hsv infection limited to the skin  eyes  or mouth  the presence of three or more recurrences of vesicles was associated with an increased risk of neurologic impairment as compared with two or fewer recurrences  
class2	syncytial giant cell hepatitis  sporadic hepatitis with distinctive pathological features  a severe clinical course  and paramyxoviral features  background and methods  we describe a new form of hepatitis  occurring in 10 patients over a period of six years  characterized clinically by manifestations of severe hepatitis  histologically by large syncytial giant hepatocytes  and ultrastructurally by intracytoplasmic structures consistent with paramyxoviral nucleocapsids  results  the patients ranged in age from 5 months to 41 years  the tentative clinical diagnosis before biopsy was non a  non b hepatitis in five patients and autoimmune chronic active hepatitis in the others  five patients underwent liver transplantation  the others died  the diagnosis of syncytial giant cell hepatitis was established pathologically  the liver cords were replaced in all 10 patients by syncytial giant cells with up to 30 nuclei  in 8 of the 10 the cytoplasm contained pleomorphic particles of 150 to 250 microns  filamentous strands  and particles of 14 to 17 nm with peripherally disposed spikes resembling paramyxoviral nucleocapsids  structures resembling degenerated forms were found in the other two patients  one of two chimpanzees injected with a liver homogenate from the index patient had an increase in the titer of paramyxoviral antibodies  probably an anamnestic reaction to previous paramyxoviral infection  suggesting that a paramyxoviral antigen but not viable virus was present in the liver homogenate  conclusions  although further virologic studies will be required for precise classification  we believe that paramyxoviruses should be considered in patients with severe sporadic hepatitis  
class2	progression of human papillomavirus type 18 immortalized human keratinocytes to a malignant phenotype  we have developed a model system for progression of human epithelial cells to malignancy  using a human papillomavirus type 18  hpv 18  immortalized human keratinocyte cell line  cells of cell line fep 1811 were nontumorigenic in athymic mice through at least 12 passages in culture  but after 32 passages were weakly tumorigenic  producing tumors that regressed  after 62 passages they produced invasive squamous cell carcinomas that grew progressively  the progression to malignancy was associated with an increase in the efficiency of forming colonies in soft agar and with altered differentiation properties  in an organotypic culture system  fep 1811 cells at passages 12 and 32 exhibited features typical of premalignant intraepithelial neoplasia in vivo  and cells at passage 68 exhibited features consistent with squamous cell carcinomas  no change in copy number of the transfected hpv 18 genome or in the level of expression of the viral transforming gene products e6 and e7 was detected between tumorigenic and nontumorigenic cells  cytogenetic analysis of cells at early  middle  and late passage levels and cells cultured from tumors revealed that several chromosomal abnormalities segregated with the tumorigenic cell populations  
class2	efficacy of induction therapy in cadaveric renal transplantation comparing rabbit antithymocyte serum and minnesota antilymphoblast globulin  from august 1986 to july 1989  98 patients receiving primary cadaveric kidney transplants received either rats  n   50  or malg  n   48  during the induction phase of a quadruple immunosuppressive protocol  patient groups were well matched  the duration of rats and malg treatment and the time of cya induction were equivalent  serum creatinine and rejection episodes up to 1 year were not statistically different  hematologic side effects resulted in dose reduction of malg in 42  of patients without adverse rejection results  in the rats group  no dosage reductions were required  one year patient survivals  96  to 100    and 1 year graft survival  82  to 85   were not significantly different in the 2 groups  infectious complications were 30  higher in the malg group and a significant factor in 2 deaths  monitoring of lymphocyte subsets revealed insignificant differences in the percent of decrease of each cell population between malg and rats groups during induction  
class2	depression  distress  lymphocyte subsets  and human immunodeficiency virus symptoms on two occasions in hiv positive homosexual men  we evaluated the extent to which depressive disorders  psychiatric distress  and psychosocial stressors are related to three measures of human immunodeficiency virus  hiv  illness  both cross sectionally and during a 6 month period  in a community sample of 124 hiv positive homosexual men  the dependent variables are immune status measured by cd4 and cd8 cell subsets  number of signs and symptoms commonly associated with hiv infection  and a cumulative index of hiv illness stage  we chose to focus on cd4 cell count because it is the immune marker most closely linked to the clinical consequences of hiv infection  we found no relationships between the independent variables and immune status or illness stage  the hiv positive men who were depressed or distressed or who reported more life stressors had no greater immunosuppression or more advanced illness stage than did the others  either concurrently or across occasions  we did find a suggestive pattern of association between depressive disorders  distress  and stressors and the number of hiv related symptoms  which warrants further study  
class2	multidisciplinary baseline assessment of homosexual men with and without human immunodeficiency virus infection  i  overview of study design  although much is known about the virus believed by most experts to be the cause of the acquired immunodeficiency syndrome and about its pathogenic actions  major areas of ignorance remain  among these are the reasons for the varying time between infection with human immunodeficiency virus and development of acquired immunodeficiency syndrome  the relationship between neurologic and medical aspects of the disease  the time course of neuropsychological findings  and the prevalence of psychiatric morbidity  we assessed 124 homosexual men who were positive for human immunodeficiency virus and 84 who were negative for the virus  in this article we describe the study design  method of recruitment  and medical and demographic characteristics of the cohort  which will be followed up for 5 years  
class2	multidisciplinary baseline assessment of homosexual men with and without human immunodeficiency virus infection  ii  standardized clinical assessment of current and lifetime psychopathology  despite numerous reports of the psychiatric consequences of human immunodeficiency virus infection  few reports describe systematic diagnostic assessments of people with human immunodeficiency virus infection  we studied the results of standardized clinical assessments of current and lifetime psychopathology in a large group of homosexual men whose serologic status was known  results indicated low rates of current mental disorders but very high rates of lifetime major depression and alcohol and other psychoactive substance abuse and dependence disorders  measures of severity of psychopathology and functioning also indicated  on the whole  good current functioning  no significant relationship was found between stage of medical illness or immune status and any measure of psychiatric disturbance  
class2	multidisciplinary baseline assessment of homosexual men with and without human immunodeficiency virus infection  iii  neurologic and neuropsychological findings  we explored the possibility that neurologic and neuropsychological changes constitute the earliest detectable manifestations of human immunodeficiency virus  hiv  infection  without knowledge of hiv status  we assessed neurologic signs and symptoms and administered a battery of neuropsychological tests to 208 homosexual men  of whom 84 were hiv negative  49 were hiv positive and asymptomatic  29 were mildly symptomatic  and 46 had significant medical symptoms but not the acquired immunodeficiency syndrome  there was no difference between the hiv negative and hiv positive men in the frequency of neurologic signs or of defective or borderline performance on any neuropsychological test  however  hiv positive men performed slightly but significantly worse than hiv negative men on tests of verbal memory  executive function  and language  similar results were obtained when comparisons were limited to hiv positive medically asymptomatic and hiv negative men  there was no degradation of neurologic status or neuropsychological performance across stages of hiv severity  but neurologic and neuropsychological summary scores correlated with cd4 cd8 ratios in the hiv positive group  ratings of neurologic signs and symptoms correlated with neuropsychological summary scores in the hiv positive group only  cognitive complaints were more frequent in the hiv positive men  they correlated with actual test performance in the hiv positive but not hiv negative men  the constellation of subjective and objective neuropsychological and neurologic findings suggests the possibility of a definable syndrome associated with hiv infection in asymptomatic individuals  
class2	a preliminary report on the neuropsychologic sequelae of human immunodeficiency virus  the neuropsychologic sequelae of acquired immunodeficiency syndrome and human immunodeficiency virus were studied by comparing the results of a neuropsychologic test battery administered to the following three groups of danish homosexual men  20 patients with acquired immunodeficiency syndrome  20 asymptomatic subjects who tested positive for the human immunodeficiency virus  and a matched control group of 20 subjects who tested negative for the human immunodeficiency virus  the group with acquired immunodeficiency syndrome performed significantly worse than the control subjects on the tests measuring concentration  memory  and psychomotor speed  the group with human immunodeficiency virus performed significantly worse than the control subjects on the tests measuring verbal memory and psychomotor speed  on the other tests  their results varied  the study supports the hypothesis that not only patients with acquired immunodeficiency syndrome but also asymptomatic subjects with human immunodeficiency virus may be neuropsychologically impaired early in the course of the disease  
class2	effectiveness of psychoeducational interventions in reducing emotional distress after human immunodeficiency virus antibody testing  to examine the effectiveness of three psychoeducational interventions in reducing emotional distress after voluntary serologic testing for human immunodeficiency virus 1 307 physically asymptomatic adults were randomly assigned to standard counseling  counseling plus a three session interactive video program  or counseling plus six individual sessions of stress prevention training  subjects were evaluated using five standardized distress measures at entry and 3 months later  among the 204 human immunodeficiency virus seronegative subjects  mean distress measures decreased significantly after all three interventions without differential treatment effects  among the 103 human immunodeficiency virus seropositive subjects  mean distress measures decreased significantly after the stress prevention training and did not significantly increase in the other two interventions  we conclude that stress prevention training is particularly helpful after notification of human immunodeficiency virus seropositivity  
class2	pathogenesis of corneal oedema associated with herpetic eye disease  corneal oedema and stromal disease  induced in rabbits by intrastromal injection of herpes simplex virus  type 1  strain re  hsv 1  re   reached a peak of 12 15 days after infection  corneal oedema as measured by ultrasonic pachymetry  and stromal disease as measured by a subjective scoring system  were closely related for 30 days after infection  morphometric analysis of wide field specular micrographs showed that no immediate endothelial cell damage occurred in either control or hsv 1 infected corneas  alizarin red s staining of corneas taken during the period of most severe oedema indicated no significant endothelial cell loss  however  visual inspection indicated numerous staining abnormalities  scanning and transmission electron microscopy provided evidence of an intact endothelial layer possessing integrated infiltrating cells  virus antigen could not be detected on endothelial cells by immunoperoxidase staining at any time during development of corneal oedema  the results indicate that corneal oedema associated with hsv 1 induced disease can occur in the absence of detectable virus replication and cytolysis of corneal endothelial cells  
class2	infectious mononucleosis presenting as bilateral acute dacryocystitis  a case of infectious mononucleosis presenting as bilateral acute dacryocystitis in a 7 year old girl is reported  acute dacryocystitis is uncommon in this age group  and an underlying systemic illness should be suspected particularly when it is bilateral  
class2	utility of bronchoscopic sampling techniques for cryptococcal disease in aids  although cryptococcal pneumonia is a well recognized complication of the acquired immunodeficiency syndrome  optimal diagnostic approaches remain to be defined  during a 32 month period  october 1984 to june 1987   11 patients were diagnosed with cp at our institution  the diagnosis was established in all 11 patients from specimens obtained via fiberoptic bronchoscopy  ten  and or double lumen catheter lavage  one   direct stains of sedimented bronchoalveolar lavage were positive for organisms characteristic of cryptococcus neoformans in nine of 11 patients  transbronchial biopsies were positive  special histologic stains  in six of eight patients  bronchial washings were positive  direct smear  in seven of ten patients  the bronchial brushings were positive on stain in six of nine patients  and in one patient  a wang transbronchial needle aspirate was positive on stain  fungal cultures were positive on the bal in seven of 11 patients  and on the bronchial washings in four of ten patients  the tbbx culture samples were all negative  zero of three   the serum cryptococcal antigen titer was elevated  median   1 1024  in all eight patients in which it was assayed  our data suggest that bal and bronchial washings have a combined sensitivity on smear equal to that of tbbx and superior to that of tbbx fungal culture  the tbbx does not appear to be necessary in this setting  in addition  an elevated serum cryptococcal antigen titer appears to be an important adjunct in the evaluation of pulmonary infiltrates in aids  
class2	the acute aseptic meningitis syndrome  the acute aseptic meningitis syndrome is an entity that presents a diagnostic challenge to the clinician  although many infectious and noninfectious etiologies exist for this syndrome  viruses  especially nonpolio enteroviruses  are the classic and most important agents encountered  the incidence of polio and mumps meningitis has declined dramatically in the vaccine era  but recently described pathogens  such as human immunodeficiency virus and borrelia burgdorferi  lyme disease agent  are now important considerations in the differential diagnosis  specifically treatable entities  eg  mycobacterial or fungal meningitis  herpes simplex encephalitis  parameningeal infection  that may mimic aseptic meningitis in their initial presentations must not be overlooked  a careful approach to the patient and a rational use of laboratory studies are the basis for establishing a specific diagnosis and assuring a favorable outcome  
class2	should family physicians test for human papillomavirus infection  an opposing view  recent advances in the field of molecular biology have expanded the knowledge of hpv manifestations  we have attempted to separate those circumstances when hpv testing may be useful in patient management and when it may not  routine screening for hpv has not yet been shown to be useful  one must weigh informing 10  of patients that they have a potentially oncogenic virus against the ability of a repeat papanicolaou smear to detect the lesion  on the other hand  hpv detection in the setting of an abnormal papanicolaou smear and an acetowhite lesion that on biopsy lacks the histologic features of cil does predict who is at high risk for cil  hpv typing should not affect clinical management  and we do not recommend it  hpv detection by in situ hybridization is a very useful adjunct to histological analysis in genital tract lesions that are clinically suggestive of an hpv lesion but where the histological analysis is equivocal  this ability to distinguish true hpv lesions from its mimics is often crucial to the patient  given the implications of having a sexually transmitted disease  
class2	infectious mononucleosis  epstein barr virus  and chronic fatigue syndrome  a prospective case series epstein barr viral infection  specifically infectious mononucleosis  typically has a more protracted course than other acute viral illnesses  some recent observers have additionally suggested the possibility that epstein barr virus  ebv  is the etiologic infectious agent in chronic fatigue syndrome  based on the finding of higher proportions of elevated antibodies to the ebv early antigen in some patients complaining of chronic fatigue  straus et al reported on 23 patients with chronic fatigue  83  of whom exhibited persistently elevated antibodies in modest titer to the early antigen  ten of these patients had never fully recovered from an episode of acute infectious mononucleosis  other studies had noted similar associations between persistently elevated antibodies to ebv specific antigens and chronic symptoms in patients who presented with chronic symptoms after mononucleosis  three important antigen complexes  demonstrable by immunofluorescence procedures  are expressed in ebv infected cells  the early antigen is thought to function perhaps in early replication of viral dna  a late antigenic complex  the viral capsid antigen  may represent  in addition to structural capsid proteins  components of the viral enzymatic machinery for late phases of replication or transformation  the epstein barr nuclear antigen is felt to function in viral transformation of host cells  
class2	vulvar intraepithelial neoplasia  a clinicopathologic study of 60 cases  sixty cases of vulvar intraepithelial neoplasia  vin  were analyzed clinicopathologically  24 vin i  9 vin ii  27 vin iii   the ages of the patients ranged from 21 to 83 years  mean  53 7   colposcopic examinations showed the presence of white areas in 29 cases  red areas in 9  acetowhite areas in 6 and other alterations in 13  one third of the lesions were multifocal  pruritus and burning were present in 65  of the cases  fifty one percent of the cases showed histologic changes suggestive of human papillomavirus  hpv  infection  the mean age of those patients was significantly lower than that of patients without hpv infection  in 15 cases of vin  hpv dna testing was performed with southern blot hybridization  in three  20   of those specimens hpv 16 episomal dna was identified  epithelial alterations surrounding the areas of vin were found in 24 cases  40   23 squamous cellular hyperplasias and 1 lichen sclerosus  different types of treatment were performed according to the different grades of vin  medical therapy  diathermocoagulation  local excision  hemivulvectomy and total vulvectomy  follow up was possible in 52 cases  with a mean of 33 months  range  3 98   two cases of vin i showed progression of disease over 12 24 months  
class2	improved detection of rotavirus shedding by polymerase chain reaction  to improve identification of children excreting rotavirus a method for the amplification of rotavirus rna by the polymerase chain reaction  pcr  was developed  the assay was compared with a solid phase enzyme immunoassay in the detection of rotavirus shedding by infants in hospital during the winter peak of rotavirus infections  forty children were studied in an intermediate care unit after transfer from intensive care units  only two were admitted primarily because of diarrhoea  the other thirty eight were admitted for management of various other disorders  rotavirus shedding was detected by enzyme immunoassay in twenty of the infants  and nine of these  aged 1 week to 8 months  remained in hospital for more than 5 days after the initial detection of rotavirus and could be studied long term  of 103 faecal samples from the nine infants  60  58   contained rotavirus rna detected by reverse transcriptase  rt  pcr  whereas only 37  36   were positive for rotavirus antigen by the immunoassay  chi 2   10 3  p less than 0 002   the geometric mean time of rotavirus shedding was 9 5  range 1 19  days as detected by rt pcr and 5 7  range 1 17  days by the immunoassay  p less than 0 018   in five of the nine children  rt pcr detected rotavirus shedding for 2 7 days longer than the immunoassay and in four children rt pcr was positive 1 or more days before rotavirus antigen was detected  further studies should attempt to find out whether infected infants are capable of spreading wild type virus during periods when they are not shedding antigen as detectable by enzyme immunoassay  
class2	spontaneous lymphocyte proliferation in htlv ii infection  we measured lymphocyte proliferation in the absence of antigenic stimulation in 45 htlv ii infected  9 htlv i infected  and 19 htlv i seronegative intravenous drug users  ivdu   lymphocyte proliferation was higher in ivdus infected with htlv ii than in seronegative ivdus but lower than among those infected with htlv i  higher rates of proliferation were also associated with needle sharing  cd4  and il2r  lymphocyte counts  and htlv i antibody titres  
class2	epidemiology of acute respiratory infections in young children from thailand  a prospective evaluation of the epidemiology and presentations of acute respiratory infections in children younger than 5 years of age admitted to children s hospital bangkok  1988 to 1989  was supported by the world health organization  there were 226 patients with the inclusion criteria  1 to 5 years of age  duration of illness less than 2 weeks  no prior antibiotic therapy  and low socioeconomic status  the disease categories included  croup  19 cases  bronchiolitis  60 cases  and pneumonia  147 cases  pathogens isolated were  respiratory syncytial virus  40   parainfluenza iii  1   influenza b  1   and adenovirus  1   bacterial infections were proved in 23 cases  no significant differences in clinical features between bacterial and viral pneumonia were found  interstitial radiographic patterns were more common in viral pneumonia whereas alveolar patterns were more common in bacterial pneumonia  however  91  of mixed radiographic patterns  interstitial and alveolar  in chest films were from viral pneumonia  
class2	viral pneumonia in the first month of life  we performed a 5 year review of 40 patients less than or equal to 30 days of age with viral pneumonia  isolates included respiratory syncytial virus  55    enteroviruses  15    rhinoviruses  15    adenoviruses  10    parainfluenza virus  7 5   and herpes simplex virus  5    most infants were previously healthy but had ill family members  nine were born at less than 37 weeks of gestation  symptoms and signs included tachypnea  decreased feeding  cough  cyanosis  lethargy  retractions  apnea  bradycardia  seizures and depressed consciousness  seasonality and clinical features  but not radiographic patterns  suggested specific pathogens  patients were moderately to severely ill  the median duration of hospitalization was 7 days  therapies administered included oxygen  90    mechanical ventilation  45    blood transfusions  25   and supplemental oxygen after discharge  27    the case fatality rate was 7 5   prematurity  ill appearance at presentation  lobar consolidation and adenovirus infection were risk factors for severe disease  
class2	sexually transmitted viral disease in women  during the past decade  the incidence of sexually transmitted viral diseases has increased dramatically  in many cases  diagnosis is difficult  consequences are severe  and curative therapy is not available at present  in this article  drs peaceman and gonik review current evidence about sexual transmission of viruses and discuss the latest methods of diagnosis  management  and prevention  
class2	voluntary human immunodeficiency virus testing  acceptance levels and identification of seropositive individuals  of 4340 clients of a clinic for those with sexually transmitted diseases who were eligible for voluntary  confidential  serologic testing for the human immunodeficiency virus  4246  97 8   consented to testing  23  0 5   were seropositive  of 94 persons who declined voluntary testing but who were tested in a blinded study  nine  9 6   were seropositive  seropositive persons who declined voluntary testing did not conceal their association with a risk group  while only 61  of seropositive individuals who accepted voluntary testing admitted to inclusion in a risk group before the test  voluntary testing appears to be insufficient  because 28  of the seropositive individuals were not identified as being seropositive  also  there was a significant deficiency associated with identification of risk at pretest counseling among persons agreeing to voluntary testing  
class2	bronchial hyperresponsiveness in normal subjects during attenuated influenza virus infection  fourteen healthy male subjects with hemagglutination inhibition antibody titers of 1 8 or less to homologous influenza a virus were studied  six subjects received live  attenuated influenza virus by nasal drops and by aerosol  although infection occurred in these six subjects  with the development of 4 fold or greater increases in hemagglutination inhibition antibody titers  they remained asymptomatic  eight subjects received placebo via the same route  and did not develop symptoms and showed no increase in antibody titer  prior to administration of virus or placebo  histamine diphosphate aerosol increased airway resistance only slightly  and there was no difference between the virus and placebo groups  two days after inoculation  bronchomotor responses in the placebo group were unchanged  p greater than 0 05   but in the virus infected group  bronchomotor responses were significantly greater than in the preinfected state  p less than 0 01   isoproterenol hydrochloride reversed and prevented the increase in airway resistance after histamine  suggesting that the bronchoconstriction was caused by smooth muscle contraction  our findings indicate that transient  asymptomatic respiratory virus infection augments airway smooth muscle responses  
class2	aggressive cavitary pulmonary sarcoidosis  pulmonary sarcoidosis in a young patient is usually a relatively benign disease that either resolves spontaneously or remains quiescent for many years  very rarely it pursues a more aggressive course leading to progressive lung destruction  we report a young patient who presented with stage iii sarcoidosis and over a period of 4 yr progressed to severe cavitary disease with frequent superinfections leading to bronchiectasis and chronic suppuration of the lung  eventually requiring a pneumonectomy  
class2	fine needle aspiration evaluation of lymphoproliferative lesions in human immunodeficiency virus positive patients  a multiparameter approach  forty six fine needle aspirates of lymphoproliferative lesions from 31 human immunodeficiency virus  hiv  positive patients were reviewed using cytomorphologic  immunocytochemical  flow cytometric  fcm   cytogenetic  and molecular studies  there were 29 lymphomas  15 small non cleaved cell  sncl   11 large cell  lcl   one small lymphocytic  and two hodgkin s   14 reactive hyperplasias  and three  atypical lymphoid proliferations   the reactive hyperplasias were characteristically polymorphic and polyclonal lymphoid populations  six of seven were diploid on fcm  the seventh was hypodiploid  higher proliferative indices  mean  11 6   and higher rna indices  mean  1 2  characterized this subgroup compared with published reactive lymphoid hyperplasias from patients without hiv positivity  aspirates of sncl showed monotonous populations of intermediate sized cells except in one patient where a giant cell syncytial variant occurred  nine of 13 sncl aspirates showed light chain restriction  jh rearrangement revealed b cell lineage in one aspirate in which immunocytochemical study was negative for kappa  lambda  b1  and leu 4  nine of 12 sncl were diploid  the mean proliferative index was 25 6  and the mean rna index 2 3  chromosomal translocations involving the c myc locus were demonstrated in five of seven sncl aspirates karyotyped  five of eight lcl showed light chain restriction the remaining three showed null cell phenotype  large cell lymphomas were diploid on tetraploid with the mean proliferative index of 22 0  and mean rna index of 2 2  one of two lcl aspirates karyotyped demonstrated c myc translocation  despite the multiparameter approach  a definitive diagnosis could not be reached in three aspirates  
class2	induction of cd4   human t lymphotropic virus type 1 specific cytotoxic t lymphocytes from patients with ham tsp  recognition of an immunogenic region of the gp46 envelope glycoprotein of human t lymphotropic virus type 1  although the humoral response to human t lymphotropic virus type 1  htlv i  has been well characterized in patients with htlv i associated neurologic disease  ham tsp   little is known about a functional htlv i specific human t cell response  such as ctl  in these patients  to define both the phenotype of the responding ctl and the fine specificity of this response  long term t cell lines were generated from two ham tsp patients who were from two different countries  patient s peripheral blood lymphocytes were repeatedly stimulated in vitro with an htlv i expressing autologous t cell line  the resultant long term t cell culture was shown to be cd4  and cytotoxic for targets expressing htlv i ag  using a panel of synthetic peptides that span hydrophilic regions of the htlv i gp46 envelope glycoprotein  the ctl lines generated from both patients were shown to recognize the same region of the htlv i envelope between amino acids 196 209 as defined by the synthetic peptide sp4a1  interestingly  this sequence overlaps a region of htlv i envelope that had also been shown to elicit a strong b cell response in ham tsp patients  amino acids 190 203   one ctl line recognized this htlv i epitope in the context of hla dq5 whereas the other ctl line was restricted by hla drw16  the generation of two independent ctl lines from two ham tsp patients from different geographic areas that recognize the same region of the htlv i envelope glycoprotein highlights the immunogenic nature of this envelope region  
class2	acquired immune dysfunction in cats with experimentally induced feline immunodeficiency virus infection  comparison of short term and long term infections  specific pathogen free domestic cats with experimentally induced feline immunodeficiency virus  fiv  infections of short duration  less than or equal to 10 months  exhibited depressed total leukocyte and neutrophil numbers and a marginally decreased lymphocyte proliferative response to pokeweed mitogen  pwm   while cats with infections of more lengthy duration  greater than or equal to 25 months  exhibited normal leukocyte and neutrophil numbers but a dramatic loss of responsiveness to both pwm and concanavalin a  con a   cats with short term infections exhibited a decrease in the percentage of cd4  lymphocytes in peripheral blood and a corresponding depression of the cd4  cd8  ratio  cats with long term infections exhibited a similar but more profound perturbation of the cd4  lymphocyte subset that also included a decrease in the absolute number of cd4  cells  the decreased responsiveness to con a and pwm in cats infected long term paralleled the decline in cd4  cell counts  and the duration of infection was directly correlated with the decrease in the percentage of cd4  cells  these data provide evidence supporting the hypothesis that fiv is the cause of an immune dysfunction in cats  with distinct similarities to that produced by human immunodeficiency virus  hiv  in people  
class2	marked elevations of serum alkaline phosphatase in patients with aids  we have observed many patients with aids who have unexplained marked elevations in serum alkaline phosphatase  to determine the frequency of alkaline phosphatase elevations in patients with aids  and to identify diagnoses  medications  and demographic factors associated with such elevations  we conducted a retrospective study of the first 90 consecutive aids cases in hospitals affiliated with the university of colorado health sciences center in denver  colorado  we found elevations of alkaline phosphatase in excess of 1 000 iu l in 17  of consecutive patients with aids  this level of elevation was less frequent in patients with kaposi s sarcoma but there was otherwise no significant association with diagnoses or medications  or transmission categories for aids  the majority of the patients with elevations to this level did not have documented opportunistic infections or biliary tract dilatation previously described in the  cholangitis  syndrome in aids patients  other explanations for these elevations for this common laboratory finding may exist  
class2	zidovudine use in aids free hiv 1 seropositive homosexual men in the multicenter aids cohort study  macs   1987 1989  zidovudine use data were examined in the multicenter aids cohort study to determine  i  if the proportion of pre aids participants  i e   cd4  cells less than 200 mm3 or aids related complex  taking zidovudine is high enough to explain a slower than expected rise in aids incidence in u s  homosexual men since mid 1987   ii  which factors are associated with starting zidovudine and clinical trials of zidovudine  and  iii  if pre aids patients  as a group  are being undertreated  data on zidovudine use  clinical trial participation  and sociodemographic  clinical  and hematologic variables were collected every 6 months from 1 195 aids free hiv 1 seropositive homosexual men from april 1987 to september 1989  overall prevalence of zidovudine use rose from 3 6  in mid 1987  visit 7  to 23  in mid 1989  visit 11   of those with less than 200 cd4  lymphocytes mm3  the prevalence of zidovudine use rose from 23   24  if those taking zidovudine or placebo as part of a clinical trial are included  at visit 7 to 58   69   at visit 11  of those with arc  20   23   were using zidovudine at visit 7 and 55   65   at visit 11  although numbers were small  the advanced arc participants  cd4  cells less than 200 mm3 and two or more symptoms  reported the highest treatment rates  50  78  80  60  and 74  at visits 7 11  respectively   by september 1989  42   31   of those with cd4  lymphocyte levels less than 200 mm3 were still not receiving zidovudine  suggesting that many high risk  pre aids individuals are being undertreated  to explore this finding further  we examined a range of sociodemographic  hematologic  and clinical variables to determine which factors best predicted initiation of zidovudine therapy outside of clinical trials  in multivariate analyses  cd4  lymphocyte number was the most consistent predictor of initiation of therapy over all four study visits  for each 100 cells mm3 deficit  the odds ratios were 2 3  95  c i  of 1 7 3 1  at visit 7 and 1 7   95  c i  of 1 4 2 0  at visit 11  symptom status and education level were also associated with starting zidovudine  but not at all visits  the relatively low predictive power of the clinical variables raises and the possibility that nonclinical factors not measured in the macs  drug cost  third party insurance restrictions  and individual preferences  may play an important role in predicting zidovudine use  finally  comparisons were made between seropositive participants starting clinical trials of zidovudine and the rest of the study population  no important differences were found in demographic or major clinical variables between clinical trial participants and zidovudine nonusers in this study  
class2	abnormal single motor unit behavior in the upper motor neuron syndrome  we studied the discharge pattern of single motor units  smus  in the left and right biceps muscles from a patient with nonspastic weakness of the left arm  detailed statistical analysis of the behavior of discharge patterns of 4 of 4 single motor units on the affected side showed abnormalities with characteristic features of an upper motor neuron lesion  five out of 5 single motor units recorded from the right biceps were normal  an upper motor neuron lesion affecting the left arm  predicted by our results  was confirmed by magnetic resonance imaging  mri   which showed a lesion in the right precentral gyrus  it appears that changes in single motor unit firing characteristics  caused by an upper motor neuron lesion  can be detected at a time when there is no evidence of increased  tone  and or hyperreflexia  spasticity  in the affected extremity  
class2	htlv i associated myelopathy associated with blood transfusion in the united states  epidemiologic and molecular evidence linking donor and recipient  six months after receiving 58 units of blood components  a 65 year old white man from new york city  with no other risk factors for human t lymphotropic virus type i  htlv i  infection  developed htlv i associated myelopathy tropical spastic paraparesis  ham tsp   investigation of blood donors identified a 25 year old white hispanic woman from florida whose platelets had been given to the patient and who was seropositive for the virus on a serum specimen obtained 2 years after the donation  she was born in cuba and had had 2 sexual relationships with men who either had been born in or had resided in the caribbean  polymerase chain reaction  pcr  studies of peripheral blood mononuclear cells indicated that both donor and recipient were infected with htlv i  molecular studies of a 595 nucleotide sequence in the 5  envelope region of htlv i indicated that the viruses from donor and recipient were identical in each of 32 positions in which published htlv i sequences demonstrate molecular heterogeneity  the donor and recipient viruses were also identical in 2 additional positions in which they differed from all published sequences  transfusion associated ham tsp has occurred in the united states  but additional cases should be prevented by screening blood donations for htlv i  molecular studies of htlv i may prove useful in defining the genetic heterogeneity of htlv i isolates in the united states and in studying transmission of this virus  
class2	the role of htlv in hiv 1 neurologic disease  we performed a serologic survey for antibodies to htlv i ii in the course of a longitudinal study of the neurologic complications of hiv 1 infection  nine  3 7   of 242 hiv 1 seropositive subjects and none of 60 hiv 1 seronegative control subjects had antibodies to htlv i ii by elisa  western blot and polymerase chain reaction confirmed the presence of htlv i in 2 subjects and htlv ii infection in 2 others  both hiv 1 htlv i coinfected subjects and 1 hiv 1 htlv ii coinfected subject had a slowly progressive myelopathy clinically identical tropical spastic paraparesis htlv i associated myelopathy  tsp ham   the presence of a myelopathy resembling tsp ham in the coinfected subjects suggests that hiv 1 may enhance the expression of neurologic disease caused by htlv  patients with a progressive myelopathy occurring in association with hiv 1 infection should be serologically tested for the presence of htlv  establishing dual infection has therapeutic and prognostic import as 1 of the hiv 1 htlv i subjects substantially improved with corticosteroids and the hiv 1 htlv ii subject with myelopathy had a marked improvement in the absence of therapeutic intervention  
class2	signs of cognitive change in hiv disease  an event related brain potential study  we recorded event related brain potentials  erps  from 2 groups of human immunodeficiency virus  hiv  positive men with no physical illness or neurologic involvement  9 asymptomatic  as   and 9 classified as having either acquired immunodeficiency syndrome  aids  7  or aids related complex  arc  2   in separate choice reaction time tasks  the subjects pressed buttons to randomly presented auditory or visual stimuli at probabilities of either 20 80 or 50 50  there were no group differences on any of the neuropsychological tests commonly used in screening batteries for hiv patients  in contrast  reduced p300 amplitudes and increased p300 latencies occurred in arc aids patients in response to both auditory and visual stimuli  while in as  patients such alterations occurred only in the visual modality  significant delays in p2 latency were found only in the auditory modality and then only in arc aids patients  arc aids patients alone showed delayed response times  and only in the auditory modality  the p300 results demonstrate alterations in stimulus evaluation and processing speed in the earliest stages of hiv disease  even before cognitive deficits can be detected by more traditional measures  
class2	syphilitic meningomyelitis  a 28 year old nonimmunocompromised man developed secondary syphilis confirmed by serum and csf findings  his course was complicated by chorioretinitis  extensive skin lesions  and spastic paraparesis secondary to syphilitic meningomyelitis  mri of the spinal cord was strikingly abnormal  
class2	peptide induced antiviral protection by cytotoxic t cells  a specific antiviral cytotoxic immune response in vivo could be induced by the subcutaneous injection of the t cell epitope of the lymphocytic choriomeningitis virus  lcmv  nucleoprotein as an unmodified free synthetic peptide  arg pro gln ala ser gly val tyr met gly asn leu thr ala gln  emulsified in incomplete freund s adjuvant  this immunization rendered mice into a lcmv specific protective state as shown by the inhibition of lcmv replication in spleens of such mice  the protection level of these mice correlated with the ability to respond to the peptide challenge by cd8  virus specific cytotoxic t cells  this is a direct demonstration that peptide vaccines can be antivirally protective in vivo  thus encouraging further search for appropriate mixtures of stable peptides that may be used as t cell vaccines  
class2	a  pap  test for men  male urethral smears as screening tool for detecting subclinical human papillomavirus infection  we have explored the potential of using immunoperoxidase staining and in situ dna hybridization techniques to detect the hpv common antigen and hpv dna  subtypes 6 11 and 16 18  in urethral smears obtained from men with no grossly visible urethral lesions  with or without hpv related clinical history  a total of 91 such smears were studied of which 25  27 5   were positive for hpv antigen  of the latter  20  80   were positive for hpv 6 11 dna  3  12   were positive for hpv 16 18 dna  one smear  4   was positive for both  and one was negative for both  the technique of obtaining male urethral smears and immunostaining them for hpv antigen is simple  rapid  specific  and far more sensitive than conventional morphologic observations  since antigen positive cells are the source for spreading hpv infection  identifying individuals with such cells can help limit the spread of infection by alerting sexual partners  and also can be used to monitor the infectious status of the patient after therapy  dna subtyping of hpv positive patients may be useful in predicting the potential for malignant transformation which varies among the different hpv subtypes  
class2	the increased frequency of cervical dysplasia neoplasia in women infected with the human immunodeficiency virus is related to the degree of immunosuppression  cytologic and histologic investigations of the uterine cervix and studies of the lymphocyte functions were performed in human immunodeficiency virus infected and human immunodeficiency virus antibody negative women to study possible linkages between human papillomavirus induced dysplasia and degree of human immunodeficiency virus induced immunosuppression  cytologic smears of the uterine cervix of 111 human immunodeficiency virus infected women were compared with findings in 76 female intravenous drug users negative for human immunodeficiency virus antibodies and in a group of 526 women of the outpatient population of the hospital  cervical dysplasia neoplasia  including five cases of invasive carcinoma  was seen in 41  of the human immunodeficiency virus infected patients  in human immunodeficiency virus negative intravenous drug users dysplasia neoplasia was seen in 9   and in the sample from outpatients in 4   including two cases of invasive carcinoma  p less than 0 01   cytologic features that were attributable to infection with human papillomavirus were observed in human immunodeficiency virus infected women four times more often than in the sample from the outpatient population  p less than 0 01   frequency and severity of dysplasia appear to increase with diminishing numbers of cd4  helper inducer t lymphocytes and correlated significantly  p less than 0 01  with a loss of blastogenic response to phytohemagglutinin  pokeweed mitogen  and tetanus toxoid  these results suggest an increased risk for the development of dysplasia of the uterine cervix in women with human immunodeficiency virus infection  which is related to the degree of immunosuppression  
class2	detection of coxsackievirus b3 rna in myocardial tissues by the polymerase chain reaction  coxsackievirus b3 is a possible etiologic agent in some forms of myocarditis and idiopathic dilated cardiomyopathy  a method for the detection of coxsackievirus b3 rna was developed using the polymerase chain reaction based on the amplification of a cdna copy of the positive strand viral rna  the fidelity of the method was established in two murine models for coxsackie b3 myocarditis  all cardiac specimens with adequate rna for study from coxsackie b3 infected mice contained detectable viral rna  in contrast to none of control specimens from noninfected mice  the sensitivity of the technique was established at approximately 1 to 100 plaque forming units of virus per gram of tissue  and the specificity was established as limited to the coxsackievirus b3 serotype among nine viruses tested  in patients with myocarditis  one of five specimens contained detectable viral rna  whereas none of 11 specimens from patients with idiopathic dilated cardiomyopathy or 21 myocardial specimens from patients with a wide variety of other cardiac disorders contained detectable coxsackie b3 viral rna  the results show that the polymerase chain reaction is a useful means for detecting coxsackie viral rna and its application should help in the evaluation of hypotheses concerning the infectious etiology of human myocarditis and idiopathic dilated cardiomyopathy  
class2	aids enteropathy  occult enteric infections and duodenal mucosal alterations in chronic diarrhea objective  to investigate occult enteric infections and morphologic changes in the small intestine in patients with advanced human immunodeficiency virus  hiv  infection and chronic diarrhea of undefined cause  design  case control study  setting  referral based clinic and hospital in tertiary care center  patients  twenty two patients with advanced hiv infection  19 with the acquired immunodeficiency syndrome  aids   3 with aids related complex  with chronic diarrhea  selected because of previously negative stool evaluations for bacterial or parasitic pathogens  were compared with 13 patients with advanced hiv infection  9 with aids  4 with aids related complex  without diarrhea by analysis of endoscopic biopsies using light and electron microscopy  viral culture  and morphometric studies  both groups were convenience samples and had at least 7 months follow up  measurements and main results  eleven of twenty two patients with hiv infection and chronic diarrhea but only 1 of 13 patients without diarrhea showed occult enteric pathogens  that is  undetected by routine studies  after extensive evaluation of duodenal and colorectal biopsies  mycobacterium avium intracellulare and microsporidia were the most common occult agents in study patients with diarrhea  5 each   patients with diarrhea and occult enteric infections had greater weight loss  mean  14 3 kg compared with 6 2 kg  p less than 0 05  and shorter survival  1 of 11 compared with 8 of 11 still alive  p less than 0 004  than those with diarrhea but no identified pathogens  defined as  aids enteropathy    duodenal morphometry showed decreased villus to crypt ratios because of villus atrophy and crypt elongation in hiv infected patients both with and without diarrhea compared with normal controls  p less than 0 001 for each   all three groups showed comparable frequencies of epithelial mitoses  conclusions  further endoscopic biopsy evaluation of patients with aids who had unexplained chronic diarrhea showed an occult infectious cause in half of the cases  however  altered villus and crypt architecture in advanced hiv infection was independent of the presence of diarrhea or enteric infection and therefore did not correlate with aids enteropathy  subnormal epithelial proliferation in response to injury could be a factor  but the underlying cause of the architectural changes remains obscure  we suggest that t cell dysfunction may play a role  
class2	influence of inhaled cadmium on the immune response to influenza virus  cadmium may exacerbate pulmonary infections  in a previous study  however  cadmium appeared to enhance mouse resistance to influenza pneumonia  we report herein on the influence of cadmium intoxication in mice on different factors of anti influenza immunity  e g   antibody response  local production of interferon  pulmonary cellular response  and the interaction between pulmonary alveolar macrophages and the influenza virus  cadmium inhalation did not affect production of antibodies or interferon  the protective effect appeared to be related to an enhanced supply to phagocytic cells into the lung  
class2	aids incubation in 1891 hiv seroconverters from different exposure groups  international registry of seroconverters  published erratum appears in aids 1991 feb 5 2  245  this study compares aids incubation in different geographic areas  calendar time of infection  exposure group and age at exposure  investigators from north america  europe and australia contributed data from 1891 people for whom dates of hiv seroconversion were known  we excluded subjects not enrolled in prospective studies at entry and those with more than 25 months between last negative and first positive sera  we also censored subjects at the time last seen and excluded all follow up after 1987 in order to minimize the impact of newly developed prophylactic therapies  the final analysis cohort contained 1171 subjects  using actuarial methods  no differences in incubation times were found among homosexual men infected in different continents or in different years  prior to and after 1 january 1985   among hemophilic people  children developed aids more slowly than adults  p   0 02   and hemophilic adults developed aids more slowly than homosexual men  p less than 0 05   mainly because homosexual men had an added risk of kaposi s sarcoma  progression time to aids was significantly faster in older hemophilic men  but not in older homosexual men  these data illustrate that aids incubation may differ in different exposure groups  probably because of different exposures to potential opportunistic pathogens  
class2	trends in survival of danish aids patients from 1981 to 1989  length of survival was analysed in relation to year of diagnosis  aids indicative disease  age  risk behaviour  zidovudine therapy  and cd4 cell count and serum immunoglobulin  ig  levels at the time of diagnosis in a group of 231 consecutive adult danish aids patients reported before 1 january 1988  the cumulative survival rate was 53   95  confidence interval 47 59   at 1 year  29   22 36   at 2 years and 18   10 26   at 3 years  length of survival increased significantly  p less than 0 001  over time for patients who were initially diagnosed with pneumocystis carinii pneumonia  pcp   17   3 31   at 2 years prior to 1986  32   16 49   in 1986 and 52   34 69   in 1987  whereas survival remained stable for patients with other aids indicative diseases  survival was similar for patients who were diagnosed with kaposi s sarcoma alone and pcp alone  independent predictors of a shortened survival were a cd4 cell count less than 200 x 10 6  l  a serum iga level greater than 4 g l  and an initial diagnosis with opportunistic infections other than pcp  in addition  the multivariate analysis suggested an improved survival in recent years for patients diagnosed with pcp  independent of other factors examined  we conclude that length of survival in aids patients is highly variable  determinants of progression include cd4 cell count  serum iga level  and presenting disease  survival has increased markedly for patients with pcp and median survival now exceeds 24 months  
class2	early and specific diagnosis of seropositivity to hivs by an enzyme linked immunosorbent assay using env derived synthetic peptides  we describe and evaluate the sensitivity and specificity of an enzyme linked immunosorbent assay  elisa  using a 22 amino acid peptide corresponding to the carboxy terminal end of hiv 1 gp120 and two 30 amino acid long cyclic peptides including the two vicinal cysteines present on hiv 1 gp41 and on hiv 2 gp36  this test was evaluated  data obtained with the western blot  wb  and the peptide based elisa on a first panel composed of sera from 547 patients attending a specialized outpatient clinic  high risk population  are in perfect agreement  moreover  39 samples that had falsely been found positive with a viral lysate based elisa were not detected by peptide based elisa  the second panel was composed of 309 sera which were difficult to resolve using both wb and viral lysate based elisa  using the peptide based elisa  134 were found clearly positive and 173 clearly negative  only two were falsely positive  finally  sera from 16 individuals examined at the time of seroconversion gave high absorbancy readings even if they were weakly reactive by wb  weak gp160 band   this test is thus highly sensitive and specific  and capable of detecting early seroconversion  it is also instrumental in clearly defining samples that are found indeterminate in the wb  and consequently it avoids the unnecessary follow up required when a false positive result is obtained using viral lysate based elisa  
class2	t cell subsets and serum immunoglobulin levels in infants born to hiv seropositive mothers  a longitudinal evaluation  t lymphocyte subsets and serum immunoglobulins were assayed in 27 neonates and 12 infants younger than 6 months  all born to hiv seropositive mothers  no differences in t lymphocyte subsets between the 27 seropositive and 34 seronegative infants were found at birth  twelve seroreverted and 14 infected children were followed  cd4  cell counts were significantly lower in the latter at 3 and 24 months of age  serum immunoglobulin levels and cd8  percentages became higher in the infected group  starting from the sixth month  while cd4  percentages and cd4  cd8  ratios became lower  starting from the twelfth month  
class2	low dose dapsone prophylaxis of pneumocystis carinii pneumonia in aids and aids related complex  the efficacy  toxicity and cost of orally administered dapsone  50 100 mg day  for prophylaxis of pneumocystis carinii pneumonia  pcp  were evaluated in 30 patients with aids or aids related complex  arc   six patients received primary and 24 secondary prophylaxis  ten patients received a maximum dose of 100 mg day and 20 a maximum of 50 mg day for a median duration of 19 weeks  22 of the 30 patients continue to receive prophylaxis as of may 1989  four patients have died  none of pneumocystis infection  one patient with aids suffered a mild relapse while receiving 50 mg day  hematologic toxicity was mild and could not be definitively attributed to dapsone therapy  rash due to dapsone was documented in two patients  a review of 33 patients at our institution with a history of pcp who received no prophylaxis demonstrated seven relapses  three of which were fatal  cost analysis revealed a significant advantage for oral dapsone over aerosolized pentamidine  
class2	cowpox catpox infection  a 19 year old veterinary nurse developed a cowpox catpox virus  cpv  infection of her right third finger following a scratch from a tom cat suffering from pneumonia  the clinical course and investigation of the infection are described and the differential diagnosis discussed  
class2	epidermodysplasia verruciformis associated papillomavirus infection complicating human immunodeficiency virus disease  three males infected with the human immunodeficiency virus  hiv  were noted to have extensive flat warts of the face and or body  in two there were also pityriasis versicolor like lesions  biopsies showed foamy  basophilic  distended cytoplasm in granular layer keratinocytes  characteristic of the human papillomavirus types seen in epidermodysplasia verruciformis  dna hybridization techniques demonstrated the presence of hpv type 8 in one patient and hpv 5 and 8 in another  patients with immune suppression due to hiv infection may demonstrate the clinical features of epidermodysplasia verruciformis with the same potentially oncogenic hpv types  
class2	l glutamine stimulates jejunal sodium and chloride absorption in pig rotavirus enteritis  rotavirus enteritis is the leading cause of diarrhea in infants worldwide  a research priority of the world health organization is to develop oral rehydration solutions containing amino acids or other additives that will stimulate intestinal absorption more efficiently than the current glucose based oral rehydration solutions  glutamine is the principal metabolic fuel of the small bowel and a putative stimulator of mucosal repair  this report describes the transport response to mucosal l glutamine following intestinal injury caused by porcine rotavirus  peak symptoms and mucosal damage were observed 2 7 days after oral rotavirus inoculation  in vitro transport studies of the maximally injured region  the midjejunum  80  reduction in lactase   surprisingly  showed transport responses to l glutamine  30 mmol l  and l alanine  30 mmol l  that were similar qualitatively and quantitatively to those observed in control tissue  subsequent application of mucosal d glucose  30 mmol l  caused additional stimulation of electrogenic na  transport  but the response to glucose was blunted  p less than 0 05  in the infected tissues  glutamine and alanine enhanced na  absorption to a similar degree  2 2 5 mueq cm 2 h 1   but glutamine stimulated equal amounts of electrogenic and electroneutral nacl absorption  whereas alanine had no significant effect on net cl  flux  glutamine is a potentially useful substrate for investigation in oral rehydration solutions for infant diarrhea  
class2	six epitopes reacting with human cytotoxic cd8  t cells in the central region of the hiv 1 nef protein  in order to identify the target epitopes recognized by specific ctl in the nef protein of hiv 1  33 peptides derived from the hiv bru sequence were tested with nef specific ctl generated from hiv seropositive donors  six different epitopes were identified and several points were remarkable  1  they were all located in two regions of the central part of the nef protein corresponding to residues 73 to 94 and 113 to 147  respectively  2  the ctl issued from a single donor could recognize several peptides of the nef protein  3  some of these peptides could be recognized in association with at least two or three different hla class i molecules  4  two different overlapping epitopes were present in a relatively short sequence of 15 amino acids  these results suggest that multiple epitopes corresponding to different hla restrictions could coexist in a relatively small region of the nef protein  the implications of these results in vaccine strategies using synthetic peptides bearing ctl epitopes are discussed  
class2	community acquired influenza c virus infection in children  to clarify the epidemiologic and clinical features of community acquired influenza c infection in children  we took specimens throughout the year from a larger number of patients with acute respiratory illnesses in a pediatric clinic in yamagata  japan  during a 2 year survey  20 strains of influenza c virus were isolated from 13 426 specimens  these isolates were recovered throughout the year  the ages of patients with influenza c virus isolates ranged from 2 months to 11 years and peaked at the age of 1 year  the clinical diagnosis of patients with influenza c virus infection included bronchitis in one child and pneumonia in four  community acquired influenza c infection in children can cause a variety of respiratory illnesses that cannot be clinically differentiated from those caused by other viruses  
class2	search for herpes simplex virus 2 and human papillomavirus genetic expression in vulvar neoplasia  specimens from vulvar carcinomas and vulvar intraepithelial neoplasia  vin  of various degrees were analyzed for the presence of herpes simplex virus 2  hsv 2  and human papillomavirus  hpv  genetic information  a search for the hpv 16 e6 protein as well as the hsv 2 antigenic determinant la1 and icsp 11 12 protein was carried out with an immunoperoxidase assay on 12 vulvar carcinomas and 6 vins  seven invasive cancers and four vins were screened for the presence of homology to hpv 16 dna and hsv 2 dna transforming sequences with southern blot hybridization  we used specimens from labial tumors and from normal vulvas and cervixes as controls  the preliminary results showed that one vulvar carcinoma and two vins contained hpv 16 dna  four vulvar carcinomas expressed the e6 protein  while all the vins were negative  homology to hsv 2 dna transforming sequences was detected in one vulvar cancer but not in any vin cases  positivity to hsv 2 icsp 11 12 was observed in 33 3  of vin cases and 75  of invasive cancers  hsv 2 la1 antigenic determinant was expressed in 33 3  of vin and 66 6  of cancer cases  
class2	studies on the transmission of viral disease via the co2 laser plume and ejecta  while recent reports have noted the presence of viral dna sequences in the laser plume  no significant effort has been made to study transmission of the virus in vivo via airborne laser debris  studies were undertaken to identify potential hazards to operating room occupants in gynecologic laser surgery  aco2 laser in the continuous wave mode using a power density of 666 w cm2 was fired through a 5 cm metal cylinder at virus infected tissues  airborne particulate debris  100 200 microns  was removed from the cylinder s inner surfaces  in one instance  deposition of the debris was found on the surgeon s eyeglasses 1 m from the site of impact despite the use of a smoke evacuator  the first set of studies involved confirmed human papillomavirus  hpv  lesions of the human female lower genital tract  specimens were collected for electron microscopy and southern blot viral hybridization  additional cervical electron microscopy specimens were recovered from the speculum during pulsed co2 laser treatment at 13 w average power during conization  electron microscopy of the vulvar debris revealed only anucleate keratinized squamous epithelial cells  cervical specimens demonstrated similar cells with nearly instantaneous vaporization of intracellular water and apparent condensation of cellular carbon  hpv southern blot testing revealed insufficient quantities of dna for that technique  the second set of studies involved bovine papillomavirus lesions from dairy cattle  the debris was transmitted to susceptible animals  the bovine studies failed to demonstrate the transmission of disease in vivo  
class2	human papillomavirus in women with vulvar intraepithelial neoplasia iii  untreated cases of vulvar intraepithelial neoplasia  vin  iii may progress to invasive vulvar carcinoma  tissues from 29 new zealand women with vin iii were examined for the presence of human papillomavirus  hpv  types 6  11  16 and 18 by in situ hybridization and polymerase chain reaction  hpv 16  the only hpv type detected in the lesions  was identified in about half the cases  hpv positive women were younger than hpv negative women  and their lesions displayed koilocytosis more often  in four of five cases in which there was a progression to invasive cancer  hpv 16 was detected in both the vin iii and invasive cancer tissue  
class2	interferon for vulvar vestibulitis  eight women with human papillomavirus associated vestibular adenitis were treated with locally administered alpha interferon  1 million units  three times weekly for four consecutive weeks  five patients had a complete remission  and one had a slight  transient improvement  with a relapse after the therapy ceased  
class2	a measles outbreak at a college with a prematriculation immunization requirement  background  in early 1988 an outbreak of 84 measles cases occurred at a college in colorado in which over 98 percent of students had documentation of adequate measles immunity  physician diagnosed measles  receipt of live measles vaccine on or after the first birthday  or serologic evidence of immunity  due to an immunization requirement in effect since 1986  methods  to examine potential risk factors for measles vaccine failure  we conducted a retrospective cohort study among students living in campus dormitories using student health service vaccination records  results  overall  70  83 percent  cases had been vaccinated at greater than or equal to 12 months of age  students living in campus dormitories were at increased risk for measles compared to students living off campus  rr   3 0  95  ci   2 0  4 7   students vaccinated at 12 14 months of age were at increased risk compared to those vaccinated at greater than or equal to 15 months  rr   3 1  95  ci   1 7  5 7   time since vaccination was not a risk factor for vaccine failure  measles vaccine effectiveness was calculated to be 94   95  ci   86  98  for vaccination at greater than or equal to 15 months  conclusions  as in secondary schools  measles outbreaks can occur among highly vaccinated college populations  implementation of recent recommendations to require two doses of measles vaccine for college entrants should help reduce measles outbreaks in college populations  
class2	safety and prophylactic efficacy of low dose rimantadine in adults during an influenza a epidemic  a placebo controlled  double blind study to evaluate the safety and prophylactic efficacy of a low dose  100 mg  of rimantadine hydrochloride against naturally occurring influenza in adults was conducted at two sites  after the onset of the influenza season  volunteers  ages  18 to 55 years  were assigned randomly to receive rimantadine or placebo daily  subjects were monitored for adverse effects and evidence of influenza virus infection weekly for six weeks  only 10  8 7   of 114 rimantadine recipients and 5  4 4   of 114 placebo control recipients reported one or more mild to moderate adverse symptoms  most of which were related to the gastrointestinal or central nervous system  compared with placebo  low dose rimantadine was highly effective in the prevention of influenza a virus infection  20 of 110 versus 7 of 112 participants  p less than 0 01  and influenza illness  7 of 110 versus 1 of 112 participants  p   0 04   influenza a leningrad 87 like  h3n2  virus was recovered from the nasopharynxes of only five placebo recipients  these findings indicate that low dose rimantadine is well tolerated and highly effective for the prevention of influenza a illness in healthy adults  
class2	alpha interferon  2b  in combination with zidovudine for the treatment of presymptomatic feline leukemia virus induced immunodeficiency syndrome  the therapeutic efficacies of human recombinant alpha interferon  ifn alpha   ifn alpha plus zidovudine  azt   and azt alone were evaluated in presymptomatic cats with established feline leukemia virus  felv  acquired immunodeficiency syndrome  faids  infection and high levels of persistent antigenemia  subcutaneous injection of 1 6 x 10 6  u of human recombinant ifn alpha 2b per kg delivered peak concentrations in plasma of 3 600 u ml at 2 h postadministration with a half life of elimination of 2 9 h  this dosage of ifn alpha could be delivered to cats for up to 12 weeks without significant clinical toxicity  oral administration of azt  20 mg kg three times daily  resulted in peak concentrations in plasma of 3 micrograms ml at 2 h with a half life of elimination of approximately 1 60 h  treatment of felv faids infected cats with ifn alpha  either alone or in combination with orally administered azt  resulted in significant decreases in circulating p27 core antigen beginning 2 weeks after the initiation of therapy  azt alone had no effect on circulating virus antigen  depending upon whether high  1 6 x 10 6  u kg   or low  1 6 x 10 4  to 1 6 x 10 5  u kg  dosage ifn alpha was used  cats became refractory to therapy 3 or 7 weeks after the beginning of treatment  at these times  ifn alpha treated animals developed antibodies to ifn alpha that were neutralizing  specific for human recombinant ifn alpha  and dose dependent in magnitude  the results of this study indicate that human recombinant ifn alpha is effective in reducing circulating virus antigenic load in cats persistently infected with felv faids  
class2	recurrent wheezy bronchitis and viral respiratory infections fifty four patients aged from 1 to 6 years who had had recurrent attacks of wheezy bronchitis were prospectively followed up for three months to find out if there was an association between different viral respiratory infections and episodes of wheezing  of the 115 episodes of upper or lower respiratory tract symptoms  virus or mycoplasma pneumoniae infection were diagnosed in 52  45    thirty four of rhinoviruses  the patients had an average of 2 1 episodes of respiratory tract symptoms the total mean  sd  duration of which was 30  2  days of the 92 days that followed  wheezing occurred during 76  66   of the 115 episodes and during a third of these the patient was admitted to hospital because of severe dyspnoea  wheezing started a mean  sd  of 43  7  hours after the first symptoms of respiratory infection and persisted for 3 8  4 2  days in patients in whom virus infection was diagnosed  the incidence of wheezing was not associated with ige mediated atopy  with positive virological tests  or with fever during virus infection  but was associated with parental smoking and more than one sibling  
class2	herpes simplex keratitis in renal transplant patients  five out of 430 patients  1 16   undergoing kidney transplantation developed an atypical clinical picture of herpetic dendritic keratitis within four weeks after surgery  it was manifested by multiple dendrites  located mainly in the corneal periphery or the limbus  developing in relatively uninflamed eyes  the response to acyclovir therapy was prolonged and took at least three weeks  additionally  subepithelial infiltrates with ultimate scarring developed in all patients  disciform keratopathy was not found  this clinical course is ascribed to the patients  immunosuppressed state  
class2	preparation and characterization of an intravenous solution of igg from human immunodeficiency virus seropositive donors  an intravenous solution of 99  pure globulin  hyperimmune igg  hivig  was obtained from pooled plasma of selected human immunodeficiency virus  hiv 1  seropositive asymptomatic donors with greater than 400 cd4  microliters cells per microliter and a high titer of antibody to hiv 1 p24 protein  hivig had high titers of antibody to p24  glycoprotein 41  gp41   and gp120  group specific neutralizing activity  and binding to the gp120 hypervariable loop region  it inhibited syncytia formation  at low concentration  it enhanced viral production of hiv 1 in infected peripheral blood monocytes but was inhibitory at higher concentration  hivig directed group specific antibody dependent cellular cytotoxicity against hiv infected targets  for a period of 6 to 28 months  plasma donors kept stable antibody titers and had a 1 0  decrease in cd4  cells per month  one gram per kilogram hivig injected in two juvenile chimpanzees was well tolerated and did not transmit hiv  as measured by negative cell culture  igm immune response to hiv proteins  and polymerase chain reaction  the mean half life of hiv 1 p24 antibody was 15 days  these preliminary data suggest that hivig is a safe product suitable for clinical trial in hiv 1 infected individuals  
class2	antibody to coxsackie b virus in diagnosing postviral fatigue syndrome objective  to study the association between coxsackie b virus infection and the postviral fatigue syndrome and to assess the immunological abnormalities associated with the syndrome  design  case control study of patients with the postviral fatigue syndrome referred by local general practitioners over one year  setting  general practitioner referrals in dunbartonshire  scotland  patients  254 patients referred with the postviral fatigue syndrome  exhaustion  myalgia  and other symptoms referable to postviral fatigue syndrome of fairly recent onset  that is  several months  and age and sex matched controls obtained from same general practitioner  11 patients were rejected because of wrong diagnoses  resolution of symptoms  and refusal to participate  leaving 243 patients and matched controls  main outcome measures  detailed questionnaire  patients and controls  and clinical examination  patients  and blind analysis of blood sample at entry and after six months for determination of coxsackie b virus igm and igg antibodies and other variables  including lymphocyte protein synthesis  lymphocyte subsets  and immune complexes   results  percentage positive rates for coxsackie b virus igm at entry were 24 4  for patients and 22 6  for controls and for coxsackie b virus igg 56 2  and 55 3  respectively  there were no significant differences between different categories of patients according to clinical likelihood of the syndrome nor any predictive value in a fourfold rise or fall in the coxsackie b virus igg titre in patients between entry and review at six months  the rates of positive antibody test results in patients and controls showed a strong seasonal variation  of the numerous immunological tests performed  only a few detected significant abnormalities  in particular the mean value for immune complex concentration was much higher in 35 patients and 35 controls compared with the normal range and mean value for total igm was also raised in 227 patients and 35 controls compared with the normal range  conclusions  serological tests available for detecting coxsackie b virus antibodies do not help diagnose the postviral fatigue syndrome  percentage positive rates of the antibodies in patients simply reflect the background in the population as probably do the raised concentrations of total igm and immune complexes  
class2	treatment of end stage chronic obstructive pulmonary disease with double lung transplantation  six patients with end stage emphysema  age 44     2 years  underwent double lung transplantation  tx  from june 1988 through may 1990  all suffered from severe inanition and required oxygen therapy  the ischemic time was 193     28 minutes  post tx immune suppression was okt3  14 days   cyclosporine  trough levels of 150     25 ng ml   azathioprine to keep wbc at 3 000 to 5 000 cu mm  1 to 3 0 mg kg day  and following okt3  a tapering prednisone regimen  two rejection episodes that occurred in two patients on post tx day 5 and 10 were treated with bolus doses of methylprednisolone  the mean hospital stay was 32     7 days  range  20 to 69 days   four patients required treatment of cytomegalovirus  cmv  infection  gastritis   donor   recipient  in one and cmv pneumonia in two   donor   recipient   a fourth   donor   recipient  had right sided candida empyema six weeks post tx  developed cmv and staphylococcal sepsis  and died 64 days post tx  one patient required pyloroplasty eight weeks post tx and one patient underwent tracheal suture line repair at eight weeks  during a follow up of 81 patients months  range  8 to 24 months   one patient had developed epstein barr viral  ebv  induced lymphoproliferative disease in the lung and one patient had developed ebv lymphoma  three patients are at work  one is continuing rehabilitation  and one is at home  double lung tx offers a definitive benefit to patients with emphysema  however  a prolonged postoperative course can be expected  viral infections remain serious but treatable problems  
class2	use of indium 111 labeled white blood cell scan in the diagnosis of cytomegalovirus pneumonia in a renal transplant recipient with a normal chest roentgenogram  opportunistic infections are common in patients after renal transplantation  this report describes a case of cytomegalovirus pneumonia in a renal transplant recipient with a normal chest roentgenogram and normal arterial oxygenation  an abnormal 111in white blood cell scan led to the discovery of a pulmonary source of his recurrent fevers  
class2	esophageal candidiasis in aids  successful therapy with clotrimazole vaginal tablets taken by mouth  in this paper we describe the results of oral therapy of esophageal candidiasis with clotrimazole vaginal tablets in 25 homosexual men with aids  of whom 19 had oral candidiasis and 16 had esophageal symptoms  therapy with clotrimazole vaginal tablets  100 mg  taken by mouth cleared the esophageal symptoms  oral candidiasis  and esophageal lesions completely in all 25 men  clotrimazole vaginal tablets are a useful alternative to other antifungal agents for the treatment of esophageal candidiasis in aids patients  
class2	incidence of hairy cell leukemia  mycosis fungoides  and chronic lymphocytic leukemia in first known htlv ii endemic population  unlike human t cell leukemia lymphoma virus type i  htlv i   htlv ii has not been convincingly linked to a malignancy  in the first 10 months of serologic screening for htlv i ii among blood donors in new mexico in 1988 1989  htlv i ii infection was found in 27 donors  htlv i ii infection was present in 1 0  1 6  of american indian and 0 16  0 27  of hispanic donors compared with 0 009  0 06  of non hispanic white donors  htlv ii was identified by dna amplification in 12 of 13 samples from indian and hispanic seropositive donors  despite apparent endemic htlv ii infection in these populations  new mexico tumor registry data showed that the incidences of hairy cell leukemia  mycosis fungoides  and chronic lymphocytic leukemia were comparable among the three ethnic groups  a population with endemic htlv ii infection has been identified  and there is no evidence of increased risk for these three malignancies in the endemic groups  
class2	cytomegalovirus infection in sexually active adolescents  to determine whether cytomegalovirus  cmv  infection in teenage girls is related to sexual activity  254 girls 12 18 years old  mean  15 8  attending a contraceptive counseling clinic were studied  participants were screened for chlamydia trachomatis  neisseria gonorrhoeae  and trichomonas vaginalis  and serum antibody to cmv was determined  demographic and sexual history data were collected by interview  the mean number of lifetime sex partners was 2 2  173  68   were seropositive  race  greater than 3 years of sexual activity  and greater than 2 lifetime sex partners were significant risk factors for cmv infection  odds ratios  or   1 8 4 7  p less than  05   using logistic regression analysis  a composite sexual activity variable was the most important risk factor for cmv infection  or  4 8  p    003   followed by race  or  3 4  p    004  and a sexually transmitted disease composite variable  or  2 4  p    016   sexual activity is an important risk factor for cmv infection in adolescent girls  
class2	pattern of respiratory syncytial virus epidemics in finland  two year cycles with alternating prevalence of groups a and b  time resolved fluoroimmunoassay with monoclonal antibodies distinguishing between respiratory syncytial virus  rsv  group a and b strains was used to analyze their prevalence in finland during 1981 1990 among 3285 patients with laboratory diagnosis of rsv  most of them hospitalized  the group typing of antigens in 608 rsv positive nasopharyngeal aspirates showed a regular alternation of group prevalence  following the cyclic occurrence of the virus  group a predominated in 73  90  of specimens from 1981 1982  1985 1986  and 1989 1990  whereas group b predominated in 70  100  of specimens from 1983 1984 and 1987 1988  the epidemiologic occurrence of verified reinfections in hospitalized children and the group typing results indicated that children greater than 6 months of age during the first infection were more resistant to severe reinfection with the homologous than with the heterologous group of virus  the study shows that group antigenic variation of rsv has a significant effect on the epidemiology of the virus  
class2	vaccination of cotton rats with a chimeric fg glycoprotein of human respiratory syncytial virus induces minimal pulmonary pathology on challenge  the cotton rat model of human respiratory syncytial virus  rsv  infection was used to study the safety and efficacy of a chimeric fg glycoprotein that was expressed in insect cells using a baculovirus vector  histologic and virologic examination of vaccinated rat lungs was done after challenge with rsv  when rats were challenged 1 month after vaccination  severe pulmonary inflammation characterized by both a mononuclear and polymorphonuclear cell infiltrate and 30  40  involvement of lung tissue was observed with a formalin inactivated rsv vaccine  the fg glycoprotein induced minimal lung inflammation  involving 2  5  of the lung   while negative controls had 1  3  lung involvement  two doses with as little as 20 ng of fg glycoprotein formulated in an aluminum hydroxide adjuvant completely protected the cotton rats from rsv challenge  thus the chimeric fg glycoprotein is highly immunogenic and induces minimal pulmonary inflammation in the cotton rat model  
class2	a field study of the safety and efficacy of two candidate rotavirus vaccines in a native american population  a double blind  randomized  placebo controlled trial was conducted to evaluate the safety and efficacy of a rhesus rotavirus vaccine and rit 4237  a bovine rotavirus vaccine  in a navajo population  infants aged 2 5 months were randomized to receive one dose of either 10 4  pfu of the rhesus rotavirus vaccine or 10 8  pfu of the rit 4237 vaccine or placebo  eleven  10 2   of 108 infants in the rhesus vaccine group  11  10 4   of 106 in the rit 4237 group  and 9  8 4   of 107 in the placebo group experienced rotavirus diarrhea during the follow up period of 17 months  thus  in this population  neither vaccine was efficacious in preventing rotavirus diarrhea  
class2	measles associated diarrhea in hospitalized children in lima  peru  pathogenic agents and impact on growth  because the causes of measles associated diarrhea are not well known  0  to 5 year old children presenting to the hospital with measles associated diarrhea  cases  n   77  or acute diarrhea only  controls  n   77  were compared  growth and diarrheal morbidity were evaluated for 1 month after acute illness  campylobacter jejuni was more frequently isolated from cases  31   than controls  16   p    03   rotavirus was absent in all cases versus 28  of controls  p less than  001   incidence density for new episodes of diarrhea was significantly greater in cases  6 5 vs  4 1  odds ratio  1 6  confidence intervals  1 09 2 34  p    01   as was duration of episodes  3 vs  2 days  p    02   both groups showed similar positive cumulative percentage weight gains throughout follow up  these data support the theory of measles as a risk factor for developing diarrhea  the bacteriologic and virologic findings may reflect the immunologic response of the host to measles infection  
class2	granulocyte colony stimulating factor enhances the phagocytic and bactericidal activity of normal and defective human neutrophils  granulocyte colony stimulating factor  g csf  stimulates proliferation of myeloid cells and may be a valuable adjunct in prevention and treatment of neutropenia associated infections  neutrophil  pmnl  phagocytic and microbicidal functions against staphylococcus aureus and candida albicans blastoconidia were therefore evaluated  bacterial phagocytosis and bactericidal activity were significantly enhanced by approximately 50  70  after preincubation of normal pmnl with g csf in concentrations of 1000 4000 units ml for 10 min at 37 degrees c  g csf in similar concentrations enhanced the defective bactericidal activity of pmnl from hiv 1 infected patients by approximately 70  150  and reached the baseline control pmnl killing  however  g csf enhanced neither phagocytosis nor fungicidal activity of normal pmnl against c  albicans blastoconidia  these data demonstrate that g csf enhances the antibacterial but not the antifungal activities of human pmnl in vitro and also improves the defective pmnl bactericidal activity of hiv 1 infected patients  
class2	recombinant murine granulocyte macrophage colony stimulating factor augments neutrophil recovery and enhances resistance to infections in myelosuppressed mice  the ability of recombinant murine granulocyte macrophage colony stimulating factor  rmgm csf  to protect myelosuppressed mice against lethal infections was evaluated  in mice myelosuppressed by cyclophosphamide  subcutaneously administered rmgm csf was a potent stimulus of granulopoiesis by increasing the number of gm csf responsive precursor cells in bone marrow followed by a profound neutrophilia  neutrophil recovery was augmented by rmgm csf in a dose dependent manner at daily doses of 0 6 5 0 micrograms mouse  in addition  rmgm csf increased the functional activity of circulating neutrophils at similar doses  when rmgm csf was administered to neutropenic mice before experimentally induced pseudomonas aeruginosa  staphylococcus aureus  or candida albicans infections  it protected against these lethal infections  resulting in increased numbers of survivors  these data suggest that rmgm csf protects neutropenic mice from lethal infections  probably by augmenting neutrophil recovery after myelosuppression and activation of mature cells  
class2	changes in plasma high density lipoprotein cholesterol and phospholipid in acute viral hepatitis and cholestatic jaundice  forty four male and female subjects aged 22 57 years were studied  thirteen patients had acute viral hepatitis  and eleven patients had cholestatic jaundice due to carcinoma of the head of the pancreas  twenty healthy volunteers who served as controls were also included  in hepatitis patients  the mean plasma levels of total cholesterol  tc  and the high density lipoprotein  hdl  phospholipid phospholipid  hdlpl pl  ratio were reduced  and hdl cholesterol  hdlc   hdl phospholipid  hdlpl  and the phospholipid total cholesterol  pl tc  ratio were normal  while total phospholipid  pl  levels and the hdlc tc ratio were significantly increased compared to the control values  in patients with cholestatic jaundice the mean plasma total cholesterol  phospholipid and hdlc levels were elevated  and hdlpl pl  hdlpl  hdlc tc and pl tc remained normal compared to the control values  a comparison within the patient groups showed that plasma tc  pl and hdlc levels were significantly increased in cholestatic jaundice when compared with the corresponding levels in hepatitis patients  the mean plasma levels of hdlpl  hdlc tc and pl tc did not show any significant variation within the patient groups  alkaline phosphatase  alp  correlated positively with tc  and total protein correlated negatively with tc and hdlpl  while albumin correlated negatively with tc  hdlc and hdlpl in cholestatic jaundice  alanine amino transferase  alat  also correlated positively with pl in cholestatic jaundice  while albumin correlated positively with tc in hepatitis  the results suggest that lipoproteins might be metabolized differently in these two forms of cholestasis  
class2	a spreadsheet for aids  estimating heterosexual injection drug user population size from aids statistics in san francisco  a single page computer spreadsheet can be used to back calculate the size of the population at risk from the reported number of aids cases and hiv seropositivity levels for that population  however  cohen  1988 35  has cautioned that  this method requires some heroic assumptions  and is  therefore  fraught with difficulty   slight variations in the definition of aids  in the progression rate  and in reported seropositivity rates used as data in the spreadsheet can make enormous differences in the results obtained through back calculation  despite the limitations of the method  an estimate of the possible size of the idu population can be derived from back calculation  with careful consideration of ethnographic realities taken into account  in san francisco  the present authors believe that there were approximately 13 000 heterosexual idus as of the end of 1989  further demographic divisions by ethnicity  age  sex  and even neighborhood could be made using the same techniques  if aids cases and seropositivity levels could be obtained for each variable  table ii predicts a cumulative 705 aids diagnoses among san francisco heterosexual idus by the end of 1993  or nearly six times as many as reported through 1988  this prediction is based on an assumption of 2 5  seroconversion per year  1989 1993  and on modest progression rate increments of 5   5   4   3   and 3  in the eleventh through fifteenth years after hiv infection  thus  it shows the magnitude of the epidemic that san francisco will shortly face and emphasizes the need to act vigorously to prevent further hiv contagion among idus as well as from them to their heterosexual partners  drug using or not   
class2	prevalence of antibody to hiv 1 among entrants to us correctional facilities prevalence of antibody to the human immunodeficiency virus type 1  hiv 1  was assessed among 10 994 consecutive male and female entrants to 10 correctional systems in the united states  the hiv 1 seroprevalence for the 10 systems ranged from 2 1  to 7 6  for men and 2 5  to 14 7  for women  seroprevalence among women was higher than among men across nine of 10 systems  using age 25 years to divide the population  hiv 1 prevalence among young women  5 2   was significantly higher than among young men  2 3    but similar to that in both older women  5 3   and older men  5 6    overall  hiv 1 rates for nonwhites  4 8   were higher than those for whites  2 5    although categories were identified across correctional systems  which may serve to focus prevention programs  variability in rates among correctional systems indicates that program planning must take local conditions into consideration  
class2	recurrent peritonitis  evidence for possible viral etiology  a 45 year old woman who was treated with continuous ambulatory peritoneal dialysis  capd  developed recurrent peritonitis characterized by cloudy effluents  elevated white blood cell  wbc  counts  predominantly lymphocytes   and negative culture results  this case report suggests that she may have had viral peritonitis as indicated by a positive viral culture  the presence of viral antibodies in serum and peritoneal dialysis effluent  pde   hematological findings  and cell surface receptor studies  the possibility of a viral cause should be considered in patients with culture negative peritonitis  especially if they do not respond to antibiotics  
class2	immune function and anti htlv i ii status in anti hiv 1 negative intravenous drug users receiving methadone  purpose  the study objective was to evaluate the effects of long term methadone use and human t cell leukemia virus  htlv  types i and ii seropositivity on the distribution of lymphocyte subsets and on lymphocyte function as measured in vitro in intravenous drug users seronegative for human immunodeficiency virus type 1  hiv 1   patients and methods  anti hiv 1 negative intravenous drug users receiving methadone maintenance therapy  n   24  were studied in a veterans administration drug abuse treatment center  these subjects were compared to 38 age  and sex matched control subjects who did not abuse drugs  hiv 1 and htlv serostatus was determined by repetitive enzyme linked immunosorbent assay and confirmed by immunoblot  lymphocyte subsets were determined by two color flow cytometry  lymphocyte function was measured by proliferative response to plant mitogens and by natural killer  nk  cell mediated cytotoxicity to a tumor cell target  results  significant differences were seen in lymphocyte phenotype in the methadone treated group  with elevations in the t cell helper subset cd4 cd26   in cd8 and cd8 i2  cells  suppressor cytotoxic t lymphocytes  and activated suppressor cytotoxic t cells  and in cd2 cd26  cells and activated total t lymphocytes  lymphocyte function was suppressed in the methadone group  with poor responses to pokeweed mitogen and phytohemagglutinin in culture  moreover  nk cell cytotoxicity was significantly reduced in the methadone group  none of these immunologic differences were attributable to htlv serostatus  conclusion  the immune abnormalities seen suggest that a clinically significant degree of immune impairment exists in methadone treated intravenous drug users  however  these abnormalities could not be explained by the presence of other retroviruses in this hiv 1 negative study group  as there was no significant difference in immune function when htlv seropositive patients were compared to htlv seronegative subjects treated with methadone  
class2	the effect of chloroquine prophylaxis on yellow fever vaccine antibody response  comparison of plaque reduction neutralization test and enzyme linked immunosorbent assay  weekly oral chloroquine prophylaxis for malaria has been associated with impaired antibody response to intradermal rabies vaccination  experimental data indicate that chloroquine may inhibit yellow fever virus in vitro  yet there has been no clinical evidence to suggest that antibody response to yellow fever vaccine is impaired by concomitant oral administration of chloroquine  a prospective trial was undertaken to evaluate the antibody response to yellow fever 17d vaccine  connaught laboratories  of volunteers who were randomized to taking either chloroquine or no drug  of fifty subjects  28 were randomized to taking chloroquine  22 were randomized to taking no drug  yellow fever 17d vaccine was administered on day 0 and blood sampled on days 0  14  35 and 210  chloroquine was administered weekly for four weeks  there was no significant difference in peak antibody titer by plaque reduction neutralization testing  prnt  between the group that took chloroquine  mean log peak of reciprocal titer 1 43     sd 0 60  with vaccine subcutaneously compared to vaccine only group  mean log peak of reciprocal titer   1 21     0 55   all fifty subjects seroconverted to yellow fever vaccine by day 210  elisa testing was also performed on all subjects  the two tests showed good correlation  spearman r   0 675   although elisa readings were positive by day 14 in significantly more subjects  p    01   we conclude that routine anti malarial doses of chloroquine do not affect antibody response to yellow fever 17d vaccine  elisa testing  a less complex and less time consuming test  correlates well with prnt and is proposed for additional trials to measure yellow fever 17d vaccine response in flavivirus non immune subjects  
class2	the role of a critical care unit in an epidemic  the role of a critical care unit in life threatening situations is well established  the management of 52 children with acute gastroenteritis and 22 children with acute paralytic poliomyelitis as part of recent epidemics is described  the solutions to the problems in the critical care management of these 74 victims  out of a total of 6197 patients admitted during the epidemics  are discussed  
class2	hiv prevalence in a midwestern emergency department  study objective  to determine the prevalence of human immunodeficiency virus  hiv  seropositivity of patients 15 years of age and older in our emergency department  design  hiv status was determined anonymously  and the seroprevalence rate was calculated  the 95  confidence intervals also were calculated  twenty demographic and predictor categorical variable were cross tabulated with hiv status to determine associations  only gender and male homosexual preference were significantly associated by fisher s exact test  type of participants  excess serum samples from 454 randomly selected patients 15 years of age and older who required venipuncture for their ed evaluation were included in the study  measurements and main results  of the 454 serum specimens  six  1 32   were positive for hiv  the 95  confidence interval was from 0 27  to 2 37   all six positive patients were men  the only statistically significant risk factors associated with hiv seropositivity were male sex  p    00112  and male homosexual preference  p    0000   conclusion  hiv seropositivity occurs in 1 32  of our ed population over the age of 15 years  the only factors that correlate with hiv seropositivity are male homosexual preference and male sex  
class2	elevated alpha tumor necrosis factor levels in spinal fluid from hiv 1 infected patients with central nervous system involvement  to assess the role of alpha tumor necrosis factor in the pathogenesis of central nervous system involvement during human immunodeficiency virus type 1 infection  we recorded clinical data and measured alpha tumor necrosis factor levels in serum and cerebrospinal fluid samples from 45 patients infected with human immunodeficiency virus type 1  classified as group ii iii  10   group iv a  5   group iv b  10   and group iv c 1  20  of the centers for disease control acquired immunodeficiency syndrome classification system and 42 controls  alpha tumor necrosis factor was above the limit of detection in only 3 of 15 sera and 3 of 15 cerebrospinal fluid samples from patients in group ii iii and group iv a  whereas it was detected in 17 of 30 sera  p less than 0 05  and 22 of 30 cerebrospinal fluid  p less than 0 0002  samples from clinically more advanced patients  group iv b and group iv c 1   alpha tumor necrosis factor mean values were 21 5 pg ml in sera and 50 0 pg ml in cerebrospinal fluid from group iv b patients and 30 4 pg ml in sera and 24 pg ml in cerebrospinal fluid from group iv c 1 patients  
class2	apparent response of subacute sclerosing panencephalitis to intrathecal interferon alpha  an 8 year old boy with subacute sclerosing panencephalitis  sspe  was treated with 1 0 to 3 0 x 10 6  iu human interferon alpha  ifn  by the intrathecal route weekly or fortnightly  pronounced improvement of clinical and electroencephalographic findings were observed in a dose dependent manner  our patient raises hope that ifn can induce sustained remission in patients with sspe  
class2	herpes simplex and human papillomavirus genital infections  controversy over obstetric management  plasma inhibitory factors  high levels of sex hormones  and depression of cell mediated immunity may interfere with the natural host resistance to viral infections during pregnancy  it is apparent that hormonal  immunologic  and vascular changes in pregnancy may account for increased replication of herpes and for enhanced growth of condylomatous lesions  the challenge is to develop a rational plan of management for pregnant patients with herpes simplex or human papilloma virus infection  there has been a reevaluation of previous recommendations for the management of herpes in pregnancy  although the consequences of neonatal infection are severe or fatal  the value of routine weekly screening is questionable  this regimen is a poor predictor of neonatal exposure to herpes since only one fourth of women shedding virus at the time of delivery can be identified by routine cultures  the mode of delivery should therefore be based on the presence or absence of lesions at the time of confinement  cesarean section should be reserved for patients with lesions or with prodromal symptoms of recurrent disease at the time of delivery  patients with ruptured membranes and active genital lesions should also be delivered by cesarean section  the spectrum of hpv related diseases in pregnancy is poorly understood  many questions remain unanswered  it may not be practical to treat very large or extensive genital warts during pregnancy  a cesarean section may be the best choice in these cases  it may be premature to recommend cesarean section for delivery of all pregnant women with symptomatic genital hpv infection  more data are needed  we recommend laser ablation of condylomatous lesions when discovered during pregnancy  laser vaporization is associated with minimal morbidity when used by experienced surgeons  trichloroacetic acid is excellent for minimal disease or for treatment of recurrences in pregnancy  since the immune system seems to play an important role in control of viral disease  we advise pregnant patients to adopt a lifestyle which promotes health  we advise a balanced diet  an appropriate exercise program  and an environment free of unnecessary stress  we suggest avoidance of cigarettes  drugs  and alcohol  
class2	serum non organ specific autoantibodies in human immunodeficiency virus 1 infection  serum samples from 66 seropositive subjects  56 with a history of intravenous drug abuse   including asymptomatic carriers and patients with persistent generalised lymphadenopathy  pgl   aids related complex  arc   and aids  were tested by indirect immunofluorescence on rat tissue sections and hep 2 cells for the presence of antibodies to nuclei  smooth muscle  intermediate filaments  anti imf  and microfilaments  anti mf   counterimmunoelectrophoresis was also used to detect antibodies to extractable nuclear antigens  smooth muscle antibodies with the v pattern or antinuclear antibodies  mainly of the speckled type  or anti imf  occurred in 35 cases  being widely distributed in all groups  such an autoantibody response resembles the  viral  autoimmunity described in various infectious diseases and in particular that of non a  non b post transfusion hepatitis  autoantibodies may be of some prognostic relevance  as the prevalence of smooth muscle antibodies v increased as the disease progressed  asymptomatic carriers 20   those with pgl 29   those with arc 47   and those with aids 63   in the pgl group autoantibody positivity correlated with the presence of skin anergy  the fact that autoantibodies were more frequently detected in patients with circulating immune complexes suggests that these can contain autoantibodies and the corresponding autoantigens  
class2	hiv associated arthropathy  hiv antigen demonstration in the synovial membrane  light and electron microscopic studies were performed on the synovial membranes of 5 patients with hiv associated arthropathy  an immunoperoxidase technique with the use of monoclonal antibodies against cd4  cd8  b and dr lymphocytes  and hiv p24 antigen was also used  mild to moderate nonspecific proliferative changes and increased vascularity of the subsynovial space were seen  electron dense deposits and viral like particles were not observed  immunohistochemical staining revealed hiv p24 positive staining in cells of the synovial lining layer and in the mononuclear cells of the subsynovial space  cd4  cd8  with predominance of cd8  and b and dr cells were also present  the presence of hiv p24 antigen may be indicative of a role  yet to be defined  in the pathogenesis of hiv associated rheumatic disorders  
class2	fibromyalgia in human immunodeficiency virus infection  tenderness was assessed by point count and by scored palpation in 51 patients with human immunodeficiency virus  hiv  infection as well as 51 patients with rheumatoid arthritis  ra  and 50 patients with psoriatic arthritis  psa   fifteen of 51  29   patients with hiv infection met criteria for fibromyalgia  based on the presence of 10 tender  of 14   fibrositic  points  similar results were observed among patients with psa  24    the prevalence of fibromyalgia was higher among patients with ra  57    patients with hiv and psa were less tender than patients with ra  fibromyalgia in patients with hiv was significantly associated with myalgia and arthralgia  but not with age  duration of hiv infection  stage of hiv disease  or zidovudine therapy  
class2	cerebrospinal fluid flow dynamics in children with external ventricular drains  fifty five children had 64 external ventricular drains  evds  placed predominantly  95   for cerebrospinal fluid  csf  shunt infections  in 9 children  a computer monitoring system measured the csf output each second continuously for up to 24 hours  the monitoring was repeated daily for up to 9 days  the state of arousal of the patients was recorded simultaneously  in all children  daily evd outputs were related to age  sex  weight  method of establishing the evd  height of the drip chamber  time since insertion  and type of infecting organism  computer monitoring revealed wide fluctuations in flow rate  with peak rates frequently greater than 20 ml h and periods of flow arrest  these changes were usually associated with increased arousal  but also occurred with sleep  the mean evd flow rate for all children was 6 3 ml h  evd output increased with age and weight  evd output decreased with gram negative or multiple organism infections and with elevation of the drip chamber  resolution of the infection  sex of the patient  and method of establishing the evd had no effect on output  these results predict that csf production increases with brain growth in humans  that csf production is depressed by gram negative and multiple organism infections  that implanted csf shunts with standard valves flow at equivalent rates to an evd in the supine position  and that the csf drainage requirements in this group are approximately equal to their evd outputs  
class2	radiographic manifestations of anomalies of the brain  congenital brain anomalies are classified as developmental anomalies  effects of teratogens  errors of histogenesis  or sequelae of infections  the imaging options for delineation of these anomalies are many  a basic understanding of the disorder is central to the effective choice of imaging modality  this review begins with a brief overview of embryogenesis then reviews the common congenital brain anomalies encountered in infants  
class2	changing disease patterns in patients with aids in a referral centre in the united kingdom  the changing face of aids objective  to study the changes in morbidity  mortality  and survival patterns in a population of patients with aids in the united kingdom from 1982 to 1989  design  a retrospective analysis of inpatient and outpatient records of patients with aids  subjects  347 patients with aids  predominantly homosexual or bisexual men  setting  departments of immunology and genitourinary medicine  st mary s hospital  london  main outcome measures  presenting diagnosis of aids  occurrence of other opportunist diseases  cause of death  and survival since aids was diagnosed  in particular for those patients with pneumocystis carinii pneumonia or kaposi s sarcoma  results  the overall proportion of patients who developed p carinii pneumonia dropped from 56   20 36  in 1984 to 24   46 194  in 1989  although it has remained the index diagnosis in about half of new patients  kaposi s sarcoma has decreased as index diagnosis from 30   20 67  to 20   15 74  over the same period  though the prevalence has remained constant at around 35   p carinii pneumonia accounted for 46   16 35  of known causes of death in 1986 but only 3   1 31  in 1989  conversely  deaths due to kaposi s sarcoma rose from 14   1 7  to 32   10 31  between 1984 and 1989  lymphoma accounted for an increased proportion of deaths among these patients with 16   5 31  of deaths in 1989  their median survival increased from 10 months in 1984 6 to 20 months in 1987  conclusions  the changing patterns of disease in patients with aids have important implications both for health care provision and future medical research  medical and nursing provision must be made for the increased morbidity of these diseases and the increased survival of these patients  research should now be directed towards developing effective treatments for the opportunist infections which are currently more difficult to treat  the secondary malignancies of aids  as well as more effective immunorestorative treatments  future changes in disease patterns must be recognised at an early stage so that resources can be adequately planned and allocated  
class2	nosocomial outbreak of cryptosporidiosis in aids patients  objective  to describe a nosocomial outbreak of cryptosporidiosis during four months after june 1989  setting  a department of infectious diseases in copenhagen  seeing about half the patients with aids in denmark  subjects  73 hiv antibody negative subjects and 60 antibody positive subjects admitted as inpatients during the transmission period of the outbreak  20 june 14 august   of whom 18  17 with aids  one with aids related complex   developed cryptosporidiosis  two further hiv negative subjects  one departmental secretary  one visiting relative  developed cryptosporidiosis  main outcome measures  cryptosporidia in stool samples  clinical symptoms  cd4 cell count  hiv antigen concentration  chemotherapeutic treatment  results  the source of the outbreak was identified as ice from an ice machine in the ward  contaminated by an incontinent  psychotic patient with cryptosporidiosis picking out ice for cold drinks  the mean incubation time was at least 13 days that is  twice that in hiv negative patients  of the 18 patients with aids who developed cryptosporidiosis  five recovered  two were symptomless carriers  three died of unrelated causes  and eight died after prolonged diarrhoea  among the 57 exposed hiv antibody positive inpatients  excluding two patients and the index case with cryptosporidiosis diagnosed elsewhere   significantly more of those who developed symptomatic cryptosporidiosis received oral sulphonamides than those who did not  91   10 11 v 48   21 44  p less than 0 05   conclusions  the clinical and epidemiological findings indicate that infection was the consequence of very small inocula  increased sensitivity to cryptosporidiosis may be an unrecognised side effect of oral sulphonamide treatment in patients with aids  
class2	identification of herpes simplex virus dna in lesions of erythema multiforme by the polymerase chain reaction  an association between erythema multiforme and herpes simplex virus infection has been supported by clinical studies and by the detection by immunofluorescence of herpes viral antigen in sera and skin biopsy specimens of patients with erythema multiforme  in rare cases  the virus has also been isolated in cultures of skin biopsy specimens of erythema multiforme  to investigate further the association between erythema multiforme and herpes simplex virus  we used the polymerase chain reaction for herpes simplex virus to examine skin lesions from patients with erythema multiforme  in this study herpes simplex virus dna was detected in 11 of 31 biopsy specimens of erythema multiforme  six additional cases showed equivocal amplification results  which is suggestive of low amounts of viral dna  seven skin and mucosal biopsy specimens with the histologic changes of herpes virus infection served as positive controls  all were positive for herpes simplex virus dna  viral dna was not detected in control biopsy specimens from skin excised for unrelated conditions  these studies support the association of herpes simplex virus in the pathogenesis of some cases of erythema multiforme  the polymerase chain reaction provides a quick and effective method of detecting herpes simplex virus in lesions of herpes associated erythema multiforme  furthermore  the polymerase chain reaction may delineate those cases of erythema multiforme that are etiologically related to herpes virus infection and therefore might be treated with acyclovir to prevent recurrence  
class2	symptomatic polyneuropathy in human immunodeficiency virus antibody seropositive men with and without immune deficiency  a comparative electrophysiological study  symptomatic polyneuropathy in human immunodeficiency virus  hiv  infection was studied in ten men with acquired immunodeficiency syndrome  aids  and in ten men without the immune deficiency  in both groups of patients electrophysiological signs of polyneuropathy of the axonal type were present in the sural  median and peroneal nerves  the aids patients had a greater reduction of the mean  sd  sural nerve action potential  3 1  2 7  microv  than in patients without aids  10 2  6 1  microv  p less than 0 01  and greater slowing of peroneal nerve conduction velocity  42 6  1 4  m s in aids patients versus 52 6  3 3  m s in patients without aids  p less than 0 0001   these findings indicate that in most hiv infected patients the severity but not the type of neuropathy depends on whether an immune deficient state has developed  seven patients with symptomatic polyneuropathy were treated with azidothymidine  azt  for an average of 10 months and compared with a group of five untreated patients with similar symptoms  no effect of azt treatment on sural or median nerve amplitude or conduction velocity or on the vibratory or temperature thresholds was observed  
class2	paraneoplastic limbic encephalitis  clinico pathological correlations  three new cases of limbic encephalitis in association with malignancy are reported  the literature on this condition is reviewed and the clinical  laboratory and histopathological features of cases proven at necropsy are correlated  the possible pathogenic mechanism of this disorder is discussed  
class2	differences in access to zidovudine  azt  among symptomatic hiv infected persons  object  to evaluate socioeconomic factors that determine whether symptomatic hiv infected persons are offered zidovudine  azt   design  cross sectional survey conducted as part of the robert wood johnson foundation s aids health services program  setting  public hospital clinics and community based aids organizations in nine american cities  patients  880 hiv seropositive outpatients interviewed between october 1988 and may 1989  main results  males were more likely to have been offered azt than were females  adjusted odds ratio 2 99  95  confidence interval 1 67 to 5 36   those with insurance were more likely to have been offered azt than were those without  adjusted odds ratio 2 00  95  confidence interval 1 25 to 3 21   and whites more likely to have been offered azt than were non whites  adjusted odds ratio 1 73  95  confidence interval 1 11 to 2 69   intravenous drug users were less likely to have been offered azt than were non drug users  adjusted odds ratio 0 44  95  confidence interval 0 28 to 0 69   persons who had had an episode of pneumocystis carinii pneumonia were more likely to have been offered azt than were persons who had aids and had not had pneumocystis carinii pneumonia  adjusted odds ratio 2 95  95  confidence interval 1 71 to 5 11   conclusion  the authors conclude that traditionally disadvantaged groups have less access to azt  the only antiretroviral agent demonstrated to increase survival of patients who have symptomatic hiv infection  
class2	a hospital based prospective study of perinatal infection with human immunodeficiency virus type 1  most infants with pediatric acquired immunodeficiency syndrome and infections with human immunodeficiency virus type 1  hiv 1  are infected perinatally by their mothers  to determine the proportion of exposed infants who are infected  we conducted a hospital based prospective study in hiv 1 infected women whose infants were delivered at a single metropolitan hospital in miami  fla  a population of uninfected women and their infants was also enrolled and followed longitudinally for 2 years to assess laboratory and clinical measurements  the median follow up is now 18 months for 82 infants born to hiv 1 infected mothers  the proportion of infected infants in this group is 0 30  25 82   none of the infants born to 110 hiv 1 seronegative mothers were seropositive  infected infants were easily distinguished from noninfected infants by virus isolation  no single immunologic or hematologic measure was predictive of infection for all infants at risk for hiv 1 infection who were 6 months of age or younger  as a group  however  infected infants could be distinguished from uninfected index infants by a number of immunologic measures by 6 months of age  the absolute number of cd4  lymphocytes and the cd4  cd8  lymphocyte ratio were the variables most predictive of infection  as in retrospective studies  clinical disease developed in 80  of infected infants within the first 24 months of life  this study provides documentation of hiv 1 perinatal transmission risk and early correlates of infection in young infants from a single hospital  
class2	ditiocarb sodium  diethyldithiocarbamate  therapy in patients with symptomatic hiv infection and aids  a randomized  double blind  placebo controlled  multicenter study  we randomized 389 symptomatic patients with human immunodeficiency virus  hiv  infection to ditiocarb sodium  400 mg m2 orally for 24 weeks  or a placebo  patients were well balanced according to centers for disease control  cdc  group  cd4  cell number  and duration of disease prior to entry  ten new acquired immunodeficiency syndrome  aids  defining opportunistic infections occurred in the treated patients and 21 in the controls  reduction of new opportunistic infections in the ditiocarb group was significant in all patients  relative risk  rr   0 44  and in patients with aids  cdc groups iv c1 and iv d   rr  0 12   the size of the effect of ditiocarb was maintained when data were reanalyzed after exclusion of a patient who progressed to pneumocystis carinii pneumonia who was not strictly cdc defined  rr  0 46   or when considering as new opportunistic infections three events  which were clinically active at entry  but for which the definitive diagnosis was made during study  rr  0 49   the administration of ditiocarb did not induce any major adverse clinical or biological reactions  we conclude that  in this study  ditiocarb was safe and reduced the incidence of opportunistic infections in patients with symptomatic hiv infection  
class2	depletion of muscle mitochondrial dna in aids patients with zidovudine induced myopathy  long term zidovudine therapy in patients with human immunodeficiency virus  hiv  infection can cause a destructive mitochondrial myopathy with histological features of ragged red fibres  rrf  and proliferation of abnormal mitochondria  in 9 zidovudine treated patients with this myopathy we found severely reduced amounts  up to 78  reduction vs normal adult controls  of mitochondrial dna  mtdna  in muscle biopsy specimens by means of southern blotting  in 2 hiv positive patients who had not received zidovudine  muscle mtdna content did not differ from that in the 4 controls  depletion of mtdna seems to be reversible  since 1 patient showed a substantial reduction in rrf and a concomitant pronounced increase in muscle mtdna content after zidovudine therapy was discontinued  depletion of muscle mtdna is probably due to zidovudine induced inhibition of mtdna replication by dna polymerase gamma and is not a secondary effect of hiv infection  
class2	risks and benefits of paracetamol antipyresis in young children with fever of presumed viral origin to examine whether antipyretic therapy in young children is associated with potential risks  interference with enhanced host defences at febrile temperatures  or benefits  improved comfort and behaviour   a randomised  double blind  placebo controlled trial of paracetamol was conducted among 225 children 6 months to 6 years of age who presented with acute  less than or equal to 4 days  fever  greater than or equal to 38 degrees c per rectum  without evident bacterial focus of infection  parents were asked to give paracetamol liquid 10 15 mg kg or placebo every 4 h as needed for fever and to avoid bathing  sponging  or other pharmacological agents  parents kept temperature and symptom diaries and recorded changes in child comfort and behaviour according to a pretested  5 category likert type questionnaire 1 2 h after every dose  there were no significant differences between treated and placebo groups in mean duration of subsequent fever  34 7 vs 36 1 h  or other symptoms  72 9 vs 71 7 h   paracetamol treated children were more likely to be rated by their parents as having at least a 1 category improvement in activity  38 vs 11   p   0 005  and alertness  33 vs 12   p   0 036  but no significant differences were noted in mood  comfort  appetite  or fluid intake  that overall improvement in behaviour and comfort with paracetamol was not impressive is underscored by the inaccuracy of parents   guess  at the end of the trial as to which agent their child had received 45  correct guesses for paracetamol and 52  for placebo  the data suggest that the clinically relevant hazards and benefits of paracetamol antipyresis have been exaggerated  
class2	cutaneous hypersensitivity reactions due to thiacetazone in hiv 1 seropositive patients treated for tuberculosis the effects of the human immunodeficiency virus  hiv  on tuberculosis management was investigated in 227 patients initially treated with a regimen containing streptomycin  isoniazid  and thiacetazone  sth   93 of these 227 were hiv seropositive  60 patients  of whom 18 were hiv seropositive  received a regimen consisting of streptomycin  isoniazid  rifampicin  and pyrazinamide  shrz  in the initial phase  and thiacetazone and isoniazid  th  in the continuation phase  cutaneous hypersensitivity reactions occurred in 22 of 111  20   hiv seropositive patients  and in 2 of 176  1   hiv seronegative patients  rr   18  95  ci 4 4 76  p less than 10  7   during the first 8 weeks of treatment 18 reactions occurred among the 93 hiv seropositive patients on sth  whereas no reaction occurred in 17 hiv seropositive patients during the initial phase of shrz th  p   0 04   none of the 18 hiv seropositive patients with cutaneous reactions who were subsequently challenged with isoniazid reacted  nor did any of the 10 tested with streptomycin  but 6 of the 7 challenged with thiacetazone reacted  3 patients  all hiv positive and with toxic epidermal necrolysis  died as a result of the cutaneous reaction  these results have major implications for tuberculosis control programmes in africa  
class2	a mouse model for investigating the molecular pathogenesis of adenovirus pneumonia  intranasal inoculation of type 5 adenovirus  ad5  produced pneumonia in mice even though the virus did not replicate  to induce the pneumonia  however  a large viral infectious dose was required  i e   10 10  plaque forming units  four strains of inbred mouse were studied  c57bl 6n  c57bl 10scn  cba n  and c3h n   all showed similar inflammatory responses  although the greatest infiltration occurred in the c57bl 6n mice  the pathological response to ad5 infection resembled that previously described in cotton rats  it consisted of overlapping early and late phases  and the infiltration contained primarily lymphocytes and monocytes macrophages with a scattering of polymorphonuclear leukocytes  the prominent early phase and the presence of polymorphonuclear leukocytes suggested that induction of cytokines may play an important role in the pathogenesis of this pneumonia  assays showed the appearance of tumor necrosis factor alpha  tnf alpha   interleukin 1  il 1   and il 6 in the infected mouse lungs concomitant with the developing early phase infiltration  only il 6 was found in the peripheral blood  il 6 reached maximum titers 6 24 hr after infection  whereas maximum levels of tnf alpha and il 1 were attained 2 3 days after infection  specific rnas for each of these cytokines were demonstrated in the infected lungs  to test the hypothesis that a cytotoxic t cell response was responsible for the second phase  which primarily consisted of a perivascular and peribronchial infiltration of lymphocytes  ad5 was used to infect c57bl 10scn nu nu and parent mice  the nude mice showed a normal early phase response  but essentially no peribronchial and only minimal perivascular infiltrations occurred  
class2	focal hepatic tuberculosis in a patient with acquired immunodeficiency syndrome  patients infected with hiv are known to have unusual manifestations of a variety of infections  we have described the third reported case of a patient with aids having an apparent pyogenic liver abscess subsequently diagnosed as focal hepatic tuberculosis  this case emphasizes the need for aggressive diagnostic procedures for evaluation of focal liver abnormalities in these patients  
class2	counseling patients seropositive for human immunodeficiency virus  an approach for medical practice  persons at risk for infection with the human immunodeficiency virus are being encouraged to learn their serostatus  while such knowledge can help patients seek appropriate medical care  it can also be distressing  we describe an approach  based on crisis counseling  for physicians to use in working with patients infected with hiv  it can help physicians in assisting patients with emotional reactions to the diagnosis as well as in directing patients to manage practical issues of concern  methods for discussing safer sex or injection practices are also presented  
class2	susceptibility to coxsackievirus b3 induced chronic myocarditis maps near the murine tcr alpha and myhc alpha loci on chromosome 14  this study was undertaken to determine the genetic control of host susceptibility to coxsackievirus b3  cvb3  induced chronic myocarditis in a mouse model  an autosomal recessive autoimmune myocardial disease  amd  gene  possibly more than one gene   which determined susceptibility to cvb3 induced chronic myocarditis in the a j and dba 2j inbred mouse strains  was mapped to a segment of chromosome 14  data from both the axb bxa recombinant inbred  ri  strains and the b10 d2 57n  h 8b congenic mice supported this linkage relationship  analysis of the axb bxa ri strain distribution patterns suggested that amd maps distal to the np 2  tcr alpha  and myhc alpha loci  
class3	comparison of chloroquine  pyrimethamine and sulfadoxine  and chlorproguanil and dapsone as treatment for falciparum malaria in pregnant and non pregnant women  kakamega district  kenya  objective  to compare treatment and protection against falciparum malaria in pregnant and non pregnant women with three drug regimens  design  prospective intervention study with six weeks  follow up  patients received one of three drug regimens in order of entry  setting  primary care hospital and secondary girls  school in rural western kenya  patients  158 of 988 pregnant women  89 primigravid and 69 multigravid  in the third trimester and 105 of 1488 non pregnant schoolgirls of reproductive age were parasitaemic  more than 500 asexual forms microliter  these women were divided into three treatment groups by gravid state  interventions  women were treated with chloroquine base 25 mg kg over three days or pyrimethamine 75 mg and sulfadoxine 1500 mg as a single dose or chlorproguanil 1 2 mg kg and dapsone 2 4 mg kg as a single dose  main outcome measures  parasitaemia and haemoglobin concentrations measured at seven day intervals for six weeks  results  primigravid women were more likely to be parasitaemic on follow up than multigravidas or nulligravidas  whose response was about the same  parasites did not clear by day 7 in primigravidas in six  20   of 30 who received chloroquine  three  8   of 35 treated with pyrimethamine and sulfadoxine  and none of 23 treated with chlorproguanil and dapsone  at day 28  83   19   and 67  of primigravidas in these treatment groups were parasitaemic  haemoglobin concentrations rose in all women  but improvement was sustained only in women who remained free of parasites  conclusions  clearance of parasites was better with either pyrimethamine and sulfadoxine or chlorproguanil and dapsone than with chloroquine  longest protection was obtained with pyrimethamine and sulfadoxine  
class3	surgical aspects of malaria  the spread of drug resistant organisms and increased international travel makes malaria a disorder of ever increasing importance  this report reviews those aspects of malaria of surgical relevance  the importance of the spleen in host defence against malaria and other infections makes splenic preservation desirable whenever possible after rupture of the spleen  tropical splenomegaly is caused by an abnormal immune response to malaria and is best managed medically  careful selection of blood donors is essential to prevent transfusion malaria  and routine antimalarial prophylaxis is indicated for blood recipients in many endemic areas  the risk of postoperative malaria may justify chemoprophylaxis in certain patients  
class3	acanthamoeba keratitis with two species of acanthamoeba  we describe a case of acanthamoeba keratitis related to soft contact lens wear  the patient presented with a 3 week history of severe uniocular pain  radial stromal infiltrates and subepithelial infiltrates with no epithelial defect  acanthamoeba was cultured from the corneal biopsy specimen  contact lens and lens case  the corneal biopsy culture grew both a  castellani and a  polyphaga as well as escherichia coli  the patient was treated with topical dibromopropamidine isethionate  brolene  drops  neomycin and polymyxin b drops and fortified gentamicin drops  gradual clinical improvement ensued  
class3	the relationship of antibody levels to the clinical spectrum of human neurocysticercosis  one hundred proven cases of cerebral cysticercosis were studied with an enzyme linked immunoassay  elisa  employing cyst fluid as antigen  with a view to detecting specific antibodies in serum and cerebrospinal fluid  csf   antibody levels were correlated with the clinical presentation of the patients  the type and number of cysts detected on their brain scans  the anatomical position of these cysts and the presence of lymphocytes in the csf  patients could be divided into two distinct categories  one with low levels of antibody in the serum and absent antibody in the csf  and the other with high levels in both the serum and the csf  this differentiation matched the clinical presentation of a benign and a malignant group  antibody levels could not be related to the type of cysts as observed on the brain scan  but depended on the anatomical position of the cyst  being lower if the cysts were confined to the cerebral cortex  a correlation of antibody levels with the number of cysts was only found in the benign group  
class3	use of ct and mr imaging to distinguish intracranial lesions and to define the need for biopsy in aids patients to explore the potential usefulness of imaging studies in the diagnosis of focal central nervous system  cns  lesions associated with acquired immunodeficiency syndrome  aids   the authors retrospectively examined the radiographic studies of 149 aids patients who presented with signs and symptoms of the three most common focal cns lesions  of these patients  74  50   had toxoplasma abscesses  45  30   had primary cns lymphoma  and 30 patients  20   had progressive multifocal leukoencephalopathy  pml   magnetic resonance  mr  imaging was more sensitive than computerized tomography  ct  in detecting lesions  especially in cases of pml  whereas ct was unable to distinguish mass lesions caused by toxoplasmosis from those caused by lymphoma  71  of the solitary lesions seen on mr images were lymphomas  these results indicate that empirical treatment for toxoplasmosis  the most common initial treatment for aids patients with neurological symptoms stemming from mass lesions  is not likely to be successful for patients with solitary lesions on mr images  rather  early biopsy is advisable  if the presence of lymphoma is confirmed  the rapid initiation of treatment can allow prolonged high quality survival  
class3	neurological sequelae of cerebral malaria in children  out of 604 gambian children admitted with falciparum malaria to one hospital between september and december  1988  308 had cerebral malaria and 203 were severely anaemic  haemoglobin less than 60 g l   14  of those with cerebral malaria died  as did 7 8  of those with severe anaemia  32  12   of children surviving cerebral malaria had residual neurological deficit  69 other children were admitted with clinical features strongly suggestive of cerebral malaria but with negative blood films  16 of these died and 3 had residual neurological deficits  the commonest sequelae of cerebral malaria were hemiplegia  23 cases   cortical blindness  11   aphasia  9   and ataxia  6   factors predisposing to sequelae included prolonged coma  protracted convulsions  severe anaemia  and a biphasic clinical course characterised by recovery of consciousness followed by recurrent convulsions and coma  at follow up 1 6 months later over half these children had made a full recovery  but a quarter were left with a major residual neurological deficit  cerebral malaria in childhood may be an important cause of neurological handicap in the tropics  
class3	prenatal diagnosis of congenital toxoplasmosis  prenatal diagnosis of congenital toxoplasmosis was attempted in 50 pregnant women at risk for giving birth to an affected child  fifteen of these patients seroconverted during pregnancy and 35 had a high initial antibody level in their first serum sample  prenatal diagnosis consisted of a combination of ultrasound screening  amniocentesis  and funipuncture at about 20 weeks  gestation  diagnosis of congenital toxoplasmosis was based on a positive toxoplasma culture of amniotic fluid or fetal blood and on the presence of specific immunoglobulin m antibodies in fetal blood  in addition  alterations in fetal hematology  cellular immunology  and fetal liver tests were indicative of infection  fetal infection was detected in six fetuses  two died in utero as a consequence of the infection and four were born after 37 weeks  gestation  despite antibiotic treatment with pyrimethamine and sulfadiazine  one child has internal hydrocephalus and chorioretinitis and another has unilateral chorioretinitis  in the two other children  the disease is still subclinical  of the 44 children born after a negative prenatal diagnosis  35 have reached the age of 1 year  toxoplasma antibodies have disappeared in all of them  investigation of the remaining nine children showed a decrease in toxoplasma antibodies  suggesting that none of them are affected  prenatal diagnosis was never associated with fetal loss  and premature delivery occurred in only two cases  we conclude that prenatal diagnosis of congenital toxoplasmosis is safe and reliable  
class3	infectious diarrhea  managing a misery that is still worldwide  infectious diarrhea is the largest single cause of morbidity and mortality in the world  bacteria  viruses  and protozoan parasites are the most common causative agents  treatment in most cases of bacterial and viral diseases consists of correcting fluid loss and electrolyte imbalance by oral or parenteral rehydration  antimicrobial therapy is reserved for very ill patients only  with the exception of cryptosporidium  for which no effective agent is yet available  all protozoan infections are treatable with metronidazole  
class3	clinicopathological features of childhood nephrotic syndrome in northern nigeria the clinicopathological features of childhood nephrotic syndrome in northern nigeria were studied in 100 consecutive patients  the patients presented with gross anasarca and very low serum albumin  which was less than 15 g l in 30 patients  the three most frequent histological diagnoses in 98 renal biopsies were membranoproliferative glomerulonephritis  25   quartan malarial nephropathy  20   and proliferative glomerulonephritis  19   together they accounted for 65 per cent of all biopsies  only nine patients had minimal change nephropathy  antigens were detected by immunofluorescence in the glomeruli of 70 of 76 biopsies  92 per cent   plasmodium malariae was detected in 25 per cent and hepatitis b surface antigen in 24 per cent  the disease was characterized by progressive deterioration in renal function and a high mortality rate of 13 per cent  nine of the 13 deaths occurred within one year of diagnosis  
class3	filarial specific igg4 response correlates with active wuchereria bancrofti infection  the filarial specific humoral immune response of adult residents of two areas of papua new guinea  differing in transmission of wuchereria bancrofti infection was compared  the majority of residents of the village of bonahoi  in an area where transmission of filariasis had been interrupted by a 20 year insecticide spray program to control malaria  showed no parasitologic signs of active w  bancrofti infection and were negative for both circulating phosphorylcholine ag and peripheral blood microfilariae  in contrast  adult residents of the village of nanaha were in an area exposed to infection  and were phosphorylcholine ag  and microfilariae positive  the antibody response of these two groups to both adult worm excretory secretory  es  ag and somatic antigen extract was examined to determine which components of the filarial specific immune response were dependent on active infection  identification of these immune responses may point to immunologic methods to evaluate control programs for lymphatic filariasis  adults from bonahoi were found to have significant immune responses to  35s  methionine labeled es ag by immunoprecipitation and to adult somatic antigen extracts by elisa and by immunoblotting  this result is consistent with the fact that these individuals were previously exposed to and or infected with w  bancrofti  similarly  residents of the endemic village had detectable immune responses to these ag irrespective of if they were microfilaremic  the most striking immunologic difference observed between the two groups was that residents of bonahoi had a dramatically reduced filarial specific igg4 antibody response to both adult somatic ag and adult es ag  these data suggest that longitudinal measurement of filarial specific igg4 levels may be a useful seroepidemiologic indicator of changes in w  bancrofti infection status  
class3	serum resistance of metacyclic stage leishmania major promastigotes is due to release of c5b 9  the mechanism of serum resistance for infective promastigotes of leishmania major was investigated  prior results suggested that the mechanism of resistance was mediated at a step after c3 deposition  equivalent amounts of c3b were deposited on serum susceptible  noninfective promastigotes harvested from log stage cultures  log  and on c resistant  infective  metacyclic promastigotes  mp  purified from stationary stage cultures  whereas binding of c9 to log was stable during incubation in serum  c9 binding to mp was minimal and unstable  because molecules bound initially to mp were released with continued incubation  failure to bind c9 was not a result of inability to activate c  the kinetics of c3  c6  and c9 consumption were similar for log and mp  deposition of c5b 7 on mp was stable  indicating that the initial steps in terminal complex formation were intact  instead  the majority of c5b 9 formed on mp was spontaneously released into the serum as sc5b 9  residual c5b 9 on mp was released with 1 m nacl  these data show that developmental modification of the promastigote membrane during transition from a noninfective to an infective stage blocks insertion of lytic c5b 9 into the promastigote membrane  
class3	analysis of the permissive association of a malaria t cell epitope with dr molecules  in this study we examined the association of a promiscuous malaria t cell epitope  cs t3  to different hla dr alleles  a large series of singly substituted or truncated variants of cs t3 was prepared and tested for the ability to be recognised in association with  or to bind to  three distinct hla dr alleles  dr1  drw11  and drw14 w6   and three natural variants of hla drw11  we found that although association with the different dr molecules mapped to identical or closely overlapping regions of the peptide  distinct substitutions could drastically influence the capacity of the peptide to interact with one but not another of the three dr molecules tested  based on analysis of the distribution of residues recognized by t cell clones restricted to the different dr alleles  we suggest that the peptide cs t3 is not bound  at least for the three dr examined  as an alpha helix  in addition we tested three subtypes of drw11 as apc for the cs t3 analogues and observed that the peptide is most likely bound in the same conformation to the three natural variants of the drw11 molecule  
class3	sensitive and specific detection of toxoplasma dna in an experimental murine model  use of toxoplasma gondii specific cdna and the polymerase chain reaction  toxoplasma gondii  an apicomplexan parasite of mammals and birds  is well recognized as a cause of encephalitis in aids patients and as a cause of congenital infections  the polymerase chain reaction  pcr  and toxoplasma cdna clones were used to diagnose t  gondii infection in an acute murine model of toxoplasmosis  diagnosis of tissue infection by southern blot hybridization with cdna clones of t  gondii was possible within 5 days of infection  this technique could detect as few as 10 000 organisms  specific t  gondii gene amplification by pcr using the primers 5 cacacggttgtatgtcggtttcgct3  and 5 tcaaggagctcaatgttacagcct3  followed by oligonucleotide hybridization using 5 gcggtcattctcacaccgacggagaaccacttcactctca3  allowed detection of t  gondii in the tissue of mice by day 2 after infection and in the blood of mice by day 5 after infection with rh strain t  gondii  this technique could detect as few as 10 organisms  thus  these techniques may be useful in the diagnosis of toxoplasmosis  
class3	tumor necrosis factor and severe malaria  to investigate the relation of tumor necrosis factor alpha  tnf alpha  to plasmodium falciparum infection  plasma tnf alpha concentrations were measured in zairian children with severe malaria  mild malaria  or other illnesses  the initial geometric mean plasma concentration of tnf alpha among 61 children with p  falciparum infection   71 pg ml  was higher than the level in 26 severely ill  aparasitemic children  10 pg ml  p less than  001   among 29 parasitemic children  initial geometric mean tnf alpha levels decreased from 77 to 5 pg ml  p less than  001  at day 7  tnf alpha levels increased with parasite density and were associated with hyperparasitemia  severe anemia  hypoglycemia  and young age but not with cerebral malaria or fatal outcome  however  tnf alpha levels were elevated equally in children with cerebral malaria and with other signs of severe malaria  with multiple linear regression  tnf alpha levels were elevated independently in children with hyperparasitemia  p    001  and severe anemia  p    04   in this study  high tnf alpha levels were associated with several manifestations of severe malaria and were not specific to cerebral malaria  
class3	effectiveness and tolerance of long term malaria prophylaxis with mefloquine  need for a better dosing regimen to measure the effectiveness and tolerance of long term malaria prophylaxis with mefloquine  the incidence of plasmodium falciparum malaria and of adverse reactions was compared in peace corps volunteers in west africa who took mefloquine every 2 weeks and in volunteers who took chloroquine phosphate weekly  mefloquine was only 63  more effective than chloroquine  the monthly incidence of p falciparum infections was one case per 100 volunteers who took mefloquine and 2 7 cases per 100 volunteers who took chloroquine  using daily proguanil  chloroguanide  hydrochloride in addition to chloroquine did not provide additional protection  all mefloquine prophylaxis failures occurred during the second week of the every 2 weeks dosing regimen in volunteers who had used mefloquine for more than 2 months  blood concentrations of mefloquine were lower during the second week of the alternate week regimen than during the first week  suggesting that blood levels are too low during the second week to suppress parasitemia  no serious adverse reactions were observed  the results indicate that a dosing regimen of 250 mg of mefloquine weekly should be considered for travelers to areas with chloroquine resistant p falciparum malaria  
class3	imported plasmodium falciparum malaria in american travelers to africa  implications for prevention strategies data from the us national malaria surveillance system were analyzed to assess characteristics of travelers who acquired plasmodium falciparum infections in africa and evaluate the impact of chloroquine resistance on the incidence of imported malaria  although the number of cases acquired in east africa has stabilized  the number of imported p falciparum infections acquired in west africa increased threefold from 1985 to 1988  and the proportion of travelers who reported failure of chloroquine prophylaxis increased from 10  to 48   fifty eight percent of patients who acquired malaria in west africa had not used chemoprophylaxis  to curb the rising incidence of p falciparum infections in american travelers  the centers for disease control revised malaria prophylaxis recommendations to include the use of mefloquine in areas of chloroquine resistance  use of malaria protection measures by travelers to west africa must also be improved  
class3	leishmania donovani chagasi  new clinical variant of cutaneous leishmaniasis in honduras  during surveillance for endemic visceral leishmaniasis on an island off the pacific coast of honduras  an unusual form of cutaneous leishmaniasis was encountered  by clinical and laboratory criteria  17 cases were identified over 5 months  children aged 4 to 15 years were primarily affected  lesions were generally few in number  small  always papular  and non ulcerative  even when present for several years  patients with skin lesions seemed otherwise healthy and were well nourished  montenegro skin tests with leishmania mexicana and l major antigens were positive in 10 of 17 patients tested  and lesions from 9 patients were positive by culture  since the summer of 1988  cases of atypical cutaneous leishmaniasis continue to occur on the island  8  as well as on the mainland of southern honduras  23   a total of 9 parasite isolates from skin lesions  4 from bone marrow of patients with kala azar  and 2 from sandflies were identified as l donovani chagasi and were indistinguishable from one another by isoenzyme analysis  
class3	strongyloides stercoralis associated with a bleeding gastric ulcer  infection with the helminthic parasite  strongyloides stercoralis  is usually acquired by skin invasion  or occasionally via ingestion of larvae   after transformation to the adult form  the parasite preferentially localises in the small intestine  especially in the duodenal and jejunal part  a remarkable feature of strongyloides is its property of endogenous reinfection  in the case of an immunocompromised host a massive infection  called hyperinfections strongyloides  may occur  numerous gastrointestinal complications of strongyloides infections  sometimes with a lethal outcome  have been reported  the intestinal manifestations are usually limited to the small bowel  and rarely involve the stomach  we report a patient with complicated strongyloides infection of the stomach  
class3	potential role of igg avidity for diagnosing toxoplasmosis  sera from 20 cases of toxoplasmic lymphadenopathy were examined by an enzyme linked immunosorbent assay toxoplasma igg avidity  elisa  at two laboratories  the results obtained were largely in agreement and showed that sera from patients with acute infection had low avidity igg  30  or less   whereas sera from patients with chronic infection had high avidity igg  40  or more   it is suggested that this type of assay could have a useful complementary role in antenatal testing for toxoplasmosis  
class3	rapid diagnosis of malaria by fluorescence microscopy with light microscope and interference filter fluorochrome staining to detect malaria parasites in bloodfilms is more sensitive  is easier to do  and is less time consuming than giemsa staining  however  standard epi illuminated  mercury vapour  fluorescence microscopes are expensive  especially for tropical countries where malaria is endemic  fluorescence microscopy with a standard light microscope and a new interference filter specially designed for the fluorochrome stain  acridine orange  was used to detect malaria parasites in thick and thin bloodfilms  in this system two fluorescence colours  green  nuclei  and red  cytoplasm   were emitted from stained parasites  thick and thin bloodfilms from patients with malaria were examined with this system  bloodfilms had been fixed and stored for 1 5 years  rapid scanning of both thick and thin bloodfilms was possible at a magnification of x200 with standard lenses  indicating that this may be a useful economic system for rapid diagnosis of malarias  
class3	exchange transfusion as an adjunct to the treatment of severe falciparum malaria  case report and review  malaria associated with complications or a fatal outcome is almost always caused by plasmodium falciparum  the mortality due to this disease parallels the degree of parasitemia  successful use of exchange blood transfusion as a therapeutic adjunct for this infection was first reported in 1974  although the efficacy of this procedure has not been established by randomized  controlled trials  the rationale for this form of therapy is based on   1  rapid reduction in the parasite load by direct removal   2  decreased risk of severe intravascular hemolysis and its consequences  disseminated intravascular coagulation and renal dysfunction    3  improved rheology with transfused blood and reduced microcirculatory sludging  and  4  improved oxygen carrying capacity with transfused erythrocytes  we describe a case of severe falciparum malaria and review the literature describing the use of exchange transfusion for treatment of this infection  
class3	short term course of corticosteroids in the treatment of resistant ascites complicating schistosomal liver disease  the aim of this work was to evaluate the effect of short term corticosteroids in resistant ascites complicating schistosomal liver disease after 4 wk or more on standard treatment  thirty seven patients were randomly allocated to two groups  group i  18 patients  was put on 40 mg furosemide and 200 mg spironolactone  in addition to a 15 day  tapering dose of prednisone  15  10  5 mg   group ii  19  patients received the same diuretics without steroids  and served as controls  at the end of a 2 wk course of therapy  the mean variations were as follows  body weight in patients in group i   cases   decreased by 9 8 kg  compared with 4 3 kg in controls  abdominal girth decreased by 7 4 cm in cases  compared with 3 6 cm in controls  urine output increased by 635 9 ml in cases  compared with 364 6 ml in controls  urinary sodium excretion increased by 16 5 meq day in cases  compared with 4 1 meq day in controls  these differences between cases and controls were found to be statistically significant  p less than 0 01   on the other hand  there were insignificant differences as regards decrease in blood urea  3 2 g dl for cases and 2 7 g dl for controls   decrease in serum creatinine  0 2 mg dl for both cases and controls   increase in serum albumin  0 3 g dl in cases and 0 2 g dl in controls   increase in serum sodium  3 2 meq l in cases and 2 7 meq l in controls   and increase in serum potassium  0 2 meq l in cases and 0 4 meq l in controls   we conclude that a short term course of corticosteroids in conjunction with standard diuretics has proved to be an effective  safe  and economical modality to relieve resistant hepatic ascites  it can be considered a temporary alternative to paracentesis with albumin infusion  
class3	eosinophilic ascites due to hyperinfection with strongyloides stercoralis  we report the case of a patient with cryptogenic cirrhosis  new onset ascites  and hyperinfection with strongyloides stercoralis who had significant eosinophilia of the peritoneal fluid  the eosinophilia resolved with treatment of the s  stercoralis infection  and did not recur during two subsequent episodes of ascites and spontaneous bacterial peritonitis  eosinophilic ascites is rare in parasitic infection  but it has been described in a variety of disorders which are discussed  
class3	a comparative study of gastrointestinal infections in united states soldiers receiving doxycycline or mefloquine for malaria prophylaxis  a double blind study of daily doxycycline  100 mg  vs  weekly mefloquine  250 mg  was performed on united states soldiers training in thailand to assess the effect of doxycycline malaria prophylaxis on the incidence of gastrointestinal infections  during a 5 week period  49   58 119  of soldiers receiving doxycycline and 48   64 134  of soldiers receiving mefloquine reported an episode of diarrhea  infection with bacterial enteric pathogens was identified in 39   47 119  of soldiers taking doxycycline and 46   62 134  of soldiers taking mefloquine  forty four percent  59 134  of soldiers receiving mefloquine and 36   43 119  of soldiers receiving doxycycline were infected with enterotoxigenic escherichia coli  etec   while 9   12 134  of soldiers receiving mefloquine and 4  of soldiers receiving doxycycline were infected with campylobacter  side effects from either medication were minimal  after 5 weeks in thailand  the percent of non etec strains resistant to greater than or equal to 2 antibiotics increased from 65   77 119  to 86   95 111  in soldiers on mefloquine and from 79   84 106  to 93   88 95  in soldiers on doxycycline  doxycycline prophylaxis did not prevent or increase diarrheal disease in soldiers deployed to thailand where etec and other bacterial pathogens are often resistant to tetracyclines  
class3	mucocutaneous leishmaniasis due to leishmania  leishmania  infantum  biochemical characterization  a vegetative mass in the right nasal cavity of a 62 year old man from palma de mallorca  spain  was found to be due to leishmania  the organism was isolated in culture and characterized by in situ hybridization  southern blot hybridization  and isoenzyme analysis  it was thus demonstrated to be the most common enzyme variant 1  mon 1  of leishmania  leishmania  infantum  
class3	leishmania mexicana complex  human infections in the republic of panama  parasites of the genus leishmania responsible for human cutaneous leishmaniasis in the new world form 2 major taxonomic divisions  the leishmania braziliensis and the l  mexicana complexes  we report the isolation and characterization of the l  mexicana complex among humans in the republic of panama  characterization was based on parasite morphology  pathogenesis in infected golden hamsters  cellulose acetate isoenzyme electrophoretic mobilities  and membrane specific monoclonal antibodies using the radioimmune binding assay technique  
class3	infectivity of the subspecies of the leishmania braziliensis complex in vivo and in vitro  the infectivity of leishmania braziliensis ssp  in relation to their growth kinetics in senekjie s medium was determined using the human macrophage cell line u937 and inbred hamsters  in both systems  infectivity was shown to be distinctive for each subspecies  while l  b  panamensis promastigotes from 6 day old cultures  early stationary phase  were more infective than parasites from any other culture day  l  b  guyanensis and l  b  braziliensis reached maximum infectivity on days 8 10 and day 10  late stationary phase of growth   respectively  although maximum infectivity occurred during stationary growth  strict growth phase dependency was not observed  the populations of parasites on these culture days were composed mostly of small  highly motile promastigotes with flagella 2 3 times the length of their cell bodies  these promastigotes resembled the infective forms transmitted by the sand fly vector  a distinct pathological picture characterized the disease caused by the different who reference strains for these subspecies in hamsters  l  b  guyanensis developed the most severe lesions  while moderate and inconspicuous lesions were observed when l  b  panamensis and l  b  braziliensis  respectively  constituted the inocula  
class3	an improved serodiagnostic procedure for visceral leishmaniasis  the enzyme linked immunosorbent assay  elisa  is a sensitive and specific serodiagnostic method for leishmaniasis  in this report  we describe how this versatile assay can be improved by the use of protein a or protein g conjugates for the specific detection of leishmania antibody in the sera of patients with visceral leishmaniasis  in direct comparisons with anti immunoglobulin conjugate  enzyme linked protein a gave significantly higher absorbance values for positive sera without a corresponding increase in absorbance values for sera from normal individuals or from patients with other diseases known to cross react with leishmaniasis  the effect was to increase the distance between positive and negative values  which aided in the interpretation of the results  this also permitted visual distinction between positive sera and negative or weakly reactive sera  the assay was effective using either blood or serum as the source of primary antibody  a further advantage of protein a over anti ig conjugate was its ability to detect specific antibody in dog as well as human sera  finally  we demonstrated the usefulness of the protein a elisa with a recombinant leishmania antigen  gp63  
class3	wasting and macrophage production of tumor necrosis factor cachectin and interleukin 1 in experimental visceral leishmaniasis  wasting and secretion of the catabolic cytokines tumor necrosis factor  tnf  cachectin and interleukin 1  il 1  were assessed in weanling syrian hamsters infected with leishmania donovani amastigotes  whereas the mean weight of uninfected animals increased progressively over 9 weeks  the mean weight of infected animals plateaued at 4 6 weeks and then decreased progressively until death  splenic mononuclear cells from control hamsters produced 11 3     8 3  sd  ng tnf 10 6  mononuclear cells 24 hr  tnf secretion in infected animals was greater than the mean     2 sd of controls in 1 of 3 hamsters at 2 weeks post infection and in 8 of 9 hamsters at weeks 4 8  the mean tnf secreted by infected animals studied at weeks 4 8 was 371  range 28 800  ng tnf 10 6  mononuclear cells 24 hr  p   0 005   control hamsters produced 7 7     2 7 pg il 1 10 6  mononuclear cells 24 hr  at 2 weeks  mononuclear cells from 2 of 3 infected animals secreted amounts of il 1 greater than the mean     2 sd of controls  all of 8 infected hamsters secreted increased amounts of il 1 at 4 8 weeks  the mean was 164  range 17 370  pg il 1 10 6  mononuclear cells 24 hr  p   0 002   in comparison to infected animals  mononuclear cells from control hamsters incubated with lipopolysaccharide  10 micrograms ml  produced 172 5 ng tnf and 44 6 pg of il 1 10 6  mononuclear cells 24 hr  the effect of visceral leishmaniasis on food intake was assessed in a separate group of animals housed individually in metabolic cages  significant reductions in weight and food intake were first observed at 2 and 3 weeks of infection  respectively  by 5 weeks  the food intake of infected animals was 46  that of controls  syrian hamsters infected with l  donovani provide an excellent model with which to study the mechanism of wasting  
class3	effects of multiple monthly doses of ivermectin on adult onchocerca volvulus  this paper assesses the effects on adult onchocerca volvulus of monthly doses of ivermectin  150 micrograms kg  given over 4  8  and 12 months to patients in guatemala  nodules were removed 4 months after the last dose  the adult o  volvulus were extracted by collagenase digestion  studied by histological techniques  and compared with worms from untreated patients  twelve monthly doses killed a proportion of the adult worms  12  of males and 22  of females   leaving the remainder relatively unaffected and the females slowly resuming embryogenesis  after 8 and 12 doses  a number of female worms had resumed embryogenesis in 1 genital tract only  and in 1 female a total degeneration of 1 ovary was seen  ivermectin also led to a marked drop in the number of male worms in nodules  no serious adverse reactions occurred and the treatment was well accepted  
class3	amebic meningoencephalitis in a patient with aids caused by a newly recognized opportunistic pathogen  leptomyxid ameba  a fatal case of meningoencephalitis due to a leptomyxid ameba in a patient with the acquired immunodeficiency syndrome is presented  this opportunistic organism has not been previously recognized as a human pathogen  a 36 year old male intravenous drug abuser died after an 18 day hospital course heralded by fever and headache and followed by nuchal rigidity and hemiparesis  computed tomography of the head showed multiple hypodense lesions  neuropathologic examination showed that in addition to human immunodeficiency virus encephalomyelitis  there was multifocal meningoencephalitis with trophozoites and cysts morphologically indistinguishable from those of acanthamoeba  these organisms were also found in the kidneys and adrenal glands  by immunofluorescence  the parasites showed antigenic identity with a free living leptomyxid ameba and failed to react with any of a spectrum of antiacanthamoeba antisera  this emphasizes the importance of immunofluorescence identification of morphologically indistinguishable ameba species  
class3	scabies in nursing homes  an eradication program with permethrin 5  cream  permethrin 5  cream was used to treat scabies in three large nursing homes under a compassionate plea protocol for chronic  therapy resistant infestations  all residents  staff  and frequent visitors were treated whether or not symptomatic  family members of these groups were treated either when symptomatic or directly exposed to scabies  nine hundred ninety five persons were treated  202 of whom were diagnosed with scabies  approximately 35   111 of 313  of nursing home residents were diagnosed with scabies  these were patients in whom multiple treatments with other scabicides were unsuccessful  at the completion of the study  195 patients were examined for efficacy of treatment  of these  91  46 7   had clearing of lesions with one medication application  77  39 5   with two treatments  and 23  11 8   with three or more treatments  the overall cure rate was 98   adverse experiences occurred in 2 4  of cases and were mild  i e   pruritus and rash   
class3	monoclonal  but not polyclonal  antibodies protect against plasmodium yoelii sporozoites  one of the primary strategies for malaria vaccine development has been to design subunit vaccines that induce protective levels of antibodies against the circumsporozoite  cs  protein of malaria sporozoites  in the plasmodium yoelii mouse model system such vaccines have been uniformly unsuccessful in protecting against sporozoite induced malaria  to demonstrate that antibodies to p  yoelii cs protein could provide protection we established a passive transfer model  passive transfer of navy yoelii sporozoite 1  nys1   an igg3 mab against the p  yoelii cs protein  protected 100  of mice against challenge with 5000 p  yoelii sporozoites  binding of nys1 to sporozoites was inhibited by incubation with  qgpgap 2  a synthetic peptide derived from the repeat region of the p  yoelii cs protein  indicating that the epitope on sporozoites recognized by this mab was included within this peptide  the levels of antibodies to  qgpgap 2 by elisa  and to sporozoites by indirect fluorescent antibody test and cs precipitation reaction were similar in sera from mice that received nys1 in passive transfer and were protected against challenge with 5000 sporozoites  and from mice that had been immunized with subunit vaccines containing  qgpgap 2 but were not protected against challenge with 40 200 sporozoites  to determine if antibody avidity  not absolute concentration could explain the striking differences in protection  we established a thiocyanate elution assay  the results suggest that nys1  the protective mab  has a lower avidity for  qgpgap 2 and for sporozoites than do the vaccine induced antibodies  although the results of the conventional antibody assays did not correlate with protection  sera from the protected animals inhibited sporozoite development in mouse hepatocyte cultures significantly more than did the sera from the unprotected  subunit vaccine immunized animals  correlating with protection  the data clearly demonstrate that antibodies to the cs protein can protect against intense sporozoite infection  improved understanding of the differences between protective mab and nonprotective polyclonal antibodies will be important in the further development of malaria vaccines  
class3	antibodies to human t lymphotropic virus type i in a population from the philippines  evidence for cross reactivity with plasmodium falciparum  residents of two areas in the philippines were tested for human t lymphotropic virus type i  htlv i   napsan  a site endemic for malaria  and a nonmalarious site  bacolod  by elisa  30  of the 1743 napsan residents were positive  western blot immunoreactivity with two or more htlv i proteins was present in 81  of the elisa positives  however  there was no reactivity with the env proteins  the frequency of this indeterminate immunoreactivity increased with the malaria antibody titer  none of the 200 bacolod sera were western blot immunoreactive  in competitive serologic assays  an htlv i lysate blocked the htlv i immunoreactivity of the napsan sera but did not reduce malaria antibody  a plasmodium falciparum lysate blocked both the htlv i and malaria immunoreactivity of the napsan sera  these results show that indeterminate htlv i immunoreactivity can be caused by p  falciparum antibody  serosurveys conducted in malaria endemic areas should consider this possibility  
class3	a comparison of 6   12   and 24 monthly dosing with ivermectin for treatment of onchocerciasis  this study was designed to examine the optimal dose and interval of administration of ivermectin  the now accepted drug of choice for onchocerciasis  two hundred liberians with onchocerca volvulus infection received 100  150  or 200 micrograms kg ivermectin or placebo and were followed for 36 months  the reaction after the second dose of ivermectin was significantly less than after the initial dose  although it was still significant in the 200 micrograms kg group  the skin microfilaria counts in the group treated 6 monthly with 150 micrograms kg was significantly less than in the group treated yearly  12 and 24 months after initial therapy   prevalence of microfilariae in the anterior chamber and punctate corneal opacities decreased progressively in all groups over 3 years  there appears to be a slight advantage  in terms of antiparasitic effect over the first 2 years  of therapy given 6 monthly compared with yearly  
class3	community based treatment of onchocerciasis with ivermectin  safety  efficacy  and acceptability of yearly treatment  the safety  acceptability  and efficacy of ivermectin during community based mass treatment of onchocerciasis was assessed  ivermectin was distributed three times  1 year apart  to the population of a rubber plantation  14 000 people  in liberia where greater than 80  of adults have onchocerca volvulus infection  in a sample of adults  the microfilarial density was reduced by 84  after 2 years of treatment  acceptance was as high as 98  during the third year  adverse reactions occurred in 6 13 in 1000 people after first treatment and in only 3 4 in 1000 receiving their second or third annual dose of ivermectin  severe adverse reactions were not seen  these data show that community based treatment with ivermectin is safe  well accepted  and effective in reducing microfilarial loads and suggest that ivermectin is the first practical drug suitable for mass treatment campaigns to control human onchocerciasis  
class3	visceral leishmaniasis in hiv infection and aids  clinical features and response to therapy  the development of visceral leishmaniasis with atypical features in an aids patient  and the recent flurry of reports of visceral leishmaniasis in hiv infected individuals prompted the review of its manifestations in the 47 reported cases  splenomegaly  which is almost always a feature of visceral leishmaniasis in the immunocompetent host  was absent in eight  antibodies to leishmania donovani  which are present in approximately 95 per cent of immunocompetent patients with visceral leishmaniasis  were absent in 29 of 45  66 per cent  of hiv infected patients tested  nine hiv positive patients with visceral leishmaniasis did not exhibit a primary clinical response to therapy with antimonials and of those who did show a response  relapse occurred in 13  at a mean 4 5 months after stopping therapy  seventeen patients are known to have died often in association with respiratory disease  leishmania was seen in one bronchial lavage specimen and in lung tissue in one post mortem performed  in order to improve the prognosis of visceral leishmaniasis in hiv infected patients diagnosis will have to be made earlier  taking account of the atypical features  and treatment will need to be improved  both initially and perhaps also by the use of long term maintenance therapy  
class3	infestation of extraocular muscle by cysticercus cellulosae  reports of orbital cysticercosis are uncommon despite the high incidence of brain and ocular involvement  infestation of extraocular muscle is exceedingly rare  two cases of cysticercosis of the extraocular muscles are reported here  surgical removal of the encysted parasites successfully resolved the infestation in both cases  
class3	meningitis due to protozoa and helminths  this article reviews the microbiology  pathogenesis  epidemiology  clinical manifestations  diagnostic tests  and recent advances in the therapy of protozoan and helminthic infections of the central nervous system  with more emphasis given to protozoan than to helminthic infections  
class3	toxoplasma gondii infection during pregnancy  t lymphocyte subpopulations in mothers and fetuses  prenatal diagnosis of fetal toxoplasmosis is possible with the use of fetal blood sampling  amniocentesis and ultrasound examination  the purpose of this study was to describe t lymphocyte subsets  cd3  cd4 and cd8  in mothers and their fetuses when toxoplasma gondii infection occurred during pregnancy  maternal and fetal blood samples were obtained in 86 cases and 9 fetuses showed t  gondii infection  control groups consisted of 30 healthy nonpregnant women and 30 pregnant women  pregnant women with t  gondii infection showed an increase in the suppressor  cd8  t subpopulation and a significant depression in the total helper  cd4  t cells  these alterations were more important in mothers whose fetus was infected  we showed the progressive maturation of the fetal immune system with a regular increase of all t lymphocyte subsets  marked alterations were observed in the 9 infected fetuses  depression of cd4 population and lower cd4 cd8 ratio   in the future these differences might be used as a new marker of the severity of fetal lesions and become a useful diagnostic tool  
class3	protection against malaria morbidity  near fixation of the alpha thalassemia gene in a nepalese population  we have previously reported that the tharu people of the terai region in southern nepal have an incidence of malaria about sevenfold lower than that of synpatric non tharu people  in order to find out whether this marked resistance against malaria has a genetic basis  we have now determined in these populations the prevalence of candidate protective genes and have performed in vitro cultures of plasmodium falciparum in both tharu and non tharu red cells  we have found significant but relatively low and variable frequencies of beta thal  beta s  g6pd      and duffy  a b   in different parts of the terai region  the average in vitro rate of invasion and of parasite multiplication did not differ significantly in red cells from tharus versus those from non tharu controls  by contrast  the frequency of alpha thalassemia is uniformly high in tharus  with the majority of them having the homozygous alpha  alpha genotype and an overall alpha thal gene  alpha   frequency of  8  we suggest that holoendemic malaria has caused preferential survival of subjects with alpha thal and that this genetic factor has enabled the tharus as a population to survive for centuries in a malaria holoendemic area  from our data we estimate that the alpha thal homozygous state decreases morbidity from malaria by about 10 fold  this is an example of selection evolution toward fixation of an otherwise abnormal gene  
class3	the effect of n alkyl modification on the antimalarial activity of 3 hydroxypyridin 4 one oral iron chelators  the antimalaria effect of iron chelators is attributed to their interaction with a labile iron pool within parasitised erythrocytes  and it was postulated that increased affinity to iron as well as increased lipophilicity may improve antimalarial activity  in the present study we have examined the antimalarial effect of 3 hydroxypyridin 4 ones  a family of bidentate orally effective iron chelators whose lipophilicity may be modified by altering the length of the r2 substituent on the ring nitrogen  a significant dose related suppression of plasmodium falciparum cultures was observed with all drugs tested in vitro at concentrations of 5 mumol l or higher  in contrast  there was a clear segregation of the in vivo effect on p berghei in rats  300 mg kg d subcutaneous  into two categories  compounds cp20  38  and 40 failed to suppress malaria  whereas cp51  94  and 96 had a strong antimalarial effect  similar or better than deferoxamine  there was a close linear correlation between the suppression of peak parasite counts and the reduction in hepatic nonheme iron induced by the various drugs tested  r    9837   the most lipophilic compounds were also the most effective in suppressing malaria and in depleting hepatic iron stores  these data indicate that 3 hydroxypyrydin 4 ones are able to suppress malaria in vivo and in vitro  because lipid solubility is an important determinant of antimalarial action  our study provides useful information regarding the selection of orally effective iron chelating compounds that may be suitable for clinical application as antimalarial agents  
class3	changes in electrocardiographic patterns at different stages of chagas  heart disease in rats  1  the resting electrocardiogram was obtained from 25 trypanosoma cruzi infected rats 30 days after infection  phase i   the resting electrocardiogram was abnormal in 12  group i  and normal in 13  group ii  animals  nineteen similar but non infected animals served as controls  both the resting electrocardiogram and the ajmaline test were performed 120 and 350 days after infection  phases ii and iii  respectively   2  with regard to the resting electrocardiogram of group i animals  left axis deviation was found in 10 of 12  83   in phase i  one of 12  8   in phase ii  p less than 0 05  and in none of phase iii  p less than 0 05   an intraventricular conduction delay was found in four of 12  33   rats in phase i  two of 12 rats  16   in phase ii  p greater than 0 05  and six of 12 rats  50   in phase iii  p greater than 0 05   the ajmaline test was abnormal in nine of 10  90   rats of group i with normal resting electrocardiogram in phase ii  and in three of six  50   animals in phase iii  p greater than 0 05   3  an intraventricular conduction delay was found in the resting electrocardiogram of one of 13  7   rats of group ii in phase iii  the ajmaline test was abnormal in one of 13  7   rats in phase ii and in one of 12  8   rats in phase iii  4  no control rat showed pathological changes  
class3	genetic control of the immune response in mice to leishmania mexicana surface protease  congenic mouse strains were tested in the lymphocyte proliferation assay for their response to the purified surface protease of leishmania mexicana  gp63   the data obtained allow us to distinguish three different patterns of response  influenced both by h 2  class ii  and non h 2 genes  mice of the c57bl 10  b10  background carrying h 2 haplotypes b q  and r were found to be high responders  those carrying h 2 haplotypes d  j  v  and z were low responders  and those with h 2a  h 2f  h 2k  h 2p  and h 2u haplotypes were intermediate responders  studies with h 2 recombinant strains indicated that the high responsiveness on the b10 background was determined by the ab allele and the low responsiveness influenced by the ad allele  other genes besides h 2 appear to have a role in the immune response as shown by the fact that some strains with balb  dba  or c3h background differed in their pattern of responsiveness from b10 background strains carrying the corresponding h 2 haplotypes  by using recombinant protein  the influence of the leishmanial surface lipophosphoglycan that might co purify with gp63  on the mhc restriction of the response to gp63 was excluded  the immune response to gp63 did not correlate with susceptibility of mouse strains to cutaneous infection with l  mexicana promastigotes  
class3	inability of malaria vaccine to induce antibodies to a protective epitope within its sequence  saimiri monkeys immunized with a recombinant protein containing 20 copies of the nine amino acid repeat of the plasmodium vivax circumsporozoite  cs  protein developed high concentrations of antibodies to the repeat sequence and to sporozoites  but were not protected against challenge  after intravenous injection of an immunoglobulin g3 monoclonal antibody  nvs3  against irradiated p  vivax sporozoites  four of six monkeys were protected against sporozoite induced malaria  and the remaining two animals took significantly longer to become parasitemic  epitope mapping demonstrated that nvs3 recognizes only four  agdr  of the nine amino acids within the repeat region of the p  vivax cs protein  the monkeys immunized with  draadgqpag 20 did not produce antibodies to the protective epitope agdr  thus  determination of the fine specificity of protective immune responses may be critical to the construction of successful subunit vaccines  
class3	techniques in endoscopic lithotripsy using pulsed dye laser  the pulsed dye laser represents a new tool in the treatment of ureteral calculi  laser energy channeled through a delicate optical fiber is used to disimpact and fragment calculi  standard ureteroscopic instruments including graspers  baskets and dilatation balloons can be used with the laser system  interchangeable optical fibers ranging from 200 to 400 micrometers deliver up to 120 mj of energy to the stone s surface  for two weeks in 1989 an endourology clinic was held in upper egypt  eighty patients ranging in age from nine years to sixty seven years old were evaluated and treated endoscopically  endoscopes ranging from 6 9f to 12 5f were used to deliver the optical fiber  all stones visualized endoscopically were fragmented  greater than 60 percent of the stones fragmented were composed of pure calcium oxalate monohydrate  schistosoma hematobium was endemic among our study group  bilharzial strictures of the distal ureter were noted in 30 percent of these patients  treatment of these strictures using both balloon dilatation and graduated teflon dilators is reviewed  techniques in treating different types of ureteral calculi were explored  large calcium oxalate dihydrate stones were treated most efficiently with the 3 point fragmentation technique  the shear off center technique was used for the calcium oxalate monohydrate calculi  variations in total energy delivered and frequency of pulsation allowed for prompt stone disimpaction as well as prevention of retrograde fragment migration  concurrent use of stone baskets and graspers with the pulsed dye laser was explored  
class3	impaired sympathetic nerve function in the inflamed rat intestine  the effect of intestinal inflammation on norepinephrine release from the myenteric plexus in the trichinella spiralis infected rat was assessed  longitudinal muscle myenteric plexus preparations were preincubated with  3h norepinephrine and release was evoked by electrical field stimulation and kcl administration  preincubation of preparations with desipramine or pretreatment of rats with 6 hydroxydopamine significantly suppressed the uptake and evoked release of  3h norepinephrine  electrical field stimulation but not kcl evoked release of  3h  norepinephrine was sensitive to tetrodotoxin  these results confirm the presence of functioning sympathetic nerves in the preparations  t  spiralis infection was associated with significant suppression of both electrical field stimulation and kcl evoked release of  3h norepinephrine on the sixth day postinfection  and the suppression persisted 100 days postinfection  no suppression of  3h norepinephrine release was seen in the worm free and noninflamed ileum of infected rats  suppression of  3h norepinephrine release from the jejunum of infected rats was attenuated by treatment with betamethasone  3 0 mg kg sc daily   these results are consistent with the hypothesis that intestinal inflammation suppresses the release of norepinephrine from the myenteric plexus in the trichinella infected rat  
class3	cardiac echinococcosis with fatal intracerebral embolism  a previously well 7 year old boy presented with sudden loss of consciousness and fitting  no evidence of trauma or space occupying lesion was identified  death occurred the next day due to cerebral infarction caused by embolised fragments from a ruptured left ventricular hydatid cyst that was found at necropsy  
class3	fatal adult respiratory distress syndrome following successful treatment of pulmonary strongyloidiasis  hyperinfection with strongyloides stercoralis occurs mostly in immunocompromised patients  including those treated with systemic steroids  a case of strongyloides induced adult respiratory distress syndrome was recently reported  and we now report a case in which fatal ards appeared to result from the successful therapy of massive parasitic infection  
class3	isolation and characterization of a new human microsporidian  encephalitozoon hellem  n  sp    from three aids patients with keratoconjunctivitis  a new human microsporidian was isolated from cultures of madin darby canine kidney cells incubated with conjunctival scrapings or corneal tissues from three aids patients with keratoconjunctivitis  the three isolates were morphologically similar to encephalitozoon cuniculi  the spores averaged 1 x 1 5 2 0 microns  had six to eight polar filament coils  displayed monokaryotic nuclei  and possessed relatively thick endospores with irregularly shaped exospores  organisms developed within a parasitophorous vacuole  by sds page analysis  the three isolates appeared to be identical but were different from e  cuniculi  identical banding patterns on western blots of the three isolates were expressed by each patient s serum  by western immunoblotting  murine antisera to e  cuniculi reacted to several antigens of the new aids related microsporidian  whereas murine antisera bound weakly to nosema corneum  the name encephalitozoon hellem  n  sp   is proposed to identify this new human microsporidian  
class3	rapid microscopic detection of malaria parasites permanently fluorochrome stained in blood smears with aluminum and morin  intra  and extracellular plasmodium parasites in fixed blood smears are easily identifiable by fluorescence microscopy after brief mordanting with aluminum ammonium sulfate and staining with morin  3 5 7 1  4  pentahydroxyflavanol   the intensely fluorescent preparations of stained parasites are strongly resistant to photodegradation and remained essentially unimpaired for two years  
class3	hosts on which nymphal ixodes ricinus most abundantly feed  to identify hosts that may serve as european reservoirs for the agent of lyme disease  borrelia burgdorferi  we determined whether nymphal ixodes ricinus feed mainly on particular mice  apodemus flavicollis or a  agrarius   voles  clethrionomys glareolus  or on sand lizards  lacerta agilis  and whether the abundance of these hosts corresponds to the seasonal activity of the subadult stages of the vector tick  in all sites  the mice appeared most heavily infested by larvae  at least seven parasitized each mouse  about three per vole and four per lizard  many fewer nymphal i  ricinus parasitized a  flavicollis and c  glareolus than did larvae  although more than 30 times as many larval than nymphal ticks parasitized the two most abundant hosts  c  glareolus and a  flavicollis   about 15 times as many fed on a  agrarius and twice as many on lizards  nymphal and larval ticks fed on rodents at about the same time  lizards were most abundantly parasitized by nymphs somewhat earlier than by larvae  early in the season of transmission of lyme disease  virtually all a  agrarius as well as lizards were potentially exposed to spirochetes borne by nymphal i  ricinus  we concluded that larval and nymphal i  ricinus differentially parasitize different hosts  because so many of these nymphs feed on them  a  agrarius may more effectively serve as reservoirs for the agent of lyme disease than do other putative reservoir hosts  the presence of lizards may inhibit transmission  
class3	detection of plasmodium falciparum infection with the fluorescent dye  benzothiocarboxypurine  the fluorescent dye benzothiocarboxypurine  bcp  intensely stains nucleic acids  the dye does not penetrate viable white blood cells but does stain these cells following fixation  it has also been found that the dye stains the nucleic acid of viable plasmodium falciparum  we have subsequently evaluated the staining of p  falciparum by benzothiocarboxypurine within red blood cells and have found that the red blood cell membrane is freely permeable to this dye and consequently p  falciparum is stained within the red blood cell  this finding prompted an in depth analysis of the dye in the laboratory and in a field study as an alternative to giemsa stained blood smears and as a means of enhancing the microscopic diagnosis of malarial infection  in a field study the bcp dye allowed detection of malaria in fresh blood at a level equivalent to the giemsa method  parasitemia ranged from 0 01  to 30    the bcp staining procedure could also be used with fixed specimens although the differential staining characteristics were lost following specimen preparation  of 111 blinded samples obtained in the field 22 were negative by giemsa stained thin smear  16 were negative on thick smear and the same 16 were negative by bcp analysis  we have found that the bcp dye offers many advantages compared with the microscopic diagnosis of p  falciparum infection with standard giemsa stains  these advantages are especially evident in conditions of low parasitemia  in the speed of staining and evaluation  and the relatively low level of training required to provide consistent results  
class3	acridine orange fluorescent microscopy and the detection of malaria in populations with low density parasitemia  detection of low density malaria parasites with giemsa stained thick smears  g ts  requires time and experience and becomes impractical with high sample loads  acridine orange fluorescent microscopy  ao fm  of capillary centrifuged blood may offer an alternative technique  we compared ao fm readings with g ts in 290 specimens from asymptomatic people in thai villages endemic for malaria  ao fm specimens were prepared in modified capillary tubes coated with acridine orange  quantitative buffy coat or  qbc tubes   and examined under a fluorescent microscope  twenty three  85 2   of the 27 specimens found positive by g ts had under 100 parasites microliters blood  less than 35 parasites 200 microscopic fields   the overall ao fm sensitivity was 78 9   range  66 7   10 15  86 7   13 15    for plasmodium falciparum  regardless of stages  the sensitivities varied from 66 7   8 12  to 91 7   11 12   ao fm performed better for p  falciparum than for plasmodium vivax and for asexual than for sexual stages of the parasite  however  the species  and stage specific results must be interpreted with caution because of the small sample sizes and very low parasite densities involved  the test specificity was 96 6   range  95 6   263 275  97 1   263 271    these levels of accuracy plus the known advantages of ao fm suggest that the test  supplemented with g ts to improve species and stage differentiation  is also useful for screening low density parasitemias  
class3	characteristics of natural antibody responses to the circumsporozoite protein of plasmodium vivax  the antibody response to the prototype circumsporozoite  cs  protein of plasmodium vivax  cspv  was studied in thai soldiers experiencing occupational malaria  seventy four  65   of 114 men followed during assignment to a malaria transmission area developed blood stage infection with p  vivax  igg antibodies against the central repeat region of the cspv protein were quantitated by elisa using the recombinant protein  ns181v20  as the capture antigen  one quarter of the subjects had detectable anti cspv antibodies at the beginning of the study  cspv antibody seroconversion was documented in 16 of 26 subjects assessed during their first observed episodes of vivax malaria  this antibody response was of moderate magnitude  fell off after the first week post diagnosis and appeared  at the low levels observed  to be unassociated with protection  continued assessment of anti cspv antibody after subjects left the transmission area found no increase associated with release of p  vivax  these findings indicate that cs antibody responses to p  vivax during occupational malaria share many characteristics with responses to p  falciparum  
class3	plasmodium vivax sporozoite antibodies in individuals exposed during a single malaria outbreak in a non endemic area  we studied seroreactivity against plasmodium vivax antigens in 62 individuals living in a small community near mantena  minas gerais  brazil  an area outside the endemic malaria zone brazil  eight months earlier  there had been transmission of p  vivax for a period of 50 days  which was then totally controlled by chemotherapy and insecticides  an anti sporozoite response  measured by elisa using a recombinant protein expressed in yeast  was detected in 45   14 of 31  of individuals eight months after infection and persisted for 20 months in 12   eighteen individuals were treated prophylactically for malaria because they lived in houses in which an overt infection had occurred  seven of these individuals were elisa positive  of these  5 had antibodies against the blood stage parasites  among 13 other individuals in the endemic area who did not have positive smears  had not been ill  and had not received prophylaxis  five were anti circumsporozoite positive up to a 40 fold serum dilution  they did not develop asexual blood stage antibodies and remained parasite free for the following 20 months  
class3	comparison of high dose ivermectin and diethylcarbamazine for activity against bancroftian filariasis in haiti  this three phase study was designed to compare high dose ivermectin with a standard diethylcarbamazine  dec  regimen for patient tolerability  potential to kill adult filaria  and duration of microfilarial suppression in 30 haitian subjects with wuchereria bancrofti microfilaremia  all were first given a 1 mg oral dose of ivermectin  phase 1  to reduce microfilaria densities  participants were randomized into three groups  group 1 received dec  6mg kg per day for 12 days   group 2 received 200 mcg kg of ivermectin  and group 3 received 400 mcg kg of ivermectin  200 mcg kg per day for 2 days   all drug regimens were well tolerated with few adverse reactions  most reactions occurred during phase i and consisted primarily of headache  fever  and myalgia  at the end of phase 1  27 of 30  90   patients were microfilaria negative  during phase 2  four of the six men receiving dec developed scrotal reactions suggesting killing adult worms  no such reactions were noted in 10 men receiving ivermectin  p less than 0 05   at one year follow up  phase 3   all treatment groups had less than 10  return to pretreatment microfilaria levels  the mean percent of baseline microfilaria counts were for group 1  0 9   range 0 5    group 2  8 2   range 0 31    and group 3  3 8   range 0 25    seven individuals in group 1 were microfilaria negative  while only one and three individuals were microfilaria negative in groups 2 and 3  respectively  these results suggest that dec causes more damage to the adult worms and greater reduction in microfilaria densities than ivermectin  but that high doses of ivermectin may suppress microfilaremia in lymphatic filariasis for periods much longer than previously reported  
class3	immunization of owl monkeys with the ring infected erythrocyte surface antigen of plasmodium falciparum  aotus nancymai were immunized with the 4 mer  8 mer  and 11 mer repeat peptides of the ring infected erythrocyte surface antigen molecule of plasmodium falciparum conjugated to diphtheria toxoid with muramyl dipeptide  mdp  as adjuvant  immunization failed to induce protective immunity against the uganda palo alto strain of p  falciparum as judged by maximum levels of parasitemia of immunized monkeys relative to those of controls  the fused polypeptide fpag632  when combined with mdp  also failed to induce protective immunity  however  the maximum level of parasitemia and serologic response to the 11 mer peptide were inversely correlated  the safety of the use of mdp was evident  
class3	a spleen is not necessary to resolve infections with plasmodium yoelii  the role of the spleen in resistance to infections with nonlethal plasmodium yoelii 17x is dependent upon the genotype of the host  thus  dba 2  d2  mice infected with p  yoelii 17x were not adversely affected by removal of the spleen  while splenectomized c57bl 6  b6  or balb c mice failed to resolve their infections and eventually died  the levels of parasitemia were lower in splenectomized mice compared to intact controls  however  splenectomized mice became as anemic as did spleen intact controls  splenectomy resulted in the appearance of large aggregates of mononuclear cells in the livers of infected mice and also altered the liver body weight ratios  these results indicate that d2 mice have a spleen independent mechanism of clearing parasites which is lacking in b6 and balb c mice  
class3	intestinal cryptosporidiosis  pathophysiologic alterations and specific cellular and humoral immune responses in rnu   and rnu rnu  athymic  rats  in order to develop an experimental model of symptomatic cryptosporidiosis in an immunosuppressed mammal  we investigated the pathophysiology of infection with cryptosporidium and the humoral and cellular host responses in rnu rnu  athymic  rats and their heterozygous  rnu    littermates by challenging suckling rats with greater than or equal to 2 5 x 10 6  cryptosporidium oocytes oro gastrically  normal and immunodeficient animals were followed for onset and duration of infection  fecal oocysts   physiologic consequences  diarrhea  impaired weight gain  brush border enzyme activities   and immunologic response  both b  and t lymphocyte mediated   homozygosity for the rnu gene was associated with protracted cryptosporidial infections  shedding for up to 52 days occurred  and delay in weight gain was noted in rnu rnu infected compared with rnu rnu uninfected rats  p less than 0 05   in contrast  cryptosporidial challenge of rnu   rats resulted in self resolving infections  occasionally with transient diarrhea lasting four days or less occurring 10 15 days after oro gastric challenge  the latter animals mounted a cell mediated immune response to cryptosporidium  three months after challenge  five of five rnu   rats demonstrated positive skin test responses to a subcutaneous 3 5 micrograms dose of cryptosporidial antigen  further  sera from 6 rnu   rats taken two to three months after oro gastric oocyst challenge exhibited specific anticryptosporidial immunoglobulin binding  a405   0 96   compared to that of seven uninfected rnu   controls  a405   0 09  p less than 0 02   macromolecules of 150  105  and 88 kd in the cryptosporidium antigen preparation were bound by serum immunoglobulin from previously infected  recovered rnu   rats  two brush border enzymes  lactase and alkaline phosphatase  were markedly reduced in the ileum 8 10 days after oro gastric challenge in rats with diarrhea and oocyst shedding  we find the rnu rnu  athymic  nude  rat provides a useful model for study of prolonged cryptosporidial infection with impaired weight loss  brush border enzyme alteration and intermittent diarrhea  these studies further suggest that a t lymphocyte population is involved in recovery from cryptosporidium infection and that this recovery is associated with both cellular and humoral immune responses to specific cryptosporidial antigenic macromolecules  this model should open further avenues for the study of the pathogenesis and protective immunity in cryptosporidial infection  
class3	the effect of chloroquine prophylaxis on yellow fever vaccine antibody response  comparison of plaque reduction neutralization test and enzyme linked immunosorbent assay  weekly oral chloroquine prophylaxis for malaria has been associated with impaired antibody response to intradermal rabies vaccination  experimental data indicate that chloroquine may inhibit yellow fever virus in vitro  yet there has been no clinical evidence to suggest that antibody response to yellow fever vaccine is impaired by concomitant oral administration of chloroquine  a prospective trial was undertaken to evaluate the antibody response to yellow fever 17d vaccine  connaught laboratories  of volunteers who were randomized to taking either chloroquine or no drug  of fifty subjects  28 were randomized to taking chloroquine  22 were randomized to taking no drug  yellow fever 17d vaccine was administered on day 0 and blood sampled on days 0  14  35 and 210  chloroquine was administered weekly for four weeks  there was no significant difference in peak antibody titer by plaque reduction neutralization testing  prnt  between the group that took chloroquine  mean log peak of reciprocal titer 1 43     sd 0 60  with vaccine subcutaneously compared to vaccine only group  mean log peak of reciprocal titer   1 21     0 55   all fifty subjects seroconverted to yellow fever vaccine by day 210  elisa testing was also performed on all subjects  the two tests showed good correlation  spearman r   0 675   although elisa readings were positive by day 14 in significantly more subjects  p    01   we conclude that routine anti malarial doses of chloroquine do not affect antibody response to yellow fever 17d vaccine  elisa testing  a less complex and less time consuming test  correlates well with prnt and is proposed for additional trials to measure yellow fever 17d vaccine response in flavivirus non immune subjects  
class3	definition of the role of contemporary surgical management in cisternal and parenchymatous cysticercosis cerebri  with increasing immigration from endemic regions  the incidence of neurocysticercosis in north america is rising  this retrospective study was undertaken to examine the role of surgery in those cases presenting with large cystic parenchymal and cisternal lesions in the current era of anthelminthic agents administered orally  a total of 237 patients presented with newly diagnosed neurocysticercosis to our institution over a recent 5 year period  mean age  31 2 years   among those who presented with cystic mass lesions predominantly affecting the brain parenchyma and cisternal spaces  20  8 4   mean age  40 2 years  with large cystic lesions subsequently underwent surgical intervention  either because of an emergent presentation or because they were refractory to medical management  clinical presentation included increased intracranial pressure  focal neurological deficit  and seizure  radiographic imaging  computed tomography and or magnetic resonance imaging  demonstrated 12 cases with cisternal lesions  7 with parenchymal lesions  and 1 involving both compartments  based on imaging guidelines  30 operative procedures  excluding shunt revisions  were performed  14 craniotomies  8 cerebrospinal fluid diversions  7 stereotactic procedures  and 1 burr hole drainage   fifteen  75   showed neurological or symptomatic improvement over a median follow up period of 36 4 months  there were three surgery related complications and no deaths  
class3	radiographic manifestations of anomalies of the brain  congenital brain anomalies are classified as developmental anomalies  effects of teratogens  errors of histogenesis  or sequelae of infections  the imaging options for delineation of these anomalies are many  a basic understanding of the disorder is central to the effective choice of imaging modality  this review begins with a brief overview of embryogenesis then reviews the common congenital brain anomalies encountered in infants  
class3	use of immunoglobulin gene rearrangements to show clonal lymphoproliferation in hyper reactive malarial splenomegaly in africa  hyper reactive malarial splenomegaly  hms   which is also known as tropical splenomegaly syndrome  can be associated with a prominent lymphocytosis in blood and bone marrow that is difficult to distinguish clinically from chronic lymphocytic leukaemia  cll   the observation that some patients with hms become resistant to treatment with anti malarial drugs has led to the suggestion that hms may evolve into a malignant lymphoproliferative disorder  to test this hypothesis  22 ghanaian patients with hms and or lymphocytosis were categorised by degree of response to proguanil according to standard clinical criteria  and dna was extracted from peripheral blood cells and screened for rearrangements of the jh region of the immunoglobulin gene with a dna probe  clonal rearrangements of the jh region were found in all 3 patients with no response  in none of 13 patients with sustained response  and in 2 of 6 patients with moderate response or relapse on proguanil therapy  the detection of such rearrangements  and hence clonal lymphoproliferation in individuals with clinical features intermediate between hms and cll  supports the hypothesis that hms may evolve into a malignant lymphoproliferative disorder  
class3	co trimoxazole for childhood febrile illness in malaria endemic regions  the efficacy of co trimoxazole for the treatment of plasmodium falciparum parasitaemia in children younger than 5 years of age was evaluated in malawi  46 children with p falciparum parasitaemia  37  of whom also met clinical criteria for a diagnosis of acute lower respiratory tract infection  were treated with 20 mg kg co trimoxazole twice daily for five days  parasitaemia  mean clearance time 2 7 days  and symptoms were rapidly abolished and improvement was maintained during follow up for 14 days  co trimoxazole may be an effective single treatment for febrile illness in young children in areas where malaria is endemic  resources are few  and diagnosis must rely on clinical findings alone  
class3	intracranial pressure in african children with cerebral malaria opening lumbar cerebrospinal fluid  csf  pressure was measured with a paediatric spinal fluid manometer in 26 of 61 kenyan children  mean age 39 months  with cerebral malaria  in all cases pressure was above normal  mean  sd 22 6  7 4  cm csf  range 10 5 36   clinical features of our patients suggest that intracranial hypertension is important in the pathogenesis of cerebral malaria in children  especially as a cause of death  we suggest that raised intracranial pressure is secondary to increased cerebral blood volume  lowering intracranial pressure may significantly reduce the mortality and morbidity of cerebral malaria  the potential risks and benefits of lumbar puncture should be considered carefully in patients with suspected cerebral malaria  
class3	onchocercacidal effects of amocarzine  cgp 6140  in latin america  an open clinical trial of amocarzine was carried out in onchocerciasis patients in ecuador and guatemala  administration after food was more effective than that during fasting  the most effective and best tolerated regimen  3 mg kg twice daily after food for 3 days  in 312 patients   killed 73  of 1477 female worms at nodulectomy 4 months after treatment  the mean microfilarial skin count was greatly reduced within a week  6 11  of day 0 value on day 8  and it remained low at least 6 months  14 18  on day 180   follow up of a higher dose 3 day regimen taken while fasting showed microfilaridermia of 7 9  of the day 0 value 2 years after treatment  
class3	cerebral falciparum malaria mimicking thrombotic thrombocytopenic purpura  we have described a patient with cerebral falciparum malaria who had rapidly progressive cns deterioration  renal failure  hemolytic anemia associated with striking and varied erythrocyte morphologic changes  and thrombocytopenia  the initial diagnosis was thrombotic thrombocytopenic purpura  ttp  of unknown origin  reexamination of the peripheral smear of this comatose patient led to correct diagnosis and effective treatment in this case of cerebral falciparum malaria  another of medicine s great mimickers  
class3	growth in children from the wosera subdistrict  papua new guinea  in relation to energy and protein intakes and zinc status  in a cross sectional study of 123 children aged 24 120 mo from the wosera subdistrict of papua new guinea  height  weight  hematocrit  hemoglobin  hair zinc  and presence of malaria were measured  two 24 h recalls were undertaken in 67 of the children aged 72 120 mo  52   73   and 76  had energy  protein  and zinc intakes  respectively  less than two thirds of the fao who unu recommendations  stunting was prevalent  29    16  were moderately wasted  the prevalence of stunting and hair zinc concentrations less than 1 68 mumol g was gender related  38  of males vs 20  of females had z scores for height for age  haz scores  less than  2  p   0 04   26  of males vs 11  of females had hair zinc less than 1 68 mumol g  p less than 0 05   analysis of variance showed that age  sex  hemoglobin  and log hair zinc influenced haz scores  depending on the age group  both sex and the log of the hair zinc values were significant factors in the older children  stunting in worsera children was related to chronic deficits in energy and protein and was excerbated in the older male children by suboptimal zinc status  
class3	the epidemiologic association of fuchs  heterochromic iridocyclitis and ocular toxoplasmosis  between january 1983 and july 1987  i examined 25 patients at the department of ophthalmology  west virginia university  who had the anterior segment characteristics of fuchs  heterochromic iridocyclitis  of these patients  16 had fundus lesions suggestive of ocular toxoplasmosis  of these 16 patients  13 had a positive serologic test for toxoplasmosis  two patients were not tested  and one patient had a negative test at 1 16  the remaining nine patients with fuchs  heterochromic iridocyclitis had no fundus lesions suggestive of toxoplasmosis  a chart review of 792 consecutive patients at the retinal unit  west virginia university  during a six month period disclosed that 24 of 590 patients  4   had chorioretinal scars suggestive of toxoplasmosis  i concluded from these data that in at least one subgroup of patients with fuchs  heterochromic iridocyclitis there is a significant association with the chorioretinal scars of toxoplasmosis  p less than  01   and this is suggestive of a causal relationship  
class4	cerebellopontine angle lipoma in a teenager  lipomas of the cerebellopontine angle are very rare lesions  to date  18 patients have been reported  17 of whom were adults  a second child is described with cerebellopontine angle lipoma  
class4	trisomy 13  a new recurring chromosome abnormality in acute leukemia  a new recurring chromosome abnormality was identified in 8 of 621 consecutive successfully karyotyped adults with de novo acute leukemia  these eight patients had trisomy 13 as the sole cytogenetic abnormality  on central morphologic review  five cases were classified as subtypes of acute myeloid leukemia  one as acute mixed lymphoid and myeloid leukemia  one as acute lymphoid leukemia  and one as acute undifferentiated leukemia  blasts of all eight cases expressed one or more myeloid differentiation antigens  three also expressed t lineage associated antigens  however  none of these had rearrangement of the t cell receptor beta  gamma  or delta genes  four of six cases tested were tdt positive  all eight patients with trisomy 13 were treated with intensive induction chemotherapy  only three entered a short lived complete remission  survival of patients with trisomy 13 ranged from 0 5 to 14 7 months  and was significantly shorter than that of the remaining patients  median 9 5 v 16 2 months  p    007   we conclude that trisomy 13 is a rare  recurring clonal chromosome abnormality in acute leukemia associated with a poor prognosis  malignant transformation of an immature hematopoietic precursor cell is suggested by the expression of antigens characteristic of both the myeloid and lymphoid lineage  the high incidence of tdt positivity  and the morphologic heterogeneity in these leukemias  
class4	abnormalities of the long arm of chromosome 6 in childhood acute lymphoblastic leukemia  to determine the biologic significance of the structural rearrangements of the long arm of chromosome 6 6q  in acute lymphoblastic leukemia  all  at diagnosis  we studied 412 consecutive children whose leukemic cell chromosomes had been completely banded and identified 45  11   children with this abnormality  the 45 cases were divided into del 6q  only  n   11   del 6q  and numerical abnormalities  n   4   del 6q  and structural abnormalities  n   23   and 6q translocations  n   7   the breakpoints of del 6q  were subgrouped  del 6  q15q21  in 11 cases  del 6   q13q21  in six  del 6  q21q23  in four  del 6  q15  in four  del 6  q15q23  in three  and other deletions in 10 cases  notably  all these deletions encompassed the 6q21 band  suggesting that this might be the locus of a recessive tumor suppressor gene  the absence of which contributes to malignant transformation or proliferation  among the seven children with 6q translocations  a previously unidentified nonrandom translocation  t 6 12  q21 p13  was noted in two cases with an early pre b immunophenotype  clinical features and event free survival were similar among children with or without 6q abnormalities  overall  children with 6q abnormalities were less likely than those without the abnormality to have a pre b immunophenotype  p    03   t cell immunophenotypes were equally represented in cases with or without 6q abnormalities  however  all four children with del 6q  and a 12p abnormality had early pre b all and all three children with del 6q  and a 9p abnormality had a t cell immunophenotype  the lack of specificity for a particular immunophenotype may imply that the gene or genes affected by 6q abnormalities are broadly active in the multistep process of lymphoid leukemogenesis  the relatively high frequency of microscopically visible del 6q  indicates the need for molecular studies to identify cases with submicroscopic deletions  
class4	the role of cellular maturation in neutrophil heterogeneity  previous studies have shown that many neutrophil  pmn  characteristics are heterogeneous but the origin of pmn heterogeneity is unknown  it is unclear if pmn functional heterogeneity is secondary to maturational differences or due to distinct subpopulations of cells that possess different functional capacities  the pmn 31d8 antigen is a useful probe for evaluation of pmn subpopulations  the majority of pmns  approximately 85   exhibit a high intensity fluorescence after 31d8 monoclonal antibody  moab  labeling  31d8 enriched or  bright  pmns  as determined by flow cytometric analysis  these cells are more functional than cells with low intensity fluorescence  31d8 diminished or  dull  pmns   various immunologic  clonogenic and functional techniques were used to study the expression of the 31d8 antigen in hl 60 cells and myeloid cells in order to evaluate antigenic and functional heterogeneity during morphologic maturation  the results of this study indicate that the percentage of 31d8 antigen positive  31d8 antigen enriched and diminished  bone marrow cells increases from 20     11  in myeloblast cells to 68     10  in promyelocytes  93     2  in myelocytes and 99     1  in bands and pmns  31d8 antigen enriched cells first appear at the myelocyte stage  32     10   and increase in bands  52     13    marrow pmns  62     13   and peripheral blood pmns  88     4    these data indicate that the heterogeneous expression of 31d8 antigen in pmns is due  at least in part  to maturational differences within the pmn population and raise the possibility that other heterogeneously expressed pmn characteristics are also maturationally derived  they also suggest that 31d8 antigenic expression may be a more precise indicator of myeloid functional maturation than maturation as identified by cellular morphology  
class4	early detection of gastric cancer objective  to see whether investigation of dyspeptic patients aged over 40 after their first consultation with the general practitioner would increase the proportions with early and operable gastric cancers  design  prospective study of gastric cancer in dyspeptic patients aged over 40 from a defined population  setting  10 general practices  six in central birmingham  four in sandwell   the queen elizabeth hospital  birmingham  and sandwell district general hospital  patients  2659 patients aged 40 or over referred with dyspepsia  main outcome measure  increase in early and operable gastric cancers detected in middle aged patients with dyspepsia  results  disease was identified in 1992 patients  75    fifty seven were found to have gastric cancer  36 being treated by potentially curative resection  including 15 with early cancer  conclusions  the investigation of dyspeptic patients over 40 at first attendance can increase the proportion of early gastric cancers detected to 26  and the proportion of operable cases to 63   such a policy has the potential to reduce mortality from gastric cancer in the population  
class4	renal carcinoma in a solitary kidney  we studied the clinical and pathological features of 26 patients with renal carcinoma of a solitary kidney  including 6 treated at this hospital  four patients had a contracted kidney and 22 had previously undergone nephrectomy  partial nephrectomy was performed in 16 patients  enucleation of the tumour in 5 and radical nephrectomy in 5 because of the size of the tumour  ex vivo surgery was carried out in 4 patients  the duration of ischaemia ranged from 15 to 365 min but was longer in those who underwent ex vivo surgery  149 to 365 min   of the 21 patients who underwent partial nephrectomy or enucleation  the serum creatinine level increased  greater than or equal to 2 0 mg dl  post operatively in 16 patients  of whom 9 required temporary haemodialysis  no recurrence has been noted in those who underwent partial nephrectomy  but 1 patient who underwent enucleation of the tumour developed a solitary pancreatic metastasis 2 years 6 months after surgery and was treated by a partial pancreatectomy  kidney preserving surgical procedures are considered to improve the quality of life  but careful follow up is necessary  
class4	cell cycling in bladder carcinoma determined by monoclonal antibody ki67  current methods of predicting prognosis in transitional cell carcinoma of the bladder fail to provide consistently reliable information about future tumour behaviour  the monoclonal antibody ki67 recognises an antigen present in actively dividing cells and ki67 reactivity has been shown to correlate with conventional prognostic indicators in several tumours  in this study  ki67 antibody was used to determine the proportions of cells undergoing active division in 26 transitional cell carcinomas of the bladder  the proportion of cells stained in muscle invasive tumours  12 3     5 4   was significantly greater than in superficial tumours  4 3     1 9   and poorly differentiated tumours showed significantly greater proportions of cells staining compared with well or moderately well differentiated tumours  these results show that ki67 reactivity correlates with high tumour stage and poor differentiation  ki67 staining provides an easy method of determining tumour cell turnover that might provide additional prognostic information  
class4	superficial bladder cancer in patients under 40 years of age  efficacy of topical prophylaxis  in patients under the age of 40 years with primary superficial bladder cancer the efficacy of adjuvant topical treatment was the same as in elderly patients  recurrences 23   progression rate 8    patients should therefore be treated on the basis of stage and grade of the tumour regardless of their age  
class4	pathological classification and follow up of prostatic lesions initially diagnosed as  suspicious of malignancy   sections from a series of prostatic specimens  n   44  in which the initial diagnosis implied a suspicion of malignancy were reviewed and the patients followed up  group 1   the aim was to categorise the morphological appearances according to current criteria and to determine the natural history of any pre malignant lesions within this group  a  control  series of patients  n   40  in whom the primary diagnosis was benign were also reviewed and their course followed  group 2   the heterogeneity of the abnormalities in group 1 was striking  of the 44 cases  pre malignant lesions were seen in 8  microinvasive adenocarcinoma in 11 and lesions not now considered pre malignant in the remaining 25  none of the 8 patients with pre malignant lesions developed clinical evidence of carcinoma over a follow up period of 8 to 12 years  in contrast  3 of the 11 diagnosed on review as having microscopic invasive adenocarcinoma developed clinically evident tumour within 5 years of surgery  of the 25 patients whose prostatic lesions were considered benign  2 developed carcinoma 12 and 13 years after surgery  only 1 of the 40 patients in group 2 had a pre malignant lesion and he did not develop tumour within 10 years  however  adenocarcinoma was diagnosed incidentally in 1 patient 3 years after surgery  it was concluded that there is a need to standardise interpretation and reporting of pre malignant lesions and microscopic foci of adenocarcinoma in the prostate  the limited results on the course of pre malignant lesions diagnosed incidentally in patients over 60 years of age do not indicate that follow up would have prompted the early diagnosis of invasive disease  
class4	papillary cystic neoplasm of the pancreas  radiological and pathological characteristics in 11 cases  clinical charts  radiological features  macroscopic and microscopic findings  and clinical follow up data were retrospectively reviewed in 11 patients with papillary cystic neoplasm of the pancreas  pcnp   the patients were nine women and two men  aged from 13 to 51 years with a mean age of 25 years  the greatest diameter of the pcnps ranged from 2 5 cm to 14 0 cm with a mean size of 7 5 cm  six tumours were located in the tail of the pancreas  two in the body and three in the head  most patients complained of abdominal pain or a mass  ultrasonographic and or computed tomography findings showed five solid  four mixed  solid and cystic  and two cystic types of tumour  angiographically  pcnp was either a hypovascular or mild hypervascular mass with a displacement of the surrounding vessels  no vascular encasement was seen  macroscopically all 11 tumours consisted of a well defined solid mass with degenerative change of various widths  including haemorrhage  necrosis or dystrophic calcification  and were represented by three radiological types of pcnp  the 11 patients with pcnp survived for from 3 to 253 months after curative resection without any signs of local recurrence or remote metastasis  pcnp usually affects the distal portion of the pancreas of young women  despite its huge size  pcnp should be explored with aggressive surgical intent because of the inherently good prognosis  
class4	ca72 4  a new tumour marker for gastric cancer  to date  tumour markers for gastric cancer have proved unreliable  in this study the value of a new serum marker  ca72 4  was compared with the serum activities of carcinoembryonic antigen  cea  and ca19 9 in a consecutive series of patients with gastric cancer  the results show that the ca72 4 assay is significantly better at separating stage i and ii disease from normal controls  p less than 0 01  than cea  n s   or ca19 9  n s    ca72 4 also gave better differentiation between patients with positive and negative nodes  p less than 0 01  and between those who were serosa positive and negative  p less than 0 01   cea differentiated between patients with positive and negative nodes  p less than 0 05  but ca19 9 could not  ca19 9 and cea could not discriminate between patients who were serosa positive and negative  in this study  at a specificity of 95 per cent  the sensitivities of cea  ca19 9 and ca72 4 were 0 25  0 41 and 0 94 respectively  these preliminary findings indicate that ca72 4 is a reliable tumour marker of disease stage and activity in gastric cancer  further longitudinal studies are required for full evaluation of its clinical utility  
class4	failure of nutritional recovery after total gastrectomy  malnutrition is reported to be an inevitable consequence of total gastrectomy  although there are few data to support this contention  six patients of median age 63 years underwent total gastrectomy for malignancy  at follow up  median 45 months  range 25 60 months  each patient was clinically tumour free and underwent dietary assessment  faecal fat and nitrogen measurement and routine haematological testing  protein and fat stores  measured by neutron activation analysis and the tritiated water dilution technique  were compared with the same measurements made before operation and with predicted values  mean  s d   dietary intake  2224 381  kcal day 1 and 81 15 g protein day 1  met the patients  estimated requirements  mean s d   serum albumin and faecal nitrogen values were normal but there was notable steatorrhoea  21 17  g day 1   body composition measurements revealed profound deficiencies of body weight  p less than 0 02   protein  p less than 0 01  and fat  p less than 0 02  before operation which were not corrected by an apparently curative total gastrectomy  p less than 0 05   although further deterioration was prevented  
class4	treatment of adenocarcinoma of the cardia with synchronous chemotherapy and radiotherapy  twenty nine evaluable patients with adenocarcinoma of the cardia were treated with synchronously administered chemotherapy  two cycles of 5 fluouracil and cisplatin and 30 36 gy of radiation to determine whether these tumours are responsive to such treatment  complete regression of tumour was observed endoscopically in 19 patients  and partial regression in four  fourteen patients had their tumours resected and in six no microscopic tumour was found in the specimen  nine patients received additional radiotherapy to a total dose of 54 60 gy instead of surgery  tumour response was associated with rapid reversal of dysphagia  only one patient required subsequent intervention for relief of dysphagia due to fibrous stricture  enhanced survival was associated with a complete endoscopic response to initial chemotherapy and radiotherapy  and a tumour of less than 5 cm in length  the median survival of responding patients was 15 months  synchronous chemotherapy and radiotherapy was of major palliative benefit in this series and merits further evaluation  
class4	manometric evaluation of jejunal limb after total gastrectomy and roux orr anastomosis for gastric cancer  total gastrectomy with roux orr anastomosis is frequently performed for gastric cancer  since intestinal motility of the roux limb has never been evaluated after this operation  pressure activity was investigated in the roux limb of ten patients  aged 51 77 years  who had undergone total gastrectomy and roux orr reconstruction  investigations were carried out during a 6 h fast and 3 h after a 605 kcal mixed meal  during fasting only two patients had activity fronts and these were abnormal  all ten patients displayed non propagating bursts of contractions and three had discrete clustered contractions and high amplitude jejunal contractions  the fed state was characterized by a severely reduced motor activity pattern and other abnormalities  total gastrectomy with roux orr anastomoses provokes a relatively severe disturbance in intestinal activity  
class4	primary hepatic malignancy  the role of liver transplantation  between january 1982 and april 1989  134 patients with a suspected liver neoplasm were referred to the liver unit  queen elizabeth hospital  birmingham  in 105  78 per cent   a primary hepatic neoplasm was histologically confirmed  and 47 patients  45 per cent  proved to have primary hepatocellular carcinoma  twenty nine orthotopic liver transplants were performed in 28 of these patients  27 per cent   twenty patients  71 per cent  survived 30 days or longer  median 11 5 months  range 2 87 months   of whom nine are currently alive  we retrospectively analysed our data to determine the influence of preoperative evaluation  histological type and staging on outcome  computed tomography proved to be superior to intraoperative assessment  86 versus 58 per cent  in diagnosing tumour positive nodes  patients with tumour negative lymphadenopathy had a better prognosis  postoperative stage i ii had a median survival of 16 months  range 3 87 months  compared with 7 5 months  range 2 20 months  for stage iii  non cirrhotic patients with hepatocellular carcinoma had the best prognosis  cholangiocellular carcinoma and cirrhotic patients with hepatocelluar carcinoma had the worst outcome with no survivors beyond 1 year  because of the advanced stage of disease at the time of presentation  the value of liver transplantation in primary liver cancer is limited  for those presenting with advanced disease confined to the liver  stage i ii  in whom conventional hepatic resection is not possible  significant benefit can be achieved in selected cases  
class4	intraoperative ultrasonography and the detection of liver metastases in patients with colorectal cancer  a total of 213 patients with carcinoma of the colon and rectum were examined to detect liver metastases  the study compared preoperative ultrasonography and inspection and palpation of the liver during surgery with intraoperative ultrasonography  preoperative ultrasonography  inspection and palpation identified 238 metastases in 42 patients  intraoperative ultrasonography detected 116 previously unrecognized metastatic tumours during 40 surgical procedures  p less than 0 01   high resolution intraoperative ultrasonography is safe and more accurate than preoperative imaging and surgical exploratory methods  the examination is simple to perform and success appears to be related to careful attention to detail  
class4	the effect of the gastrin receptor antagonist proglumide on survival in gastric carcinoma  gastric cancer remains a disease with a very poor prognosis  and there is no safe and effective form of therapy for advanced disease  evidence is now abundant to show that gastrin stimulates the growth of both gastric and colorectal cancer cells in vitro and in vivo  and that blockade of gastrin receptors can prolong survival in xenografted nude mice  we have thus performed a randomized  controlled study of the gastrin cholecystokinin receptor antagonist proglumide as therapy in 110 patients with gastric carcinoma  proglumide had no overall effect on survival  mantel cox statistic   0 5  p   0 48   the 95  confidence interval for the proglumide treated group was 260 to 474 days compared to 230 to 372 days for the control group  no significant difference was seen with proglumide  which has a relatively low affinity with the gastrin receptor and also has partial agonist activity  drugs that are far more specific and potent gastrin receptor antagonists are becoming available  which may have a greater effect on survival  and further clinical trials of such compounds are clearly indicated to determine the efficacy of hormonal control of gastrointestinal malignancy  
class4	induction chemotherapy with a new regimen alternating cisplatin  fluorouracil with mitomycin  hydroxyurea and bleomycin in carcinomas of nasopharynx or other sites of the head and neck region  sixty six patients with locally advanced  stages iii and iv  carcinoma of the head and neck were treated with three cycles of induction chemotherapy  consisting of cisplatin  fluorouracil  fu  infusion  bleomycin  mitomycin  and hydroxyurea  followed by radiotherapy and or surgery  there were 48 men and 18 women with a median age of 55 years  range  18 to 75 years  and karnofsky performance status of 80  range  40 to 90   primary site was nasopharynx  28 patients   followed by larynx  12  and others  26   forty one  62   patients were presented with stage iv disease  the response rate to induction chemotherapy was 27  complete response  50  partial response  20  stable disease  and 3  progressive disease  there was no significant difference in response rate between patients with cancer of nasopharynx or other sites  p greater than 0 1   survival was 61  at 24 months  patients with cancer of nasopharynx had a better survival than those with other primaries  p   0 033   toxicities from chemotherapy included alopecia  73    nausea vomiting  66    leukopenia  54    stomatitis  36    anemia  32    thrombocytopenia  16    and diarrhea  9    grade iv toxicity was not observed  induction chemotherapy with this new regimen resulted in a high response rate but may not be superior to cisplatin and fu alone  it can be safely combined with radiotherapy as a potentially curative therapy in squamous cell carcinoma of the head and neck  chemotherapy followed by radiation therapy may yield survival similar to radical surgery in laryngeal and other head and neck cancers  
class4	treatment of patients with isolated axillary nodal metastases from an occult primary carcinoma consistent with breast origin  the records of 42 patients who had axillary metastases compatible with a clinically occult breast primary were reviewed  forty patients had mammography performed as part of their evaluations  mastectomy yielded the primary tumor in one of 13 patients  biopsy yielded positive results in one of five  among the 29 patients who did not undergo mastectomy  16 received breast irradiation  and 13 were simply observed for signs of the primary tumor  for the patients who did not undergo mastectomy  the 5 year actuarial risk for appearance of a primary was 17  in the irradiated group versus 57  in the nonirradiated group  p   0 06   patterns of failure are correlated with stage and local and systemic therapy  the results affirm our belief that patients with axillary metastases histologically consistent with breast tumor should be treated identically to patients with similar nodal stages and proven breast primaries  
class4	cancer chemotherapy after solid organ transplantation  to assess how well chemotherapy is tolerated after solid organ transplantation  we reviewed our experience at the children s hospital of pittsburgh with five patients aged 1 to 12 years  four patients had a liver transplant  indications for which were hepatoblastoma in two patients  hepatic failure secondary to wilms  tumor chemoradiotherapy in one patient  and familial intrahepatic cholestasis in one patient  a fifth patient received a cardiac transplant for unresectable angiosarcoma of the right atrium  after transplant  chemotherapy was given for the treatment of the primary malignancy in four of the patients  the patient with familial intrahepatic cholestasis received chemotherapy for secondary lymphoproliferative disease that had not responded to the cessation of immunosuppression  all patients other than this patient were on immunosuppression with prednisone  0 5 to 2 mg kg daily  and cyclosporine  to maintain serum levels at 800 to 1000 ng ml radioimmunoassay  throughout the duration of chemotherapy  courses of chemotherapy included one or more of the following agents  adriamycin  adr  20 mg m2 daily  three patients   cyclophosphamide  ctx  1 gm m2  one patient   cisplatin  cddp  90 mg m2  one patient   vincristine  vcr  greater than 0 75 to 1 5 mg m2  three patients   actinomycin d  act d  7 5 micrograms kg  one patient   ifosfamide  i  1800 mg m2  one patient  and etoposide  vp 16  100 mg m2  one patient   all patients received greater than or equal to 3 courses  range  3 to 9  mean  5  of chemotherapy every 3 to 4 weeks  dose reductions were made because of neutropenia in three patients but none were greater than 50   severe rejection was seen in one patient who had  however  manifested evidence of rejection prior to his first postoperative course of chemotherapy  no nephro or cardiac toxicity was seen  this preliminary experience suggests that chemotherapy is well tolerated after solid organ transplantation  
class4	autopsy documented cure of multiple myeloma 14 years after m2 chemotherapy  multiple myeloma was diagnosed in a 65 year old woman in 1974 who thereafter received five drug m2 chemotherapy  all protein abnormalities subsequently returned to normal and serial bone marrow studies documented complete bone marrow remission  destructive bone lesions persisted radiographically  but did not progress  in 1987  a localized sigmoid adenocarcinoma was resected  in 1988  the patient presented with multiple brain metastases associated with a primary pulmonary adenocarcinoma that proved rapidly fatal  at autopsy  no evidence of multiple myeloma was found  this report describes the first tissue documented cure of multiple myeloma 14 years after diagnosis and initiation of m2 chemotherapy  the possible association of multiple myeloma with other malignancies is also discussed  
class4	pulmonary metastases from ameloblastoma of the mandible treated with cisplatin  adriamycin  and cyclophosphamide  a case of delayed pulmonary metastases from an ameloblastoma of the mandible  which occurred 20 years after surgical resection of the primary tumor but with no recurrence at the primary site  is reported  combination chemotherapy using cisplatin  adriamycin  and cyclophosphamide has produced a very good clinical and radiologically documented response in this case  
class4	prospective evaluation of radiologically directed fine needle aspiration biopsy of nonpalpable breast lesions  the application of fine needle aspiration biopsy  fnab  to the diagnosis of nonpalpable breast lesions was evaluated with a new method which uses standard needle localization under mammographic guidance to assure accurate sampling by fnab  this method was prospectively applied to 100 mammographically detected breast lesions in 100 women  mean age  53 years   all 100 patients underwent surgical excision of these nonpalpable lesions after cytologic aspiration  sufficient aspirated material was obtained for cytologic diagnosis from 91 patients  91    the histologic and cytologic interpretations were then compared  twenty malignancies were ultimately diagnosed by histology  12 invasive ductal carcinoma  six ductal carcinoma in situ  and two lobular carcinoma in situ   of which 17 had been cytologically diagnosed  there were no false positive diagnoses of malignancy by fnab  false negative readings  3 3   included two cases of lobular carcinoma in situ and one case of ductal carcinoma in situ  this technique thus demonstrated a sensitivity of 85   specificity of 100   and overall diagnostic accuracy of 96 7  for the nonsurgical detection of malignancy in nonpalpable breast lesions  these results suggest that the established safety  reliability  and cost effectiveness of fnab can be maintained in this clinical setting  this procedure may obviate the need for open surgical biopsy in those patients with an unequivocal diagnosis of malignancy  it can also be done using standard techniques and equipment available in many community hospitals  
class4	sacral plexus injury after radiotherapy for carcinoma of cervix  a 42 year old woman developed lower extremity weakness and sensory loss 1 year after external and intracavitary radiotherapy for stage ib carcinoma of cervix  she has been followed for 5 years posttreatment  and the neurologic abnormalities have persisted  but no evidence of recurrent carcinoma has been found  we believe this to be a rare case of sacral plexus radiculopathy developing as a late complication after radiotherapy  suggestions are made for improving the radiotherapy technique to prevent this complication in future cases  
class4	relationship of 4f2 antigen with local growth and metastatic potential of squamous cell carcinoma of the larynx  the 4f2 antigen is a cell membrane glycoprotein which arises early in the g0 g1 phases of the cell cycle  this molecule is present in all established human cell lines and most malignant human cells  the authors used an indirect immunophosphatase method to study 50 squamous cell carcinomas of the larynx and ten lymph node metastases  corresponding to six primary tumors  for 4f2 expression  the tumors showed several patterns of 4f2 staining which were correlated with different behaviors and prognoses of the neoplasms  three different patterns  no staining  peripheral staining  and diffuse 4f2 expression  are described as are their relationships with metastatic behavior of the carcinomas  tumors with metastases were found only in the third group  p   0 0001   these results led to the following conclusions   1  the 4f2 antigen is present in squamous cell carcinomas   2  its distribution reflects the tumor spreading pattern  and  3  it correlates with differentiation and metastatic behavior  
class4	tumor antigen 4  its immunohistochemical distribution and tissue and serum concentrations in squamous cell carcinoma of the lung and esophagus  the immunohistochemical distribution and concentrations of tumor antigen 4  ta 4  in tissues and serum were determined in patients with benign and malignant diseases  including 27 patients with squamous cell carcinoma  scc  15 in the lung and 12 in the esophagus   tumor antigen 4 immunoreactivity was present in the cytoplasm of many scc tissues  especially in the hyperparakeratotic region  and in the cytoplasm of differentiated squamous cells of the intermediate layer of normal epithelia of various organs  but not in those of other types of lung cancers or benign pulmonary diseases  consistent with the results of immunostaining  the ta 4 concentrations in scc tissues of the lung  esophagus  and normal squamous epithelia were much higher than in those of lung cancer other than scc  benign pulmonary diseases  normal lung  and submandibular gland tissues  the ta 4 concentration in scc tissue tended to increase with increasing grades of differentiation  serum ta 4 was elevated in 15 of 27 patients with scc but in no patients with other types of lung cancer or benign diseases  these results indicate that ta 4 is an antigen related to the differentiation of squamous cells and that tumor cells of scc can release a large amount of ta 4 into circulation whereas normal squamous epithelia cannot  
class4	myocarditis or acute myocardial infarction associated with interleukin 2 therapy for cancer  the hearts of eight patients aged 22 to 67 years  mean  41 years  who died during or within 4 days of interleukin 2  il 2  based immunotherapy for treatment of renal cell carcinoma or melanoma were studied at necropsy  death resulted from combined cardiorespiratory failure in two patients  sepsis in four patients  acute myocardial infarction in one patient  and myocarditis in one patient  transmural left ventricular necrosis was present in one of the two patients with significant atherosclerotic coronary artery narrowing  noninfectious myocarditis was present in five patients  the inflammatory infiltrate was lymphocytic in four and composed of a mixture of eosinophils and lymphocytes in one  although treatment related deaths associated with high dose il 2 therapy are uncommon  1 5  in 652 consecutive patients   the potential for significant myocardial ischemia or myocarditis exists  and careful monitoring for arrhythmias or myocardial failure is warranted  
class4	postoperative active specific immunization in colorectal cancer patients with virus modified autologous tumor cell vaccine  first clinical results with tumor cell vaccines modified with live but avirulent newcastle disease virus  published erratum appears in cancer 1991 apr 15 67 8  2124  sixteen patients with colorectal carcinoma dukes  stage b2  c  or d were treated with an autologous virus modified tumor cell vaccine after potential curative tumor resection  r0 resection   an inoculum of 1 x 10 7  cells incubated with 32 hemagglutination units of nonirradiated newcastle disease virus  ndv  was given intracutaneously up to four times at 10 day intervals  the delayed type hypersensitivity  dth  skin reaction was measured  the vaccination was well tolerated  in 11 of 16 patients an increasing reactivity against the vaccine was observed during the vaccination procedure  a challenge test using autologous tumor cells without ndv after the vaccination cycle revealed a specific antitumor sensibilization in 12 patients  the dth response was not due to bacterial contamination or sensibility to the virus  histologic examination of the vaccination site showed a dense infiltration of predominantly helper t lymphocytes  we conclude that in most of the patients treated active  specific immunization led to a specific antitumor sensitivity  
class4	acute t cell leukemia lymphoma mimicking hodgkin s disease with secondary htlv i seroconversion  the authors observed a pleiomorphic lymphoma mimicking hodgkin s lymphoma in a french guyana black woman lacking antibodies for human t cell lymphoma leukemia virus type i  htlv i   after two courses of chemotherapy with either mechlorethamine  vincristine  procarbazine  and prednisone  mopp  or doxorubicin  bleomycin  vincaleukoblastine  and dacarbazine  abvd   a typical acute t cell leukemia lymphoma developed with htlv i seroconversion  specific htlv i dna sequences were detected using the polymerase chain reaction  pcr  on a lymph node biopsy obtained before chemotherapy  the mechanisms of the seroconversion are discussed  
class4	immunohistochemical studies on the main entrance route of ca19 9 into the peripheral venous blood of gastric cancer patients  correlation with ca19 9 levels in peripheral and portal blood  the correlation between ca19 9 levels of portal and peripheral venous blood  and immunohistochemical variables of cancer lesions was examined in 53 gastric cancer patients and eight patients with benign diseases  immunohistochemically  ca19 9 was found in 33  62 5   of 53 primary lesions  the antigen was found in the cancer cells of invasive lymphatics and node metastases of every ca19 9 localized cancer  although the cancer cells in veins showed little or no ca19 9  there was little or no antigen in the cancer cells in veins  lymphatics  or metastases of 20 ca19 9 nonlocalized primary lesions  patients with ca19 9 nonlocalized cancer or with benign diseases showed no elevation of the antigen levels in peripheral or portal blood  ca19 9 levels of portal blood  mean  76 4 u ml  positive rate  33 3   were not different from those of peripheral blood  mean  91 5 u ml  positive rate  33 3    additionally  the antigen levels of the blood in patients with lymphatic invasion or node metastases were significantly higher than those in patients without the invasion or the metastases  and every patient without the invasion showed no elevation of the antigen  these results suggest that production of the antigen in cancer cells may be a premise of ca19 9 elevation in peripheral blood and that ca19 9 may be drained by the thoracic duct of the lymphatic system via node metastases or invasive lymphatics  but not by the hematogenous portal system  
class4	colonic polyamine content and ornithine decarboxylase activity as markers for adenomas  polyamine content  putrescine  spermidine  and spermine  or ornithine decarboxylase  odc  activity was measured in normal appearing colonic mucosa from patients undergoing colonoscopy  comparisons were made between those with and those without adenomatous polyps  colonic mucosal polyamine content was measured in 44 persons  mean putrescine content was 1 25     0 26  se  nmol mg protein in 22 patients with adenomatous polyps compared with 0 53     0 12 nmol mg protein in patients without polyps  p less than 0 02   tissue content of spermidine and spermine did not differ between these two groups  ornithine decarboxylase activity was measured in tissue from 45 patients  mean odc activity was 2 84     0 73 pmol hr mg protein in 23 persons with adenomatous polyps compared with 1 15     0 18 pmol hr mg protein in persons without polyps  p less than 0 05   mucosal putrescine and odc activity are elevated in patients with adenomatous polyps compared with patients without polyps  these biochemical markers may prove helpful in improving surveillance methods for colorectal cancer and premalignant adenomatous polyps  
class4	establishment of an erythroid cell line  jk 1  that spontaneously differentiates to red cells  the authors established a new hemopoietic cell line  jk 1  from a patient with chronic myelogenous leukemia in erythroid crisis  this jk 1 line predominantly consists of immature cells  but a small number of mature erythroblasts and red cells can be consistently seen without any specific differentiation inducer  the jk 1 cells grow in suspension culture supplemented with human plasma and carry double philadelphia chromosomes  hemoglobin staining with benzidine was positive for about 20  of cells and the type of the hemoglobin was for the most part hbf  surface marker analysis revealed jk 1 cells positive for glycophorin a  ep 1  and hae9  the proportion of mature cells was elevated by the addition of delta aminolevulinic acid  erythropoietin  epo  enhanced the growth of jk 1 cells either in the suspension or in methylcellulose semisolid culture  the total number of epo receptors was 940 per cell  of which 220 sites had an affinity higher than the other 720 sites  this is the first report of an established human erythroid cell line which spontaneously undergoes terminal differentiation  
class4	regional differences in the intranodal distribution of tumor cells  the intranodal distribution of tumor cells was examined in 103 mesenteric and 135 axillary nodes to determine the frequency of a circumferential type of distribution and its relationship  if any  to central necrosis  eighteen percent of the mesenteric nodes removed at surgery from patients with colon cancer contained a circumferential rim of viable tumor cells in an area corresponding wholly or in part to the normal location of the marginal sinus  in each case this rim of tumor cells surrounded a large central area of necrosis  in contrast  only one of the 135 axillary nodes removed from patients with breast cancer demonstrated this pattern  these findings suggest that by interrupting blood and lymph vessels  the circumferential spread of tumor cells underlies development of central necrosis  previously described structural dissimilarities between mesenteric and axillary nodes may explain the striking difference in incidence of this pattern in these nodes  
class4	flow cytometric dna analysis of parathyroid tumors  implication of aneuploidy for pathologic and biologic classification  the previous cytometric studies on parathyroid tumors have provided conflicting data regarding the relationship between dna content and histopathology  resulting from differences in technical methods and data analysis  this study measured nuclear dna of parathyroid tumors by flow cytometry in fresh material and determined whether dna aneuploidy really assists in making a pathologic diagnosis of carcinoma or not  from may 1987 through april 1989  65 consecutive patients operated on for primary hyperparathyroidism had dna analysis of the freshly excised parathyroid tumors  three of the patients had metastatic lesions of parathyroid carcinoma in the lung  cervical lymph nodes  and lung and mediastinal lymph nodes  respectively  pathologic classifications of the lesions from the other 62 patients were 54 adenomas  four carcinomas  and four hyperplasias  in all the latter patients  hyperplasia was associated with a multiple endocrine neoplasia syndrome  unequivocal evidence of aneuploidy was found in all of the metastatic lesions and 60  of the primary lesions of the carcinomas  in 9  of the adenomas and in 50  of the hyperplasias  therefore  parathyroid carcinomas were more apt to be aneuploid than were adenomas  p   0 0015  both sided testing   in each of the cases of aneuploid hyperplasia  a small aneuploid peak was found  the high incidence of aneuploidy in patients with multiple endocrine neoplasia type 1 may indicate the presence of clonal heterogeneity of hyperplastic glands and the presence of an abnormal subset of cells that have malignant potential  cell distribution analysis did not provide any significant information beyond ploidy level  in conclusion  dna flow cytometric analysis of dna ploidy patterns is a valuable adjunct to the histopathologic diagnosis of parathyroid neoplasms  
class4	brush cytology in the diagnosis of colonic neoplasms  during a three year period  1986 1988   234 colonic brush specimens were received in the authors  laboratory  nine samples  4   were deemed unsatisfactory for evaluation because of inadequate cellularity and or poor fixation  in 11 cases concomitant or follow up histologic specimens were not available  the remaining 214 specimens included 82 malignant neoplasms  88 neoplastic polyps  adenomas   and 44 nonneoplastic lesions  sixty seven  82   of malignant neoplasms were correctly diagnosed by brush cytology  three cases of adenoma with severe dysplasia or in situ carcinoma were diagnosed as adenocarcinoma by cytology  no false positive diagnoses were made of nonneoplastic lesions  brush cytology was found to be a more sensitive technique in the diagnosis of colon cancer than endoscopic biopsy  82  and 74  sensitivity  respectively   the combination of the two techniques increased the sensitivity to 90  and improved the overall accuracy of the test  seventy one  82   of the colonic adenomas were correctly diagnosed by cytology  brush cytology is a convenient  safe  and accurate technique which should be used concurrently with endoscopic biopsy or polypectomy  
class4	soft tissue sarcoma with additional anaplastic components  a clinicopathologic and immunohistochemical study of 27 cases  this clinicopathologic study concerns 27 cases of  dedifferentiated  soft tissue sarcoma  dsts   including 14 liposarcomas  six leiomyosarcomas  five chondrosarcomas  and two rhabdomyosarcomas  in addition  the authors conducted an immunohistochemical survey of 23 cases and an electron microscopic examination of three  the findings were compared with observations of 32 cases of de novo malignant fibrous histiocytoma  mfh   all tumors contained additional distinct anaplastic portions indistinguishable from mfh under conventional light microscopy  ultrastructurally  and in cases of immunoreactivity for alpha 1 antichymotrypsin and alpha 1 antitrypsin and on lectin histochemical findings for ricinus communis agglutinin and concanavalin agglutinin  the desmin reactivity present in anaplastic portions of 14 dsts and in eight de novo mfh is taken to mean that myofibroblasts are present in these tumors  the anaplastic components of dsts are presumed to represent the proliferation of another clone of undifferentiated mesenchymal cells that fail to differentiate along any specific lineage other than fibroblast like cells  histiocyte like cells  and myofibroblasts  nineteen patients died of tumor and four are alive and well 1 6  1 7  2 1  and 5 2 years after the initial treatment  respectively  
class4	continuing care for cancer pain relief with oral morphine solution  one year experience in a regional cancer center  this report is a prospective study of 223 patients with intractable cancer pain who were offered continuing care during the year 1988 at the pain relief unit  kidwai memorial institute of oncology  bangalore  india  with a minimum follow up of 4 months and a maximum follow up of 16 months  a high percentage of pain relief was attained within a mean duration of 4 days  which on follow up was maintained at a steady level in most patients  91 1    oral morphine could not be continued in three patients because of vomiting  the main side effects noticed were nausea and vomiting  itching  and constipation  at any time during the first 140 days  only 30  of patients had side effects and appropriate medication successfully managed these side effects  during the rest of the study period  the side effects were minimal  oral morphine used with proper adjuncts offers the best pain palliation in most patients  with minimal side effects  
class4	clinical prognostic factors in patients with posterior uveal malignant melanoma  the authors evaluated the prognostic value of clinically assessed variables for predicting length of survival until death from metastatic disease in 237 patient with a primary choroidal or ciliary body melanoma  using multivariate cox proportional hazards modeling  the authors identified the largest linear basal tumor diameter  mm   estimated by indirect ophthalmoscopy and fundus drawing  the location of the anterior margin of the tumor relative to the ocular equator and ora serrata  and the age of the patient at the time of treatment as the best combination of the clinically assessed variables for predicting survival  for each patient in this group  the authors computed a prognostic index based on the best multivariate cox model  they showed that patients with low  intermediate  and high values of prognostic index had low  intermediate  and high melanoma related mortality rates  respectively  during the first 5 to 8 posttreatment years  these results suggest that   1  clinically assessed variables evaluated according to a standardized protocol are useful for predicting the survival of treated patients with posterior uveal melanoma and  2  ophthalmologists who assess potential clinical prognostic variables consistently may identify subgroups of patients with comparable mortality risk on the basis of noninvasive testing  
class4	mammographic screening of women with increased risk of breast cancer  five hundred one women from dallas county  texas who participated in the american cancer society 1987 texas breast screening project were selected because of a self reported family history of breast cancer  cases   they were matched with 501 randomly selected women from the same county with no family history  controls   although there was a statistically significant trend with age for an increasing proportion of women to report having undergone mammography  there was no significant difference when comparing mammographic histories of cases with controls after controlling for age  31 5  versus 35 1   p   0 33   significantly more cases  79   perceived their risk for breast cancer to be moderate or greater compared with controls  54   p less than 0 0001   but mammographic histories were not different when controlling for perceived risk  both cases and controls cited lack of physician referral and cost as their reasons for not having undergone mammography  women at increased risk for breast cancer  because of their family history  are not undergoing regular mammographic screening despite their self awareness of the increase in their risk  
class4	murine monoclonal anti idiotype antibody as a potential network antigen for human carcinoembryonic antigen  carcinomas of the gastrointestinal tract are not curable by standard therapies  thus  new therapeutic approaches for this disease are needed  this study proposes the use of anti id mab as ag substitutes to induce anti tumor immunity in gastrointestinal cancer patients  recently  we have generated and characterized one monoclonal anti id antibody  designated 3h1  ab2   which mimics biologically and antigenically a distinct and specific epitope of the 180 000 m w  carcinoembryonic antigen  cea  primarily expressed in high density by human pancreatic and colonic tumor cells  this epitope is unique to cea and not present on other cea related lower m w  members of the ag family also found on normal tissues  the antigenic determinant as defined by the mab 8019  ab1  against which the ab2  3h1 was raised  is absent on normal adult tissues by immunoperoxidase staining and haematopoietic cells including granulocytes by flow cytometry analysis  anti id  ab2  3h1 induced cea specific antibodies in mice and rabbits  the immune sera from both mice and rabbits competed with ab1 for binding to the colon carcinoma cell line ls174t and inhibited the binding of radioiodinated ab1 to ab2  this indicates that anti anti id  ab3  in mice and rabbits share idiotopes with ab1  8019   furthermore  monoclonal ab3 that bind to cea have been generated from mice immunized with 3h1  the ab3  both polyclonal as well as monoclonal  immunoprecipitated the same 180 000 m w  cea as ab1  8019  by western blotting analysis and showed almost identical immuno staining patterns as ab1 on colonic adenocarcinoma tissue sections from several patients  collectively these data suggest that ab2 3h1 could potentially be used clinically as a network ag for immunotherapy of patients with cea positive tumors  
class4	il 2 pe40 prevents the development of tumors in mice injected with il 2 receptor expressing el4 transfectant tumor cells  a number of different immunotherapeutic reagents are currently being developed to target il 2r for the treatment of leukemia  graft rejection  and certain autoimmune diseases  previously  we have shown that il 2 pe40  a chimeric protein composed of human il 2 linked to the n terminus of a truncated form of pseudomonas exotoxin  pe   could effectively kill a variety of cell lines in vitro expressing either low  intermediate  or high affinity il 2r  here  we demonstrate that il 2 pe40 can successfully retard or prevent the growth of a lethal ascites tumor or a solid tumor composed of el4j murine thymoma cells transfected with the p55 murine il 2r  the transfected line  el4j 3 4  expresses 1 000 to 3 000 high affinity il 2r  survival extension in the ascites model was achieved by initiating treatment either after 4 to 6 h or within 5 days post tumor injection in both athymic nude and c57bl 6 mice  similarly  the growth of an aggressive s c  solid tumor could also be inhibited  extension of survival was not achieved either by using the truncated toxin alone not attached to il 2 or by using an il 2 pe40asp553 mutant lacking a functional toxin  survival extension was not caused by il 2 activated nk or other host effector mechanisms as il 2 pe40 was unable to prevent the receptor negative el4j parental line from forming a lethal ascites or a solid tumor  thus  il 2 pe40 is a potent  specific cytolytic reagent that may prove useful in the arsenal of anti il 2r immunotherapeutics  
class4	regulation of hla class ii molecule expressions by ifn gamma  the signal transduction mechanism in glioblastoma cell lines  we examined the signal transduction mechanism responsible for the ifn gamma induced hla class ii molecule expressions on glioblastoma cell lines  t98g and a172  a series of experiments demonstrated that the activation of protein kinase c  pkc  is involved in the dr and dp molecule expressions on t98g cells  in addition to the activation of pkc  calcium influx appeared to be involved in the dr and dp molecule expressions on t98g  northern blot analyses with actinomycin d or cycloheximide revealed that these second messengers induce the transcription of dra and b and dpa and b genes without de novo protein synthesis  furthermore  we examined the region of the dpb gene that is responsible for ifn gamma induced gene transcription by gene transfer of a series of 5  and 3  deletion mutants in which the upstream region of the dpb was linked to a reporter gene  chloramphenicol acetyltransferase  by using these deletion mutants  it appeared that the region between  152 and  126 bp contains a critical ifn gamma responsive element  taken together  these results suggest that ifn gamma activates pkc and stimulates calcium influx  resulting in the induction of transcription of dra and b and dpa and b genes without de novo protein synthesis  in dpb gene  we speculate that preexiting protein s  phosphorylated by pkc in the presence of ca2  might directly bind or indirectly interact with the region between  152 and  126 bp of the upstream sequence  leading to the induction of the transcription  possibly in concert with other nuclear protein s  bound to the promoter sequences   
class4	low doses of il 4 injected perilymphatically in tumor bearing mice inhibit the growth of poorly and apparently nonimmunogenic tumors and induce a tumor specific immune memory  the ability of ril 4 to trigger host reactivity against both a chemically induced fibrosarcoma  ce 2  and a spontaneous adenocarcinoma  ts a  of balb c mice was studied  daily local s c  administration around tumor draining lymph nodes of 10 injections of progressive amounts  0 00001 to 1000 pg day  of ril 4 induced appreciable inhibition of the growth of both tumors after a dose response survival curve peaking at 0 1 pg day  inasmuch as ril 4 has no direct antitumor activity  as shown by in vitro tests  host immune reactivity plays a fundamental role in this lymphokine activated tumor inhibition  lati   lati  in fact  is abolished when recipient mice are sublethally irradiated or treated with cyclosporin a  or when the reactivity of cd4  lymphocytes is suppressed  whereas it is not affected by anti asialo gm1 antibody  the morphologic data show that ril 4 lati rests on the recruitment of several cell reaction mechanisms  among which those that are nonspecific seem to predominate  ril 4 lati also leads to a state of long lasting and specific immune memory  the growth of a second contralateral tumor challenge is significantly impaired after lati  this immune memory takes place after lati of both the poorly immunogenic ce 2 fibrosarcoma and the ts a adenocarcinoma  previously classed as nonimmunogenic on the basis of immunization protection tests  in the latter case  adoptive transfer experiments show that thy 1  lymphocytes and  in particular  the cd4 cell depleted t lymphocyte subpopulation  are responsible for the immune memory  finally  the ability of ril 4 to trigger lati is greater than that of the most effective doses of ril 2  ril 1 beta  and ifn gamma  whereas its association with ril 1 beta induces a more effective immune memory  
class4	endemic kaposi s sarcoma in human immunodeficiency virus type 1 seronegative persons  demonstration of retrovirus like particles in cutaneous lesions  in 1984  greek physicians reported on the clustering of cases of kaposi s sarcoma  ks  on the peloponnesus peninsula  to gain more insight into its pathogenesis  we studied the seroepidemiologic and clinicopathologic characteristics of 12 greek ks patients  eight male four female  five of whom were residents of an endemic area on the peloponnesus  these patients were in good general health with ages ranging from 48 to 80 years  had no clinical signs of immunodeficiency  and combined the features of both classic and epidemic ks in that they displayed not only involvement of acral areas but also widespread mucocutaneous lesions  routine laboratory data were within normal limits  no patient had htlv 1 and hiv 1 2 antibodies  but all patients had antibodies to several herpesviruses  the histopathology was characteristic of ks with the peculiar feature of a dense infiltrate composed predominantly of cd4  t lymphocytes  immunoenzymatic morphologic studies of the ks cells were consistent with their origin from lymphatic endothelium  outstanding ultrastructural findings were tubuloreticular structures and cylindrical confronting cisternae  structures that are indicative of an ongoing viral infection  indeed  extensive electronmicroscopic studies resulted in the detection of retrovirus like particles in close association to ks cells in five of 12 patients  this in situ observation opens the possibility that this retro virus contributes to ks development  
class4	elevated serum levels of soluble interleukin 2 receptors in small cell lung carcinoma  the presence of the soluble form of the interleukin 2 receptors  sil 2r  was evaluated in the serum of 21 patients with small cell lung carcinoma  sclc  and 37 patients with non small cell lung carcinoma  non sclc  by means of an enzyme linked immunosorbent assay  the sil 2r level was measured serially in patients with sclc both during and after therapy  the mean serum level of sil 2r in patients with sclc was 3 8 times higher than that of 47 healthy controls and was 1 9 times higher than in 37 patients with non sclc  six patients with sclc had very high levels of sil 2r  ranging from five to 52 times the mean level observed in normal controls  tumor cells in the pleural fluid of the patient with highest levels were positive with monoclonal antibodies to il 2r  cd25   nkh 1  okdr  and okt9  a longitudinal study in this patient showed a good correlation between tumor activity and sil 2r levels  also  the sil 2r levels decreased in patients responding to therapy  these results suggest that some sclcs secrete sil 2r and that the serial measurements of the serum sil 2r levels can be used as a noninvasive tumor marker in this disease  
class4	abnormal processing of pro igf ii in patients with hepatoma and in some hepatitis b virus antibody positive asymptomatic individuals  hepatomas are a common malignancy in countries with a high prevalence of hepatitis b virus infections  these tumors may present with severe persistent hypoglycemia  we have studied the possible relationship of production of insulin like growth factor ii  igf ii  by these tumors and the development of hypoglycemia  mean igf ii concentration was not significantly higher in 23 patients with hypoglycemia than in nine patients with euglycemia  542     61  se  micrograms l vs 382     52 micrograms l   serum igf i was more suppressed in patients with hypoglycemia  16     3 micrograms l  than in patients with euglycemia  57     18 micrograms l   because an increased percentage of igf ii in serum of patients with hypoglycemia who have other tumors is present as partially processed pro igf ii   big  igf ii   we passed sera of patients with hypoglycemia and patients with euglycemia with hepatomas through acidic bio gel p 60 columns  we found that 57      4 6  of the igf ii in sera from patients with hypoglycemia was present as big igf ii compared with 22      3  in patients with euglycemia with hepatomas  not significantly different from that in normal controls   four of 11 apparently healthy control subjects who were hepatitis b virus positive also had increased percentages of big igf ii  suggesting that abnormal processing of pro igf ii may result from subtle changes in liver function with this infection  it remains to be determined whether these subjects with increased big igf ii are at increased risk for the development of hepatomas  in conclusion  we have confirmed marked suppression of igf i in the sera of patients with hepatoma and hypoglycemia  
class4	central nervous system haemangioblastoma  a clinical and genetic study of 52 cases  fifty two cases of haemangioblastoma were reviewed for their clinical  genetic and prognostic features  of 34 patients with apparently isolated cerebellar lesions  postoperative outcome was good in 79   six isolated spinal lesions presented more insidiously and morbidity was related to incomplete resection  twelve  23   of the patients definitely had von hippel lindau disease  vhld   the true proportion may be higher as this diagnosis was not definitely excluded in many of the remainder  only ten patients with seemingly isolated cerebellar tumours were appropriately investigated and two had evidence of vhld  four out of 26 cases  15   with apparently completely resected  isolated  cerebellar lesions later developed recurrent tumours  brainstem and supratentorial haemangioblastomas were rare and were always associated with vhld  the cerebellar or spinal haemangioblastomas due to vhld had no distinctive clinical features compared with isolated tumours and there was considerable overlap in age of onset between the two groups of cases  all patients with an apparently isolated cns haemangioblastoma should be investigated for evidence of von hippel lindau disease  
class4	extradural implantation of sacral anterior root stimulators  a technique for extradural deafferentation of the s2 to s5 segments and extradural implantation of stimulating electrodes is described  and its application to twelve patients with spinal cord lesions is reported  nine patients use their implants for micturition  and seven are fully continent  the advantages and disadvantages of this technique compared with the more usual intrathecal procedure are discussed  
class4	stiffman syndrome  a rare paraneoplastic disorder  an unusual case of the stiffman syndrome  associated with an oat cell carcinoma of the bronchus  is reported  pathological examination showed that it was due to an encephalomyelitis similar to that seen in paraneoplastic disorders  this suggests that atypical cases of the stiffman syndrome may occasionally be paraneoplastic  
class4	ldh isoenzymes in cerebrospinal fluid in various brain tumours  this study examined the isoenzymatic pattern of ldh in the cerebrospinal fluid  csf  as well as the ratio between the five fractions of ldh among patients with various brain tumours  carcinomatous meningitis and control groups  ldh 1 ldh 2 less than 1 was found significant for carcinomatous meningitis  p less than 0 001  and brain metastases  p less than 0 001   ldh 1 ldh 2 ratio was found to be significantly lower in carcinomatous meningitis than in brain metastases  p less than 0 05   no ldh 1 ldh 2 ratios smaller than 1 were found in the other groups  the ldh 1 ldh 2 ratio smaller than 1 was found in the early stage of carcinomatous meningitis without other evidences of the involvement of the leptomeninges  examination of ldh 1 ldh 2 can be found as an adjunctive method to identify brain metastases and carcinomatous meningitis at the initial stage  
class4	changes in surgical treatments  the example of hysterectomy versus conization for cervical carcinoma in situ  from 1969 through 1985  4584 women in the state of new mexico were diagnosed with carcinoma in situ of the cervix  of these women  65 5  underwent hysterectomy while 31 1  had a conservative therapy  primarily conization   over the 17 year period  there was a steady increase in the percentage of women receiving conservative therapies  from 11 8  in 1969 to 50 3  in 1985  younger women  unmarried women and american indian women were more likely to receive conservative therapy  this marked shift in therapeutic approach occurred during a time of apparent controversy as to the optimal treatment for cervical carcinoma in situ  and illustrates a rapid change in surgical practice in the absence of any controlled trials comparing the two major treatment modalities  
class4	prolonged administration of oral etoposide in patients with relapsed or refractory small cell lung cancer  a phase ii trial  twenty two patients with recurrent small cell lung cancer  sclc  were treated with single agent etoposide 50 mg m2 d by mouth for 21 consecutive days  eleven patients had received previous chemotherapy with cyclophosphamide  doxorubicin  and vincristine  cav  or etoposide  cae  or both  cave   four of the latter patients also received salvage treatment with cisplatin and etoposide  ep   nine patients had been treated with ep as induction therapy  while two patients had received high dose cyclophosphamide  etoposide and cisplatin  hdcep   altogether  18 patients had received previous intravenous etoposide  the median time off chemotherapy was 4 5 months  range  1 to 28 9 months   ten patients  45 5   95  confidence interval  ci   27  to 65   achieved a complete or partial response  responses were most common in patients who had responded to previous chemotherapy and who had not received any treatment in the 90 days before initiation of oral etoposide  median response duration was 4 months  range  1 5 to 9 5 months  and median survival was 3 5  months  range  1 0 to 15  months   leukocyte and platelet nadirs were 1 800 microl and 160 000 microl  respectively  during cycle 1 of treatment and occurred between days 21 and 28  overall  total leukocyte count decreased to less than 1 000 microl during 10 of 56 cycles  18    five patients required six hospitalizations for neutropenia and fever  there were two toxic deaths due to sepsis  platelet counts less than 50 000 microl occurred in 14 cycles  25    alopecia developed in all patients  gastrointestinal toxicity was uncommon  this schedule of etoposide administration warrants further study in combination with other active agents in previously untreated patients with sclc  
class4	intraperitoneal lymphokine activated killer cell and interleukin 2 therapy for malignancies limited to the peritoneal cavity  autologous lymphokine activated killer  lak  cells and recombinant human interleukin 2  ril 2  were administered intraperitoneally  ip  to 24 patients with malignancies limited to the peritoneal space  ten patients had ovarian cancer  12 had colorectal cancer  and one patient each had endometrial carcinoma and primary small bowel adenocarcinoma  all ovarian cancer patients  three of twelve colorectal cancer patients  and one patient with endometrial carcinoma had received prior therapy  patients received il 2 100 000 u kg every 8 hours intravenously  iv  for 3 days  and 2 days later underwent daily leukapheresis for 5 days  lak cells were generated in vitro by incubating the peripheral blood mononuclear cells in il 2 for 7 days and were then administered ip daily for 5 days through a tenckhoff catheter  davol  inc  cranston  ri  together with il 2 25 000 u kg ip every 8 hours  all but one patient completed at least one cycle of therapy  toxic side effects included minor to moderate hypotension  fever  chills  rash  nausea  vomiting  abdominal pain and distension  diarrhea  oliguria  fluid retention  thrombocytopenia  and minor elevations of liver function tests  all of these rapidly improved after discontinuation of il 2  one patient had a grand mal seizure  and one suffered a colonic perforation  these were felt to be treatment related  ip fibrosis developed in 14 patients and limited repeated cyclic administration of this therapy in five patients  two of 10  20   ovarian cancer patients and five of 12  42   colorectal cancer patients had laparoscopy  or laparotomy documented partial responses  we conclude that lak cells and ril 2 can be administered ip to cancer patients  resulting in moderate to severe short term toxicity and modest therapeutic efficacy  further investigation of this form of adoptive immunotherapy modified to address the problem of ip fibrosis and with lower ip il 2 doses is justified by these initial results  
class4	therapy of renal cell carcinoma with interleukin 2 and lymphokine activated killer cells  phase ii experience with a hybrid bolus and continuous infusion interleukin 2 regimen  forty seven patients with metastatic or unresectable renal cell carcinoma were treated with interleukin 2  il 2  and lymphokine activated killer  lak  cell therapy  using a hybrid il 2 regimen  il 2 was administered initially by intravenous bolus  10 5  u kg  cetus corp  emeryville  ca  every 8 hours for 3 days  during the priming phase  and subsequently by continuous infusion  3 x 10 6  u m2 for 6 days   during this second treatment period  in vitro generated lak cells were administered  despite selection of patients for good performance status  ps   29  ps 0  18  ps 1  prior nephrectomy  43 of the 47 patients   and low tumor burden  the response rate was low  two complete  crs  and two partial responses  prs   for an overall objective response rate of 9    toxicity was comparable to that experienced with the high dose bolus regimen  these results suggest that the dose and schedule of il 2 administration may influence the likelihood of response to il 2 in renal cell carcinoma  
class4	interleukin 2 therapy in patients with metastatic malignant melanoma  a phase ii study  forty seven patients with metastatic malignant melanoma were treated with two 5 day cycles of 100 000 u kg recombinant interleukin 2  il 2  intravenously  iv  every 4 hours separated by 1 week  this dose and schedule of il 2 were identical to those used in a previous combined il 2 and lymphokine activated killer  lak  cell phase ii clinical trial of the il 2 lak working group  patient eligibility criteria  and clinical management guidelines were similar to those used in the previous trial  forty six patients were assessable for response  objective responses were observed in 10 of 46 patients  two complete responses  crs   eight partial responses  prs   or 22  with responses occurring in lung and liver as well as lymph nodes and subcutaneous sites  the median response duration was 8 months  toxicity was significant  three patients developed myocardial infarction  and one patient died during therapy  overall the toxicity and response rate for single agent il 2 are similar to that observed with il 2 administered in combination with lak cells in the previous trial  these results suggest that single agent therapy with il 2 when administered in this schedule has significant antimelanoma activity in humans  and that lak cells generated from peripheral blood add little to the antimelanoma activity of this dose and schedule of il 2  
class4	phase i study of interleukin 2 and interferon alfa 2a as outpatient therapy for patients with advanced malignancy  twenty six patients were treated in this phase i study with the combination of interleukin 2  il2  administered as a continuous infusion and interferon alfa 2a  ifn alpha 2a  administered intramuscularly to patients in an outpatient setting  the maximum tolerated dose of both agents given as outpatient therapy was 2 x 10 6  u m2 days 1 to 5 of il2 and 9 x 10 6  u m2 days 1  3  and 5 of ifn alpha 2a for 4 consecutive weeks  a 2  to 4 week rest period was permitted after each 4 weeks of treatment  fatigue was the treatment limiting toxicity  and serious clinical or laboratory abnormalities occurred infrequently during this study  patients with colon cancer metastatic to the liver tolerated treatment worse than patients with other tumors  twelve of the 15 patients with renal cell cancer were assessable for response determinations  of these 12 patients  three exhibited complete tumor regression  three have had partial objective regression  and three patients experienced stabilization of rapidly progressive disease  this therapy appears to be well tolerated in an outpatient treatment setting and shows significant activity against advanced renal cell cancer  
class4	multimodal therapy for the management of primary  nonmetastatic ewing s sarcoma of bone  a long term follow up of the first intergroup study  a total of 342 previously untreated eligible children were entered into the first intergroup ewing s sarcoma study  iess  between may 1973 and november 1978  in group i institutions  patients were randomized between treatment 1  radiotherapy to primary lesion plus cyclophosphamide  vincristine  dactinomycin  and adriamycin  doxorubicin  adria laboratories  columbus  oh   vac plus adr   or treatment 2  same as treatment 1 without adr   and group ii institutions randomized patients between treatment 2 or treatment 3  same as treatment 2 plus bilateral pulmonary radiotherapy  vac plus bpr    the percentages of patients relapse free and surviving  rfs  at 5 years for treatments 1  2  and 3 were 60   24   and 44   respectively  there was strong statistical evidence of a significant advantage in rfs for treatment 1  vac plus adr  versus 2  vac alone   p less than  001  and 3  p less than  05  and also of treatment 3 versus 2  p less than  001   similar significant results were observed with respect to overall survival  patients with disease at pelvic sites have significantly poorer survival at 5 years than those with disease at nonpelvic sites  34  v 57   p less than  001   among pelvic cases  there was no evidence of differing survival by treatment  p    81   but among nonpelvic cases  there was strong evidence of differing survival by treatment  p less than  001   the overall percentage of patients developing metastatic disease was 44   the percentages by treatments 1  2  and 3 were 30   72   and 42   respectively  the overall incidence of local recurrence was 15   and there was no evidence that local recurrence rate differed by treatment  patient characteristics related to prognosis  both with respect to rfs and overall survival experience  were primary site  nonpelvic patients were most favorable  and patient age  younger patients were more favorable   
class4	adjunctive surgery after chemotherapy for nonseminomatous germ cell tumors  recommendations for patient selection  one hundred eighty five patients who underwent surgery within 6 months of completing chemotherapy were identified from 360 patients with nonseminomatous germ cell tumors  nsgct  treated with memorial hospital front line cisplatin  or carboplatin based combination chemotherapy protocols between 1979 and 1988  clinical  pathologic  and radiologic features were correlated with the pathologic findings at surgery  the size of a residual retroperitoneal mass  the degree of shrinkage that occurred with chemotherapy  and the presence of teratomatous elements in pretreatment pathology specimens were each correlated with the pathologic findings of retroperitoneal resections after chemotherapy  multivariable logistic regression analysis of those undergoing retroperitoneal resections identified the size and shrinkage of the residual mass and the prechemotherapy lactate dehydrogenase  ldh  and alphafetoprotein  afp  levels as the best predictors of finding only necrotic debris  no factors could be found  however  that could selectively exclude patients who had residual viable malignancy or teratoma in the retroperitoneum  of 39 patients with residual retroperitoneal masses measuring less than or equal to 1 5 cm in maximal diameter  three had residual malignancy and five had teratoma resected  no factors were identified for residual lung or mediastinal masses that could be used to select a group of patients who could safely avoid surgery  if serum markers have normalized after chemotherapy for nsgct  resection of all residual abnormalities on imaging studies of the retroperitoneum  lungs  and mediastinum is recommended  in addition  retroperitoneal lymph node dissection  rplnd  is recommended for all patients with initial bulky metastases  greater than or equal to 3 cm in diameter  in the retroperitoneum  irrespective of the findings of postchemotherapy computed tomography  ct   
class4	hepatic venoocclusive disease in autologous bone marrow transplantation of solid tumors and lymphomas  retrospective review of 291 solid tumor and lymphoma patients undergoing autologous bone marrow transplantation  bmt  was performed to determine the influence of pretransplant characteristics and preparative regimen to the development of hepatic venoocclusive disease  vod   twelve patients  4 1   developed a clinical syndrome of right upper quadrant  ruq  tenderness or hepatomegaly  jaundice  and ascites  with or without encephalopathy  within 40 days of marrow reinfusion  evidence of metastatic liver disease was the only pretransplant characteristic predictive for vod  p    0002   sex  age  histology  hepatitis b serology  and elevated liver function tests were not predictive  no individual preparative agent had a significant effect on the development of vod  however  a single 2 hour infusion of carmustine  bcnu   greater than or equal to 450 mg m2  led to an increased incidence of vod when compared with the same dose administered in a fractionated schedule  p    0258  when given with two other chemotherapeutic agents  seven of eight autopsy specimens confirmed the clinical diagnosis of vod  the four patients in whom clinical vod resolved had lower median peak bilirubins  7 3 v 15 9 mg dl   lower median peak creatinines  2 1 v 4 1 mg dl   and relatively quick engraftment of neutrophils  mean  18 7 days   one of the four patients in whom vod resolved had other grade 4  life threatening  toxicities in contrast to eight of eight who succumbed  in summary  vod is an uncommon complication in autotransplantation of solid tumors and lymphomas  our data suggest caution in selecting patients with known metastatic liver disease and consideration of a fractionated bcnu schedule especially in combination with other alkylating agents  
class4	bone marrow transplantation for myelodysplasia and secondary acute nonlymphoblastic leukemia  twenty three patients with primary myelodysplasia  mds  or secondary myelodysplasia acute nonlymphocytic leukemia  mds anll  were treated with allogeneic or syngeneic bone marrow transplantation  bmt   only one patient was in a chemotherapy induced hematologic remission  graft versus host disease prophylaxis included methotrexate  methotrexate plus cyclosporine  cyclosporine  or t cell depletion using one of two anti cd5 monoclonal antibodies  for patients with primary mds  the median age was 19 years  range  11 to 41 years  and the actuarial disease free survival was 56      21   median follow up  2 years  range  0 8 to 5 years   there were three graft failures  two with autologous recovery  and two early deaths  outcome appeared to be related to french american british  fab  classification  for patients with secondary mds anll  the median age was 28 years  range  3 to 16 years  and the actuarial disease free survival was 27      13   median follow up  5 years  range  2 5 to 8 5 years   there were no graft failures  two relapses  and four early deaths  the presence of marrow fibrosis per se did not predict for graft failure  p    21   however  the use of t cell depleted marrow in patients with marrow fibrosis resulted in graft failure in three of five individuals  our results suggest that in patients with primary mds or secondary mds anll  bmt should be considered early in the course of the disease  and that attempts at inducing a remission prior to bmt appeared to be unnecessary  in mds patients with marrow fibrosis  t cell depletion should be avoided  
class4	response of oral leukoplakia to beta carotene  leukoplakia is associated with increased risk of oral cancer and is considered a premalignant lesion  retinoids  particularly 13 cis retinoic acid  can frequently reverse leukoplakia  however  these drugs have considerable toxicity and are not suitable for large scale use in the prevention of oral cancer  beta carotene is a naturally occurring  nontoxic carotenoid with biologic properties that suggest that it might be efficacious against oral leukoplakia  in 1986  we began a randomized study of 13 cis retinoic acid  1 mg kg d  versus beta carotene  30 mg d  in leukoplakia  however  owing to the marked differences in toxicity between the two compounds outlined in the consent form  11 of the initial 16 eligible patients refused to participate unless they were  guaranteed  beta carotene  therefore  the study design was changed to a phase ii trial of beta carotene in which the compound was given daily for 3 months  responding patients were continued for another 3 months of treatment  all lesions were examined histologically at entry  responses were monitored by bidimensional measurements and photography done at entry  then monthly while on treatment and at study completion  twenty four evaluable patients were treated  and 17 had major responses  two complete  15 partial   a response rate of 71   95  confidence limits  53  to 89    there was no significant toxicity requiring drug discontinuation or dose reduction  these results indicate that beta carotene has substantial activity in oral premalignancy  because of its lack of toxicity  it is an excellent candidate for a preventive agent for oral cancer  
class4	antagonism of serotonin s3 receptors with ondansetron prevents nausea and emesis induced by cyclophosphamide containing chemotherapy regimens the control of nausea and emesis in cancer patients receiving chemotherapy poses a significant management problem  in this randomized  double blind  placebo controlled study  we evaluated the effect of serotonin s3 receptor blockade with ondansetron  gr 38032f  on the prevention of nausea and vomiting induced by cyclophosphamide containing chemotherapy  cyclophosphamide was given in doses of 500 to 600 mg m2 and ondansetron as three intravenous  iv  doses of 0 15 mg kg  most patients had breast cancer  cyclophosphamide was given in combination with doxorubicin  65  of patients  or with fluorouracil  85  of patients  50  with adriamycin  doxorubicin  adria laboratories  columbus  oh  and 35  with methotrexate   all placebo treated patients experienced vomiting  whereas 70  of patients treated with ondansetron did not vomit  p    008   median nausea scores were 8 mm on ondansetron and 65 mm on placebo  p less than  001   seventy percent of patients treated with ondansetron retained their normal appetite  compared with 10  of placebo patients  adverse events occurred in six placebo patients and one ondansetron patient  diarrhea and headache were the most common events  both occurring more frequently in the placebo group  there were no extrapyramidal reactions  and the only significant biochemical change occurred in a placebo treated patient  these results suggest that serotonin s3 receptor antagonists represent a novel  effective  and safe mode of therapy for nausea and emesis induced by cyclophosphamide containing chemotherapies  in addition  our observations are compatible with the view that serotonin  acting on s3 receptors  mediates the nausea and emesis occurring after cyclophosphamide chemotherapy  
class4	phase i study of repeated cycles of high dose cyclophosphamide  etoposide  and cisplatin administered without bone marrow transplantation forty two patients with advanced malignancy judged unlikely to respond to standard treatment received high dose combination chemotherapy with cyclophosphamide  etoposide  and cisplatin in a phase i trial  twenty two of these patients who had at least a partial response  pr  to the first cycle of therapy received a second cycle  and eight patients received three or more cycles of therapy  bone marrow replacement was not used  the maximum tolerated doses  mtds  were cyclophosphamide 2 5 g m2 on days 1 and 2  etoposide 500 mg m2 on days 1  2  and 3  and cisplatin 50 mg m2 on days 1  2  and 3  hematologic toxicity was not dose limiting by study design  recovery to an absolute granulocyte count above 100 microl occurred at a median of 9 days from onset  range  3 to 23 days  at the mtd  recovery was delayed after the third cycle  only one patient on his third cycle failed to recover peripheral blood counts and died of sepsis an day 43  hematologic toxicity was not dose dependent  nonhematologic toxicities included emesis  fatigue  alopecia  diarrhea  and anorexia and were generally well tolerated  the dose limiting toxicities were fatal pulmonary or cardiac toxicities in five of nine patients treated at the highest dose level  patients likely to do well can be selected by tumor type  response to prior therapy  and performance status  nine of 36 assessable patients had a complete response  cr  and 13 a pr for a response rate of 61   five patients  12   remain alive and free of disease at 15 to 32 months  repeated cycles of dose intensive combination therapy can produce long term disease free remissions in patients with refractory tumor types  the toxicity of the regimen is acceptable if patients are carefully selected  
class4	pharmacodynamics in cancer therapy  our understanding of anticancer pharmacodynamics  and the relationships between pharmacologic measurements and clinical effects  has grown markedly in recent years due to advances in analytical and computational technology  although methotrexate plasma levels have been empirically used to guide leucovorin dosing during high dose methotrexate therapy  there has been no other standard use of therapeutic drug monitoring in oncology  more recently  investigators have attempted to titrate precisely the dose of antineoplastic agents based on previously derived models and real time analysis of plasma drug or tissue concentrations  studies have been completed or are in progress using hexamethylene bisacetamide  etoposide  teniposide  fluorouracil  fura   and cytarabine  ara c   future studies will focus on optimal sampling strategies  analysis of intermediate biochemical end points  combination chemotherapy  modulation by colony stimulating factors  and more sophisticated pharmacodynamic models  
class4	surgical treatment of thyrotropin secreting pituitary adenomas  thyrotropin secreting pituitary adenomas have been diagnosed more frequently as radiographic techniques and biochemical assays have improved  however  they remain uncommon and are unfamiliar to most neurosurgeons  this report concerns eight patients with hyperthyroidism  inappropriately elevated levels of serum thyrotropin and alpha subunit  and radiographic evidence of pituitary tumor  all underwent surgery and had pathological confirmation of a thyrotropin secreting adenoma  and most had been subjected to prior ablation of the thyroid gland  only one tumor was a microadenoma  the others ranged in size from 1 4 to 12 cm  and invasion of parasellar structures was common  thyrotropin  triiodothyronine  thyroxine  and alpha subunit were measured preoperatively and at intervals postoperatively  coexistent hormonal abnormalities  which occurred in all patients  included acromegaly and hyperprolactinemia and were also monitored  all four patients who had tumors less than 2 cm in diameter remain alive  complete extirpation of tumor in these patients produced rapid correction of all hormonal abnormalities and resolution of clinical hyperthyroidism  the other four patients had larger invasive tumors  two died soon after surgery  one died of disseminated tumor 8 years after presentation  and one remains alive with residual tumor  tumors secreting thyroid stimulating hormone are less easily cured by surgery than are other types of pituitary adenoma because of the large size and invasive features that many attain during the delay to diagnosis  medical therapy can subdue the tumor but not cure it  the experience with these patients establishes the importance of early diagnosis and surgical excision for successful treatment  and demonstrates the utility of modern diagnostic techniques for finding these lesions  as occurs in nelson s syndrome after adrenalectomy for cushing s disease  ablation of the target organ may allow the tumor to convert to a more clinically malignant form which is resistant to cure  
class4	monosomy 22 in rhabdoid or atypical tumors of the brain  cytogenetic studies of three rare childhood brain tumors were performed  two children presented with pure rhabdoid tumors  the third child had a tumor composed of a mixture of rhabdoid elements with neuroepithelial  epithelial  and mesenchymal tissue   an atypical teratoid tumor  all three tumors demonstrated monosomy 22 as the only cytogenetic abnormality  the cytogenetic findings suggest that loss of a gene or genes on chromosome 22 may be involved in the initiation or progression of these malignant tumors  further studies on additional fresh tumor specimens are warranted  however  it is possible that cytogenetic studies may be used as an additional means of diagnosing rhabdoid or atypical teratoid tumors of the brain  
class4	meningiomas mimicking cerebral schwannoma  a brain tumor with histological features reminiscent of schwannoma with underlying meningioangiomatosis was subjected to electron microscopic and immunohistochemical analysis  which confirmed the neoplasm as a meningioma  this prompted reexamination of a similar tumor  described in a previous publication as a cerebral schwannoma  with identical immunohistochemical techniques  the results obtained favored alteration of this diagnosis to that of meningioma  this experience has led the authors to recommend the use of immunohistochemistry techniques when evaluating unusual intracranial neoplasms  
class4	clonal origin of pituitary adenomas  benign pituitary adenomas are among the most common neurosurgical tumors and account for a diversity of clinical syndromes due to their hormone content and release  to determine whether these tumors arise from a single cell or multiple cells  the authors studied x chromosome inactivation in deoxyribonucleic acid  dna  isolated from pituitary adenomas in women  tumors of three different hormonal subtypes were examined  one tumor contained cells immunoreactive for prolactin and human growth hormone  one tumor contained foci immunoreactive for the beta subunits of luteinizing hormone and follicle stimulating hormone  and the third tumor had no immunoreactive prolactin  human growth hormone  beta subunits of thyroid stimulating hormone  luteinizing hormone  or follicle stimulating hormone  or the alpha subunit  analysis of the dna revealed that  in each of the three pituitary tumors  one x chromosome was active in all cells and one x chromosome was inactive  indicating that each of these tumors was monoclonal in origin  it is concluded that clinically evident pituitary tumors arise from a genetic mutation in a single cell  
class4	characteristics and biological role of steroid hormone receptors in neuroepithelial tumors tissue samples from 57 patients with neuroepithelial tumors  25 glioblastomas  18 anaplastic astrocytomas  and 14 astrocytomas  were analyzed in order to evaluate the presence of estrogen  progesterone  glucocorticoid  and androgen receptors  glucocorticoid  and androgen specific binding proteins were present in 38 6  and 21 6  of the cases  respectively  only a few tumors showed estrogen or progesterone receptors  a correlation was found between grade of anaplasia  patient s sex and age  and presence of glucocorticoid and androgen receptors  the biological role of these two receptors was investigated in 10 primary cell cultures derived from neuroepithelial tumors  for this purpose  dexamethasone and testosterone were added to culture medium at different concentrations  from 50 to 0 016 micrograms ml   a significant stimulation of the cell growth was observed in four of five glucocorticoid receptor positive cultures when dexamethasone in doses ranging from 2 to 0 016 microgram ml was added to the culture  no modulation of the growth was observed in glucocorticoid receptor negative cultures at the same doses  higher dexamethasone doses induced a significant decrease of the growth index independently from the glucocorticoid receptor status  all of the cultures tested for testosterone activity were negative for androgen receptors  this hormone induced an inhibition of the growth index at doses ranging from 50 to 0 4 micrograms ml  the data suggest that neuroepithelial tumors contain specific glucocorticoid and androgen binding proteins  glucocorticoid receptors modulate the growth of cultured neuroepithelial tumors in the presence of different concentrations of dexamethasone  
class4	hormonal dependency of cerebral meningiomas  part 1  female sex steroid receptors and their significance as specific markers for adjuvant medical therapy  female sex steroid receptors were examined in 50 human cerebral meningiomas  for estrogen receptors  high affinity binding sites  dissociation constant  kd   0 05 to 0 2 nm  were found in the cytosolic fraction with a capacity of less than 4 fmol mg protein in 10 meningiomas using a dextran coated charcoal  dcc  assay  in the same cytosolic fraction  the solid phase enzyme immunoassay revealed only one cytosol with a positive colorimetric reaction equal to 5 fmol mg protein  however  in the nuclear compartment  none of the tumors stained positively for estrogen receptors with immunohistochemical techniques  in addition  the most convincing evidence for the absence of estrogen receptors was obtained by in situ hybridization using an oligonucleotide probe complementary to a fraction of the human receptor messenger ribonucleic acid  mrna   in none of the 50 meningiomas was the expression of estrogen mrna coding for the estrogen receptor detected  for progesterone receptors  high affinity binding sites  kd  0 3 to 2 6 nm  were found in 49 of the 50 tumors using a dcc assay  in the same cytosols  solid phase enzyme immunoassay revealed that each tumor was positive for progesterone receptors  however  in the nuclear compartment  only five tumors had partially positive staining for progesterone receptors with immunohistochemical techniques  within the confines of this study  it is concluded that  1  the estrogen receptor is generally absent in meningioma tissue  and 2  the progesterone receptor is mainly absent in the nuclear compartment  leading to the conclusion that the cytosolic progesterone receptor may be an inactive form  this study suggests that female sex steroid receptors are not primarily involved in the proliferative rate of cerebral meningiomas and that they are of no current significance as markers for adjuvant medical therapy of most meningiomas  
class4	hormonal dependency of cerebral meningiomas  part 2  in vitro effect of steroids  bromocriptine  and epidermal growth factor on growth of meningiomas  cell culture and biochemical techniques have been employed to examine the effects of steroids  bromocriptine  and epidermal growth factor  egf  on the growth and proliferative potential of meningiomas  in cell culture  the growth of meningiomas was not altered by progestogens  antiprogestogens  or 17beta estradiol  the progestogen  norethisterone  had no effect on the uptake by meningiomas cell cultures of 3h thymidine  furthermore  cytosolic deoxyribonucleic acid  dna  polymerase activity of meningiomas did not correlate with the progesterone receptor status of the same tumors  in contrast  the androgen antagonists  cyproterone acetate and 11 alpha hydroxyprogesterone  and the dopamine agonist  bromocriptine  all inhibited the in vitro growth of meningioma cells  the growth of meningioma cell cultures was stimulated by egf  and there was a positive correlation between the egf content and dna polymerase activity in meningioma cytosols  these results demonstrate that female sex steroids do not influence growth of meningiomas in vitro  whereas antiandrogens and bromocriptine have an antiproliferative effect  consequently  bromocriptine and antiandrogens may have a role in the medical treatment of meningiomas  in addition  these results suggest that egf may be involved in the genesis and or progression of meningiomas  
class4	fourth ventricular schwannoma  case report  a schwannoma arising from the dorsum of the pontomedullary junction and presenting as an exophytic mass in the fourth ventricle is described  a ventricular schwannoma has not previously been reported in the literature  the presenting clinical and radiographic features and the pathology of this tumor are summarized  and an explanation is sought for its unusual location  
class4	myxomatous cyst of the brachial plexus  case report  the case of a myxomatous cyst of the brachial plexus is presented  the clinical course is reported  and the frequency of the lesion  diagnostic workup  histopathology  and surgical therapy are discussed  
class4	intradural epithelial cyst at the craniovertebral junction  case report  a case of an intradural epithelial cyst at the craniovertebral junction is reported in a 37 year old man  the classification of these rare lesions is discussed  
class4	lymphocele  the spectrum of scintigraphic findings in lymphoceles associated with renal transplant  lymphocele is a well recognized complication of renal transplant surgery  we performed a retrospective review of 305 renal transplant patients with over 2 500 scintigraphic exams to describe the pattern of activity on technetium 99m dtpa blood flow and dynamic imaging  and iodine 131 oih studies  diagnostic criteria for a lymphocele were ultrasonic evidence of a perirenal fluid collection and analysis of that fluid that demonstrated bun  creatinine  and electrolytes similar to the patient s plasma  scintigraphic findings were attributed to a lymphocele if abnormalities were in the same area as the ultrasound fluid collection  scintigraphic findings attributable to lymphocele resolved in all patients following surgical drainage or peritoneal window placement  six of the 11 documented lymphoceles demonstrated a cold defect on initial dynamic images that  filled in  to equal background activity and another exceeded background  three cases showed a rim of increased activity surrounding the lymphocele   rim sign    
class4	scintigraphic evaluation of aggressive fibromatosis  despite its benign microscopic appearance  aggressive fibromatosis has potential to recur and infiltrate neighboring tissues  therefore  it is necessary to determine the exact extent before therapy  in the present study  11 cases of aggressive fibromatosis were examined scintigraphically using  99mtc v  dimercaptosuccinic acid  11 cases  and 67ga citrate  7 cases   technetium 99m  v  dimercaptosuccinic acid demonstrated all lesions  while 67ga citrate detected 57  of the cases  
class4	n  18f fluoroacetyl d glucosamine  a potential agent for cancer diagnosis positron labeled substrates such as sugars  amino acids  and nucleosides have been investigated for the in vivo evaluation of biochemical processes in cancerous tissue  hexosamines are obligatory structural components of many biologically important macromolecules  including membrane glycoproteins and mucopolysaccharide  we evaluated a new synthesized pharmaceutical  n  18f fluoroacetyl d glucosamine  18f fag   which is a structural analog of n acetyl d glucosamine  c3h hemsnrs mice bearing spontaneous hepatomas were used for the tissue distribution study  at 60 min after injection  high uptakes were found in tumor  5 16  mean value of  dose g   liver  3 71   and kidney  3 27   the tumor uptake of 18f fag showed the highest value in all tissue  in the pet study  vx 2 carcinoma of the rabbit was clearly visualized  our preliminary results suggest that 18f fag has potential as a new agent for tumor imaging  
class4	invasive squamous cell carcinoma of the mandible presenting as a chronic osteomyelitis  report of a case  a case of invasive squamous cell carcinoma of the mandible initially thought to be chronic osteomyelitis is reviewed  discussion of the origin of the tumor and several imaging techniques used for differentiating maxillofacial infection from neoplasm are discussed  the difficulty of diagnosis of chronic painful maxillofacial lesions illustrates the need for a high degree of suspicion concerning any inflammatory lesion not responding to appropriate therapy  accurate diagnosis and treatment of such lesions most often necessitates microscopic examination  
class4	detection of human papillomavirus genomic dna in oral epithelial dysplasias  oral smokeless tobacco associated leukoplakias  and epithelial malignancies  human papillomavirus  hpv  is an infectious agent that is increasingly associated with mucosal cancers  in particular cancer of the cervix  the present investigation was undertaken in an attempt to determine whether hpv could be easily detected in biopsies of oral tissues  specifically oral squamous cell carcinomas  oral epithelial dysplasias  smokeless tobacco keratoses  verrucous hyperplasia  and verrucous carcinoma  in situ dna hybridization methods were used to isolate specific hpv genomes  among 100 instances of benign leukoplakia  only 4  of non tobacco related and 10  of smokeless tobacco related lesions harbored viral sequences  we were able to detect viral sequences in dysplastic lesions 3  of the time  alternatively  17  and 20  of the verrucous hyperplasias and verrucous carcinomas were positive for viral nucleic acids  six percent of the squamous cell carcinomas harbored hpv  on the basis of these findings  it is concluded that hpv of known genotype can be identified in oral premalignant and malignant neoplasms  
class4	desmoplastic variant of ameloblastoma  report of a case and review of the literature  a case of desmoplastic variant of ameloblastoma is reported  the lesion  in a 36 year old japanese woman  was successfully treated by partial maxillectomy  reconstruction was carried out with a block of hydroxyapatite about 7 years and 6 months later  six cases  including our case  reported up to the present are summarized and reviewed  
class4	characterization of the effect of two 4 methyl piperidine derivatives of hemicholinium 3  a 4 and a 5  on choline transport  a 4 and a 5 are tertiary and n methyl quaternary 4 methylpiperidine analogs of hemicholinium 3  hc 3   previous work in this laboratory has shown a 4 and a 5 to be inhibitors of the sodium dependent  high affinity choline uptake system  sdhacu   their effects on choline transport were characterized further using neuroblastoma 41a3 cells  these cells rapidly take up choline through two separate mechanisms  a sdhacu system and a sodium independent  low affinity uptake system  silacu   a 4  a 5 and hc 3 decreased 5 microm choline transport in a dose dependent fashion  the compounds were unable to decrease choline transport at 250 microm choline suggesting that they are inactive with respect to silacu  all three compounds significantly increased the km but not the vmax for the sdhacu system  suggesting a competitive mechanism of inhibition  ki values ranged from 18 to 25 microm for a 4  20 to 26 microm for a 5 and 68 to 75 microm for hc 3  dose response curves for inhibition of choline transport by a 5 and hc 3 were not changed by a 24 hr pre exposure of the cells to each inhibitor  however  after a 24 hr pre exposure to a 4  a significantly different dose response curve was obtained compared to the dose response curve for a 4 in untreated cells  after a 24 hr pre exposure  a 4 hr recovery period was sufficient to remove the effect of each compound  these data suggest that a 4 and a 5  like hc 3  inhibit the sdhacu  competitively and reversibly  
class4	ruptured mature cystic teratoma of the ovary with recurrence in the liver and colon 17 years later  a case report  a mature cystic teratoma of the ovary occurred in a 51 year old woman and recurred as a large intrahepatic tumor mass as well as a small mass in the transverse colon 17 years after rupture  intraperitoneal spillage of tumor contents and subtotal surgical removal of the ovarian lesion and peritoneal implants  the patient was treated with a partial hepatectomy and a segmental transverse colectomy  the recurrent lesions  which contained histologically fully mature teratomatous elements only  were excised  the result was a complete cure  to our knowledge this is the first documented report on such a complication of mature cystic teratoma of the ovary  
class4	conservative therapy for adnexal torsion  a case report  adnexal torsion has traditionally been treated with oophorectomy because of the fear that untwisting the ovarian pedicle may result in a thrombotic embolus  such a patient had bilateral adnexal torsion secondary to dermoid cysts  since standard therapy  oophorectomy  was performed  the patient was surgically castrated  a review of the literature revealed no reported cases of a thrombotic embolus arising from the untwisting of twisted adnexa and supported conservation of the adnexa rather than routine extirpation  except when necrotic  
class4	localization of trophoblastic disease with vaginal ultrasonography  a report of two cases  two patients had elevated beta human chorionic gonadotropin levels and normal abdominal ultrasound examinations  in both instances transvaginal ultrasonography demonstrated a persistent nodule of trophoblastic disease confirmed at the time of hysterectomy  this new imaging modality can assist in the diagnosis of persistent trophoblastic disease in the uterus  
class4	an unusual manifestation of paget s disease of bone  spinal epidural hematoma presenting as acute cauda equina syndrome  neurologic sequelae of paget s disease of bone include involvement of the spinal cord or cauda equina due to mechanical compression by enlarged vertebrae  ischemia caused by a spinal artery  steal syndrome or neoplasm  we describe a patient with paget s disease of bone who presented with acute cauda equina syndrome due to a spinal epidural hematoma  clinicians need to recognize this entity since surgical intervention may result in a favorable outcome  
class4	presentation of breast carcinoma as volkmann s contracture due to skeletal muscle metastases  metastases to the skeletal muscles are extremely rare  they usually occur during the course of a pulmonary or digestive carcinoma  we describe a case of breast carcinoma presenting with forearm muscle metastases and volkmann s type contracture  
class4	increasing annual incidence of primary malignant brain tumors in the elderly between 1973 and 1985  total age adjusted cancer incidence in the united states  all races  men and women  rose by 10 7   with an average annual percentage change of  0 9   analysis of reported age specific incidence of primary malignant brain tumors over the same years demonstrates that incidence rates increased dramatically between 1973 1974 and 1985  in 1985  incidence rates for persons aged 75 79  80 84  and 85 years of age and over were 187   394   and 501   respectively  of rates in 1973 1974  similar increases were found in both men and women  analyzed separately and combined  average annual percentage changes in primary brain tumor incidence were  7 0    20 4   and  23 4  in these age ranges  respectively  reported incidence in younger persons varied little over the same period of time  the most common histologic type of primary brain tumor in the elderly was of glial origin  predominantly the glioblastoma multiforme and astrocytoma  these tumors are highly malignant and invariably fatal  two possible causes may explain the increased incidence in the elderly  the introduction and extensive use of x ray computed tomography since 1973 and or a true increase in incidence occurring independently of diagnostic advances  
class4	methionine dependency of malignant tumors  a possible approach for therapy when methionine  met   an essential amino acid  was substituted for by its precursor homocysteine  hcy  in the culture medium  normal cells such as fibroblasts proliferated normally  in contrast  many tumor cells failed to grow or grew at a lower rate  met dependency is acquired simultaneously with cell transformation  as observed with hbl 100  a human mammary epithelial cell line that acquired increased malignancy as a function of in vitro passage number  and nih 3t3  j10   a mouse fibroblast line transformed by transfection with the human hras oncogene  a relationship was observed between met dependency and metastatic potential of the rms 21  rms s4t  and rms j1 sublines derived from rms 0  a rat rhabdomyosarcoma cell line  the higher the metastatic potential of the cell line  the higher the concentration of met required to maintain its proliferation  met independent cells derived from the rms 0 line  obtained by a progressive decrease of met in the culture medium lost their tumorigenicity when injected into rats fed with met deprived diets  in addition  the in vitro motility of rms s4t tumor cells  a marker of metastatic capability  decreased in met free hcy complemented  met  hcy   medium  similarly  rms 0 tumor cells  preincubated in a met  hcy  culture medium for 24 hours  evidenced a decreased capacity to form lung colonies when injected into syngeneic rats  the median number of lung colonies was 27 and 3  p less than  05  for cells cultivated in met  hcy  and met  hcy  media  respectively  an amino acid defined mixture reproducing casein composition was used as a protein source in the diets fed to rms j1 tumor bearing rats  dietary substitution of hcy for met  i e   met deprivation  resulted in decreased tumor growth  from 44 4     1 0 to 40 6     1 4  p less than  05  and prevention of metastatic spread  from 37 to 0  p less than  05   in conclusion  exogenous met can be substituted for hcy to maintain the survival of normal cells but is essential for tumor cell growth in vivo as well as in vitro  therefore  this defect of cancerous versus normal cells could be used for a therapeutic purpose  
class4	low metastatic potential of clone from murine colon adenocarcinoma 26 increased by transfection of activated c erbb 2 gene  we investigated the effect of an activated c erbb 2 gene  also known as erbb2  on metastatic potential  the c erbb 2 gene was activated by mutation of the valine at position 659 within the transmembrane domain to glutamic acid  the activated c erbb 2 expression vector was transfected into low metastatic potential nl 4 cells  which were established from a metastatic variant of murine colon adenocarcinoma 26  all 10 clones produced lung metastases in balb c mice injected via the tail vein  eight of the 10 clones expressed messenger rna  mrna  of activated c erbb 2 and showed morphological alteration  seven of the eight produced significantly enhanced experimental metastatic activity compared with that of untransfected nl 4 or nl 4neo cells  and one had metastatic ability similar to that of nl 4 cells  two clones did not express c erbb 2 mrna and did not show morphological alteration or highly metastatic phenotype  five of the 10 clones subcutaneously implanted in the flank failed to produce metastasis in the lungs or other organs of the mice  the metastatic ability of the other five clones was not determined  these results indicate that the activated c erbb 2 gene can enhance experimental but not spontaneous metastatic potential in nl 4 cells  suggesting participation of the gene in the metastatic process after initial arrest and lodgement in the capillary bed  
class4	new active analogues of vitamin d with low calcemic activity  in conclusion  a number vitamin d analogues have been developed that have very low calcemic activity but retain several other properties of 1 25  oh 2d3  including the ability to differentiate leukemia and skin cells  to enhance the immune response  and to suppress parathyroid hormone levels  although the mechanism of this selective activity is not yet clear  these analogues may provide new insights into the differences in action of 1 25  oh 2d3 in various target tissues  most importantly  the selective action of these analogues may be exploited for the treatment of diseases such as leukemia  psoriasis and hyperparathyroidism  
class4	effect of prostaglandin e in multiple experimental models  v  effect on tumor host interaction  prostaglandin e  pge  has long been incriminated as a cause of the immunosuppression seen in cancer patients and for the increased rates of tumor growth due to the impairment of the immunologic response to the tumor  we have investigated the effect of pge on tumor host interaction by utilizing a parenterally administered long acting pge derivative  16 16 dimethyl prostaglandin e  dpge   administration of dpge was found to decrease the rate of tumor growth but at a cost of decreasing tumor free body mass  the dpge did not alter resting metabolic rates but did alter some parts of brain dopamine metabolism and significantly decreased the serum level of multiple amino acids  in conclusion  elevated pge levels may significantly alter metabolism in tumor patients  
class4	malignant melanoma occurring during pregnancy  a report of the northern israel oncology center  1968 1988   medical records of seven patients treated within a 20 year period for malignant melanoma during pregnancy were reviewed  no significant detrimental prognostic effects could be attributed to pregnancy  the current literature on melanoma and pregnancy is discussed  based on this  pregnancy seems not to be contraindicated in melanoma patients  
class4	cyclophosphamide and ifosfamide combination as neoadjuvant chemotherapy for locally advanced nonsmall cell lung cancer  a meta analytic review  twenty three patients with marginally resectable and unresectable non small cell lung cancer  stages iiia and iiib  were treated by neoadjuvant chemotherapy  all patients received three cycles of preoperative chemotherapy with two alkylating agents  cyclophosphamide 2 5 g m2 intravenously  i v   and ifosfamide 3 5 g m2 i v   mesna 12 g m2 was given additionally to prevent drug hematuria  six of 23 patients  26   had partial response  of the seven patients who underwent thoracotomy  two were completely resected  but with macroscopic residual disease  mean time to progression for the whole group was 7 months  fifteen patients had progression of disease  with local metastases only in six  and distant metastases in eight  after administering 52 chemotherapy cycles  cyclophosphamide ifosfamide doses were cut down  as eight of 16 patients required hospitalization for fever during neutropenia nadirs  this two alkylating  non cisplatin  regimen  unlike cisplatin based regimens  was ineffective  and further trials are not recommended  
class4	renal vein leiomyosarcoma  the 11th case of primary leiomyosarcoma of the renal vein is reported  unique features of this case included concomitant resection of an isolated hepatic metastasis  intraoperative radiation therapy  and the use of electron microscopy and immunohistochemical stains in confirming the diagnosis  a review of the previously reported cases shows a tendency toward slow tumor growth and infrequent recurrence  18    metastases are common  82    primarily to the lung and liver  aggressive surgical resection and adjuvant radiation therapy  including intraoperative radiation therapy  are recommended  adjuvant chemotherapy should be considered  although its benefits at present are unclear  
class4	adrenal carcinosarcoma  the clinical and pathologic features of a case of adrenal carcinosarcoma are reported  although synchronous malignancy of the adrenal gland has been described  no case of an adrenal tumor combining both carcinomatous and sarcomatous elements has been previously documented  this neoplasm is extremely aggressive with distant metastasis arising from the sarcomatous component  and rapid progression despite multimodal therapy  
class4	distinguishing malignant mesothelioma from pulmonary adenocarcinoma  an immuno histochemical approach using a panel of monoclonal antibodies  a panel of six monoclonal antibodies  mabs  was employed to evaluate antigen expression in pulmonary adenocarcinomas and mesotheliomas  monoclonal anti human milk fat globulin  hmfg 2   anti carcinoembryonic antigen  np 2   anti epithelial membrane antigen  ema   anti cytokeratin  pkk 1   anti tumor associated antigen 72  b72 3   and anti human myelomonocytic antigen  leu m 1  antibodies were used to localize their respective antigens in formalin fixed  paraffin embedded tumors by using the avidin biotin complex immunoperoxidase technique  in all  28 mesotheliomas obtained from ohio state university anatomic pathology files and from a southwest oncology group  swog  protocol were compared to 22 pulmonary adenocarcinomas by using this mab panel  none of the mesotheliomas demonstrated positive staining with mabs np 2  anti cea  or leu m 1  however  95   21 22  of adenocarcinomas stained with one of these two antibodies  although neither of these two mabs stained all adenocarcinomas  each antibody demonstrated positive immunostaining in more than 90  of the adenocarcinomas studied  therefore  mabs np 2 and leu m 1 are  individually  quite useful for distinguishing mesothelioma from adenocarcinoma  however  in our study  no single mab could be used to distinguish these two tumor types in every case  mab b72 3 stained 91   20 21  adenocarcinomas but also stained 7   2 28  of mesotheliomas  mab hmfg 2 reacted positively with 95  of adenocarcinomas  but also stained 39  of the mesotheliomas  usually in a membranous pattern  mabs ema and pkk 1 were not found useful in distinguishing mesothelioma from adenocarcinoma  we conclude that mabs leu m 1 and np 2 were both useful in distinguishing mesothelioma from pulmonary adenocarcinoma in that positive staining was demonstrated in adenocarcinomas and not mesotheliomas  
class4	clinicopathological features of elevated lesions of the duodenal bulb  we present here our findings on patients with an elevated lesion of the duodenal bulb  all these patients were treated in our clinics between the years 1984 and 1988  these lesions were present in 36 of 8 802 patients who underwent upper gastrointestinal pan endoscopy  two patients had a duodenal carcinoma  2 an adenoma  and 1 a brunner s gland adenoma  there were 15 with a hyperplastic polyp  3 with a heterogenic gastric mucosa  3 with brunner s gland hyperplasia  6 with duodenitis  and 4 with regenerative mucosa  among these 36 lesions  only 69   25 lesions  were evident on the upper gastrointestinal x ray series  adenoma and brunner s gland adenoma were of a pedunculated form of the gross type and had an irregular surface mucosa  both duodenal carcinomas were detected by endoscopic biopsy and were resected  histologically  these lesions were limited to the submucosal layer and were of the non pedunculated polypoid form  but there were no other characteristic endoscopic features  in comparison with other elevated lesions  thus  upper gastrointestinal endoscopy with routine observations of the duodenal bulb plus endoscopic biopsy will lead to a definite diagnosis of these elevated lesions and to the early detection and treatment of this rare malignant lesion  
class4	utility of surgical margins in the radiotherapeutic management of soft tissue sarcomas  seventy four adult patients with localized soft tissue sarcomas were treated with radiation therapy following surgery between 1965 and 1988  fifty three were treated after the first excision of their tumor with 6  11 3   local recurrences  twenty one received radiation after excision of recurrent disease with 11  52 4   local failures  p less than  0005   metastatic disease occurred in 14  26 4   of the primary tumors and 8  38 1   with multiple previous excisions  p less than  48   of those patients treated for primary sarcoma  there were no local failures with pathologically wide margins or if a single margin was microscopically positive  local failure occurred in 4 of 26  15 4   if the tumor was merely enucleated and in 2 of 11  18 2   who had grossly positive surgical margins  p not significant   local failure was also more common in truncal locations  33 3   as compared with extremity locations  8 7   p    1359   additional factors analyzed which adversely affected prognosis included tumor grade  stage  and inadequate radiation dose  
class4	acral melanoma  a review of 185 patients with identification of prognostic variables  one hundred eight five patients with acral melanoma treated since 1972 were reviewed  these included 53 subungual lesions  123 plantar lesions  and 9 palmar lesions  eighty percent presented with stage i disease  mean age was 57 years  males outnumbered females 1 1 1  seventeen percent  17   were blacks  actuarial 10 year survival was 58  for stage i patients and 35  for stage ii patients  univariate cox regression analyses identified 5 prognostic variables affecting survival  stage at diagnosis  p less than 0 001   race  p less than 0 001   ulceration  p   0 012   clark s level  p   0 014   and thickness of the primary lesion  p   0 013   factors unrelated to survival included sex of the patient  site  volar vs  subungual   histology  and treatment with amputation  multivariate analysis for patients with stage i lesions identified race  p   0 001  and ulceration  p   0 018  as significant variables  with thickness approaching significance  p   0 094   in an additional series of 71 patients with melanomas arising from extremity sites near the junction of glabrous and non glabrous skin  survival was significantly poorer for those arising from glabrous skin  p   0 024   and reflects a higher incidence of metastatic disease at diagnosis  specific active immunotherapy was the principal adjuvant used for these patients  and survival was comparable to that reported with regional perfusion therapy  acral melanoma a  has a strong racial predilection  b  carries a grave prognosis  and c  arises from glabrous skin  it is a clinical entity distinct from other extremity melanomas  surgical management with either wide excision or amputation is appropriate for the primary lesion  
class4	long term experience with a totally implanted catheter system in cancer patients  long term experience with totally implanted catheter systems  tics  is limited  we retrospectively evaluated the performance and long term complications of tics for intravenous infusion in cancer patients  134 systems were implanted in 128 patients  the median duration of implantation was 144 weeks with 49 systems implanted for more than one year  complications related to surgical factors included malposition of reservoir  2    skin perforation or wound dehiscence  1 5   and pneumothorax  less than 1    complications not related to surgical factors included  drug extravasation  1 5    mechanical malfunction  1 5    vein thrombosis  less than 1    clotting of the reservoir or catheter  2    skin infection  1 5    and sepsis  less than 1    the total complication rate was 13   most complications resolved spontaneously or with medical treatment and only 6 patients  4 6   required re implantation of a second system  we conclude that with long term usage of tics  the complication rate remains low  making it a safe and viable alternative for patients requiring long term intravenous therapy  
class4	cutaneous malignant melanoma in rochester  minnesota  trends in incidence and survivorship  1950 through 1985 in rochester  minnesota  107 incidence cases of cutaneous malignant melanoma  in 46 male and 61 female patients  were diagnosed during the years 1950 through 1985  overall crude incidence rates were 6 0 and 6 6 per 100 000 males and females  respectively  evaluation of trends in 9 year periods showed that the rates increased from 3 2 to 8 9 for males  p   0 015  and from 4 4 to 11 7 for females  p less than 0 001   age specific rates suggested that the highest incidence occurs in the age groups 50 to 59 years and 70 years or older for males and 40 to 49 years and 70 years or older for females  lesions were most common in the head and neck area among males  p   0 044  and on the lower extremities among females  p   0 018   the most frequent histologic type was superficial spreading melanoma  61    five year survival was diminished overall for patients with cutaneous malignant melanoma  0 72 in comparison with 0 88 expected for the general population  statistically significant risk factors for survival were depth of invasion of the lesion  clark level   thickness of the lesion  histologic type  and age of the patient  
class4	diagnosis of corticotropin producing bronchial carcinoid tumors causing cushing s syndrome cushing s syndrome due to ectopic production of adrenocorticotropic hormone  corticotropin  has been recognized for many years  traditionally  clinicians have thought that most cases were due to lung carcinomas and that the clinical manifestations differed from those for pituitary dependent cushing s syndrome  we report two cases of corticotropin producing bronchial carcinoid tumors that were clinically and biochemically indistinguishable from pituitary dependent cushing s syndrome  review of the literature revealed that bronchial carcinoid tumors are the most common cause of cushing s syndrome due to ectopic secretion of corticotropin  on biochemical and anatomic studies  they are frequently indistinguishable from pituitary dependent cushing s syndrome and thus may be difficult to diagnose  inferior petrosal sinus sampling for corticotropin and computerized imaging of the chest may be the best aids in making the diagnosis  
class4	adult t cell leukaemia lymphoma in brazil and its relation to htlv i in a series of fourteen patients with adult t cell lymphoma leukaemia  atll  in brazil the main features were lymphadenopathy  hepatosplenomegaly  hypercalcaemia  and high leucocyte counts  with abnormal lymphoid cells which had irregular nuclei  the series included the youngest patient with atll so far  18 months   analysis with monoclonal antibodies showed a mature t cell phenotype  cd4   cd8    antibodies to htlv i and or integration of htlv i proviral dna were found in eleven patients  in the other three htlv i dna could not be demonstrated even by means of the polymerase chain reaction  they therefore had htlv i negative atll  this report of atll in brazil corroborates serological reports that htlv i may be endemic in some parts of that country  follow up studies are required to identify precisely the main route of transmission of htlv i in south america and the risk factors for the development of atll in carriers  
class4	conservation surgery for glomus jugulare tumors  the value of early diagnosis  the results of lateral cranial base surgery for glomus jugulare tumors are gratifying when normal anatomy and function can be preserved  the goal of conservation surgery is to preserve normal ear anatomy and cranial nerve function  in general  conservation surgery is tumor size dependent  thus  excellent states of functional recovery depend upon accurate early diagnosis  this paper reviews the technical aspects of transtemporal conservation skull base tumor surgery while also reviewing our experience with nearly 100 glomus jugulare patients  adjuvants to early diagnosis will be highlighted from a review of presenting symptoms  clinical signs  and related diagnosis  our objective is to provoke a high index of suspicion in physicians charged with the responsibility of diagnosing these tumors  diagnostic guidelines are proposed  
class4	local control of auricular  periauricular  and external canal cutaneous malignancies with mohs surgery  three hundred ninety seven patients with 407 cutaneous malignancies of the auricle  periauricular region  and cartilaginous external ear canal were reviewed  tumors were most commonly located in the preauricular and postauricular regions  followed by the helix  concha  antihelix  and ear canal  all lesions were excised with mohs microscopic control of margins  for lesions requiring lateral temporal bone resection  an adaptation of fresh tissue microscopic control was used to analyze deep and anterior margins suspected of harboring residual tumor  two year minimum follow up of 229 patients with periauricular and auricular tumors  n   231 tumors  and 14 patients with cartilaginous ear canal tumors  n   14 tumors  revealed recurrence rates of 6 9  and 14 3   respectively  recurrences were most common in cases of large tumors  greater than 2 5 cm   basal cell carcinomas with morphea elements  and multiply recurrent lesions  we conclude that mohs surgery is comparatively effective  though not uniformly curative  and can be adapted to supplement excision of large tumors in these regions  
class4	olfactory neuroblastoma  clinicopathologic and immunohistochemical characterization of four representative cases  olfactory neuroblastomas are rare tumors whose clinical prognosis is not predictable by assessment of initial stage or grade  the pathologic diagnosis is often difficult because of the wide range of the patient s age and histologies  in this report  we document that the diagnosis of olfactory neuroblastoma can be clarified by immunohistochemical demonstration of a unique antigenic profile that can be obtained in routinely processed biopsies  we describe four cases of olfactory neuroblastoma diagnosed and treated from 1979 to 1989  each confirmed by immunohistology  one of our patients was misdiagnosed twice at an outside institution  first as having nasopharyngeal carcinoma and then as having small cell  undifferentiated  oat cell  carcinoma  despite accurate tumor diagnosis and appropriate therapy  we found that there was no apparent correlation of clinical outcome with kadish clinical stage or histologic grade of tumor  
class4	le fort i osteotomy approach to the skull base  horizontal osteotomy allows the surgeon to safely down fracture the maxilla for wide exposure of the central skull base  this surgical approach is easily extended posteriorly in the midline to include the clivus and the arch of c1  providing 8 cm of horizontal anterior exposure and 5 cm of posterior  wide operative exposure and a low rate of complications afford superior functional and cosmetic preservation in removing tumors of the central cranial base  
class4	imaging of pharyngeal and laryngeal carcinomas with indium 111 labeled monoclonal anti cea antibodies  localization of primary tumors  metastases  or recurrences in 13 consecutive patients with histological verification of squamous cell or adenocarcinoma was made with radioimmunodetection using monoclonal radiolabeled anti cea antibody  all surgical specimens stained immunohistochemically  except one  were positive for cea  of the known 19 tumor sites 17 were visualized in antibody scans  there were two positive findings that did not prove to be positive during 12 month follow up  the scintigram findings did not correlate with cea serum concentrations that  with one exception  were normal in all patients  
class4	surgical therapy of the eyelids in patients with facial paralysis  patients with facial paralysis have a degree of lagophthalmos and paralytic ectropion  we present our experience in the surgical management of 25 consecutive patients treated for these problems  paralytic lagophthalmos was corrected using gold weights inserted into the upper eyelid  the advantages and disadvantages of this surgical technique are reviewed  medial canthoplasty and lateral canthoplasty were performed to rectify paralytic ectropion  ancillary procedures included browpexy  upper lid blepharoplasty  and temporalis sling  the results were excellent in 23 of 25 patients and good in the remaining two  after a minimum of 6 months  follow up  there were no complications  the authors believe that the above procedures will yield consistently excellent cosmetic and functional results in patients with paralysis of the eyelids  
class4	endoscopic laser surgery for early glottic carcinoma  a clinical and experimental study  the purpose of this study is to define the indications for using the co2 laser for the treatment of early glottic cancer  for this purpose  52 consecutive laser resections of tis to t2 vocal cord carcinomas were studied prospectively  in addition  laser resection was performed in eight human cadaver larynges  which were then examined histologically using whole organ sections  both tumor size and tumor location had important influences on tumor resectability by laser  all of the tis  78  of t1  and one of four t2 carcinomas were successfully treated by laser surgery alone  of the 10 carcinomas involving the anterior commissure  only four could completely be resected with the laser  of these four  two recurred in the anterior commissure  this finding is corroborated by the histologic study  which clearly shows that anterior commissure resection poses problems  the only laser resection complication of early glottic cancer was persistent hoarseness in one third of the patients  it is concluded that co2 laser resection is a safe and effective alternative treatment for patients with tis and t1 glottic carcinoma  provided the anterior commissure is free of tumor  
class4	clinical classification and staging for primary malignancies of the maxillary antrum  a study of 51 patients with primary malignant maxillary sinus neoplasms was conducted  none of the patients had neck nodes and or metastases  and each had 5 year follow up  the tumors were staged according to the 1983 and 1988 american joint committee on cancer staging systems for maxillary sinus cancers  there were 13 early stage  t1  t2  and 38 advanced  t3  t4  tumors in both systems  cox regression analyses of survival curves showed increasingly worse prognoses for advanced tumors in both t staging systems  further analyses showed a significant difference in survival between t3 and t4 in the 1988  but not in the 1983 system  there were no significant differences in survival according to treatment modality or histological type of malignancy  we conclude that the 1988 system prognosticates successfully for t stage  1 to 4  and demonstrates significant improvement in detecting t3 versus t4 differences compared to the 1983 system  the 1988 system applies equally for epidermoid cancer and other malignancies of the antrum  
class4	magnetic resonance in pediatric and adolescent neuroimaging  with improved availability and a practical understanding of the principles of utilization  mri will continue to replace ct and us in pediatric neuroimaging  just as it has impacted upon the more invasive modalities  in general  us remains the procedure of choice for screening of fetal and infant cns abnormalities  and ct continues as the principal screening modality beyond infancy and especially for acute  emergent presentations  mri has now emerged as a primary option for screening as well as for more definitive assessment of many intracranial and most intraspinal conditions  
class4	ulcerative colitis and colorectal cancer  a population based study  background  the risk of colorectal cancer is increased among patients with ulcerative colitis  the magnitude of this increase in risk and the effects of the length of follow up  the extent of disease at diagnosis  and age at diagnosis vary substantially in different studies  methods  to provide accurate estimates of the risk of colorectal cancer among patients with ulcerative colitis  we studied a population based cohort of 3117 patients given a diagnosis of ulcerative colitis from 1922 through 1983 who were followed up through 1984  results  ninety two cases of colorectal cancer occurred in 91 patients  as compared with the expected incidence  the incidence of colorectal cancer in the cohort was increased  standardized incidence ratio  ratio of observed to expected cases    5 7  95 percent confidence interval  4 6 to 7 0   less extensive disease at diagnosis was associated with a lower risk  for patients with ulcerative proctitis  the standardized incidence ratio was 1 7  95 percent confidence interval  0 8 to 3 2   for those with left sided colitis  2 8  95 percent confidence interval  1 6 to 4 4   and for those with pancolitis  extensive colitis  or inflammation of the entire colon   14 8  95 percent confidence interval  11 4 to 18 9   age at diagnosis and the extent of disease at diagnosis were strong and independent risk factors for colorectal cancer  for each increase in age group at diagnosis  less than 15 years  15 to 29 years  30 to 39 years  40 to 49 years  50 to 59 years  and greater than or equal to 60 years   the relative risk of colorectal cancer  adjusted for the extent of disease at diagnosis  decreased by about half  adjusted standardized incidence ratio   0 51  95 percent confidence interval  0 46 to 0 56   the absolute risk of colorectal cancer 35 years after diagnosis was 30 percent for patients with pancolitis at diagnosis and 40 percent for those given this diagnosis at less than 15 years of age  conclusions  close surveillance and perhaps even prophylactic proctocolectomy should be recommended for patients given a diagnosis of pancolitis  especially those who are less than 15 years of age at diagnosis  
class4	somatostatin receptor imaging in the localization of endocrine tumors background and methods  a number of different tumors have receptors for somatostatin  we evaluated the efficacy of scanning with 123i labeled tyr3 octreotide  a somatostatin analogue  for tumor localization in 42 patients with carcinoid tumors  pancreatic endocrine tumors  or paragangliomas  we then evaluated the response to octreotide therapy in some of these patients  results  primary tumors or metastases  often previously unrecognized  were visualized in 12 of 13 patients with carcinoid tumors and in 7 of 9 patients with pancreatic endocrine tumors  the endocrine symptoms of these patients responded well to therapy with octreotide  among 20 patients with paragangliomas  8 of whom had more than one tumor  10 temporal  tympanic or jugular   9 carotid  and 10 vagal tumors could be visualized  one small tympanic tumor and one small carotid tumor were not seen on the scan  conclusions  the 123i labeled tyr3 octreotide scanning technique is a rapid and safe procedure for the visualization of some tumors with somatostatin receptors  a positive scan may predict the ability of octreotide therapy to control symptoms of hormonal hypersecretion  
class4	the t 15 17  translocation of acute promyelocytic leukaemia fuses the retinoic acid receptor alpha gene to a novel transcribed locus  retinoic acid is a vitamin a derivative with striking effects on development and cell differentiation  several nuclear retinoic acid receptors  rars   acting as ligand inducible transcription factors  have been characterized and indirect evidence suggests that they have distinct roles  one of the most intriguing properties of retinoic acid is its ability to induce in vivo differentiation of acute promyelocytic leukaemia  apl  cells into mature granulocytes  leading to morphological complete remissions  because the rar alpha gene maps to chromosome 17q21  ref  14   close to the t 15 17   q21 q11 22  translocation specifically associated with apl  we analysed rar alpha gene structure and expression in apl cells  we report here that  in one apl derived cell line  the rar alpha gene has been translocated to a locus  myl  on chromosome 15  resulting in the synthesis of a myl rar alpha fusion messenger rna  using two probes located on either side of the cloned breakpoint  we have found genomic rearrangements of one or other locus in six patients out of eight  demonstrating that the rar alpha and or myl genes are frequently rearranged in apl and the breakpoints are clustered  these findings strongly implicate retinoic acid receptor alpha in leukaemogenesis  
class4	response of the lambert eaton myasthenic syndrome to treatment of associated small cell lung carcinoma  we evaluated the outcome in 16 patients with lambert eaton myasthenic syndrome  lems  associated with histologically verified small cell carcinoma  scc   thirteen patients received specific tumor therapy  chemotherapy  radiation therapy  or resection  and most also received pharmacologic and immunologic treatment for lems  seven of 11 patients surviving for more than 2 months after tumor therapy showed substantial neurologic improvement  1 patient being in complete remission at 7 years   in 3 of 11 improvement was transient  an emg index of disease severity  compound muscle action potential amplitude in abductor digiti minimi  was significantly increased at final follow up  p less than 0 01  n   11   a pretreatment amplitude greater than 3 0 mv was a good prognostic sign  we conclude that a combined treatment approach in scc lems usually results in neurologic improvement  
class4	effect of plasmapheresis on serum and csf autoantibody levels in cns paraneoplastic syndromes  we compared the effect of plasmapheresis on antineuronal autoantibody titers in the serum and csf of 3 patients with cns paraneoplastic syndromes  plasmapheresis reduced the serum autoantibody titer to 20  of the initial levels in the 3 patients  but the csf autoantibody titer decreased only in the patient with severe damage of the blood brain barrier  
class4	intraoperative radioimmunodetection of ovarian cancer using monoclonal antibody b72 3 and a portable gamma detecting probe  to assess the value of radioimmunoguided surgery in the intraoperative detection of ovarian cancer  we used monoclonal antibody b72 3  radiolabeled with 125i  and a hand held gamma detecting probe in 13 women with ovarian cancer undergoing exploratory laparotomy  b72 3  which recognizes a tumor associated glycoprotein  tag 72  was injected 12 29 days preoperatively  intraperitoneally in four cases  intravenously in nine  and by both routes in one   intraoperatively  the abdomen was surveyed with the probe and probe counts were correlated with biopsies and excised specimens studied by routine histologic stains  probe counts were positive in four of seven evaluable patients with histologically confirmed disease  in three of these four patients  the probe detected cancer in specimens interpreted as normal on frozen histologic sections  the probe also identified microscopic cancer in the one patient who had no gross disease  the specificity of the probe was 70   preoperative computed tomography was normal in all patients  including those with tumors as large as 3 cm  this pilot study shows the ability of radioimmunoguided surgery to detect occult ovarian cancer  
class4	computed tomography guided fine needle aspiration of retroperitoneal lymph nodes in gynecologic oncology  computed tomography guided fine needle aspiration was performed on 30 retroperitoneal lymph nodes in 29 patients with gynecologic cancer  there were no serious complications  review of the cytologic material demonstrated malignant cells in 83  of the aspirates  because the predictive value of a positive aspirate approaches 100   therapy for metastatic disease can be initiated in these patients with the need for an open biopsy  among five aspirates in which malignant cells were not seen  the cellularity of the specimen appeared to be the critical factor determining the predictive value of the aspirate  whereas neither of two patients with negative aspirates of adequate cellularity has developed recurrent disease  two of three patients with hypocellular negative aspirates have  because a hypocellular negative aspirate from a retroperitoneal lymph node may not be a true reflection of disease status  either repeat aspiration or open biopsy is advisable  
class4	prognostic factors for outcome of and survival after second look laparotomy in patients with advanced ovarian carcinoma  in ovarian cancer stages iib iv  pre treatment variables and variables obtained intraoperatively at second look laparotomy were investigated for their prognostic influence on the outcome of 109 patients and survival after second look laparotomy in 131 patients  the subjects came from a randomized trial of sequential versus alternating combination chemotherapy  the overall median survival after second look laparotomy was 62 months  logistic regression analysis identified stage and hysterectomy plus bilateral salpingo oophorectomy and omentectomy as significant prognostic covariates for second look laparotomy outcome  based on a cox multivariate stepwise analysis  independent prognostic factors for survival after second look laparotomy were secondary residual tumor size  pre treatment histologic differentiation grade  and performance status  a high differentiation grade and a good performance status at the start of therapy thus still had a prolonging effect on survival after second look laparotomy  the prognostic power of these pre treatment variables was increased substantially by the addition of the secondary residual tumor size variable  the 3 year survival rate after second look laparotomy for high  and low risk patients was 15 and 87   respectively  second look laparotomy thus provides prognostic information in patients with advanced ovarian carcinoma  but the benefit in terms of survival is still unclear  
class4	ovarian metastases are rare in stage i adenocarcinoma of the cervix  over a 32 year period at the university of california  los angeles medical center  all cases of adenocarcinoma and adenosquamous carcinoma of the uterine cervix were reviewed to determine the incidence of ovarian metastases in stage i disease  one of 25 patients  4 0   who underwent an exploratory laparotomy and radical hysterectomy had a microscopic ovarian metastasis  a literature review identified nine additional patients who had ovarian metastases and stage i adenocarcinoma of the cervix  including our series  the overall reported rate of ovarian metastases is 1 8   all ten patients had at least one of the following additional characteristics  they were postmenopausal  they had adnexal pathology  or they had positive pelvic lymph nodes  thus  ovarian preservation is warranted in premenopausal patients who do not have ovarian pathology or evidence of other metastatic disease at surgery  bilateral oophorectomy may be performed if frozen section examination of enlarged or suspicious nodes documents metastases  if the ovaries are left in the pelvis at the completion of the surgical procedure and microscopic spread to other pelvic tissues is documented  pelvic irradiation can be administered  
class4	the fallacy of the screening interval for cervical smears  one hundred seventy four women with invasive cervical carcinoma were interviewed about their cervical smear histories to assess the accuracy of self reporting and to relate the smear history with patient and tumor characteristics  patients reported significantly more frequent  more recent  and more normal smears than were documented in medical records  the interval between onset of cancer symptoms and previous smear correlated directly with advanced stage  sixteen women with normal smears within 36 months had significantly more advanced cancers than did 25 women with recent abnormal smears  women with recent normal and abnormal smears had similar sociodemographic and behavioral characteristics  because of inaccuracies in patients  self reported smear histories and cancers developing in women with recent normal smears  we conclude that a specific screening interval should not be relied upon  
class4	cold knife and laser conization for cervical intraepithelial neoplasia  in a 5 year study  425 women had conization performed for cervical intraepithelial neoplasia  cin  i  ii or iii  conization was performed only in cases of positive endocervical curettage or when colposcopy was inconclusive  in all other cases  local destruction was the operation of choice  in the early years of the study  conization was done by the cold knife method  n   201   whereas co2 laser was used in the latter part of the study  n   224   success and complication rates were the same for the two methods  abnormal cytology after conization was found in a total of 53 cases  12 5    but a histologic confirmation of residual or recurrent cin was made in only 27 women  6 4    this corresponds to a success rate of 92  after cold knife and 95  after laser conization  the cin grading of the residual or recurrent cin was similar to or less than the cin diagnosis of the cone  because our success rate was comparable to that of other series with much less strict referral criteria  our policy seems adequate  
class4	primary invasive carcinoma of the vagina  a retrospective review was conducted of 53 women with invasive carcinoma of the vagina and without documented exposure to diethylstilbestrol who were seen at the university of california irvine medical center  long beach memorial medical center  and saddleback memorial medical center from 1976 1988  forty seven  89   had squamous cell carcinoma and six  11   adenocarcinoma  thirty seven  70   were treated with whole pelvis irradiation and brachytherapy  nine with surgery alone  and the other seven with a combination of treatments  the crude and corrected 2 year survival rates for the entire group were 47 and 69   respectively  those with previous pelvic surgery were more likely to develop serious treatment related complications  there was a statistically significant correlation between previous hysterectomy and the diagnosis of primary invasive carcinoma of the vagina after the onset of symptoms  women diagnosed during routine examination  before symptom onset  tended to have a survival advantage  all women  including those who have had hysterectomy  should be counseled to continue gynecologic cancer surveillance regardless of age  
class4	does the treatment of genital condylomata in men decrease the treatment failure rate of cervical dysplasia in the female sexual partner  three hundred ninety women treated for cervical dysplasia by local tissue ablation were studied retrospectively to test the hypothesis that the treatment failure rate is lower if the male sexual partner is also treated  in 190 cases  the male sexual partner was examined and treated successfully for genital condylomata  controls were 200 women treated during the same time period and closely matched to the study group regarding age  race  socioeconomic status  histologic grade of dysplasia  distribution of the lesions  and methods of therapy  but the male partner was neither examined nor treated  the treatment failure rate for women whose partners were also treated was not significantly different from that for women whose partners were not treated  6 8 versus 7 5   p greater than  05   suggesting that treating genital condylomata in men does not affect the failure rate of cervical dysplasia in female sexual partners  
class4	carbon dioxide laser vaporization of diaphragmatic metastases for cytoreduction of ovarian epithelial cancer  three patients with international federation of gynecology and obstetrics state iiic ovarian adenocarcinoma underwent co2 laser vaporization of large volume  5 6 cm  and miliary right hemidiaphragmatic metastases at the conclusion of standard debulking surgery to effect optimal cytoreduction  destruction of diaphragmatic metastases was accomplished rapidly with no added morbidity or blood loss  the hand held co2 laser is a useful modality for removal of isolated large  and small volume diaphragmatic disease  particularly if only the peritoneum is involved  and avoids the morbidity that may accompany entry into the pleural space  
class4	removal of large symptomatic intrauterine growths by the hysteroscopic resectoscope  fifty three patients underwent 55 procedures with a resectoscope for the removal of large symptomatic intrauterine growths  the presenting complaint was menorrhagia  menometrorrhagia  or heavy postmenopausal bleeding in 38 patients  excessive menses plus infertility in 13 patients  and infertility alone in two patients  forty three patients had pedunculated or sessile submucous myomas and ten patients had large endometrial polyps  the long term results are based on 45 patients followed for longer than 1 year  excessive bleeding was controlled in 40 of the 43 women  93    failure to control abnormal bleeding was apparent within the first year  seven of the 12 infertility patients  58   delivered live born infants  five patients have undergone subsequent hysterectomies  9    two patients had repeat resectoscopic removal of myomas and two had subsequent non resectoscope myomectomies  no major complications were encountered  
class4	colposcopic survey of papanicolaou test negative cases with hyperkeratosis or parakeratosis  a colposcopic survey was performed in 269 consecutive women with negative cytology showing hyperkeratosis or parakeratosis  a colposcopy guided biopsy specimen of cervical abnormalities was taken in 88 cases  and human papillomavirus infection  hpv  was detected histologically in 25 cases  no cervical intraepithelial neoplasia  cin  was detected  the detection rate of hpv was not significantly different from that observed in a consecutive series of 1073 papanicolaou test negative subjects self referred for colposcopy  colposcopic screening of subjects showing hyperkeratosis or parakeratosis with otherwise negative smears is not recommended because it does not allow detection of cytologically false negative cin  
class4	detection  prevalence  and prognosis of asymptomatic carcinoma of the cervix  between 1979 1986  82 of 407 patients  20   treated for infiltrative carcinoma of the cervix were asymptomatic at the time of diagnosis  sixteen  20   of these 82 patients had stage ia  60  73   had stage ib  and six  7   had stage iia disease  asymptomatic patients represented 16 of 23  70   of stage ia  60 of 196  31   of stage ib  and six of 77  8   of stage iia  in the netherlands  population screening for cervical carcinoma is conducted on women aged 35 55 years  to examine the prevalence of asymptomatic cervical carcinoma and the way in which it was detected in different age groups  we studied the patients referred to our department  among the patients younger than 35 years with cervical carcinoma  20 of 70  29   were asymptomatic with disease detected by incidental screening  whereas eight of 177  5   in the group 55 years or older had been detected by incidental screening  in the age category 35 55 years  54 of 160  34   were asymptomatic  patients aged 35 55 years had undergone population screening or incidental screening  in the patients 55 years or older  asymptomatic disease was significantly less prevalent than in younger patients  only one of the 66 asymptomatic patients in stage ib or higher suffered tumor recurrence  among symptomatic patients  25 of 136  18   with stage ib and 17 of 71  24   with stage iia had tumor recurrence  despite the favorable prognosis of patients with asymptomatic carcinoma  asymptomatic presentation could not be shown to be a significant prognostic factor  as were tumor diameter and lymph node status  
class4	window operation  an alternative treatment method for bartholin gland cysts and abscesses recently  we developed the  window operation  as a more effective way to treat bartholin gland cysts and abscesses  the window operation was used to treat 25 bartholin cysts and 22 bartholin abscesses during a 3 year period from october 1  1986 to september 30  1989  under local anesthesia  a small piece of skin including the cyst wall was excised in an oval shape  and suturing was performed along the excised margin  postoperative antibiotics were given in cases of acute inflammation  a new mucocutaneous junction was observed at the 4 week postoperative checkup  no complications or recurrences have been observed during the study period  the window operation can be an alternative method of treatment for bartholin gland cysts or abscesses  
class4	vaginal mullerian cyst presenting as an anterior enterocele  a case report  a case is discussed of an extremely large vaginal mullerian cyst that presented as an anterior enterocele  sonographic and radiologic studies are described  the patient underwent operative excision of the cyst with reconstructive vaginoplasty  
class4	contemporary management of a potentially lethal fetal anomaly  a successful perinatal approach to epignathus  prenatal diagnosis of epignathus  a teratoma originating in the oropharynx  has been reported previously  however  in many of these cases the neonates succumbed to acute respiratory distress secondary to airway obstruction at the time of birth  we describe a case of antepartum diagnosis of epignathus using ultrasonography and magnetic resonance imaging as complementary techniques  the ability to accurately define the fetal anomaly permitted us to plan a unique strategy for peripartum management  after cesarean delivery of the infant from the uterus  the umbilical cord was not clamped and the fetoplacental circulation was left undisturbed  a tracheostomy was then performed  after which the umbilical cord was clamped and the infant was stabilized  several hours later  a debulking procedure was performed in the operating room to remove the tumor from its attachment to the bony palate  both mother and infant did well postoperatively  the ability to plan and perform a controlled tracheostomy while the infant remained oxygenated and ventilated proved to be lifesaving in this case  
class4	diabetes insipidus associated with craniopharyngioma in pregnancy  a case is presented of a pregnancy complicated by a suprasellar mass diagnosed at 27 weeks  gestation  this patient developed diabetes insipidus  which was successfully treated with 1 desamino 8 d arginine vasopressin  thyrotropin releasing hormone and acth stimulation tests were also abnormal  requiring the institution of thyroid and cortisol replacement therapy  the patient was delivered at 34 weeks  gestation secondary to worsening visual field testing  a craniotomy was performed in the postpartum period with removal of a craniopharyngioma  with successful medical treatment and careful observation  surgical intervention may be postponed until postpartum or until a gestational age with lower neonatal morbidity and mortality is reached  
class4	capillary hemangioma of the maxilla  a report of two cases in which angiography and embolization were used  this article presents two clinical cases of capillary hemangiomas of the maxilla  such lesions are rare  as demonstrated by the review of the literature included in this article  the presentation  differential diagnosis  histopathology  management  and follow up for each case are discussed  our rationale for approaching these types of lesions  as well as our opinion that microembolization should be considered as a first line approach to treatment  is presented  
class4	oral squamous cell carcinoma arising in a patient with long standing lichen planus  a case report  the risk of malignant transformation of oral lichen planus remains a controversial point  many previous reports have been discounted on the basis of inadequate information or lack of histologic confirmation of lichen planus  we report a well documented case of long standing cutaneous and oral lichen planus in which squamous cell carcinoma of the dorsal portion of the tongue occurred  there is an apparent difference in the sites of oral carcinomas in patients with lichen planus compared with the general population  this suggests that lichen planus increases the risk of oral cancer in affected sites  
class4	contiguous enlarged dental follicles with histologic features resembling the who type of odontogenic fibroma defective odontogenesis and or retarded eruption of teeth can be associated with histologic features akin to odontogenic fibroma in the dental follicles  unerupted mandibular premolar and molar teeth of a 24 year old man were surgically exposed  yet the teeth failed to erupt  about a year and a half later  radiographs indicated further enlargement of the follicle of the premolar  and both teeth were subsequently surgically removed  histologically  the follicles were composed of mature collagenous tissue among which epithelial islands and numerous clusters of calcified bodies were present  indirect immunofluorescence showed positive staining for type i and type iii collagen  which exhibited a sparse distribution  but not for the aminoterminal propeptide of type iii procollagen  the hamartomatous nature of the lesions is discussed with emphasis on their histologic resemblance to the who type of odontogenic fibroma  
class4	a dentist s dilemma  nonsurgical endodontic therapy or periapical surgery for teeth with apparent pulpal pathosis and an associated periapical radiolucent lesion  first presented is a brief review of nonsurgical versus surgical treatment of radicular cysts  this is followed by a consideration of the use of radiographs for differential diagnosis of periapical radiolucent lesions  some of the nonendodontic local and systemic lesions that can occur periapically are then presented  next examined are the fallibilities of pulp vitality testing methods  the need for histopathologic examination of periapical lesions is the subject of the next discussion  the dentist s dilemma is then examined  should teeth with apparent pulpal pathosis and an associated periapical radiolucent lesion have routine surgical treatment including biopsy or should they be treated nonsurgically and have periodic follow ups  a possible resolution of this dilemma is the final consideration  
class4	interferon activation of latent natural killer cells and alteration in kinetics of target cell lysis  clinical implications for oral precancerous lesions  reduced natural killer cell activity was observed in patients with oral leukoplakia and submucous fibrosis compared with normal control subjects  however  the number of target binding lymphocytes was found to be normal in these precancers  treatment of effector cells with interferon alpha resulted in highly elevated active killer cell activity  although no change was observed in target binding lymphocyte counts  this finding could imply that precytotoxic cells that are activated by interferon exist in peripheral blood or that direct recruitment of a new cell population takes place  in addition  altered target lysis kinetics was observed  with interferon activated killer cells demonstrating a tremendous lytic activation that is completed so quickly that a statistical kinetic analysis could not be accurately done  because natural killer cell activity is an important effector system in immunosurveillance against tumors  its modulation with interferon may be an exciting clinical possibility in the control of malignant transformation or oral precancers  
class4	tyrosine rich crystalloids in a polymorphous low grade adenocarcinoma  a polymorphous low grade adenocarcinoma with tyrosine rich crystalloid deposits is reported  the literature is reviewed  and diagnostic and histogenetic implications of this finding are discussed  
class4	periapical lesions of mandibular bone  difficulties in early diagnostics  it is often difficult to establish a correct diagnosis on the basis of initial clinical and roentgenologic symptoms in mandibular bone disease  in this paper these problems are discussed  and some suggestions are made to overcome them  the discussion is based on cases of osteogenic sarcoma  histiocytic lymphoma  and chronic osteomyelitis  the patients were a boy and two middle aged women  all of them with primary clinical symptoms of pain and swelling  diffuse roentgenologic changes in mandibular bone  uncertain response to treatment  and an unusual progress of the disease  
class4	preventing cervical cancer by treating genital warts in men  why male sex partners need androscopy  the increased incidence of cancer of the genitourinary and anorectal areas has been directly related to the coexistence of genital human papillomavirus infection  the diagnosis and treatment of condyloma acuminatum in men is important not only to prevent cancer but also to decrease the reservoir of virus that is being transferred to women  screening with androscopy  examination of male genitals with a colposcope after a vinegar solution has been applied to the skin  is indicated for all men who are at risk for this infection  treatment options include chemical application  cryosurgery  laser therapy  and interferon injections  to be effective  treatment must include both sexual partners  
class4	clinical recognition and evaluation of peptic ulcer disease  when a patient has epigastric pain that worsens 1 to 3 hours after meals  the possibility of peptic ulcer disease should be considered  completely typical clinical presentations in patients younger than age 50 justify empirical therapy when no physical or laboratory findings suggest a mimicking disorder  esophagogastroduodenoscopy should be undertaken when response to therapy is incomplete  symptoms recur quickly  or dyspeptic symptoms present for the first time in a patient older than age 50  when gastric ulcers are diagnosed radiographically  endoscopy and biopsy at multiple sites should be done to exclude malignant disease  intractable duodenal ulcers may necessitate endoscopic biopsy of antral and duodenal mucosa to rule out an associated helicobacter pylori infection  which may modify therapeutic approaches  zollinger ellison syndrome is rare but should be suspected when ulcer disease presents atypically or aggressively or in families  diagnosis is not difficult to confirm  
class4	new findings in treatment of colon cancer  patients with colon cancer involving regional lymph nodes  stage c disease  have a 5 year survival rate of only 30  to 40   and the majority die of recurrent disease  recent trials have shown increased survival rates with postoperative use of fluorouracil plus levamisole  the authors discuss these findings and the implications on treatment recommendations for stage c colon cancer  
class4	cloning of the cdna for human 12 lipoxygenase  a full length cdna clone encoding 12 lipoxygenase  arachidonate oxygen 12 oxidoreductase  ec 1 13 11 31  was isolated from a human platelet cdna library by using a cdna for human reticulocyte 15 lipoxygenase as probe for the initial screening  the cdna had an open reading frame encoding 662 amino acid residues with a calculated molecular weight of 75 590  three independent clones revealed minor heterogeneities in their dna sequences  thus  in three positions of the deduced amino acid sequence  there is a choice between two different amino acids  the deduced sequence from the clone plt3 showed 65  identity with human reticulocyte 15 lipoxygenase and 42  identity with human leukocyte 5 lipoxygenase  the 12 lipoxygenase cdna recognized a 3 0 kilobase mrna species in platelets and human erythroleukemia cells  hel cells   phorbol 12 tetradecanoyl 13 acetate induced megakaryocytic differentiation of hel cells and 12 lipoxygenase activity and increased mrna for 12 lipoxygenase  the identity of the cloned 12 lipoxygenase was assured by expression in a mammalian cell line  cos cells   human platelet 12 lipoxygenase has been difficult to purify to homogeneity  the cloning of this cdna will increase the possibilities to elucidate the structure and function of this enzyme  
class4	p53 mutations in colorectal cancer  immunohistological staining of primary colorectal carcinomas with antibodies specific to p53 demonstrated gross overexpression of the protein in approximately 50  of the malignant tumors examined  benign adenomas were all negative for p53 overexpression  to determine the molecular basis for this overexpression we examined p53 protein expression in 10 colorectal cancer cell lines  six of the cell lines expressed high levels of p53 in elisa  cell staining  and immunoprecipitation studies  direct sequencing and chemical mismatch cleavage analysis of p53 cdna by using the polymerase chain reaction in these cell lines showed that all cell lines that expressed high levels of p53 were synthesizing mrnas that encoded mutant p53 proteins  in two of those four cell lines where p53 expression was lower  point mutations were still detected  thus  we conclude that overexpression of p53 is synonymous with mutation  but some mutations would not be detected by a simple immunohistochemical analysis  mutation of the p53 gene is one of the commonest genetic changes in the development of human colorectal cancer  
class4	transforming growth factor beta stimulates mammary adenocarcinoma cell invasion and metastatic potential  the experimental metastatic potential of 13762nf mammary adenocarcinoma clone mtln3 was tested after pretreatment in serum free medium containing transforming growth factor  tgf  beta 1 at 0 5000 pg ml  lung colonies were measured 2 weeks after inoculation in syngeneic f344 rats  and a bell shaped dose response curve with 2  to 3 fold increase in number of surface lung metastases was seen  maximal enhancement occurred at the 50 pg ml dose level  the effect was specific because addition of neutralizing anti tgf beta antibody blocked the stimulatory activity at all levels of tgf beta 1 pretreatment  but when antibody was given alone  neutralizing anti tgf beta antibody had no effect on untreated cells  increased metastatic potential appears to be from an increased propensity of cells to extravasate as tested in the membrane invasion culture system  mtln3 cells penetrated reconstituted basement membrane barriers 2  to 3 5 fold more than did untreated control cells  depending upon length of tgf beta 1 exposure  increased invasive potential is apparently due  in part  to a 2  to 6 fold increase in type iv collagenolytic  gelatinolytic  and a 2 4 fold increase in heparanase activity  tgf beta 1 treatment of mtln3 cells did not alter their growth rate or morphology in the presence of serum  however  growth was inhibited in serum free medium  likewise  adhesion to human umbilical vein endothelial cell monolayers or to immobilized reconstituted basement membrane or fibronectin matrices was unchanged  these results suggest that tgf beta 1 may modulate metastatic potential of mammary tumor cells by controlling their ability to break down and penetrate basement membrane barriers  
class4	loss of heterozygosity on chromosomes 17 and 18 in breast carcinoma  two additional regions identified  the loss of heterozygosity  loh  at specific regions of the human genome in tumor dna is recognized as evidence for a tumor suppressor gene located within the corresponding region of the homologous chromosome  restriction fragment length polymorphism analysis of a panel of primary human breast tumor dnas has led to the identification of two additional regions on chromosomes 17q and 18q that frequently are affected by loh  deletions of each of these regions have a significant correlation with clinical parameters that are associated with aggressive breast carcinomas  previous restriction fragment length polymorphism analysis of this panel of tumors has uncovered several other frequently occurring mutations  loh on chromosome 18q frequently occurs in tumors with concomitant loh of loci on chromosomes 17p and 11p  similarly  tumors having loh on 17q also have loh on chromosomes 1p and 3p  this suggests that certain combinations of mutations may collaborate in the development and malignant progression of breast carcinomas  
class4	chemical carcinogenesis  too many rodent carcinogens  the administration of chemicals at the maximum tolerated dose  mtd  in standard animal cancer tests is postulated to increase cell division  mitogenesis   which in turn increases rates of mutagenesis and thus carcinogenesis  the animal data are consistent with this mechanism  because a high proportion  about half  of all chemicals tested  whether natural or synthetic  are indeed rodent carcinogens  we conclude that at the low doses of most human exposures  where cell killing does not occur  the hazards to humans of rodent carcinogens may be much lower than is commonly assumed  
class4	long term survival after chest wall reconstruction with musculocutaneous flaps  reconstruction of chest wall defects with musculocutaneous flaps permits resection of advanced chest wall tumors and of tissues severely damaged by radiotherapy in patients who in a previous era were not surgically treatable  to determine the long term outcome from this surgery  the records of 96 patients who had undergone chest wall resection with musculocutaneous flap reconstruction were reviewed  median survival for the entire group was 20 5 months  but a more accurate prediction of outcome could be obtained by dividing the patients into three groups  in group i  patients free of known malignancy and undergoing resection of radionecrotic tissues  median survival was 60 0 months  in group ii  patients with resectable disease and free of tumor following surgery  median survival was 31 1 months  in group iii  patients incompletely resected or known to have metastatic disease following surgery  median survival was only 12 5 months  even in group iii  however  some individuals achieved prolonged survival and lasting benefits from the surgery  so these data should not be used to exclude patients from undergoing necessary palliative procedures  
class4	a clinicopathological study of the paraneoplastic neuromuscular syndromes associated with lung cancer  the highest incidence of remote neuromuscular disorders in cancer has previously been reported in lung carcinoma  the clinical incidence of neuromuscular disorder was estimated and correlated with muscle histology and the histological type of lung tumour in 100 patients with lung carcinoma who were studied prospectively  thirty five patients had small cell carcinoma and 65 patients non small cell lung cancer  clinically  33 patients had a polymyopathy  of whom 18 had a cachectic myopathy and 15 had a proximal myopathy  two patients had lambert eaton myasthenic syndrome  one presented with dermatomyositis and one had evidence of ectopic acth production   cachexia was more common in non small cell cancer  proximal myopathy was more common in small cell cancer  ninety nine patients had abnormal muscle histology  74 had type ii atrophy  12 had type i and ii atrophy  one had type i atrophy and 12 had necrosis  the majority of patients were affected sub clinically and the clinical entities of cachectic and proximal myopathy did not correspond to previous pathological classifications  atrophy was not related to the duration of tumour symptoms  ageing  clinical type of myopathy or histological type of lung tumour  and was statistically different from that seen in controls  qualitatively  the presence of weight loss  muscle wasting and metastatic disease were not factors in the development of atrophy  similarly  necrosis was not related to the type of lung tumour  the presence of metastases  ageing  weight loss  muscle wasting  duration of tumour symptoms or the clinical form of myopathy  this study demonstrates that lung carcinoma has a direct effect on the motor unit  including atrophy  a necrobiotic myopathy and lambert eaton myasthenic syndrome  clinical assessment does not accurately assess the  remote  neuromuscular effects of cancer on the motor unit  
class4	oral findings in hiv infected patients attending a department of internal medicine  the contribution of intraoral examination towards the clinical management of hiv disease the occurrence of oral mucosal lesions was studied in 70 consecutive human immunodeficiency virus  hiv  infected patients  including 35 patients with aids  who had been admitted to a department of internal medicine  lesions of the oral mucosa were observed in 52 patients  74 per cent   oral candidiasis  50 per cent   hairy leukoplakia  14 per cent   periodontal disease  13 per cent   and oral kaposi s sarcoma  4 per cent  were the most common lesions  oral mucosal lesions suggestive of hiv infection were present in ten of 12 patients of unknown hiv status in whom pneumocystis carinii pneumonia was suspected  close cooperation between the medical and dental professions is recommended since accurate intraoral examination can make a valuable contribution towards the clinical management of hiv infected patients and may influence the cdc classification of this disease  
class4	a predominantly adrenaline secreting phaeochromocytoma  a 61 year old woman who presented with diabetes  nausea  weight loss and sweating was found to have a phaeochromocytoma secreting adrenaline  with a small amount of n methyladrenaline  there was no significant increase in noradrenaline secretion  she was normotensive  and developed profound hypotension in response to the alpha adrenergic antagonist phenoxybenzamine  these features are unusual in phaeochromocytoma  but similar features occurred in the very few previous reported cases of pure adrenaline secreting phaeochromocytoma  we conclude that it is important to identify such patients  so that they should not be given alpha adrenergic antagonist drugs  
class4	cervical lymph node metastasis  assessment of radiologic criteria  to estimate the accuracy of different radiologic criteria used to detect cervical lymph node metastasis in patients with head and neck carcinoma  seven different characteristics of 2 719 lymph nodes in 71 neck dissection specimens from 55 patients were assessed  three lymph node diameters  their location  their number  the presence of a tumor  and the amount of necrosis and fatty metaplasia were recorded  the minimal diameter in the axial plane was found to be the most accurate size criterion for predicting lymph node metastasis  a minimal axial diameter of 10 mm was determined to be the most effective size criterion  the size criterion for lymph nodes in the subdigastric region was 1 mm larger  11 mm   groups of three or more borderline nodes were proved to increase the sensitivity but did not significantly decrease the specificity  radiologically detectable necrosis  3 mm or larger  was found only in tumorous nodes and was present in 74  of the positive neck dissection specimens  shape was not a valuable criterion for the radiologic assessment of the cervical lymph node status  
class4	normal pituitary gland  coronal mr imaging of infundibular tilt  to determine the prevalence of pituitary infundibular deviation or tilt as a normal variant  coronal magnetic resonance  mr  images of 50 patients who had been examined for reasons other than pituitary disease were evaluated retrospectively  forty six percent of the patients had a more or less pronounced tilt of the pituitary stalk  this tilt was due to developmental lateral eccentricity of the pituitary gland in relationship to the midline of the brain in 34  and to ontogenic eccentric insertion of the pituitary infundibulum off the midline of the gland in the other 12   this high frequency of stalk deviation in patients without pituitary disease suggests that such displacement by itself should not be used to support the presence of pituitary microadenoma on mr images or computed tomograms  
class4	gd hp do3a in clinical mr imaging of the brain  as part of a phase ii clinical trial  14 patients with presumed intracranial neoplastic disease underwent magnetic resonance  mr  imaging before and after intravenous injection of gadolinium 1 4 7 tris carboxymethyl  10  2  hydroxypropyl  1 4 7 10 tetraazacycl ododecane  hp do3a   this neutral  nonionic  gadolinium chelate has lower osmolality  when formulated at equimolar concentrations  and superior in vitro stability compared with gadopentetate dimeglumine  the safety profile of gd hp do3a permitted administration of doses up to 0 3 mmol kg  three times the dose of gadopentetate dimeglumine approved by the u s  food and drug administration  in this limited clinical trial  gd hp do3a proved to be a safe and efficacious agent in mr imaging of the head  the only change documented in patient monitoring was that of slight skin redness at the injection site immediately after administration in two patients  no statistically significant changes due to administration of the agent were noted in laboratory evaluations  these results differ from those obtained with gadopentetate  which induces a transient rise in serum iron and bilirubin levels in up to 26  of patients  administration of higher doses of gd hp do3a  either 0 2 or 0 3 mmol kg  appeared to provide improved enhancement  no decrease in efficacy at these high doses was noted  
class4	temporal bone  three dimensional ct  part ii  pathologic alterations  three dimensional  3d  surface renderings were obtained from routine axial computed tomographic  ct  images in 15 patients with a variety of complex temporal bone abnormalities  the 3d ct reformations served as an adjunct to conventional sectional ct examination  while no diagnosis was substantially changed because of the 3d ct images  they did provide a more global perspective in cases of large tumors and fractures and at the postmastoidectomy site  three dimensional ct surface reformations are now practical and may be potentially useful for visualizing temporal bone lesions characterized by complex destructive change  
class4	primary ewing sarcoma  follow up with ga 67 scintigraphy  while avid accumulation of gallium 67 citrate and technetium 99m methylene diphosphonate  mdp  occurs initially in most cases of primary ewing sarcoma  uptake after therapy is less well defined  thirty patients with ewing sarcoma who underwent ga 67 and bone scintigraphy at diagnosis  at completion of therapy  and at relapse from 1978 to 1988 were evaluated  all 30 patients showed less primary site ga 67 activity following therapy  twenty three of 28 patients who underwent corresponding bone scintigraphy showed less uptake  but residual activity was usually more intense than with ga 67  avid reaccumulation of ga 67 occurred in four of five patients with primary site relapse  while patients who underwent bone scintigraphy showed less change  it was concluded that a greater decrease in ga 67 than in tc 99m mdp uptake often occurs in patients successfully treated for primary ewing sarcoma  information obtained at ga 67 scintigraphy is most likely to be helpful if results of bone scintigraphy remain abnormal or if occult relapse is suspected  
class4	vertebral hemangiomas  fat content as a sign of aggressiveness  thirty two vertebral hemangiomas  vhs  were evaluated with nonenhanced computed tomography  ct   t1 weighted magnetic resonance  mr  imaging  ct enhanced with contrast material  and selective spinal arteriography  the stroma between the osseous trabeculae was found to correspond to either fatty tissue or soft tissue or both  all 11 asymptomatic vhs showed complete fatty stroma at ct and increased signal intensity at mr imaging  in contrast  all four compressive vhs had soft tissue attenuation at ct  three compressive vhs showed low signal intensity on mr images  predominantly fatty stroma at ct and increased signal intensity at mr imaging were associated with normal or only slightly increased vascularization at selective spinal arteriography or contrast enhanced ct  while soft tissue stroma at ct and low signal intensity at mr imaging were associated with distinct hypervascularization  the authors  experience suggests that fatty vhs may represent inactive forms of vh  while soft tissue content at ct and low signal intensity at mr imaging may indicate a more active vascular lesion with potential to compress the spinal cord  ct and mr imaging may be especially valuable for evaluating patients with clinical signs or symptoms of uncertain origin and findings compatible with vh at plain radiography  
class4	prevalence of carcinoma in situ and other histopathological abnormalities in testes from 399 men who died suddenly and unexpectedly  to determine the prevalence of carcinoma in situ of the testis and other testicular histopathological abnormalities in the general male population  we examined gonads from 399 men 18 to 50 years old who died suddenly and unexpectedly  no sign of malignancy was found in any of these gonads  however  3 of the 399 men had been previously treated for testicular tumor or carcinoma in situ  thus  the over all prevalence of testicular neoplasia in the population studied was 0 8   95  confidence limits 0 2 to 2 2    this frequency is of the same magnitude as the lifetime risk of testicular cancer in the danish male population  the median weights of the left and right testes were 19 3 and 19 7 gm   respectively  this difference was statistically significant  p   0 00003   thus  our study confirmed that on average the left testis is smaller than the right testis  the median weight of the gonads collected in our study was 0 9 gm  lower than the weight of testes examined 40 years earlier at the same department of forensic medicine  however  this difference was not statistically significant  p   0 17   microscopic examination of the gonadal specimens revealed that 83  of the men exhibited complete spermatogenesis  including late spermatids in all tubules  in the age group studied we found no age related changes in testicular weight or in the proportion of tubules with degenerative changes  such as spermatogenic arrest  the sertoli cell only syndrome or hyalinization  
class4	application of the monoclonal antibody ki 67 on prostate biopsies to assess the fraction of human prostatic carcinoma  the feasibility of using the monoclonal antibody ki 67 as a proliferation marker in human prostatic carcinoma was studied on aspiration and core biopsy specimens obtained from 50 patients suspected of having prostate cancer  in 32 prostatic adenocarcinomas the ki 67 index varied from 0 3 to 13 3   mean 4 3  in cytological smears and from 0 8 to 17 8   mean 5 1  in frozen sections from histological core biopsies  no significant correlation between the percentage of cells positive for ki 67 and the histological tumor differentiation could be established  in 18 patients with benign prostatic hyperplasia the ki 67 index varied from 0 to 3 0   mean 1 2  and from 0 to 3 8   mean 1 4  in cytological and histological material  respectively  the differences in the observed ki 67 index between benign and malignant prostatic tissues are of statistical  p less than 0 001  and of clinical significance  nine patients who underwent endocrine treatment or radiotherapy entered a followup protocol in which the ki 67 staining procedure was applied to periodically obtained cytological aspiration biopsies  during month 1 after the start of therapy a statistically significant  p less than 0 05  decrease in the ki 67 index to 58  of the initial values was found  while at 2 and 3 months the proliferative fraction showed a further decrease to 27 and 7   respectively  as a marker  the monoclonal antibody ki 67 was shown to provide a reliable method to estimate the proliferative cell fraction of human prostate cancer  
class4	diagnostic accuracy and appropriateness of care for seborrheic keratoses  a pilot study of an approach to quality assurance for cutaneous surgery in 1985 there were more than 40 million visits for ambulatory surgical procedures in the united states  although benign cutaneous lesions are among the most frequent conditions to receive surgical treatment in ambulatory settings  their treatment is seldom subject to peer review  in this pilot study we assessed diagnostic accuracy and appropriateness of care using information available from the surgical pathology laboratory  we assessed these two measures of physician performance for 527 seborrheic keratoses removed by 133 clinicians affiliated with four different institutions  overall  a correct preoperative diagnosis was provided in only 49  of cases  dermatologists had the highest diagnostic accuracy  61  vs 35  for all other physicians   an appropriate procedure for the actual pathological diagnosis was performed in only 50  of cases  lesions with a correct preoperative diagnosis were more than eight times more likely to receive appropriate care  our data suggest that many clinicians fail to note a correct diagnosis of common cutaneous lesions before surgical removal  and many patients are treated with procedures that are more invasive than necessary for the final pathological diagnosis  because the approach used in this pilot study relies on data already available  it has promise as a low cost method of monitoring the quality of care of ambulatory surgery  
class4	gynecologic cancer in patients with subacute cerebellar degeneration predicted by anti purkinje cell antibodies and limited in metastatic volume  between 1982 and 1989  19 patients with gynecologic carcinoma  paraneoplastic cerebellar degeneration  and seropositivity for anti purkinje cell cytoplasmic antibodies were identified at our institution  seven of the patients had no clinical  computed tomographic  or magnetic resonance imaging evidence of cancer but had undergone laparotomy solely because anti purkinje cell antibodies were found in their serum  all had high grade adenocarcinoma  cerebellar symptoms preceded or coincided with the initial cancer diagnosis in 15 patients and preceded the diagnosis of recurrent cancer in 4 patients  the cancers were 14 ovarian  2 fallopian tube  2 surface papillary  and 1 poorly differentiated metastatic adenocarcinoma in a periaortic lymph node  two remarkable surgical observations in patients with high grade ovarian and tubal cancers were the conspicuous lack of peritoneal implants and the small metastatic volume  a comparison of the 8 patients who had primary stage iii cancer with 24 matched control patients without paraneoplastic cerebellar degeneration revealed no difference in primary tumor volume but a significantly smaller volume of metastatic tumor in the seropositive group  p   0 05   anti purkinje cell antibodies were not detected in 111 neurologically normal patients with advanced ovarian cancer  the small metastatic volume in the face of high grade and advanced stage malignancy in seropositive patients with paraneoplastic cerebellar degeneration suggests that an immune response to the tumor  presumably cross reactive with cerebellar cells  may impair the metastatic process  earlier diagnosis and treatment of cancer  based on prompt serologic testing  may offer an improved neurologic and oncologic prognosis  
class4	endorectal ultrasonographic staging of rectal carcinoma  endorectal ultrasonography is a valuable imaging method for examination of the rectum and perirectal tissues  we assessed 50 patients with known rectal carcinoma prospectively by using a 7 0 mhz endorectal transducer to determine the depth of invasion of the rectal wall by tumor and the presence of lymphadenopathy  tumors were staged by using the astler coller modification of the dukes staging system  and the results were compared with histologic staging of the surgical specimen  ultrasonography had an accuracy of 80   a sensitivity of 92   and a specificity of 76  for detection of invasion of the perirectal fat  ultrasonography was sensitive in the detection of perirectal lymphadenopathy but was not specific in distinguishing benign from malignant nodes  
class4	tumor angiogenesis and metastasis  correlation in invasive breast carcinoma  background  experimental evidence suggests that the growth of a tumor beyond a certain size requires angiogenesis  which may also permit metastasis  to investigate how tumor angiogenesis correlates with metastases in breast carcinoma  we counted microvessels  capillaries and venules  and graded the density of microvessels within the initial invasive carcinomas of 49 patients  30 with metastases and 19 without   methods  using light microscopy  we highlighted the vessels by staining their endothelial cells immunocytochemically for factor viii  the microvessels were carefully counted  per 200x field   and their density was graded  1 to 4    in the most active areas of neovascularization  without knowledge of the outcome in the patient  the presence or absence of metastases  or any other pertinent variable  results  both microvessel counts and density grades correlated with metastatic disease  the mean      sd  count and grade in the patients with metastases were 101     49 3 and 2 95     1 00 vessels  respectively  the corresponding values in the patients without metastases were significantly lower  45     21 1 and 1 38     0 82  p   0 003 and p less than or equal to 0 001  respectively   for each 10 microvessel increase in the count per 200x field  there was a 1 59 fold increase in the risk of metastasis  95 percent confidence interval  1 19 to 2 12  p   0 003   the microvessel count and density grade also correlated with distant metastases  for each 10 microvessel increase in the vessel count per 200x field  there was a 1 17 fold increase in the risk of distant metastasis  95 percent confidence interval  1 02 to 1 34  p   0 029   conclusions  the number of microvessels per 200x field in the areas of most intensive neovascularization in an invasive breast carcinoma may be an independent predictor of metastatic disease either in axillary lymph nodes or at distant sites  or both   assessment of tumor angiogenesis may therefore prove valuable in selecting patients with early breast carcinoma for aggressive therapy  
class4	an epidemiologic study of abuse of analgesic drugs  effects of phenacetin and salicylate on mortality and cardiovascular morbidity  1968 to 1987  background  phenacetin abuse is known to produce kidney disease  salicylate use is supposed to prevent cardiovascular disease  we conducted a prospective  longitudinal epidemiologic study to examine the effects of these drugs on cause specific mortality and on cardiovascular morbidity  methods  in 1968 we evaluated a study group of 623 healthy women 30 to 49 years old who had evidence of a regular intake of phenacetin  as measured by urinary excretion of its metabolites  and a matched control group of 621 women  salicylate excretion was also measured  all subjects were examined over a period of 20 years  results  life table analyses of mortality during the 20 years  with adjustment for the year of birth  cigarette smoking  and length of follow up  revealed significant differences between the groups in overall mortality  study group vs  control group  74 vs  27 deaths  relative risk  2 2  95 percent confidence interval  1 5 to 3 3   deaths due to urologic or renal disease  relative risk  16 1  95 percent confidence interval  3 9 to 66 1   deaths due to cancer  relative risk  1 9  95 percent confidence interval  1 1 to 3 3   and deaths due to cardiovascular disease  relative risk  2 9  95 percent confidence interval  1 5 to 5 5   the relative risk of cardiovascular disease  fatal or nonfatal myocardial infarction  heart failure  or stroke  was 1 8  and the 95 percent confidence interval 1 3 to 2 6  the odds ratio for the incidence of hypertension was 1 6  and the 95 percent confidence interval 1 2 to 2 1  the effects of phenacetin on morbidity and mortality  with adjustment for base line salicylate excretion  were similar  in contrast  salicylate use had no effect on either mortality or morbidity  conclusions  regular use of analgesic drugs containing phenacetin is associated with an increased risk of hypertension and mortality and morbidity due to cardiovascular disease  as well as an increased risk of mortality due to cancer and urologic or renal disease  the use of salicylates carries no such risk  
class4	human t cell leukemia virus type i infection as an oncogenic and prognostic risk factor in cervical and vaginal carcinoma  the seroprevalence of human t cell leukemia virus type i  htlv i  antibody in 6701 healthy females and 226 women with gynecologic malignancies  all living in an adult t cell leukemia endemic area in southwestern japan  was investigated to determine whether htlv i infection was a risk factor influencing oncogenesis and prognosis  the seroprevalences in cervical carcinoma patients younger than 59 years and in vaginal carcinoma patients of all ages were significantly higher than in age matched healthy controls  the ratios of observed to expected htlv i seroprevalence in patients younger than 59 with cervical carcinoma and in vaginal carcinoma patients were 2 92 and 7 36  respectively  among the patients with cervical carcinoma or vaginal carcinoma  the tumor recurrence rate in htlv i carriers was significantly higher than that in htlv i seronegative patients  our results suggest that htlv i infection may be oncogenic and may affect the prognosis in some patients with cervical or vaginal carcinoma  
class4	flow cytometric analysis of dna content in partial hydatidiform moles with persistent gestational trophoblastic tumor  hydatidiform moles may be classified as partial or complete based on genetic and pathologic criteria  between january 1979 and january 1990  17  5 5   of 310 patients followed for partial mole developed persistent gestational trophoblastic tumor  tissues from 14 partial moles were available for flow cytometric analysis of dna content  eleven partial moles  85   were triploid  two  15   were diploid  and one dna histogram was uninterpretable  all patients with triploid partial moles achieved complete remission with one course of single agent chemotherapy  the two with diploid partial mole required multiple courses of chemotherapy to achieve gonadotropin remission  although the dna content of most partial moles with persistent gestational trophoblastic tumor was triploid  diploid partial moles with persistent tumor were less sensitive to single agent chemotherapy  
class4	appendectomy in primary and secondary staging operations for ovarian malignancy  appendectomy was performed at primary or secondary staging operations in 100 patients with ovarian malignancies  of 80 patients who underwent appendectomy at the time of their primary surgery  25  31 2   had appendiceal metastases  among 47 patients who were believed to have disease limited to the pelvis at the time of surgery  stage i  n   34   ii  n   7   iiia  n   5   and those designated stage iiic solely on the basis of microscopic para aortic nodal metastasis  n   1   the appendix was involved with disease in only two patients  4 3    however  among 33 patients with advanced disease  stage iiib  n   6   iiic except those designated iiic solely on the basis of microscopic paraaortic nodal metastasis  n   19   and iv  n   8   the appendix was involved with disease in 23 patients  69 7    p less than  001   poorly differentiated tumors and serous histologic cell types more frequently metastasized to the appendix  64  15  6  and 8  for grades 3  2  and 1 and borderline histology  respectively  p less than  001  and 48  13  and 8  for serous  endometrioid  and mucinous  p less than  001   of 20 patients who underwent appendectomy at their secondary staging procedure  two had metastases  metastatic disease in the appendix was microscopic in nine of 27 patients  because the frequency of appendiceal metastasis is similar to that of other metastatic sites in stages i and ii ovarian cancer  it should be removed at primary staging procedures  appendectomy should also be performed in patients with advanced ovarian malignancies if it contributes to cytoreduction or at the time of secondary staging procedures  
class4	rhabdomyosarcoma of the ciliary body  rhabdomyosarcoma is the most common malignant orbital tumor of childhood  it has twice been reported to arise within the globe from the iris  in addition  teratoid medulloepithelioma  a tumor arising from the ciliary epithelium  can contain a rhabdomyoblastic component  often in combination with other heteroplastic elements  the authors report what may be the first recorded case of an embryonal rhabdomyosarcoma of the ciliary body  possibly representing a one sided differentiation of a malignant teratoid medulloepithelioma  
class4	cystic adenoma of the pigmented ciliary epithelium  clinical  pathologic  and immunohistopathologic findings  a 51 year old white man was found to have a deeply pigmented mass in the ciliary body and peripheral choroid of his right eye with an associated vitreous hemorrhage  although the tumor appeared to be a ciliochoroidal melanoma  a melanocytoma and adenoma of the pigment epithelium also were considered in the differential diagnosis  the tumor was removed by a large partial lamellar sclerocyclochoroidectomy  results of histopathologic evaluation showed a cystic adenoma of the pigmented ciliary epithelium  to the authors  knowledge  this was the first immunohistopathologic study of this tumor  results of the study showed marked immunoreactivity for low molecular weight cytokeratins  vimentin  and s 100 protein  these immunohistochemical studies are consistent with the origin of this tumor from pigment epithelial cells  
class4	evaluation of argon laser surgery in children under 13 years of age  argon laser surgery is an effective treatment for ectasias and congenital port wine stains  however  its use in children under the age of 13 is controversial  this paper reviews 202 children under the age of 13 who underwent argon laser treatments for congenital port wine stains  spider angiomas  epidermal nevi  and lentigines  the clinical characteristics of port wine stains in 170 children are discussed  good to excellent results  moderate to complete clearing  in port wine stains were obtained in 60 percent of patients and seemed to correlate best with lack of blanchability on pressure  hypertrophic scarring was seen in only 7 children  all of whom had undressed wounds  no significant scarring has been seen in any subsequent child who had maintained a dressed wound postoperatively  
class4	hepatocellular carcinoma within siderotic regenerative nodules  appearance as a nodule within a nodule on mr images  large regenerative nodules in cirrhotic livers may accumulate iron and develop internal iron poor foci of hyperplasia or malignancy  magnetic resonance examinations were performed on 23 patients with biopsy proved cirrhosis  a  nodule within nodule  appearance was noted in two patients  this appearance consisted of markedly low intensity of a large nodule on gradient echo images  with one or two internal foci that were isointense to the liver  each of the large nodules was 2 cm in diameter  and each of the internal foci was less than 1 cm  serum alpha fetoprotein levels were normal in both patients  aspiration biopsy performed in one patient failed to show malignancy  but histologic confirmation of hepatocellular carcinoma was obtained eventually in both cases  the nodule within nodule sign  which reflects the unique histopathology of hepatocellular carcinoma in large siderotic regenerative nodules  is strongly suggestive of early hepatocellular carcinoma  even if serologic markers and biopsy results do not support this diagnosis  
class4	invasive lobular carcinoma  mammographic findings in a 10 year experience from january 1  1976 to december 30  1985  1 966 cases of breast carcinoma were diagnosed and treated at malmo general hospital  malmo  sweden  of these cases  185  9 4   involved invasive lobular carcinoma  ilc   mammography in 137 cases demonstrated the following findings  spiculated opacity  53    architectural distortion  16    poorly defined opacity  7    normal or benign findings  16    and parenchymal asymmetry  4    radiographic definition of the ilc lesion varied greatly with projection  the craniocaudal view demonstrated significant findings more frequently than either the oblique or lateral views  secondary radiographic findings were present in 31   microcalcifications were rare  and physical findings were present in 89   because of its diffuse growth pattern and tendency to form lesions with opacity equal to or less than that of the parenchyma  ilc can be extremely difficult to detect mammographically  therefore  the radiologist must be alert for subtle mammographic signs of malignancy and highly suspicious of any abnormal physical findings regardless of the mammographic appearance  
class4	mammographic follow up of low suspicion lesions  compliance rate and diagnostic yield  all recommendations for mammographic follow up of low suspicion lesions seen at mammography during a 6 month period were reviewed to establish compliance rate and eventual outcome  one hundred forty four of 2 650 mammograms  5   showed minimal abnormalities that warranted short term and periodic mammographic follow up  rates of compliance at 4 months and at 1  2  and 3 years were 88   71   60   and 47   respectively  progressive mammographic change was found in 10 patients  only one of whom had a carcinoma  it was concluded that mammographic follow up of low suspicion lesions is a reasonable alternative to surgical biopsy  although patient compliance remains a significant problem  
class4	immediate postoperative mammogram for failed surgical excision of breast lesions in a series of 200 consecutive preoperative needle localizations of non palpable breast lesions  128 lesions  64   were calcified and 72 lesions  36   were noncalcified on preoperative mammograms  radiographs of the surgical specimen failed to confirm excision of 11 lesions  5 5    seven calcified and four noncalcified  these 11 patients were taken directly from the surgical suite to the radiology suite  where an immediate postoperative mammogram was obtained  in five patients  2 5    immediate postoperative mammograms showed surgical failure with the lesion still present  in six patients  3 0    immediate postoperative mammograms showed that the lesion had been removed  even though the lesion had not been identified on surgical specimen radiographs  no errors occurred in the interpretation of immediate postoperative mammograms  a fact corroborated by examination of surgical specimens obtained at repeat surgery in three patients and identification of skin calcifications in two patients  and with follow up mammograms in six patients  whenever a discrepancy between preoperative localization radiographs and surgical specimen radiographs exists  the authors suggest immediate postoperative mammography to improve the diagnostic process  
class4	data compression  effect on diagnostic accuracy in digital chest radiography  high resolution digital images make up very large data sets that are relatively slow to transmit and expensive to store  data compression techniques are being developed to address this problem  but significant image deterioration can occur at high compression ratios  in this study  the authors evaluated a form of adaptive block cosine transform coding  a new compression technique that allows considerable compression of digital radiographs with minimal degradation of image quality  to determine the effect of data compression on diagnostic accuracy  observer tests were performed with 60 digitized chest radiographs  2 048 x 2 048 matrix  1 024 shades of gray  containing subtle examples of pneumothorax  interstitial infiltrate  nodules  and bone lesions  radiographs with no compression  with 25 1 compression  and with 50 1 compression ratios were presented in randomized order to 12 radiologists  the results suggest that  with this compression scheme  compression ratios as high as 25 1 may be acceptable for primary diagnosis in chest radiology  
class4	biologic aggressiveness of palpable and nonpalpable prostate cancer  assessment with endosonography  the biologic aggressiveness of palpable versus nonpalpable prostate cancer was evaluated in 666 patients studied with endosonography over a 24 month period  biologic aggressiveness was defined by a combined histologic and grade stage category score  in 314 patients suspected of having prostate cancer 328 biopsies were performed  carcinoma was detected in 99 patients  by means of both palpation and endosonography  n   80   endosonography alone  n   9   and palpation alone  n   8   two cancers were not detected with either palpation or endosonography  all patients with normal results of digital examination had a combined grade stage category score lower than 9  fifty five of 69 patients  80   with abnormal results of digital examination and available histologic data had a histologic score of 6 or higher  38 of these patients  69   had a combined grade stage category score of 9 or higher  although the number of patients is small  these data suggest that nonpalpable cancers are biologically less aggressive than palpable ones and that the advantage of endosonography over palpation in detection of clinically significant cancers is limited  
class4	congenital cystic disease of the seminal vesicle  thirteen cases of congenital seminal vesicle cysts with pathologic correlation were diagnosed between 1970 and 1988  twelve of the 13 patients had ipsilateral renal anomalies  intravenous urography  performed in 11 of the 13 patients  demonstrated associated renal anomalies  computed tomography  performed in nine of the 13 patients  demonstrated associated renal anomalies and displayed the cystic seminal vesicles  transabdominal or endorectal ultrasonography  performed in eight patients  allowed characterization of the seminal vesicle masses as cystic  magnetic resonance imaging  performed in three of the 13 patients  accurately demonstrated dilated ejaculatory ducts into which ectopic ureters inserted  the fluid in the seminal vesicle cysts had an increased signal intensity on t1  and t2 weighted sequences  seminal vesiculographic study demonstrated anomalous communications with the seminal tract  cystic disease of the seminal vesicles can be either congenital or acquired  congenital cysts are associated with anomalies of the ipsilateral mesonephric duct  
class4	insulinomas  localization with selective intraarterial injection of calcium  to facilitate the noninvasive preoperative localization of islet cell tumors less than 15 mm in diameter  the authors examined the use of calcium as an insulin secretagogue in an arterial stimulation venous sampling  asvs  technique  in four patients with episodic hypoglycemia  calcium gluconate  0 01 0 025 meq ca2  kg  was injected directly into branches of the celiac plexus  gastroduodenal  splenic  and hepatic arteries  and the superior mesenteric artery  in all patients  serum levels of insulin rose abruptly in blood samples taken from the right hepatic vein 30 and 60 seconds after the infusion of calcium into the artery supplying the tumor  injection into an artery not supplying the tumor did not result in a similar rise  accurate localization of the insulinomas was verified at surgery in three patients  in the fourth patient  who did not undergo surgery  arteriographic results were positive for insulinoma at the predicted site  on the basis of these results  the authors believe noninvasive asvs may replace invasive portal venous sampling as the most effective method for the localization of occult insulinomas  
class4	complications of percutaneous abdominal fine needle biopsy  review  to determine whether the increasing use of percutaneous fine needle biopsy of abdominal lesions is associated with an increase in serious complications  the author updated a literature search and evaluated a questionnaire  distributed among selected hospitals in the united states in 1986 and 1987  that followed up a questionnaire distributed in 1983  the updated literature review revealed a total of 24 deaths and 20 needle tract seedings  the updated questionnaire revealed five deaths after 16 381 biopsies  0 031    whereas the previous questionnaire had shown four deaths after 63 108 biopsies  0 006    two similar european questionnaires revealed mortality rates of 0 008  and 0 018   respectively  of the total of 33 deaths  21 involved biopsies of liver lesions  six involved pancreatic biopsies  seventeen of the 21 deaths after liver biopsies were secondary to hemorrhage  five of the six deaths after pancreatic biopsies were due to pancreatitis  of the 23 instances of needle tract seeding  10 occurred after biopsies of pancreatic malignancies  the frequencies of needle tract seeding in the four questionnaires were 0 005   0 006   0 003   and 0 009   respectively  although infrequent  serious complications may be associated with this procedure  the author makes suggestions that may help minimize them  
class4	selective catheterization of the inferior petrosal sinuses  new catheter design  catheters for selective catheterization of the right and left inferior petrosal sinuses have been developed to replace the complex tip deflector catheter guide wire system currently used  the new catheters are easily formed from commonly available straight catheters with the use of steam  they have been successfully tested in 22 patients  the only complications were minor groin hematomas  
class4	petrosal sinus sampling  technique and rationale  bilateral simultaneous sampling of the inferior petrosal sinuses is an extremely sensitive  specific  and accurate test for diagnosing cushing disease and distinguishing between that entity and the ectopic acth syndrome  it is also valuable for lateralizing small hormone producing adenomas within the pituitary gland  the inferior petrosal sinuses connect the cavernous sinuses with the ipsilateral internal jugular veins  the anatomy of the anastomoses between the inferior petrosal sinus  the internal jugular vein  and the venous plexuses at the base of the skull varies  but it is almost always possible to catheterize the inferior petrosal sinus  in addition  variations in size and anatomy are often present between the two inferior petrosal sinuses in a patient  advance preparation is required for petrosal sinus sampling  teamwork is a critical element  and each member of the staff should know what he or she will be doing during the procedure  the samples must be properly labeled  processed  and stored  specific needles  guide wires  and catheters are recommended for this procedure  the procedure is performed with specific attention to the three areas of potential technical difficulty  catheterization of the common femoral veins  crossing the valve at the base of the left internal jugular vein  and selective catheterization of the inferior petrosal sinuses  there are specific methods for dealing with each of these areas  the sine qua non of correct catheter position in the inferior petrosal sinus is demonstration of reflux of contrast material into the ipsilateral cavernous sinus  images must always be obtained to document correct catheter position  special attention must be paid to two points to prevent potential complications  the patient must be given an adequate dose of heparin  and injection of contrast material into the inferior petrosal sinuses and surrounding veins must be done gently and carefully  when the procedure is performed as outlined  both inferior petrosal sinuses can be catheterized in more than 98  of patients  the complication rate is low  and the theoretical risk of major morbidity or death is less than 1   neither has yet occurred  to our knowledge   the most common complication is groin hematoma  
class4	liver and pancreas  improved spin echo t1 contrast by shorter echo time and fat suppression at 1 5 t  t1 weighted spin echo magnetic resonance  mr  images have had limited soft tissue contrast at 1 5 t  the authors investigated the effects of echo time  te  minimization and fat suppression on mr images of the liver and pancreas  two sets of mr images were obtained with identical repetition times and other parameters  in 10 subjects with seven liver lesions  images with tes of 20 and 12 msec were compared  in 18 additional subjects with seven liver lesions and five pancreatic carcinomas  images with identical tes but with and without fat suppression were compared  contrast to noise ratios  cnrs  were greater with a te of 12 msec than with a te of 20 msec for liver versus spleen  7 6 vs 4 9  p    014  and liver versus lesion  6 9 vs 3 9  p    031   in patients without fatty liver  cnr for six lesions versus liver was greater  9 5 vs 6 0  p    014  with fat suppression  cnr between glandular pancreas and cancer was most conspicuous with fat suppression  but fat planes were less distinct  minimization of te improves t1 weighted images significantly  fat suppression also improves cnr  but the disadvantages of fat suppression do not allow elimination of conventional t1 weighted images  
class4	mr imaging of blood borne liver metastases in mice  contrast enhancement with fe ehpg  to determine whether iron iii ethylenebis  2 hydrophenylglycine   fe ehpg   a prototype hepatobiliary magnetic resonance imaging agent  can enhance the liver to tumor contrast to noise ratio  c n  in models of liver tumors in mice  two types of cell inoculation were used  intrahepatic implantation of m5076 sarcoma and intrasplenic injection of colon tumor  c 26  or m5076 sarcoma  significant enhancement of the liver to tumor c n and or improved visualization of small lesions was consistently observed on t1 weighted images obtained after injection of the contrast material  for intrahepatic implants  the c n on postinjection t1 weighted images was superior to that on t1  and t2 weighted preinjection images  for the c 26 metastatic liver lesions of larger diameter  greater than 5 mm   the c n on postinjection t1 weighted studies was superior to that on preinjection t1 weighted images but was comparable to that on preinjection t2 weighted images  however  higher c n after administration of fe ehpg improved visualization of medium sized  3 5 mm  and small  1 3 mm  metastatic lesions in both m5076 and c 26 models  these results demonstrate that mr imaging with appropriate hepatobiliary agents appears promising for early detection of liver metastases  
class4	pancreatic cancer versus chronic pancreatitis  diagnosis with ca 19 9 assessment  us  ct  and ct guided fine needle biopsy  the authors prospectively performed serum ca 19 9 assessment  ultrasound  us   computed tomography  ct   and ct guided fine needle aspiration biopsy  fnab  of the pancreas in 81 consecutive patients with suspected chronic pancreatitis or pancreatic neoplasm  the final diagnosis was pancreatic cancer in 54 patients and chronic pancreatitis in 27 patients  ca 19 9 assessment  us  ct  and fnab were considered nondiagnostic  respectively  in 0   25   19   and 6  of cases  when a definite diagnosis was rendered  the positive predictive value was 90  for ca 19 9 assessment  95  for us  98  for ct  and 100  for fnab  the negative predictive value was  respectively  69   95   86   and 100   the accuracy of all diagnostic and nondiagnostic studies was 81  for ca 19 9 assessment  72  for us  77  for ct  and 94  for fnab  it is concluded that ct guided pancreatic fnab is the most reliable examination for enabling differential diagnosis of pancreatic cancer and chronic pancreatitis  when the pancreas is well visualized at us  the negative predictive value for pancreatic cancer is more accurate than that of ca 19 9 assessment and ct  
class4	primary bone tumours of the thoracic skeleton  an audit of the leeds regional bone tumour registry  an audit of the leeds regional bone tumour registry found that primary bone tumours of the thoracic skeleton constituted 90 of the 2004 cases  4 5    thirty seven per cent occurred in the ribs  32  in the scapulae  11  in the thoracic vertebrae  11  in the sternum  and 9  in the clavicles  malignant tumours were more common than benign  54 v 36  and occurred in an older population  mean ages 47 and 31 years   the scapula was the most common site for malignant lesions and the ribs the most common site for benign tumours  chondrosarcoma was the commonest tumour in older patients  fibrous dysplasia and plasmacytoma in the middle age group  and eosinophilic granuloma in children  presenting symptoms were a poor guide to whether the lesion was malignant or not  this and the small proportion of correct preoperative diagnoses indicate the need for early biopsy  bone tumour registries provide a valuable source of cumulative information about uncommon tumours and facilitate accurate diagnosis  teaching  and research  
class4	adult respiratory distress syndrome after limited resection of adenocarcinoma of the lung  two cases of the adult respiratory distress syndrome developed after limited resection for lung carcinoma  no other known precipitants were evident  the adult respiratory distress syndrome is a clinical expression of acute lung injury that may arise from various insults and include air and blood borne factors  tumour related blood borne factors may have contributed to lung injury in these cases  
class4	specific binding sites for insulin like growth factor i in the ovarian stroma of women with polycystic ovarian disease and stromal hyperthecosis  women with polycystic ovarian disease and hyperthecosis have hyperinsulinemia and insulin resistance  it is possible that insulin in supraphysiologic concentration exerts its steroidogenic action on ovarian stromal cells through insulin like growth factor i receptors  we undertook this study to investigate whether the ovarian stroma of women with hyperthecosis has specific binding sites for insulin or insulin like growth factor i  ovarian stromal tissue was obtained from seven women with normal ovulatory cycles and from five women with hyperthecosis of the ovaries  binding studies with insulin tagged with iodine 125 and insulin like growth factor i tagged with iodine 125 revealed specific binding sites both for insulin and insulin like growth factor i in the ovarian stroma  the binding of insulin tagged with iodine 125 in the ovarian stroma of women with hyperthecosis  3 4      1 1       se  per 100 micrograms protein  was significantly  p less than 0 04  lower than that observed in normal premenopausal women  8 3      1 6  per 100 micrograms protein   by contrast  the specific binding of insulin like growth factor i tagged with iodine 125 in the ovarian stroma of women with hyperthecosis  7 1      1 7  per 100 micrograms protein  was higher than that observed in the ovarian stroma from normal women  4 5      1 7  per 100 micrograms protein   although the difference was not statistically significant  the affinity constants for these high affinity receptors were similar  1 2 to 3 6 x 10 9  l mol  in the two groups of women  these results indicate that  1  the ovarian stroma has specific binding sites both for insulin and for insulin like growth factor i   2  in women with hyperthecosis  the ovarian stroma has decreased binding sites for insulin but has normal concentrations of insulin like growth factor i receptors  and  3  in women with hyperthecosis  stimulation of ovarian androgen synthesis by insulin may be mediated through the insulin like growth factor i receptors  
class4	evidence of heterogeneous mechanisms in lipoprotein lipid alterations in hyperandrogenic women  fifty one hyperandrogenic women had their lipoprotein lipid profiles determined  free and albumin bound testosterone was associated with triglycerides and with high density lipoprotein cholesterol independent of fasting insulin levels  percent ideal body weight  and waist hip ratio  to gain insight into mechanisms of these lipid alterations  the women were subgrouped according to apparent source of androgen excess  whereas all groups had low levels of high density lipoprotein 2 cholesterol and high triglyceride concentrations  only in those with high luteinizing hormone to follicle stimulating hormone ratios was free and albumin bound testosterone associated with triglycerides and high density lipoprotein cholesterol independent of fasting insulin levels  relationships between percent ideal body weight and waist hip ratios  free and albumin bound testosterone  sex hormone binding globulin  fasting insulin and 2 hour insulin levels and blood pressure are not significant in all subgroups  suggesting differing endocrinological influences and differing mechanisms for lipoprotein lipid alterations  
class4	which clinical variables predict an abnormal double contrast barium enema result  objective  to determine the relations among patient history  symptoms  objective indicators  and abnormal double contrast barium enema results in outpatients  patients and setting  seven hundred and ninety four patients receiving care in a large multispecialty medical group  design  physicians completed a form before ordering a double contrast barium enema  listing information about patient history  symptoms  and objective findings  including the results of a complete blood count  stool hemoccult  and sigmoidoscopy  measurements and main results  outcome measures were colon cancer and any abnormal finding  the results of 18 6  of the barium enemas were abnormal  the most frequent positive findings were of polyps  8 8   and colon cancer  2 9    over 50  of the barium enemas were ordered solely on the basis of symptoms  yet there was no statistical correlation between symptoms and colon cancer or any positive finding  using logistic regression  four variables were shown to be significant predictors of colon cancer  p less than 0 05   abnormal sigmoidoscopy  iron deficiency anemia  positive stool hemoccult results  and relevant history  the respective odds ratios of these variables were 3 76  95  ci  2 89 to 4 90   2 86  ci  2 13 to 3 74   1 87  ci  1 46 to 2 39   and 1 91  ci  1 44 to 2 52   respectively  in a patient without any of these indicators  the predicted probability of having colon cancer was only 0 7   in a patient with at least two objective indicators  the probability of having colon cancer was greater than 15   conclusions  symptoms without objective indicators or pertinent risk factors do not correlate with an abnormal double contrast barium enema result  objective indicators are useful predictors of an abnormal barium enema result  particularly when looking for colon cancer  
class4	spindle and epithelioid cell nevus  spitz nevus   natural history following biopsy  a clinical follow up study of 49 cases of spindle and epithelioid cell nevus is presented to address the question about the potential for local recurrence  only 19  39   of the 49 lesions were initially excised en toto  and the remainder  30 cases  had positive margins  six of the latter spindle and epithelioid cell nevi were reexcised  and no evidence of a residual nevus was found in five of the six cases  there were no recurrences in the 49 patients during an average follow up period of 5 0 years  range  1 to 10 years   the rarity of recurrent spindle and epithelioid cell nevus would justify a conservative approach to management  with clinical follow up alone recommended after a subtotal excision  when the pathologic diagnosis is unequivocal  
class4	vestibular papillae of the vulva  lack of evidence for human papillomavirus etiology  vestibular papillae of the vulva are usually considered as anatomical variants of the vestibular mucosa  clinically  however  they are quite often interpreted as condylomata acuminata and recent studies have suggested that they could be related to human papillomavirus infection  this prompted us to search for human papillomavirus dna using the southern blot hybridization technique  by analyzing biopsy specimens taken from 29 patients who presented with papillae of the vestibular mucosa  human papillomavirus sequences were detected only in two  6 9   cases  by the same technique  human papillomavirus sequences were detected in 24  96   of 25 vulvar warts used as the control specimens  thus  it appears unlikely that vestibular papillae are related to human papillomavirus infection  they are usually distinguishable from condylomata acuminata by clinical examination alone  
class4	 cystic papilloma  in humans  demonstration of human papillomavirus in plantar epidermoid cysts  fourteen cases of plantar epidermoid cyst were studied immunohistochemically and five of them were also studied electron microscopically for the presence of human papillomavirus  in eleven cases  the test results were positive for papillomavirus antigens  and in five of them  papillomaviruslike particles were observed by electron microscopy  histological examination showed most of the cysts to contain intracytoplasmic eosinophilic bodies in cells of the cyst wall as well as the vacuolar structures in the keratinous mass within the cavity  these findings suggest an etiologic association between the papillomavirus and plantar epidermoid cysts  the  cystic papilloma  produced in rabbits by the shope papillomavirus has been clearly demonstrated  we propose that human papillomaviruses play an important role in the genesis of plantar epidermoid cysts  this is the first report on the possible existence of a cystic papilloma in humans  
class4	regressing atypical histiocytosis  aberrant prothymocyte differentiation  t cell receptor gene rearrangements  and nodal involvement  two cases of regressing atypical histiocytosis were studied  new findings reported include the presence of cd1 epitope on large atypical histiocytoid cells and apparent early lymph node involvement  because regressing atypical histiocytosis may demonstrate aberrant thymic differentiation antigen expression and t cell receptor gene rearrangements  initial lymph node involvement  and eventuation in conventional lymphoma in some cases  the alternative term regressing phase anaplastic lymphoma is proposed as a more accurate designation for this entity  
class4	unusual skin tumors in langerhans  cell histiocytosis  a case of langerhans  cell histiocytosis with unusual skin manifestations in the form of multiple large skin tumors is described  the skin lesions responded partially to chemotherapy with etoposide and prednisone  and residual lesions were excised surgically  the patient developed central diabetes insipidus during treatment  
class4	occupational sunlight exposure and melanoma in the u s  navy  melanoma is the second most common cancer  after testicular cancer  in males in the u s  navy  a wide range of occupations with varying exposures to sunlight and other possible etiologic agents are present in the navy  person years at risk and cases of malignant melanoma were ascertained using computerized service history and inpatient hospitalization files maintained at the naval health research center  a total of 176 confirmed cases of melanoma were identified in active duty white male enlisted navy personnel during 1974 1984  risk of melanoma was determined for individual occupations and for occupations grouped by review of job descriptions into three categories of sunlight exposure   1  indoor   2  outdoor  or  3  indoor and outdoor  compared with the u s  civilian population  personnel in indoor occupations had a higher age adjusted incidence rate of melanoma  i e   10 6 per 100 000  p    06   persons who worked in occupations that required spending time both indoors and outdoors had the lowest rate  i e   7 0 per 100 000  p    06   incidence rates of melanoma were higher on the trunk than on the more commonly sunlight exposed head and arms  two single occupations were found to have elevated rates of melanoma   1  aircrew survival equipmentman  sir   6 8  p less than  05   and  2  engineman  sir   2 8  p less than  05   however  there were no cases of melanoma or no excess risk in occupations with similar job descriptions  findings on the anatomical site of melanoma from this study suggest a protective role for brief  regular exposure to sunlight and fit with recent laboratory studies that have shown vitamin d to suppress growth of malignant melanoma cells in tissue culture  a mechanism is proposed in which vitamin d inhibits previously initiated melanomas from becoming clinically apparent  
class4	the risk of large bowel cancer after partial gastrectomy for benign ulcer disease  the relative risk  standardized incidence ratio  sir  for colorectal cancer after partial gastrectomy for ulcer disease was examined in a population based cohort comprising 6459 patients operated during 1950 to 1958  follow up through 1983 revealed 131 cases of colorectal cancer versus 150 3 expected cases  sir   0 87  95  confidence limits 0 73  1 03   the relative risk was decreased during the first 19 years of follow up  sir   0 75  0 58  0 96  and close to equal thereafter  sir   1 02  0 79  1 29   sex  age at operation  type of operation  and diagnosis at operation  stomach or duodenal ulcer  did not affect the relative risk significantly  confounding by socioeconomic status is one conceivable explanation for the decreased relative risk during the first years of follow up  whereas the increasing risk with longer duration of follow up might be a consequence of the surgical procedure itself  
class4	removal of radiation induced cataracts in patients treated for retinoblastoma  experience with removal of radiation induced cataract in patients treated for retinoblastoma is limited  we retrospectively reviewed the records of 38 patients with retinoblastoma  42 eyes  who underwent removal of radiation induced cataract from 1973 to 1989  nineteen eyes  45   without macular tumors or severe radiation complications had final visual acuities in the range of 20 20 to 20 50  one eye  2 4   developed a rhegmatogenous retinal detachment and four eyes  9 5   were noted to have amblyopia after cataract removal  three eyes  7   developed retinoblastoma recurrence  one with extension of retinoblastoma into the subconjunctival space through the previous sclerotomy  exenteration was performed and the patient was alive after 8 years  cataract removal can be visually beneficial in selected patients with radiation induced cataracts  
class4	respiratory epithelium in a cystic choristoma of the limbus  a female newborn had a cystic  whitish gray mass at the inferotemporal limbus of the left eye  at age 3 weeks  the newborn underwent excision of the tumor  corneal patch grafting  and superior sector optical iridectomy  histopathologic and electron microscopic examination of the excised tissue revealed a choristoma consisting of cysts lined with respiratory epithelium  to our knowledge  respiratory epithelium in a limbal choristoma has not been previously reported  
class4	control of interleukin 1 beta expression by protein kinase c and cyclic adenosine monophosphate in myeloid leukemia cells  we have examined the signal transduction pathways leading to the expression of the interleukin 1 beta  il 1 beta  gene in human myeloid leukemia cells lines  two cell lines representing different stages of differentiation were used  hl 60  promyelocytic  and thp 1  mature monocytic   in accordance with previous studies  it was observed that a protein kinase c  pkc  activator  phorbol myristate acetate  pma   was a sufficient stimulus for induction of the il 1 beta messenger rna  mrna  expression and il 1 beta protein production in both of these cell lines  a structural analog of cyclic adenosine monophosphate  dbcamp  or agents elevating the endogenous camp levels  prostaglandin e2  forskolin  were not alone able to induce il 1 beta expression  but they strongly enhanced the pma induced il 1 beta production and il 1 beta mrna accumulation  nuclear run off analysis showed that this elevation in il 1 beta mrna levels was due to an increased rate of transcription  if dbcamp was added 6 hours before pma to the cultures  no enhancement in the il 1 beta production was seen  implying that for this enhancing effect both of these signals must be present simultaneously  pkc inhibitor  h7  also blocked effectively the pma plus dbcamp induced il 1 beta production  while the protein kinase a  pka  inhibitor  ha1004  had no effect  suggesting that pka activation is not involved in the mechanism of action of camp in this case  collectively  the present findings show that camp dependent signals can have a positive regulatory effect on the pkc dependent activation of the il 1 beta gene in cells derived from different stages of myeloid differentiation  
class4	potentiation of the erythropoietin response by dimethyl sulfoxide priming of erythroleukemia cells  evidence for interaction of two signaling pathways  erythropoietin  epo  and dimethyl sulfoxide  dmso  are believed to induce the differentiation of transformed erythroid cells by different signal transduction pathways  we have now obtained evidence for the interaction of these pathways  we used a rauscher murine erythroleukemia cell line with a relatively low  8  to 10   hemoglobinization response to epo alone  pretreatment of these cells for 1 day with dmso followed by its removal and the addition of epo resulted in a marked enhancement of the epo specific hemoglobinization  we have designated this effect  dmso priming   this priming effect of dmso on the epo response was both time dependent and dmso concentration dependent  dmso priming potentiated the epo response in three ways  firstly  dmso priming increased the total number of epo responsive cells from 8  to 10  to 40  to 60   secondly  dmso priming reduced the time required to reach the optimal epo induced response from 4 days to 2 days  thirdly  the epo dose response curve was left shifted approximately 20 fold  dmso priming was also associated with a marked increase in epo receptor density characterized by an apparently new receptor population and by the appearance of positive cooperativity between receptors  our results suggest that the dmso priming effect is due to potentiation of the epo signaling pathway  thus resulting in a much more rapid and dramatic epo induced hemoglobinization response  
class4	different effect of benzylacyclouridine on the toxic and therapeutic effects of azidothymidine in mice  it has been reported that in vitro uridine  urd  can reverse azidothymidine  azt  cytotoxicity without decreasing anti human immunodeficiency virus  hiv  activity  our studies in mice have shown that daily oral doses of benzylacyclouridine  bau   an inhibitor of urd breakdown  also reduces azt hematologic toxicity  presumably by elevating the plasma concentration of urd  we now extend these murine studies and report the effect of various doses of exogenous urd  various doses of bau  or the combination of bau and urd  administered daily  on azt induced toxicity  in mice receiving concomitant azt  daily doses of urd of 1 000 to 2 000 mg kg increase peripheral reticulocytes and slightly reduce azt induced hematologic toxicity  however  the range of effective doses is narrow  and higher doses of urd  greater than 3 000 mg kg d  significantly enhance hematologic toxicity  at its most effective dose   2 000 mg kg d   urd produces 28  mortality  in contrast  bau doses up to 300 mg kg d reduced azt related hematologic toxicity in a dose dependent manner without mortality  higher daily doses of bau and the combination of bau with low doses of urd were not more effective  studies conducted in mice infected with the rauscher murine leukemia virus  rlv  indicate that bau does not impair the antiretroviral effect of azt when administered at doses that reduce azt induced anemia and leukopenia  these findings may be significant for the treatment of patients with acquired immunodeficiency syndrome  aids  and aids related complex  
class4	long term  5 to 20 years  evolution of nongrafted aplastic anemias  the cooperative group for the study of aplastic and refractory anemias  in the presence of aplastic anemia  aa   therapeutic choices should be determined while taking into account not only changes for immediate improvement  but also both the risks for late occurring complications and the following quality of life  we report here data concerning a long term clinical survey  5 to 18 years with a median of 12 years  including 156 nongrafted patients receiving androgen therapy  all patients were alive more than 5 years after diagnosis  40  of patients included at time of diagnosis in our multicentric analysis   between the 5th and the 13th year follow up  21 patients died of various causes either related to aa or to its treatment  12 of infection or hemorrhage secondary to pancytopenia  6 relapses and 6 that had never been improved  2 with paroxysmal nocturnal hemoglobinuria  pnh    5 of leukemia  1 of a non hodgkin s lymphoma  2 of late side effects following transfusion  1 acquired immunodeficiency syndrome and 1 chronic b hepatitis   and a single case of myocardial infarction  the latter could possibly result of androgen therapy   thirteen patients in total developed pnh  among which 10 had clinical symptoms including 2 deaths  and 3 exhibited only biologic abnormalities   few long term side effects of androgens could be noticed  adult height was normal in patients treated during childhood and so was young women s fertility  no malignant hepatoma occurred  this survey allows the recording of late spontaneous hematologic improvement  between 5 and 10 years of evolution   this occurred in 50  of patients that had remained cytopenic 5 years after diagnosis  although bone marrow stem cell concentration remained abnormal after 10 years of evolution  85  of patients had a normal red blood cell count  80  a normal polymorphonuclear count  and 66  a normal platelet count  all patients who did not show late complications had an excellent quality of life  
class4	transformation associated alterations in interactions between pre b cells and fibronectin  marrow stromal elements produce as yet uncharacterized soluble growth factors that can stimulate the proliferation of murine pre b cells  although close contact between these two cell types appears to ensure a better pre b cell response  we have now shown that freshly isolated normal pre b cells  ie  the b220   surface mu  fraction of adult mouse bone marrow  adhere to fibronectin  fn  via an rgd cell attachment site  as shown in a serum free adherence assay  and they lose this functional ability on differentiation in vivo into b cells  ie  the b220   surface mu  fraction   similarly  cells from an immortalized but stromal cell dependent and nontumorigenic murine pre b cell line originally derived from a whitlock witte culture were also found to adhere to fibronectin  fn  via an rgd cell attachment site  moreover  in the presence of anti fn receptor antibodies  the ability of this immortalized pre b cell line to proliferate when co cultured with a supportive stromal cell line  m2 10b4 cells  was markedly reduced  down to 30  of control   this suggests that pre b cell attachment to fn on stromal cells may be an important component of the mechanism by which stromal cells stimulate normal pre b cell proliferation and one that is no longer operative to control their more differentiated progeny  two differently transformed pre b cell lines  both of which are autocrine  stromal independent  tumorigenic in vivo  and partially or completely differentiation arrested at a very early stage of pre b cell development  did not bind to fn  in addition  anti fn receptor antibodies were much less effective in diminishing the ability of these tumorigenic pre b cells to respond to m2 10b4 cell stimulation  which could still be demonstrated when the tumorigenic pre b cells were co cultured with m2 10b4 cells at a sufficiently low cell density  analysis of cell surface molecules immunoprecipitated from both the nontumorigenic and tumorigenic pre b cell lines by an anti fn receptor antibody showed an increase in very late antigen  vla  alpha chain s  in both tumorigenic pre b cell lines and a decrease in the beta 1 chain in one  interestingly  all of the pre b cell lines expressed similar amounts of messenger rna for the beta 1 chain of the fn receptor  these results suggest that alteration of fn receptor expression on pre b cells may represent a mechanism contributing to the outgrowth of leukemic pre b cells with an autocrine phenotype and capable of stromal cell independent  autonomous growth  
class4	in vitro drug sensitivity of cells from children with leukemia using the mtt assay with improved culture conditions  the knowledge about drug resistance in childhood leukemias and acute lymphoblastic leukemia  all  in general is limited  this is because of the lack of a suitable in vitro drug sensitivity assay  which is in part due to low in vitro all cell survival  we recently adapted the highly efficient 3  4 5 dimethylthiazol 2 yl  2 5 diphenyl tetrazolium bromide  mtt  assay to test cells from all patients and showed that its results were comparable with those of the disc assay  up to now the most valid but laborious assay  in this study  in vitro drug sensitivity was assessed in cells from 82 children with leukemia  79 of whom had all  with the mtt assay  dose response curves were obtained for 6 mercaptopurine  6 thioguanine  6 tg   prednisolone  pred   daunorubicin  dnr   vincristine  vcr   cytosine arabinoside  ara c   l asparaginase  l asp   mafosfamide  and mustine  a cytotoxic effect of methotrexate could be detected in only a few cases  large interindividual differences in drug sensitivity were detected  compared with leukemia cells from newly diagnosed patients  leukemia cells from relapsed patients were significantly more in vitro resistant to 6 tg  pred  ara c  mafosfamide and mustine but not to dnr  vcr  and l asp  improvements of culture medium and methods to increase mtt reduction were studied  from 10 components tested  addition of insulin and bovine serum albumin to serum containing medium improved all cell survival  addition of succinate did not increase the amount of mtt reduction  we conclude that the in vitro mtt assay highly facilitates large scale studies on drug resistance of all patients that can lead to rational improvements in existing treatment protocols  
class4	analysis of interferon inducible genes in cells of chronic myeloid leukemia patients responsive or resistant to an interferon alpha treatment  recombinant human interferon alpha  ifn alpha  can induce a hematologic remission in patients with chronic myeloid leukemia  however  some patients are resistant and others develop late resistance to the ifn alpha treatment  to understand the molecular mechanism of this resistance  we have analyzed the expression of 10 ifn inducible genes in the cells of three resistant patients  two responsive patients  and six healthy controls  northern blot hybridizations showed that all the genes were induced in in vitro ifn alpha treated peripheral blood cells of the patients and healthy controls  these genes were also inducible in peripheral blood and bone marrow cells of two out of two resistant patients administered an injection of ifn alpha  we conclude that the resistance to the ifn alpha treatment of the chronic myeloid leukemia patients we studied is not due to  1  the absence of induction of any of the 10 ifn inducible genes we studied  including the low molecular weight 2  5 oligoadenylate synthetase   2  the presence of an antagonist of ifn alpha in the peripheral blood or bone marrow cells  and  3  the presence of neutralizing anti ifn alpha antibodies  
class4	down s syndrome and acute leukemia in children  an analysis of phenotype by use of monoclonal antibodies and electron microscopic platelet peroxidase reaction the clinical  hematologic  and immunophenotypic features in 20 patients with down s syndrome  ds  and acute leukemia were analyzed  of the 20 patients  all 14 patients who were 3 years old and less were diagnosed as having acute megakaryoblastic leukemia  amkl  by use of platelet specific monoclonal antibodies and platelet peroxidase  ppo  reaction in electron microscopy  they were characterized by the presence of bone marrow fibrosis  having a history of myelodysplastic syndrome  mds  and a poor response to chemotherapy  only one patient has remained in continuous complete remission for more than 1 year  acute leukemia in six patients who were older than 4 years was classified as common acute lymphoblastic leukemia antigen  calla  positive acute lymphoblastic leukemia  all   in one of six patients classified as all  the leukemic blasts simultaneously expressed myeloid associated surface antigens  all six patients achieved a complete remission and have remained in continuous complete remission and have remained in continuous complete remission from 10 to 52 months from the initial diagnosis  although it has been suggested that the distribution of types of acute leukemia in patients with ds is similar to that in normal children  the present study shows that the distribution of acute leukemia types is quite different from that in patients without down s syndrome  
class4	serum erythropoietin levels in patients receiving intensive chemotherapy and radiotherapy  to investigate the potential role of recombinant human erythropoietin  rhepo  in patients receiving intensive cytotoxic therapy  we measured the endogenous levels of epo in 31 patients undergoing bone marrow transplantation  bmt   seventeen patients underwent allogeneic bmt and 14 underwent autologous bmt  on average  10     4 units of red blood cells  rbcs  were transfused per patient  the mean rbc transfusion requirement of the autologous bmt patients was significantly greater than that of the allogeneic recipients  12     3 v 8     4  p less than  01   although both groups were maintained at comparable hematocrits  epo levels were measured by radioimmunoassay  ria   for each patient  baseline serum epo levels were determined at time of admission to the hospital  subsequent samples were collected within 24 hours of completing chemotherapy and or radiotherapy  and on days 7  14  and 28  after bmt  hematocrits  hcts  were measured daily  all patients had an initial serum creatinine less than or equal to 1 5 mg dl  despite considerable differences in absolute epo levels among individuals  a characteristic pattern was observed  following admission to the hospital and initiation of cytotoxic therapy  the average hct decreased and the average epo level initially increased  the mean serum epo levels peaked on day 7 post bmt  284     190 mu ml  and fell steadily thereafter  while the average hcts on day 7 and on day 28 post bmt were not significantly different  28     4 6  v 29     3 3   respectively   the average serum epo levels decreased fourfold  p less than  01  during this same period  moreover  day 28 post bmt mean epo levels were inappropriately low  p less than  05  when compared with a reference population with bone marrow failure and normal controls who had not received cytotoxic therapy  we conclude that the endogenous epo response appears to be blunted during the 3 to 4 weeks immediately post bmt  therefore  clinical trials assessing the efficacy of the administration of rhepo in the treatment of anemias associated with cytotoxic therapy are warranted  
class4	cd11c  leu m5  expression characterizes a b cell chronic lymphoproliferative disorder with features of both chronic lymphocytic leukemia and hairy cell leukemia  chronic lymphocytic leukemia  cll  and hairy cell leukemia  hcl  are two common chronic lymphoproliferative disorders  each having characteristic clinical  morphologic  and immunologic features  phenotypically  cd5 reactivity in cll and cd11c  leu m5  reactivity in hcl have characterized these two leukemias among b cell disorders  in this study  we report 14 cases of a novel chronic lymphoproliferative disorder characterized by lymphocytosis and cd11c expression  but morphologically similar to cll  the patients  ages ranged from 46 to 81 years  median 62   eleven had palpable splenomegaly  five with markedly enlarged spleens  only one patient had generalized lymphadenopathy  the white blood cell count ranged from 5 2 to 131 0 x 10 9  l  median 20 8   the morphologic diagnosis in all cases was cll  with the cells usually having abundant cytoplasm  no morphologic features  of hairy cells were evident  tartrate resistant acid phosphatase cytochemistry was negative in all cases  bone marrow biopsies were available in 8 of 14  four showed focal nodular infiltrates and two had diffuse infiltrates similar to cll  two showed only minimal interstitial involvement  all cases expressed multiple b cell markers  and 12 of 14 had monoclonal surface immunoglobulin  the leukemic cells of all cases strongly expressed cd11c  while cd5 was expressed in 7 of 14  only 1 of the 14 cases expressed the lymph node homing receptor  leu 8  this unique group of leukemias appears to represent the malignant transformation of lymphocytes arising from a stage of lymphocyte differentiation between that found in typical cases of cll and that of hcl  cd11c is known to have an important function in cellular adhesion and may be important in determining the pattern of lymphocyte tissue distribution found in this group of patients  
class4	detection of breakpoint cluster region  negative and nonclonal hematopoiesis in vitro and in vivo after transplantation of cells selected in cultures of chronic myeloid leukemia marrow  philadelphia  ph1  chromosome positive clonogenic progenitors usually disappear within 4 to 6 weeks in long term cultures established from the marrow of patients with chronic myeloid leukemia  cml   in contrast  coexisting chromosomally normal hematopoietic cells are relatively well maintained  thus  even though normal cells are initially undetectable  they may become the predominant population  recently  we have begun to explore the potential of such cultures as a strategy for preparing cml marrow for autografting  and based on cytogenetic studies of the differential kinetics of ph1 positive and ph1 negative clonogenic cells  have chosen a 10 day period in culture to obtain maximal numbers of selectively enriched normal stem cells  here we present the results of molecular analyses of the cells regenerated in vivo for the initial three cml patients to be treated using this approach by comparison with the differentiated cells generated by continued maintenance of an aliquot of the autograft in vitro  using a slightly modified culture feeding procedure to enhance the production and release of cells into the nonadherent fraction after 4 weeks  for the one patient whose genotype made molecular analysis of clonality status also possible  these analyses showed that cells with a rearranged breakpoint cluster region  bcr  gene were not detectable by southern blotting in either in vitro or in vivo populations of mature cells that might be assumed to represent the progeny of primitive cells present at the end of the initial 10 days in culture  production of bcr negative cells was also shown to be temporally correlated with the appearance of nonclonal hematopoietic cells both in culture and in vivo  these findings provide support for the view that prolonged maintenance of cml marrow cells in long term culture may allow molecular characterization of both the bcr genotype and clonality status of cells with in vivo regenerative potential  
class4	chemoprotective effects of recombinant human il 1 alpha in cyclophosphamide treated normal and tumor bearing mice  protection from acute toxicity  hematologic effects  development of late mortality  and enhanced therapeutic efficacy  in this study  recombinant human il 1 alpha  rhil 1 alpha  was used to protect normal and tumor bearing balb c mice from the acute toxicity caused by lethal doses of cyclophosphamide  cy  and 5 fluorouracil  pretreatment of mice for 7 days with 10 000 u day of rhil 1 alpha protected 70 to 100  of mice from the acute death induced by lethal doses of both cy  380 mg kg  and 5 fluorouracil  250 mg kg   in contrast  post treatment of mice with single or multiple doses of rhil 1 alpha was not chemoprotective  pretreatment of mice with rhil 1 alpha increased the acute ld90 of cy from 380 mg kg to greater than 500 mg kg in normal mice  an ld90 dose modifying effect of at least 1 25  was accompanied by a more rapid recovery from neutropenia and a less severe reduction in the number of bone marrow single lineage monocyte  myeloid  or myelomonocytic colonies  some of the mice  10 to 50   that were successfully protected by pretreatment with rhil 1 alpha died after day 50  these mice consistently presented with extensive pulmonary inflammation and fibrosis at death  mice bearing murine renal cancer  renca  were also protected from the acute toxic effects of cy  450 mg kg  by pretreatment with rhil 1 alpha  renca bearing mice pretreated with rhil 1 alpha and either sublethal  300 mg kg  or lethal  450 mg kg  doses of cy exhibited enhanced survival times over those of untreated renca bearing mice  interestingly  the cause of death in renca bearing mice that ultimately failed treatment with rhil 1 alpha plus 300 mg kg cy was recurrent tumor  whereas most mice treated with rhil 1 alpha plus 450 mg kg cy had no detectable tumor  although several died from late pulmonary inflammation and fibrosis  thus  the dose escalation of cy in rhil 1 alpha pretreated mice results in greater antitumor effects of cy  however  the dose escalation of some cytotoxic agents allowed by the use of myelostimulatory agents can result in late fatal complications not detected in acute toxicity testing  
class4	role of histamine in natural killer cell mediated resistance against tumor cells  the formation of lung metastases by i v  injected b16 melanoma  f1 and f10 strain  cells in swiss albino  c57bl 6  and balb c mice was reduced by a single dose of histamine given 24 h before tumor cell inoculation  the antimetastatic effect of histamine was specifically mediated by histamine h2 receptors  h2r   it was blocked by the h2r antagonist ranitidine and mimicked by dimaprit  a specific h2r agonist but not by an h2r inactive structural analog of this compound  nor dimaprit  or the h1r agonist 2 thiazolyl ethylamide  a single dose of any of the h2r antagonists ranitidine  tiotidine  famotidine  or cimetidine drastically augmented metastasis  effects of h2r interactive compounds on b16 metastasis required intact nk cells  as judged by the inability of histamine or ranitidine to affect b16 metastasis after nk cell depletion in vivo using antibodies to asialo gm1  nk cell mediated lysis of yac 1 lymphoma cells in vivo was enhanced by histamine and reduced by ranitidine within 4 h after inoculation of tumor cells  the antimetastatic effect of il 2 was potentiated by histamine  in some experiments  combined treatment with a low dose of il 2  6000 u kg  and histamine completely eliminated metastasis  whereas concomitant treatment with ranitidine abrogated antimetastatic effects of il 2  animals treated with ranitidine and il 2 displayed the same level of enhanced metastasis as those treated with ranitidine alone  the presented data are suggestive of an earlier unrecognized role for histamine in nk cell mediated resistance against metastatic tumor cells  
class4	efficacy of interferons on bowenoid papulosis and other precancerous lesions  preliminary results of an open randomized trial of recombinant interferon gamma in patients suffering from bowenoid papulosis are described  recombinant interferon gamma was given subcutaneously to 12 patients at a daily dose of 4 x 10 6  i u  by injection  four patients each were assigned to one of three treatment groups consisting of continuous therapy  group a  with three subcutaneous injections per week for 13 weeks  intermittent block therapy  group b  with four six week cycles consisting of five injections on days 1  3  5  7  and 9 of each cycle  and intermittent single dose therapy  group c  with six four week cycles consisting of only one subcutaneous injection on day one of each cycle  at the twenty sixth week after onset of therapy  complete responses were seen in three of four patients of treatment group a  whereas in the treatment groups b and c only one patient  respectively  responded partially  these results suggest that in contrast to condylomata acuminata bowenoid papulosis lesions respond better to continuous than to intermittent interferon gamma injections  
class4	non aids associated kaposi s sarcoma  classical and endemic african types   treatment with low doses of recombinant interferon alpha  in the treatment of the classical and endemic african forms of kaposi s sarcoma  ks   radiation therapy and chemotherapy have been widely used with varying degrees of success and morbidity  we here report our preliminary experiences with low doses of recombinant interferon alfa 2b  rifn alpha 2b  in the treatment of these types of ks  non linked to the acquired immunodeficiency syndrome  aids   ten consecutive patients  eight patients with classical and two with endemic ks  with a median age of 62 years were treated long term with 5 x 10 6  units of rifn alpha 2b  introna  given subcutaneously three times weekly for at least 6 months  of the 10 patients  six presented with cutaneous disease only  and four had additional visceral involvement  after 6 months of treatment  seven of the 10 patients had a major response of the cutaneous lesions  and three patients showed stable skin diseases  of the four patients with additional visceral disease  one patient showed a complete regression of an intramyocardial tumor involving the right atrium and ventricle  whereas in the three other patients stabilization of the visceral lesions with marked symptomatic improvement occurred  on the whole  the long term results over a median duration of 12 months  range  7 to 30  are also satisfactory  ifn alpha continued to control ks in all patients  the treatment was generally well tolerated  no serious side effects were observed  our preliminary data suggest that low dose rifn alpha 2b regimens are effective in classical and endemic african ks  however  further studies are needed to establish the exact role for ifn alpha as alternative to radiation and chemotherapy  
class4	clinical evaluation of interferons in malignant melanoma  the evaluation of interferons in the treatment of malignant melanoma has been mainly in the treatment of advanced disease using interferons as the sole agent or in combination with other agents  studies of the value of interferons as adjuvant therapy in high risk primary melanoma patients are necessary  but no results have been published to date  human interferon alpha produces low response rates as a sole agent  but in combination with cimetidine  a 30  response rate has been achieved  recombinant alpha interferons give responses of 15  20  in advanced melanomas  and combination with cimetidine does not enhance the response rate  recombinant alpha interferons have been used in combination with other interferons  cimetidine  monoclonal antibodies  and cytotoxics  with either no or small improvement in response rates  dtic with recombinant interferon alpha 2a has been shown to produce objective response rates of 26   with low toxicity and maintenance of quality of life  a randomized trial with dtic as the sole agent  compared with combination treatment  is being conducted to determine the significance of this finding  
class4	long term adjuvant therapy of high risk malignant melanoma with interferon alpha 2b  fifty three high risk melanoma patients in stage i and 15 patients in stage ii were treated after standard surgical intervention with adjuvant therapy with recombinant interferon alpha 2b  rifn alpha 2b  therapy for a total period of 20 months  concomitant patients  stage i  n   82  stage ii  n   33  with identical stages and prognostic factors without adjuvant therapy were used to evaluate the efficacy of rifn alpha 2b therapy  no difference in 5 year relapse incidence and overall survival rates could be detected  however  it appears that patients of both stage i and stage ii benefit from long term adjuvant rifn alpha 2b therapy  because during the treatment period  20 months   the incidence of relapses was lower in comparison to controls  after stopping treatment the incidence of relapse is equal in treated and control groups  according to the results of our study  we suggest using continuous low dose rifn alpha 2b therapy for adjuvant treatment of malignant melanoma  
class4	photochemotherapy alone or combined with interferon alpha 2a in the treatment of cutaneous t cell lymphoma  eighty two patients with either mycosis fungoides  mf  or parapsoriasis en plaques were treated with psoralens ultraviolet a light  puva   clinical and histologic parameters were followed for a period from 6 months to 10 years  complete clinical clearing of lesions was observed in 51 patients  62   and most of them were in limited plaque mf group or parapsoriasis en plaque  the mean total dose of puva for complete clearing was less for early mf  thirty one patients  38   relapsed and responded to additional puva  patients in early stages of the disease remained clear for up to 68 months after the first course of puva  post treatment skin biopsies with early mf showed histologic clearing  a new combination therapy for mf is presented in 15 patients  recombinant interferon alpha 2a  roferon a   administered intramuscularly combined with puva were tested in a phase i trial  interferon doses were from 6 30 million units three times weekly  disease stages ranged from i b to iv b  complete responses were obtained in 12 of 15 patients  and partial responses seen in 2 of 15 patients  for an overall response rate of 93   the median duration of response exceeded 23 months  range  3 to 25 months   all responding patients have been maintained on therapy  the dose limiting toxicities were constitutional symptoms such as fevers and malaise  93 3    leukopenias  40 0    mental status changes consisting of depression and confusion  33 3    and photosensitivity  26 6    interferon plus puva appear to be highly effective regimens for the treatment of patients with cutaneous t cell lymphomas  
class4	interferon alpha and etretinate combination treatment of cutaneous t cell lymphoma  eleven patients suffering from cutaneous t cell lymphoma  mycosis fungoides  were treated with recombinant interferon alpha 2a in combination  seven patients  or alone  two patients  one in combined treatment  went into clinical complete remission  and five experienced partial remission  two patients progressed during therapy  and two were nonevaluable because they stopped treatment early due to side effects  dosages of interferon were from 3 to 36 million units daily for 3 months  and thereafter 3 times weekly  etretinate  0 7 mg kg  was given orally  the study showed that recombinant interferon alpha 2a in combination with etretinate or alone can induce remission of cutaneous t cell lymphoma  
class4	recombinant ifn alpha in lymphomas  the effectiveness of interferon  ifn  therapy in malignant lymphoma is analyzed in this review  although various treatment regimens including ifn at various dose levels have so far not proved to have curative potential  a substantial palliative effect has been noted in hairy cell leukemia and in some non hodgkin lymphomas of low grade malignancy  early stages of lymphoma disease are more responsive to ifn therapy  and this holds true also for chronic lymphocytic leukemia  in which ifn treatment is usually not effective in progressed disease after chemotherapy  concepts of early phase treatment and of remission maintenance by using ifn therapy are discussed on the basis of the data from several studies  
class4	cytostatic and cytotoxic effects of recombinant tumor necrosis factor alpha on sensitive human melanoma cells in vitro may result in selection of cells with enhanced markers of malignancy  monolayer cultures of the human melanoma cell lines stml 12  stml 11  stml 14  third  respectively  twenty fifth subculture   and skmel 28 derived from specimens representing different stages of tumor progression were treated with 10 10 000 u ml rtnf alpha applied for 72 h  the effects of rtnf alpha on cell proliferation  dna synthesis  cell viability  cloning efficiency  cell division  cell morphology  and the immunophenotype were studied in triplicate experiments  the cell line stml 14 3  revealed a significantly dose dependent reduction of growth due to both cytostatic and cytotoxic activities of rtnf alpha as well as a decrease of ce  increased numbers of cells in prophase were observed 24 h after addition of r tnf alpha  in addition  dislocation of chromosomes in the metaphase  formation of micronuclei  and dose dependent increases of cells exhibiting micronuclei and the dna amount per cell were detected at the end of treatment  on the other hand  only a slight sensitivity to the anti proliferative effect of rtnf alpha was observed with stml 14 25  and skmel 28  whereas stml 12 and stml 11 were significantly resistant  the last four cell lines were serially subcultivated and presented common phenotypic patterns with more malignant characteristics than the cell line stml 14 3  before treatment  overall  rtnf alpha enhanced the malignant immunophenotype of the cell lines tested  it increased the expression of the  late  melanoma progression markers a 10 33 and a 1 43  and ki67  and it decreased the expression of the  early  progression marker k 1 2  the expression of hla i  hla dr  and icam 1 was also enhanced after rtnf alpha treatment  whereas in contrast to other cytokines  rtnf alpha did not induce the de novo expression of hla dr in hla dr negative melanoma cell lines  these findings indicate that rtnf alpha induces cytostasis and decreases cell viability of certain rtnf alpha sensitive melanoma cells  these effects may result in selection of rtnf alpha non sensitive human melanoma cell populations with higher proliferation rates and a more aggressive immunophenotype in vitro  
class4	high incidence of antibodies to htlv i tax in blood relatives of adult t cell leukemia patients  adult t cell leukemia  atl  is caused by the human t cell leukemia virus type i  htlv i   although the mechanisms of the leukemogenic process are unknown  the tax gene may have a role in this process  because clustering occurs with htlv i and atl  members of atl families were examined for antibodies to the tax protein and compared with matched htlv i positive blood donors  to investigate the antibody response to this protein  a plasmid  pbhx 4  was constructed to express a recombinant tax protein  r tax   for atl patients and their htlv i antibody positive blood relatives  the rate of seroreactivity with the r tax protein was 67 3   35 52   compared with 51 6   97 188  for htlv i antibody positive control blood donors  p less than  05   the difference between direct offspring of atl patients and matched htlv i blood donors was even greater  84 2   16 91  vs  44 2   42 95   p less than  005   thus  tax antibody positivity in direct offspring of atl patients may reflect differences in time or route of htlv i infection  alternatively  it might reflect genetic differences in host susceptibility or virus strain  
class4	tumor associated neurological dysfunction prevented by lazaroids in rats  the efficacy of u 74006f and u 78517f in the treatment of blood tumor barrier permeability and tumor associated neurological dysfunction was evaluated in a brain tumor model in rats  u 74006f is a 21 aminosteroid and u 78517f is a 2 methylamino chroman  rats with stereotactically implanted walker 256 tumors were treated with methylprednisolone  u 74006f  u 78517f  or vehicle  0 05 n hcl  on days 6 through 10 following implantation  neurological function and vascular permeability were assessed on day 10  methylprednisolone and u 74006f were equally effective at preventing neurological dysfunction compared to the control group  p less than 0 01   u 78517f was slightly less effective than u 74006f and methylprednisolone but was significantly better than vehicle in preventing neurological dysfunction  delivery of methylprednisolone resulted in a significant decrease in tumor vascular permeability  p less than 0 006  while u 74006f and u 78517f had no effect on permeability  this suggests that u 74006f and u 78517f prevented tumor associated neurological dysfunction by a mechanism other than decreasing permeability in tumor capillaries  and that u 74006f or u 78517f could prove useful in the treatment of brain tumors  
class4	epidermoid cysts of the brain stem  report of three cases  the authors report the cases of three patients with epidermoid cysts which insinuated themselves into the brain stem  in all three patients  the tumor occupied the pons  although in one it was predominantly located in the medulla  the cyst contents and nonadherent tumor capsule were removed in all three patients  but no attempt was made to remove tumor densely adherent to the brain stem  one patient s cyst was removed in one operation  but maximal resection in the other two required two operations  after surgery  sixth nerve function completely returned in one patient  another patient had a stable pontine gaze palsy but developed new facial weakness  and the third patient had stable cranial nerve deficits with a diminished hemiparesis  the last patient developed a pseudomeningocele and communicating hydrocephalus  and required a lumboperitoneal shunt  in all three patients  computerized tomography scans demonstrated hypodense tumors not enhanced by contrast material  magnetic resonance imaging was performed on two patients  in both  the tumors showed increased signal intensity relative to brain on t1 weighted images and decreased signal intensity relative to brain on t2 weighted studies  magnetic resonance imaging  the most accurate modality for localizing these lesions and determining their extent  was also invaluable for postoperative monitoring and follow up evaluation  safe and adequate resection includes decompression of cyst contents and removal of nonadherent portions of the cyst capsule  cyst wall adherent to the brain stem  however  should not be removed  
class4	pseudopsammomatous meningioma with elevated serum carcinoembryonic antigen  a true secretory meningioma  case report  a sphenoid wing meningioma in a 60 year old woman was accompanied by elevated serum carcinoembryonic antigen  cea  levels  which returned to normal after removal of the tumor  light microscopic examination revealed a secretory meningioma containing numerous pseudopsammoma bodies and a prominent vascular pattern  immunohistochemical analysis showed the tumor cells and pseudopsammoma bodies to be cea positive  this case illustrates the possibility that secretory meningioma may be associated with clinically detectable secretion of cea  the report also documents the rare occurrence of elevated serum cea in a primary benign intracranial tumor  
class4	the fastigial pressor response  case report  a distinct vasomotor and cardioregulatory response first identified experimentally was elicited intraoperatively in a 6 year old girl by local mechanical stimulation in the vicinity of the fastigial nucleus of the cerebellum  these findings are discussed in the light of current experimental knowledge of the anatomy and physiology of the fastigial pressor response  
class4	correlates of survival and the daumas duport grading system for astrocytomas  in order to examine the correlation between prognosis and the histological features of nuclear atypia  mitosis  endothelial proliferation  and necrosis in supratentorial adult astrocytomas  the authors reviewed 251 such cases treated at the massachusetts general hospital between 1972 and 1980  one point was given for the presence of each feature  the total number of features was translated into a grade as follows  none of the four features   grade 1  one patient   one feature   grade 2  36 patients   two features   grade 3  33 patients   and three or four features   grade 4  181 patients   the period of survival was significantly associated with grade  the presence or absence of each of the four histological features  patient s age  type of operation  radiation therapy  and extent of tumor  log rank  p less than 0 05   the variables associated with grade were age  p less than 0 001  and radiation therapy  p less than 0 02   after adjustment for these variables using a cox proportional hazards model  the difference in overall survival time between patients in grades 2 and 3 was not statistically significant  when comparable groups of patients were examined in terms of age or receipt of radiation therapy  the median survival times differed markedly  patients 50 years of age or less had a median survival time of 68 months  grade 2 tumors   29 months  grade 3 tumors   and 13 months  grade 4 tumors   patients over 50 years of age had a median survival time of 6 months  grade 2 and 4 tumors  and 9 months  grade 3 tumors   those patients who had received radiation therapy had a median survival time of 68 months  grade 2 tumors   21 months  grade 3 tumors   and 11 months  grade 4 tumors   those patients who did not receive radiation therapy had a median survival time of 1 month  grade 2 tumors  and 2 months  grade 3 and 4 tumors   over half of these patients died within 2 months of surgery  this grading system  originally proposed by daumas duport  et al   is simple  objective  and reproducible  and correlates well with survival times  the authors recommend that astrocytomas be graded on a scale of 1 to 4  with grade 1 reserved for the rare adult supratentorial astrocytoma with none of the four histological features  
class4	idiopathic and glucocorticoid induced spinal epidural lipomatosis  pathological overgrowth of the epidural fat in the spine has been described and reported nearly exclusively in patients either with cushing s syndrome or on chronic intake of glucocorticoids for a variety of clinical disorders  the authors report four patients with documented spinal lipomatosis  three pathologically and one radiologically   only one of these patients received corticosteroids  and none had an underlying endocrinological abnormality  all four patients were adult males with a mean age at onset of symptoms of 43 years  range from 18 to 60 years   the symptoms ranged from simple neurogenic claudication and radicular pain to frank myelopathy  myelography followed by computerized tomography were instrumental in the diagnosis of the first three patients  the fourth was diagnosed by magnetic resonance imaging  the thoracic spine was involved in two cases and the lumbosacral area in the other two  the different treatment modalities were tailored according to the symptomatology of the patients  these included weight reduction of an overweight patient with minimal neurological findings in one case and decompressive laminectomy and fat debulking to achieve adequate cord decompression in the remaining three cases  two patients improved significantly  the condition of one stabilized  and the fourth required a second decompression at other spinal levels  the various modalities of treatment and their potential complications are discussed  
class4	intratumoral oxygen pressure in malignant brain tumor  oxygen pressure  po2  in brain tumors  po2 in brain cortex surrounding the tumors  and pao2 were measured simultaneously during total resection in 16 patients with previously untreated brain tumors in order to detect hypoxic regions within the tumors  when the inhaled o2 n2o ratio was 1 3 under enflurane anesthesia  mean pao2 was 109 2     5 8 mm hg  a rather high value when compared with that obtained when air is inhaled under atmospheric pressure  the simultaneously measured intratumoral po2 and po2 in brain cortex surrounding the tumor were 15 3     2 3 and 59 8     6 5 mm hg  respectively  each intratumoral po2 value was significantly lower than that of po2 in brain cortex surrounding the tumor  mean less than 30 mm hg  wilcoxon signed rank test  p less than 0 005  and influenced the oxygen effects on radiation  these results appear to confirm that there are hypoxic regions within human brain tumors  a comparison between intratumoral po2 and either the angiographic or contrast enhanced computerized tomography scans of the tumor vasculature disclosed no correlation  
class4	pediatric spinal epidural metastases  a total of 2259 children with solid malignant tumors were treated at st  jude children s research hospital between the years 1962 and 1987  of these  112  5   developed spinal epidural metastasis with spinal cord compression during the course of their disease process  metastatic epidural spinal cord compression was caused most commonly by ewing s sarcoma and neuroblastoma  followed by osteogenic sarcoma  rhabdomyosarcoma  hodgkin s disease  soft tissue sarcoma  germ cell tumor  wilm s tumor  and  rarely  hepatoma  there was no significant difference in outcome between patients with small cell tumors  neuroblastoma  hodgkin s disease  and germ cell tumors  who received only chemotherapy and or radiation therapy and the patients with similar lesions who received a decompressive laminectomy alone or prior to chemotherapy and or radiation therapy  patients with spinal cord compression from metastatic sarcoma  ewing s sarcoma  soft tissue sarcoma  osteogenic sarcoma  and rhabdomyosarcoma  showed a significant improvement with decompressive laminectomy alone or before medical therapy  compared to those who received radiation therapy and or chemotherapy without posterior decompression  pediatric tumors invade the spinal canal via the neural foramen  compressing the spinal cord in a circumferential manner  allowing decompressive laminectomy  posterior approach  to be an effective surgical approach  sixty six percent of children who had no evidence of motor or sensory function below the level of the compression became ambulatory after surgical decompression and medical treatment  regardless of tumor type  
class4	photodynamic therapy of spontaneous cancers in felines  canines  and snakes with chloro aluminum sulfonated phthalocyanine  this is the first report on the photodynamic treatment with a second generation sensitizer  chloro aluminum sulfonated phthalocyanine  caspc  of spontaneously arising tumors and on the photodynamic therapy  pdt  of snake neoplasms  each of 10 cats  2 dogs  and 3 snakes presenting with a variety of tumor types  squamous cell carcinoma  mast cell malignant tumor  and mixed carcinoma sarcoma  was given an intravenous injection of 1 mg of caspc per kilogram body weight 48 hours prior to irradiation with 675 nm light  some larger tumors  greater than 1 5 cm deep  were surgically debulked prior to pdt  no significant systemic toxicity or skin photosensitization was observed in any animal  the tumor responses were comparable to those seen with conventional cryotherapy  hyperthermia  or surgery  pdt with caspc of these cases led to 67   12 of 18  complete response  22   4 of 18  partial response  and 11   2 of 18  no response  less than 50  reduction in tumor size   four cases could not be evaluated  since the overall tumor response to caspc is very good  and the problem of skin photosensitivity is nonexistent  it is expected that using caspc pdt to eradicate human tumors would also yield comparable results  further studies with long term follow up are necessary to optimize the use of caspc pdt in veterinary and human medicine  
class4	increased expression of the laminin receptor in human colon cancer  it has been proposed that among the various cell surface proteins capable of interacting with laminin  the 67 kd high affinity laminin receptor plays a crucial role during tumor invasion and metastasis  in this study  the expression of laminin receptor precursor messenger rna  mrna  and 67 kd protein was analyzed in human colon adenocarcinoma  in 22 of 23 patients with colon cancer  we found a 2  to 23 fold increase in levels of laminin receptor precursor mrna in the cancer tissues compared with those in matched normal adjacent colonic mucosa  in 10 of 11 cases studied  the level of 67 kd laminin receptor  detected by affinity purified anti laminin receptor synthetic peptide antibodies on immunoblots of matched tumor and normal tissue extracts  was higher in the colon carcinoma tissue  immunodetection of laminin receptor in tissue sections using anti laminin receptor peptide antibodies confirmed that the increased expression of laminin receptor was specifically associated with the cancer cells  in a series of 72 paraffin sections of colon lesions  we observed a correlation between the expression of the laminin receptor and the dukes  classification  our observations indicate that increased expression of laminin receptor precursor mrna is associated with enhanced levels of the 67 kd laminin receptor as well as with the invasive phenotype of colon carcinoma  detection of this metastasis associated gene product may be a valuable adjunct in the evaluation of human colon cancer  
class4	effect of prior cancer chemotherapy on human tumor specific cytotoxicity in vitro in response to immunopotentiating biologic response modifiers  tumor specific cytotoxicity was measured in fresh human biopsy specimens by a modification of the differential staining cytotoxicity assay  imuvert  a cytokine inducer derived from serratia marcescens  which produces broad spectrum activation of both macrophages and lymphocytes  was dramatically more effective when it was tested in tumors obtained from patients with previously treated  chemotherapy responsive adenocarcinomas  breast and ovary  than when it was tested in tumors obtained from either previously untreated patients or previously treated patients with chemotherapy refractory adenocarcinomas  colon  lung  pancreas  stomach  kidney  gallbladder  uterus  and prostate   similar findings  relating to prior chemotherapy treatment status  were obtained for tumor necrosis factor and interferon gamma  but not for interleukin 2 or interferon alpha  on the basis of these findings and on other evidence in the literature  we speculate that response to chemotherapy produces massive release and processing of tumor antigens  we further speculate that this response leads to a state in which the human immune system is primed  via in situ vaccination  to respond to exogenous macrophage activation signals with potent  specific antitumor effects  
class4	elevated expression of the c fes proto oncogene in adult human myeloid leukemia cells in the absence of gene amplification  expression of the 93 kd tyrosine kinase encoded by the human c fes proto oncogene  also known as fes  is restricted to mature hematopoietic cells of the granulocytic and monocytic lineages  suggestive of a function essential to normal myeloid differentiation  however  recent studies have shown that c fes can transform fibroblasts if sufficient levels of gene expression are achieved  these findings indicate that strict regulation of the c fes gene is critical to normal myeloid development  whereas elevated c fes expression may contribute to malignant transformation  in the present study  we compared the c fes messenger rna  mrna  levels in leukemia blasts from patients with myeloid or lymphoid leukemia with those of peripheral monocytes from a normal donor with the use of a quantitative ribonuclease protection assay  the presence of c fes mrna was readily detected in both acute myeloid leukemia  aml  and chronic myeloid leukemia  cml  cells  but c fes mrna was present in low levels or was absent in lymphoid leukemia cells  the leukemia cells of two of five aml patients and four of four cml patients expressed more c fes mrna than monocytes from a normal donor  with more than a threefold elevation in the cells of one cml patient  no evidence of amplification or rearrangement of the c fes gene was detectable by southern blot analysis of myeloid leukemia dna  suggesting that the variation in c fes mrna levels are related to differences in transcriptional activity and or message stability  these results indicate that elevated c fes expression is a common feature of myeloid leukemia cells that could potentially contribute to the leukemia phenotype  
class4	comparisons of diet and biochemical characteristics of stool and urine between chinese populations with low and high colorectal cancer rates  in an investigation of the roles of diet and stool biochemistry in human colorectal carcinogenesis  24 hour food  urine  and stool samples were collected from randomly selected participants from two populations with a fourfold difference in colorectal cancer risk  chinese in sha giao  people s republic of china  low risk   and chinese americans of similar ages in san francisco county  calif  in the united states  high risk   the findings supported the hypotheses that colorectal cancer risk is increased by the consumption of high fat  high protein  and low carbohydrate diets and is associated with high levels of cholesterol in stool as well as increased daily outputs of 3 methyl histidine and malonaldehyde in urine  however  risk does not increase with low stool bulk and low total stool fibers  
class4	phase i trial of piritrexim capsules using prolonged  low dose oral administration for the treatment of advanced malignancies  a phase i trial of piritrexim was conducted by use of a prolonged  low dose oral schedule  a number of different regimens were tested  including daily dosing for 21 days followed by 7 days of no drug therapy  continuous dosing  and daily dosing for 5 of 7 days for 3 consecutive weeks followed by a week of rest  dose escalation was accomplished by increasing the dosing frequency from once a day to twice a day and then to three times a day and by increasing the number of days of administration  fifty one patients with advanced cancer were entered in the study  one hundred twenty four  96   of 129 courses were considered assessable  myelosuppression proved to be the dose limiting toxic effect  other toxic effects included stomatitis  nausea and vomiting  anorexia  diarrhea  skin rash  fatigue  and elevation of liver transaminase levels  antitumor activity was observed in patients with melanoma and bladder cancer  and disease stabilization occurred in those with sarcoma and pheochromocytoma  the recommended dosing schedule for phase ii clinical trials is 25 mg three times a day for 5 days for 3 consecutive weeks followed by 1 week of no drug therapy  
class4	magnetic resonance imaging of facial nerve neuromas  facial nerve neuromas are uncommon tumors often confused with other tumors of the temporal bone and cerebellopontine angle  radiologically  it may be impossible to differentiate an intracanalicular facial nerve neuroma from an acoustic neuroma  we present three case reports of facial nerve neuromas arising within the internal auditory canal to show the important magnetic resonance imaging features of these tumors  one tumor extended into the cerebellopontine angle  middle cranial fossa  and middle ear  another filled the internal auditory canal and extended through the cerebellopontine angle to the brain stem  the third occurred in a patient who had neurofibromatosis as well as numerous other intracranial tumors  we feel that gadolinium enhanced magnetic resonance imaging provides the most useful information in the preoperative assessment of this disorder  
class4	hematoporphyrin photodynamic therapy  is there truly a future in head and neck oncology  reflections on a 5 year experience  photodynamic therapy  which consists of the selective destruction of tumors using a combination of a photosensitizer administered systemically  dihematoporphyrin ether  and an argon dye pumped laser  has provoked profound interest amongst oncologists and has particularly titillated head and neck oncologists with its potential  unfortunately  no multi institutional trials for head and neck tumors have been introduced  and the literature is replete with anecdotal reports from individual researchers on the management of advanced cancers for palliation  superficial early cancers  and field cancerization of the mucosa   condemned mucosa    a personal 5 year experience with 41 head and neck cancers was reviewed  as was the current literature  an attempt was made to place in perspective the true role and future direction of this technology  
class4	rapid sequence treatment of advanced squamous cell carcinoma of the upper aerodigestive tract  a pilot study  a review of the literature suggested that prolonged treatment time may lessen the probability of cure for patients with advanced squamous cell carcinoma of the upper aerodigestive tract  to shorten treatment time  rapid sequence treatment  rst  was devised in which chemotherapy  surgery  and irradation were administered in a total treatment time of 8 weeks  twelve patients were treated and followed 3 years or longer  medical complications were minor  osteonecrosis occurred in each of the first five patients and was the only major complication of the protocol  surgical techniques were modified  and no additional patient developed osteonecrosis  no patient developed local or regional recurrence  two patients developed distant metastases and three other patients developed second primaries  absolute survival was 50   rapid sequence treatment is an aggressive and potentially hazardous protocol that yielded encouraging results in this pilot study  
class4	extended retrolabyrinthine transtentorial approach to petroclival lesions  in this communication  an extension of the retrolabyrinthine approach that has permitted safe  effective access to the petrous tip and clivus is presented  the basic technique involved complete mastoidectomy  preservation of the middle and inner ear structures  removal of the sigmoid and middle fossa plates  middle and posterior fossa craniotomies  ligation of the superior petrosal sinus  and division of the tentorium  nine cases that exemplified the versatility of this approach constituted the basis of this paper  2 cholesteatomas  2 basilar artery aneurysms  2 chordomas  and 3 meningiomas  the indications for  and complications of  this method have been discussed  
class4	molecular pathologic study of human papillomavirus infection in inverted papilloma and squamous cell carcinoma of the nasal cavities and paranasal sinuses  nasal inverted papilloma is a rare benign tumor occasionally associated with squamous cell carcinoma  to determine the etiological role of human papillomavirus in inverted papilloma  and to clarify the relationship between human papillomavirus and malignant transformation of this benign tumor  we retrospectively analyzed inverted papillomas from 26 patients  7 of whom had squamous cell carcinoma  we used an immunohistochemical method and molecular pathologic techniques  or dot blot hybridization of dna extracted from paraffin embedded tissues  in situ hybridization  and polymerase chain reaction  human papillomavirus was detected in 5 of 26 patients  19    3 patients with human papillomavirus 11 and 2 patients with human papillomavirus 16  the latter 2 patients had inverted papillomas associated with squamous cell carcinoma  we speculate that human papillomavirus may be related to the malignant transformation of inverted papillomas  
class4	a novel metalloproteinase gene specifically expressed in stromal cells of breast carcinomas  a gene has been identified that is expressed specifically in stromal cells surrounding invasive breast carcinomas  on the basis of its sequence  the product of this gene  named stromelysin 3  is a new member of the family of metalloproteinase enzymes which degrade the extracellular matrix  the suggestion is that stromelysin 3 is one of the stroma derived factors that have long been postulated to play an important part in progression of epithelial malignancies  
class4	germ line transmission of a mutated p53 gene in a cancer prone family with li fraumeni syndrome tumour suppressor genes  whose usual function seems to be controlling normal cell proliferation  have been implicated in many inherited and sporadic forms of malignancies much evidence supports the concept of tumour formation by loss of function mutations in suppressor genes  as predicted by the two hit model of knudson and demars  the suppressor gene  p53  is affected in such a manner by numerous mutations  which occur in a variety of human tumours  these mutations usually represent the loss of one allele and the substitution of a single base in the other  we have now analysed the p53 gene in a family affected by li fraumeni syndrome  a rare autosomal dominant syndrome characterized by the occurrence of diverse mesenchymal and epithelial neoplasms at multiple sites  in some instances the neoplasms seem to be related to exposure to carcinogens  including ionizing radiation  the li fraumeni family that we studied had noncancerous skin fibroblasts  nsf  with an unusual radiation resistant phenotype  dna derived from the nsf cells of four family members  spanning two generations  had the same point mutation in codon 245  ggc    gac  of the p53 gene  this mutation leads to substitution of aspartic acid for glycine in one of the regions identified as a frequent target of point mutations in p53  the nsf cell lines with the mutation also retained the normal p53 allele  this inherited p53 mutation may predispose the members of this family to increased susceptibility to cancer  
class4	hemorrhagic pituitary adenomas  clinicopathological features and surgical treatment  forty five  9 9   of 453 pituitary adenomas operated on between january 1973 and november 1988 demonstrated hemorrhagic changes at surgery  24 had a blood collection  12 had a blood collection associated with hemorrhagic necrosis  and 9 had hemorrhagic necrosis  thirteen patients  28 9   experienced the acute symptoms of pituitary apoplexy  whereas another 32 had an  asymptomatic  hemorrhage  that is  the clinical course was comparable to an uncomplicated adenoma  nineteen tumors  42 2   showed marked suprasellar extension  8  17 8   showed moderate extension  and 11  24 5   showed slight extension  another 2  4 4   were laterosellar and 5  11 1   were intrasellar  invasive behavior was present in 32 cases  71 1   and this may suggest another hypothesis to explain the pathogenesis of tumoral hemorrhage  the incidence of hemorrhagic complications in invasive adenomas with marked suprasellar extension was particularly impressive  therefore  we do not suggest preoperative bromocriptine treatment in this type of tumor  two of 14 patients operated on by the transcranial route died after surgery  whereas there was no operative mortality in the 31 patients operated on by the transsphenoidal route  it proved advantageous to operate as early as possible  even during the acute phase of pituitary apoplexy  the transsphenoidal approach gave the best results  but to achieve satisfactory late results multidisciplinary treatment was necessary  namely  postoperative radiotherapy in 23 patients  bromocriptine in 12  and endocrine replacement therapy in almost all  in an average follow up period of 6 2 years  5  11 1   symptomatic recurrences were observed  
class4	the association of hydrocephalus with intramedullary spinal cord tumors  a series of 25 patients  171 patients with intramedullary spinal cord tumors were operated on  of which 25 patients  15    mostly children  developed symptomatic hydrocephalus  twenty patients  12   had malignant tumors  with 13 of the 20 cases  63   complicated by increased intracranial pressure and ventriculomegaly  of the remaining 151 patients with benign tumors  89    only 12  8   developed symptomatic hydrocephalus  in an effort to understand the relationship between hydrocephalus and intramedullary spinal cord tumor  the authors analyze the level and histology of the neoplasm  as well as its association with spinal cysts  a review of the neurosurgical literature reveals that 34 similar cases of hydrocephalus associated with intramedullary spinal cord tumors have been reported to date  the authors note that the presence of hydrocephalus in patients with malignant intramedullary astrocytomas is associated with a shorter rate of survival than in those patients with high grade lesions but without hydrocephalus  apparently due to rapid tumor progression  the ventriculomegaly seen with benign spinal cord gliomas has no statistically significant effect upon long term prognosis  
class4	preoperative superselective arteriolar embolization  a new approach to enhance resectability of spinal tumors  the extent of surgical resection of spinal tumors is frequently limited by blood loss and technical difficulty associated with the vascularity of the tumors  we report here the use of superselective percutaneous arterial embolization to reduce the rate of blood loss at the time of surgical resection and enhance resectability  the types of tumors treated were metastatic renal carcinoma  metastatic thyroid carcinoma  metastatic melanoma  and giant cell tumor of the sacrum  two of the patients required repeated embolization and surgery for recurrent symptoms  the estimated blood loss in seven of nine procedures performed on the six patients ranged from 300 to 800 ml  after which no transfusion was required  in two procedures  extensive resection of very large tumors resulted in larger losses of blood  and postoperative transfusion was necessary  no significant complications of embolization or surgery occurred  a key factor in our embolization technique is the use of microfibrillar collagen  which allows occlusion of tumor vessels as small as 20 microns and may prevent reconstitution of the embolized vessels by collateral flow  we conclude that preoperative arterial embolization enhances the resectability of a variety of spinal tumors by reducing intraoperative blood loss  this may provide an additional benefit by reducing the risk related to postoperative transfusion  by permitting a more aggressive surgical approach  the use of preoperative embolization also has the potential to improve outcome in patients with spinal tumors  
class4	meningiomas involving the clivus  a six year experience with 41 patients  a series of 41 meningiomas involving the clivus operated on from july 1983 to january 1990 is reported  the presenting symptoms and signs of these patients were similar to those reported previously  all the patients were evaluated by pre  and postoperative thin section  high resolution computed tomography using soft tissue and bone algorithms  most of the patients also underwent magnetic resonance imaging  the regions of the clivus involved by tumor were divided into upper  middle  or lower regions on the basis of anatomical landmarks  the diameter of the tumor was measured in three axes  and a tumor volume and a tumor equivalent diameter were computed to categorize tumors as small  medium  large  or giant types  there were 9 medium  27 large  and 5 giant tumors in this series  some simple and some complex operative approaches were employed to effect tumor removal  large and giant tumors often required more than one operative approach to remove the tumor  intraoperative technical difficulties included tumor consistency  vascularity  dissection from the brain stem  and vascular and cranial nerve encasement  postoperative computed tomographic scans documented total excision in 32 patients  78    residual tumor remained in the clival or cavernous sinus areas  these patients were either being observed  or were treated with gamma knife radiosurgery  there was one operative death due to pneumonia  2    and three patients  7   suffered permanent major neurological changes  presumably due to vascular occlusions in the posterior circulation  in the follow up period  which ranged from 3 to 76 months  2 patients  6   with tumors that had appeared to be totally excised experienced recurrence  these patients were treated by a second operation  alone or in combination with radiation therapy  two patients who had subtotal excisions  25   had evidence of regrowth  in 2 patients  tumor growth continued despite gamma knife radiosurgery or external beam radiotherapy  
class4	surgical resection of intrinsic brain stem lesions  an overview  a major limitation to the effective treatment of intrinsic mass lesions of the brain stem has been the inability to clearly define the pathological anatomy radiographically  the improved soft tissue resolution offered by magnetic resonance imaging  as compared with axial computed tomography  now makes it possible not only to accurately distinguish anatomical relationships  but also to predict the pathological nature of the lesion  accordingly  we have been encouraged to pursue a more aggressive approach to intrinsic lesions of the brain stem that appear well circumscribed on magnetic resonance imaging scan  the object of this paper is to report the successful treatment of four intrinsic lesions of the brain stem and to present an overview of the relevant published experience  
class4	spinal hemangioblastoma  syrinx  and hydrocephalus in a two year old child  a two year old child presented with an acute inability to bear weight  radiological investigation revealed a large cervicothoracolumbar syrinx of no known cause  during investigation  acute communicating hydrocephalus developed  which required a shunt  at surgery  a small thoracic spinal cord hemangioblastoma was discovered and excised  complete recovery with collapse of the syrinx followed  the clinical features of this rare childhood tumor and its associated effects are discussed  
class4	esthesioneuroblastoma with intracranial extension  the authors present five cases of olfactory neuroblastoma with intracranial extension operated on in the department of neurosurgery in collaboration with otorhinolaryngologists  this tumor is most frequently reported as growing inside the nasal cavities  and it can extend to the paranasal sinuses  cases presenting initially as intracranial tumors have been infrequently reported  at present  histological diagnosis of this tumor is aided by the use of electron microscopy and immunocytochemistry  total resection combined with radiation therapy remains the most satisfactory treatment  
class4	cryptic osteoid osteoma of the cranium  case report  osteoid osteoma is an uncommon benign tumor of bone that rarely involves the cranium  if often causes local pain that is worse at night  characteristically relieved by aspirin  and does not correlate with the size of the lesion  the diagnosis depends on skull radiographs and computed tomography  this report describes a case in which radiographs showed nothing abnormal  the diagnosis and operative localization were accomplished with radionuclide bone scanning  thus  the possibility of radiographically cryptic lesions must be considered in the evaluation of atypical head pain syndromes  
class4	intracerebral solitary plasmacytoma  we report a rare occurrence of intraparenchymal plasmacytoma and review the literature  the clonal nature of the neoplasm is demonstrated by immunohistochemical and molecular techniques  the importance of the latter techniques in ruling out other pathological entities is stressed  
class4	mohs micrographic surgery  mohs micrographic surgery is a versatile technique for the treatment of nonmelanoma skin cancers  especially recurrent  invasive  or infiltrating basal cell carcinomas  it provides unsurpassed cure rates by using 100  surgical margin control  and it achieves maximal preservation of normal tissue  at the conclusion of tumor extirpation  the defect is ready for immediate reconstruction  with better understanding of the mohs micrographic surgery technique  it can be more effectively used as part of a coordinated multidisciplinary approach to the treatment of patients with difficult cutaneous and paracutaneous neoplasms  
class4	hyperandrogenism in peripubertal girls  androgens arise from either adrenal or ovarian secretion or by peripheral conversion of secreted precursors  the adrenals and ovaries normally contribute about equally to testosterone and ad production  dhas is the major adrenal 17 ks  testosterone is the major circulating form of androgen  more than 96  of plasma testosterone is bound to shbg  the free testosterone seems to be the bioavailable fraction  hyperandrogenism must be considered in any girl with premature or excessive development of public hair or acne  menstrual irregularity  whether it be oligo amenorrhea or dysfunctional uterine bleeding   or obesity  the most common cause of premature public hair development  pubarche  is premature adrenarche  the most common cause of hyperandrogenism presenting in a teenage girl is polycystic ovary syndrome  however  the differential diagnosis includes  exaggerated adrenarche   late onset congenital adrenal hyperplasia  virilizing tumors  cushing s syndrome  hyperprolactinemia  acromegaly  and abnormalities of androgen action or of metabolism  the plasma free testosterone is a more sensitive indicator of hyperandrogenism than is the total testosterone concentration  the pattern of response of plasma free testosterone  dhas  and cortisol to dex suppression testing is diagnostic of the source of androgen excess  most hyperandrogenic adolescents will be found to have pcos  the treatment is chosen according to particular symptoms  such as menstrual irregularity  hirsutism  or obesity  
class4	transhepatic portal vein catheterization for localization of insulinomas  a ten year experience  one of the most important factors in the management of insulinomas is the ability to localize the tumor accurately either before or during surgery  we prospectively carried out transhepatic portal venous sampling  thpvs  for tumor localization in 35 of 40 patients with organic hyperinsulinism during a 10 year period  in 32 patients who underwent thpvs and in whom a single tumor was subsequently identified surgically  the maximal insulin gradient was located in the vicinity of the tumor in 100  of cases  specific regionalization of the tumor on the basis of the site of the maximal insulin gradient to one of three regions  the tail  the body neck region  and the head uncinate region  gave a sensitivity of 81  and a specificity of 91   in contrast  the use of specific cutoff levels for the insulin gradient as a guide to the presence of a tumor in one of these three regions did not increase the accuracy  leading instead to a significant loss of sensitivity with no comparable increase in specificity  there were no major complications from the procedure in any patient  the initial use of computed tomographic ultrasound scanning and selective angiography localized only 46  of tumors  whereas subsequent thpvs led to the accurate preoperative localization of 100  of all tumors submitted to surgery  although the surgeon would have identified 81  of the tumors correctly at operation  in 19   n   6  he would have failed  four tumors were in the uncinate and two were in the head  it seems that in patients with proved or established organic hyperinsulinism  thpvs may continue to be of value  if only to regionalize the tumor  especially those in the pancreatic head and uncinate process so as to preclude noncurative operations on the body and tail of the pancreas  
class4	adenomyomatosis of the gallbladder  a premalignant lesion  gallbladder cancer is the most common malignant tumor of the biliary tract  but its early diagnosis is uncommon  the use of ultrasonography has increased the detection of benign gallbladder tumors  and the premalignant potential of gallbladder adenomas is now undisputed  adenomyomatosis of the gallbladder has recently been suggested to have malignant potential  and we report a case of adenocarcinoma of the gallbladder occurring in localized adenomyomatosis that was successfully treated by radical curative surgery  the more rigorous use of ultrasonography and a more aggressive approach to  benign  polypoid lesions of the gallbladder may represent the best way of achieving early diagnosis and cure in gallbladder cancer  
class4	greenfield filter as primary therapy for deep venous thrombosis and or pulmonary embolism in patients with cancer  in 1985  as a result of the high complication rate associated with anticoagulants in patients who have cancer and deep venous thrombosis  dvt  and or pulmonary embolism  pe   we established a policy of placing greenfield filters  gfs  as primary therapy instead of anticoagulation  since 1985 we have been asked to consult in the treatment of 18 patients with cancer and with dvt and or pe  and we have placed a gf in each of these patients  this represented 34   18 53  of the filters placed during that same period  over the same 4 year period  11 patients with cancer and dvt and or pe underwent anticoagulation therapy  the purpose of this study was to compare the results of anticoagulation versus gf insertion in these two groups of patients  a significantly higher number of major complications  n   4  occurred in the anticoagulation group  p less than 0 05  fisher s exact test  than in the gf group  n   0   the four complications that occurred in the anticoagulation group included three bleeding episodes  tumor bleeding  gastrointestinal bleeding  and hip hematoma  and one pe  despite adequate anticoagulation  two patients died as a direct result of these complications  pe and gastrointestinal bleeding   the three patients with bleeding complications each required a transfusion of more than 3 units of blood  all four of the patients with complications had metastatic disease  pancreatic carcinoma  chronic lymphocytic leukemia  prostate carcinoma  and uterine carcinoma   although this is a small  nonrandomized  nonprospective study  the data seem to indicate that gf placement is safer than anticoagulation for dvt or pe in patients with cancer and particularly in patients with metastatic disease  we conclude that gf insertions may be a better primary treatment than anticoagulation  
class4	leucine kinetics in patients with benign disease  non weight losing cancer  and cancer cachexia  studies at the whole body and tissue level and the response to nutritional support  we have performed intraoperative isotopic infusions of carbon 14 labeled leucine in 65 patients to define the abnormalities in protein metabolism at both the whole body and tissue level in patients with weight losing and non weight losing cancer  eighteen patients had benign disease  26 had non weight losing cancer  and 21 had cancer cachexia  samples of plasma and expired breath were taken to determine rates of whole body protein synthesis  wbps   whole body protein catabolism  wbpc   net protein catabolism  and albumin fractional synthetic rates  tissue samples were taken to determine the fractional synthetic rates  fsr  of protein in muscle  liver  cancer  and the tissue in which the cancer arose  in addition  in 14 patients the effect of nutritional support on protein metabolism was assessed  in all parameters examined we were unable to detect any significant differences between patients with no cancer and the patients with non weight losing cancer  in contrast  patients with cancer cachexia had a significant elevation  p less than 0 005  in wbpc compared with the other two groups  wbps was also elevated  to a lesser extent  in the patients with cancer cachexia  and the rate of net protein catabolism was increased significantly  p less than 0 05   patients with cancer cachexia also had significantly higher values of fsr of protein in muscle  p less than 0 05   liver  p less than 0 05   and albumin  p less than 0 01  compared with the other two groups  in addition  the protein fsr in the cancer rose progressively when the values for the primary cancer were compared with those for nodal and systemic metastases  further  although nutritional support resulted in an increase in host muscle protein synthesis  p less than 0 04   there was no promotion of fsr of protein in cancer  we conclude that patients with cancer cachexia are actively losing protein as a result of an increase in wbpc that is only partially compensated for by an increase in wbps  there are compensatory increases in protein synthesis in muscle and liver  but these increases in host protein synthesis are insufficient to keep pace with the combined effect of the accelerated rate of protein synthesis in the cancer per se and the accelerated rate of net protein catabolism at the whole body level  in response to nutritional support  there is a significant increase in the muscle protein synthesis  but we could not demonstrate any increase in cancer protein synthesis  
class4	gastric duplication cyst communicating with the pancreatic duct  a rare cause of recurrent abdominal pain  a 41 year old woman with recurrent attacks of postprandial abdominal pain was found on endoscopic retrograde cholangiopancreatography and subsequent computed tomographic scan to have an enteric duplication within the substance of the pancreas with communication to the pancreatic duct  celiotomy demonstrated a noncontiguous gastric duplication cyst  internal drainage was curative  
class4	myogenic regulatory protein  myod1  expression in childhood solid tumors  diagnostic utility in rhabdomyosarcoma  transcripts for the muscle regulatory gene myod1 are expressed during normal skeletal muscle myogenesis and in rhabdomyosarcomas but not in other tissues or in soft tissue sarcomas  here we report the distribution of myod1 protein  determined by reactivity with anti myod1 polyclonal sera in normal tissues  rhabdomyosarcoma cell lines  and in a variety of pediatric solid tumors  the distribution of myod1 protein was highly restricted in normal tissues and was detected only in fetal skeletal muscle and more faintly in adult skeletal muscle  all six human rhabdomyosarcoma cell lines analyzed expressed myod1 mrna transcripts as well as immunoreactive protein  the immunohistochemical expression of myod1 protein was then examined in 49 surgical specimens from a variety of pediatric solid tumors  each of 16 rhabdomyosarcoma specimens was positive for myod1  including four that did not express the intermediate filament protein desmin  two of five specimens originally designated sarcoma type indeterminate  sti  and two of three specimens originally designated extraosseous ewing s sarcoma  eoe  were positive for myod1  suggesting commitment to myogenic differentiation  three of eight wilms  tumors  which also expressed desmin and had clearly evident myogenic elements  also were positive for myod1  tumors that failed to express myod1 protein included neuroblastoma  primitive neuroectodermal tumor  non hodgkins lymphoma  embryonal sarcoma of the liver  malignant fibrous histiocytoma  malignant rhabdoid tumor  and ewing s sarcoma of the bone  these results indicate that expression of myod1 protein is highly restricted in normal human tissues and that expression of this gene product in malignant tissue may be diagnostic for rhabdomyosarcoma  furthermore myod1 staining may be a valuable adjunct in the classification of pediatric soft tissue sarcomas  
class4	vimentin expression appears to be associated with poor prognosis in node negative ductal nos breast carcinomas  vimentin expression in tumors from 83 node negative and 112 node positive patients with infiltrative ductal not otherwise specified  nos  breast carcinomas has been compared with 5 year survival  for node negative  but not for node positive patients  there was a significant inverse relation between vimentin expression and survival  five year survival of node negative patients with vimentin positive tumors was significantly worse compared with vimentin negative tumors  p less than 0 0001   in the node negative group  only 36  of patients with vimentin positive tumors but 82  of patients with vimentin negative tumors survived 5 years  tumors of all eight node negative patients with ductal nos cancer who died in the first 27 months expressed vimentin  multivariate analysis of the node negative group showed a strong correlation of vimentin expression and overall survival  but weak and not significant correlation between histologic grade or size and overall survival at 5 years  thus vimentin expression seems to be a strong indicator of poor prognosis in node negative ductal nos breast carcinomas  
class4	study of neu protein expression in mammary paget s disease with and without underlying breast carcinoma and in extramammary paget s disease  correlation between neu c erbb 2 her 2 gene amplification and overexpression of the neu gene product has been reported in tumors of glandular origin  especially ductal breast carcinomas  formalin fixed and dewaxed sections from 23 cases of mammary  mpd  and 9 cases of extramammary  epd  paget s disease were immunohistochemically stained by means of the monoclonal antibody 3b5 directed against an intracellular domain of the neu gene protein  all mpds exhibited a distinct membrane staining of tumor cells independent of the presence of ductal breast carcinomas found in 18 cases  all these breast carcinomas also were positive for neu staining  in contrast to mpd  all epds were negative  normal epidermis was always negative  northern blot analysis sustained the immunohistologic findings in that the presence of neu mrna could be demonstrated in two of three cases with mpd  negativity in one case was due to dilution effects by nontumor cells  our results suggest that paget cells of mammary and extramammary localization  although very similar phenotypically  derive from different genetic accidents  furthermore neu positivity in all mpds and all underlying ductal carcinomas suggests common genetic alterations for both tumors  however the finding of five neu protein positive mpds without associated ductal breast carcinomas may suggest a somewhat different transformation process  
class4	detection of htlv i proviral sequences in cd30 positive large cell cutaneous t cell lymphomas  to investigate the possibility that cutaneous t cell lymphomas of large cell type may be associated with human t cell leukemia lymphoma virus type i infection in nonendemic regions  tissue samples from six cases of large cell cutaneous t cell lymphoma and four cases of small cell cutaneous t cell lymphoma were screened for the presence of integrated proviral human t cell leukemia lymphoma virus type i dna  combined use of southern blot hybridization and enzymatic dna amplification revealed human t cell leukemia lymphoma virus type i specific sequences in all cases of large cell cutaneous t cell lymphoma and in none of the cases of small cell cutaneous t cell lymphoma  these results suggest that in nonendemic areas  a significant proportion of large cell cutaneous t cell lymphoma cases are associated with human t cell leukemia lymphoma virus type i  
class4	immunodetection of the metastasis associated laminin receptor in human breast cancer cells obtained by fine needle aspiration biopsy  fine needle aspiration biopsy of the breast is a very useful technique for the evaluation of a suspect lesion before surgical removal  increased expression of the 67 kd laminin receptor has been associated with the metastatic phenotype of cancer cells  particularly in colon and breast cancers  in this study  the expression of laminin receptor was evaluated using the immunoperoxidase technique in 81 breast aspirates  26 benign and 55 neoplastic lesions   cells obtained from benign samples exhibited a low level of laminin receptor antigen detected by affinity purified antibody raised against a cdna derived laminin receptor peptide  in contrast  71  of smears obtained from malignant breast lesions contained cells that were strongly stained by the antibody  heterogeneous expression of the laminin receptor was noted in both breast aspirates and fixed tissue specimens  these data suggest that the immunodetection of laminin receptor in cells obtained by fine needle aspiration of breast lesions could be a valuable adjunct in the prognostic evaluation of breast lesions  
class4	proliferation markers ki 67 and p105 in soft tissue lesions  correlation with dna flow cytometric characteristics  frozen tissue immunoreactivity with ki 67  a monoclonal antibody that recognizes a nuclear antigen in nonresting or proliferating cells  was compared to dna flow cytometry results  from fresh tissue  in a diverse group of 60 soft tissue lesions  both dna index and ki 67 score were independently reported to be associated with grade and prognosis in sarcomas  but no direct comparison of these two variables was made  it was attempted to measure proliferative activity in fixed paraffin embedded tissues immunohistochemically in a subset of lesions using an antibody to another nuclear proliferation antigen  p105  lesions were given a grade according to lesion category  reactive  1  benign  2  low grade malignant  3  and high grade malignant  4   ki 67 reactivity correlated relatively well with this grading system  r   0 59   benign lesions usually exhibited a low ki 67 score and malignant lesions usually but not always exhibited a high score  for example  some malignant fibrous histiocytomas contained only rare positive cells  some disparity between ki 67 score and grade and within histologic types indicates some independence from these features  a fact that may be important when correlation with prognosis is performed  however ki 67 did not correlate well with flow data such as percentage s phase  r   0 30   percentage s   g2m phases  r   0 37   or dna index  r   0 39   this probably is due to the fact that ki 67 also marks cells in the g1 phase  whereas these are excluded in flow data analyses  anti p105 highlighted almost all nuclei in all cases tested  including fibromatosis  and did not correlate with ki 67 score  histologic grade or dna flow cytometric data  results with p105 could not be favorably affected by titration experiments  it is reasonable to conclude that the ki 67 score is a variable related to but independent of histologic grade  histologic type  and dna flow values  whether it is prognostically important in human sarcomas  as has been suggested  awaits further clinicopathologic study  
class4	alternative splicing of endothelial cell fibronectin mrna in the iiics region  functional significance  transforming growth factor beta 1  tgf beta 1  is thought to play a role in modulating vascular cell function in vivo  in vitro  it decreases endothelial cell proliferation and migration  we postulated that these biologic activities could be mediated through tgf beta 1 modulation of specific gene expression  therefore we differentially screened a human umbilical vein endothelial cell cdna library with cdnas prepared from both untreated and tgf beta 1 treated bovine aortic endothelial cells  using this technique  we isolated many tgf beta 1 induced cdna clones  sequence analysis of these cdnas showed that many of them corresponded to alternatively spliced fibronectin mrnas  these fibronectin clones all contained the extradomain i  ed i  but three different forms of the type iii connecting segment  iiics   these different fibronectin cdnas were expressed in bacteria and the recombinant proteins used to study the effects of iiics alternative splicing on cell attachment  spreading  and migration in bovine aortic endothelial and smooth muscle cells and b16f10 melanoma cells  the results of these experiments show that attachment and spreading of bovine aortic endothelial and smooth muscle cells depend primarily on the presence of the arg gly asp ser  rgds  sequence in the recombinant fibronectin proteins  however attachment and spreading of bovine aortic endothelial cells are modulated by alternative splicing in the iiics region  specifically splicing of the iiics region decreases spreading and increases migration rates of the endothelial cells  on the contrary  using a cell line  b16f10 melanoma cells  that is known not to require the rgds sequence for adhesion confirmed previous findings that b16f10 melanoma cells do not require the presence of the rgds sequence for attachment and spreading  indeed b16f10 cells were able to attach and spread on two recombinant proteins that did not contain the rgds sequence  however attachment and spreading of b16f10 were dramatically inhibited when a 75 base pair dna fragment was removed from the 5  end of the iiics region  these results suggest that various regions of the fibronectin molecule may be able to interact with different cell populations to promote cell attachment and spreading  and that alternative splicing may modulate this process  
class4	a three dimensional system for long term culture of human colorectal adenomas  studies of the adenoma carcinoma sequence in the colon and rectum have been limited by the paucity of experimental models of adenoma growth and progression  progress recently was reported in the development of monolayer culture systems  the principal objective of this study was to develop a primary culture system for colorectal adenomas that would simulate three dimensional in vivo growth  we used a calcium alginate encapsulation technique that was previously described for established tumor cell lines  briefly  fresh resected specimens were washed  minced into small multicellular particles called microadenomas  and encapsulated in 1  calcium alginate pellets  the pellets were maintained in minimum essential medium containing 10  fetal bovine serum at 37 degrees c in humidified atmosphere of 95  air  5  co2  ten of eleven adenomas  including six tubular  three tubulovillous  and one villous have been successfully cultured for 34 to 162 days  cell viability was confirmed histologically by light and electron microscopy  the cells were characterized as epithelial by morphologic features and ultrastructural studies  which showed a high degree of cellular differentiation  including villous brush borders and many desmosomes  both tubular and villuslike structures have been observed in vitro  correlating in some cases with the histology of the parent adenoma  measurements of proliferative activity by  3h thymidine autoradiography or immunohistochemical staining with the monoclonal antibody ki 67 demonstrated growth fractions of 9  to 25   a simple  highly efficient primary culture system was developed for the long term maintenance of adenomas that promotes three dimensional growth patterns and growth rates analogous to those seen in vivo  this model provides an opportunity to develop an experimental system for longitudinal studies of pathologic and molecular parameters in adenoma progression to carcinoma  
class4	isolation of a complementary dna clone encoding an autoantigen recognized by an anti neuronal cell antibody from a patient with paraneoplastic cerebellar degeneration  we isolated a complementary dna clone encoding a 52 kd protein recognized by an anti neuronal cell antibody in serum from a patient with paraneoplastic cerebellar degeneration associated with uterine carcinoma  the recombinant protein expressed in prokaryotic cells was specifically recognized by the anti neuronal cell antibody from the patient  and its molecular weight was identical to that of antigenic proteins in the cerebellum  the deduced protein consisted of 450 amino acids dominated by hydrophilic residues  the calculated relative molecular mass was 51 238  and the predicted value of the isoelectric point was 4 99  this complementary dna sequence and the deduced protein sequence have not been reported previously  and the sequences showed no homologies with the complimentary dna or the amino acid sequences in the genbank  embl  or nbrf databases  including the complementary dna for a 34 kd cerebellar protein  cdr34  that is recognized by an anti purkinje cell antibody  unexpectedly  the transcript of this gene was detected not only in the cerebellum and the brain stem but also in an extraneural tissue  the intestine  
class4	cutaneous vasculitis associated with pheochromocytoma  we describe a patient who presented with constitutional symptoms  severe hypertension  and purpuric lesions over the knees  thighs  and penis  the patient was eventually diagnosed as having multiple endocrine neoplasia type ii  with cutaneous leukocytoclastic vasculitis  the cutaneous vasculitis persisted despite treatment with high dose systemic corticosteroids  but rapidly resolved after the removal of bilateral pheochromocytomas  this case demonstrates cutaneous leukocytoclastic vasculitis in association with pheochromocytoma  
class4	chromatin structural analysis of the 5  end and contiguous flanking region of the myeloperoxidase gene  myeloperoxidase  mpo  synthesis is known to be associated with the promyelocyte stage of myeloid differentiation  in particular the downregulation of mpo gene transcription is associated with myeloid cell maturation  we examined the changes in the deoxyribonuclease i hypersensitive sites within the 5  end of the mpo gene and its 5  flanking region during dimethyl sulfoxide  dmso  induced differentiation of hl 60 cells to determine the changes in chromatin structure that accompany this process  the locations of hypersensitive sites surrounding the 5  end of the gene in proliferating  uninduced cells were determined  three were observed in the 5  flanking region and one within the gene  progressive changes in all sites accompanied the downregulation of mpo transcription after treatment with dmso  no evidence of hypersensitivity was observed in the chromatin region examined after 8 days of dmso exposure  the results provide an example of the changes that occur in the chromatin structure of a gene as it is inactivated during differentiation  
class4	allogeneic marrow transplantation in patients positive for hepatitis b surface antigen  twenty patients who were positive for hepatitis b surface antigen  hbsag  underwent allogeneic marrow transplant for malignancy or other underlying hematologic disease between 1975 and 1986  after transplant  one patient had serologic evidence of hepatitis b virus  hbv  reactivation whereas three patients had evidence of an immune response to hbv  among four patients with serologic follow up of 1 year or more  three remained positive for hbsag and one became hbsag negative  six patients  30   developed clinical evidence of venocclusive disease and seven patients  35   developed acute graft versus host disease involving the liver  but the incidence of these complications was similar to that expected among patients who are not carriers of hbsag  three patients died with hepatorenal failure  but all three had venocclusive disease and the contribution of hbv infection to liver failure was unclear  available liver specimens obtained at autopsy  six patients  or biopsy  two patients  all showed either hbsag  one specimen  or hepatitis b core antigen  four specimens  or both  three specimens  by immunoperoxidase staining  although hbv reactivation leading to hepatic failure has been reported among allogeneic marrow transplant recipients as well as other immunocompromised patients  we did not observe an increase in the incidence of severe liver disease after transplant among these 20 patients positive for hbsag at the time of transplant  and do not consider positivity for hbsag to be a contraindication to allogeneic marrow transplantation  
class4	use of leukocyte depleted platelet concentrates for the prevention of refractoriness and primary hla alloimmunization  a prospective  randomized trial  compared with conventional transfusion regimes a strong reduction in hla alloimmunization and refractoriness to platelet transfusions is obtained when both red blood cell concentrates  rbcs  and platelet concentrates  pcs  are depleted of leukocytes by filtration  because most of the leukocyte contamination is introduced by transfusion of rbcs  filtration of rbcs appears rational  but uncertainty exists regarding the degree of leukocyte depletion of pcs needed for the prevention of hla alloimmunization and refractoriness  we conducted a prospective trial and randomized patients with acute leukemia to receive leukocyte depleted pcs prepared either by centrifugation  mean leukocyte count 35 x 10 6  pc of 6 u  or by filtration  mean leukocyte count less than 5 x 10 6  pc of 6 u   both groups received rbcs that were filtered after prior removal of the buffy coat  clinical refractoriness occurred in 46   12 of 26  of the evaluable patients that were transfused with centrifuged pcs and only in 11   3 of 27  in the filtered group  p less than  005   de novo anti hla antibodies were detected in 42   11 of 26  patients in the centrifuged group and only in 7   2 of 27  of the patients receiving filtered pcs  p less than  004   in 8 of 11 alloimmunized patients in the centrifuged group antibodies were detected in the first 4 weeks of transfusion therapy while none of the patients in the filtered group became immunized against hla antigens during that period  we conclude that for the prevention of hla alloimmunization and refractoriness to platelet transfusions from random donors  both rbcs and pcs have to be leukocyte depleted by filtration  
class4	six years  audit of laboratory workload and rates of referral for colposcopy in a cervical screening programme in three districts objective  to determine laboratory workload and rates of referral for colposcopy in a three district cervical screening programme during 1983 9 to assess the feasibility of accommodating call up of all women at risk  recall at three year intervals  now five year intervals   and investigation of women with all degrees of abnormality  design  analysis of computerised screening histories dating back to 1977 of women screened in the avon cervical screening programme  setting  three district health authorities covering the population of bristol and weston super mare  comprising 800 000 people  of whom 250 000 were female residents aged 20 to 64  subjects  196 977 women aged 20 to 64 screened in cervical screening programme since 1983  results  laboratory workload devoted to follow up of women with abnormalities increased sharply between 1987 8 and 1988 9  with increases of 54   from 2075 to 3196  in the number of smears for follow up of severe dyskaryosis and invasive cancer  40   from 1925 to 2695  for mild and moderate dyskaryosis  and 49   from 1793 to 2677  for borderline change  the increases were partly explained by the introduction in april 1988 of protocols for follow up and investigation based on guidance in an intercollegiate working party report  the proportion of women with mild and moderate dyskaryosis who were recommended for referral for colposcopy increased steadily from 9 9  in 1983 4 to 79 9  in 1988 9  and for borderline change the proportions were 3 5  and 13 6  respectively  of all women tested in 1988 9  referral for colposcopy was recommended in 3   conclusions  the increase in laboratory follow up work identified  if it continued  could result in half of existing laboratory capacity in avon being devoted to follow up work by 1993  with little prospect of maintaining call  recall  and quality control  investigation of all women with minor cytological abnormalities is neither justifiable nor sustainable and will undermine the benefits of screening by increasing the rate of false positive results and the financial costs  
class4	how district health authorities organise cervical screening  published erratum appears in bmj 1990 nov 24 301 6762  1209  objectives  to examine how district health authorities organised cervical screening with respect to department of health guidelines and to determine their assessment of the problems encountered  design  postal questionnaire sent to all 190 district health authorities in england in 1989  participants  190 district health authorities in england  main outcome measures  population coverage of screening  quality of smear testing  and follow up of abdominal test results in comparison with national guidelines for district cervical screening services  and problems encountered by districts  results  replies were received from 178  94   of districts  in 143 of which the person named as responsible for cervical screening contributed  all districts implemented a computer managed scheme  150 by the target date of 31 march 1988  but not all of these conformed with the guidelines  at the time of the survey only just over half called women in the target age group of 20 64 and only 70  expected to meet the target date of 13 march 1993 for completing the call  considerable variation was evident among the schemes with regard to how they dealt with issues related to population coverage  quality of testing  and follow up of abnormal results  the problems most commonly identified by the districts  n   174  were laboratory workload  107  61    computer software  104  60    availability of resources  78  45    non attendance  77  44    rate of opportunistic screening  62  36    and investigation and treatment  60  34    conclusions  current practice in running cervical screening schemes needs to be examined to determine the extent to which it contributes to the goal of reducing mortality from cervical cancer  
class4	diagnosis of abdominal masses with percutaneous biopsy guided by ultrasound objective  to assess the accuracy and safety of percutaneous biopsy of abdominal masses guided by ultrasound  design  prospective study  setting  combined gastroenterology service  scarborough hospital  patients  108 consecutive patients identified as having a discrete mass on diagnostic ultrasound examination of the abdomen  intervention  a sample of tissue was obtained with an aseptic technique under local anaesthesia  an 18 steel wire gauge needle  tru cut  was mounted in a spring loaded firing device  biopty gun  that was advanced under simultaneous ultrasound scanning  permitting precise localisation of the target organ  main outcome measure  results of histological examination of tissue specimens  results  biopsy failed in four patients  adequate histological specimens were obtained in 104 patients with masses in the liver  31   pancreas  37   kidney  10   and adrenal glands  six  and in 20 undiagnosed abdominal and retroperitoneal masses  follow up was until death or confirmation of the diagnosis  three complications but no deaths occurred  malignancy was suspected in 84 patients before biopsy  this was confirmed in 70 patients  in 26 of whom confirmation of dissemination obviated the need for further investigation  in 10 patients biopsy indicated a previously unsuspected primary tumour  and in 12 it showed only a benign lesion  among 24 patients considered to have benign disease biopsy showed an unsuspected neoplasm in seven  use of biopsy thus had a major effect on clinical management in 55 patients  four false negative but no false positive diagnoses resulted from the procedure  conclusion  percutaneous biopsy of abdominal and retroperitoneal masses under ultrasound guidance is a safe and accurate method of obtaining a histological diagnosis  the results obtained have a considerable effect on clinical management  
class4	etoposide  current and future status  etoposide  vp 16 213  is an antineoplastic agent with demonstrated efficacy against a broad spectrum of human malignancies  including testicular  germ cell  lung  and other cancers  etoposide can be synergistic with other agents  as part of combination chemotherapy  etoposide has become a so called standard in therapies for testicular cancer and small cell lung cancer  its activity in tumors such as lymphoma and leukemia  as well as solid tumors  identifies etoposide as a highly important chemotherapeutic agent  cellular and animal models have shown that the cell kill and tumor response depend on both dose and time of exposure  recent clinical studies again show that dose and schedule of etoposide can have important effects on clinical response to the drug  further research should now continue   1  on the use of etoposide as part of initial therapy in several cancers  and  2  in higher doses and prolonged schedules to optimize this agent s potential  
class4	new chemotherapies for ovarian cancer  systemic and intraperitoneal podophyllotoxins  the epipodophyllotoxin derivatives etoposide and teniposide have been evaluated intermittently for possible use in the treatment of ovarian cancer  conflicting studies suggest that variables such as dose and prior treatment have a major influence on outcome  response rates ranged from 0  to 40  in five series with teniposide  and from less than a 10  overall response rate to greater than a 10  complete response rate in nine studies with etoposide  one study documented activity with oral etoposide  however  because all patients had received various prior chemotherapies  firm conclusions regarding the activity of etoposide could not be drawn  these results  and the expectation of synergy with etoposide and cisplatin  led to several studies that combined etoposide with platin compounds by the systemic and intraperitoneal  ip  routes  various studies have used intravenous drug combinations of these agents in both previously treated and untreated patients  one study  which used carboplatin instead of cisplatin  reported only seven failures among 26 previously untreated patients  conversely  the prominent toxicities reported by another study were discouraging  and responses did not exceed what might be expected from cisplatin alone  studies of analogous combinations administered ip are ongoing  a favorable experience  which was initially reported by the university of california  san diego group   is being confirmed by other investigators  this has prompted the incorporation of etoposide into first line strategies  the pharmacologic advantage of etoposide by the ip route  related to its high protein binding  may provide appropriate dose intensity against ip disease while sparing systemic toxicities  finally  systemic dose intensity with autologous bone marrow support indicates some promise for etoposide in combination with high dose alkylating drugs  
class4	etoposide in the management of non small cell lung cancer  etoposide is a phase specific  schedule dependent derivative of podophyllotoxin that appears to act by inhibiting dna topoisomerase ii  early preclinical work demonstrated sharp activity in mouse leukemias and possible synergy with cisplatin  as a single agent  either orally or intravenously   it demonstrated limited benefit in non small cell lung cancer  nsclc   with response rates around 10   in combination with cisplatin  it has become a mainstay of chemotherapeutic efforts  either as primary therapy or in conjunction with radiation  response rates in advanced disease average around 30   climbing to more than 50  in patients with stage iiia or iiib disease  more recent work suggests that the issue of the true synergy of etoposide with cisplatin in nsclc needs reassessment  the relative roles of etoposide and cisplatin in the combination are unclear  as several studies conflict  pharmacokinetic data suggest that multiple daily fractions of etoposide are superior to prolonged infusions  warranting several future trials  the current major role for etoposide plus cisplatin would appear to be in multimodality therapy where the combination can be readily combined with radiation and or surgery  several other agents have been studied with etoposide or etoposide plus cisplatin  mitomycin  vindesine  doxorubicin  cyclophosphamide  ifosfamide  and carboplatin   but it is unclear whether the addition of any of them offers any response or survival advantage  
class4	recent advances in etoposide therapy for non small cell lung cancer  non small cell lung cancer  nsclc  continues to be a major health problem in the us  in 1990  approximately 120 000 new cases will be diagnosed  and the majority of these patients will have either unresectable disease or resected disease that has a relatively low chance of being cured  a variety of chemotherapy treatments have been evaluated in patients with advanced nsclc  the objective of this review is to summarize the results of the chemotherapy trials in stage iii and iv nsclc patients  
class4	current strategies in the management of locoregional and metastatic gastric carcinoma  gastric carcinoma remains a significant cause of death worldwide  a patient s prognosis depends on the degree of gastric wall penetration  presence of lymph node metastases  and location of the primary site  metastatic gastric carcinoma is currently incurable  however  chemotherapy continues to evolve at a rapid pace  active agents include 5 fluorouracil  5 fu   doxorubicin  cisplatin  methotrexate  mitomycin  and etoposide  combination etoposide  doxorubicin  and cisplatin  eap  has been reported to result in encouragingly high response rates  including a 10  complete response rate in patients with metastatic gastric carcinoma  trials are now under way to confirm these results  similarly  another etoposide based combination  etoposide  leucovorin  and 5 fu  elf   has resulted in an equally good response rate but less toxicity than eap  the 5 fu  doxorubicin  and methotrexate  famtx  regimen  previously reported to have an excellent response rate  is also being investigated further  for patients with locoregional carcinoma  curative resection rate is often unsatisfactorily low  however  curative resection is consistently associated with improved survival  between 23 and 26 months   in patients with potentially resectable carcinoma  two significant problems must be recognized   1  a low rate of curative resection and  2  the development of widespread carcinoma despite curative resection  despite many attempts  the postoperative strategies of adjuvant chemotherapy have been ineffective  new strategies must be investigated aggressively  combination etoposide  5 fu  and cisplatin  efp  has been administered preoperatively and postoperatively to patients with resectable gastric carcinoma  resulting in an encouraging curative resection rate  greater than 70   and manageable toxicity  based on promising results reported with eap in patients with unresectable locoregional carcinoma of the stomach  a trial of preoperative and postoperative eap in potentially resectable carcinoma of the stomach is now under way  
class4	etoposide in the management of metastatic breast cancer  etoposide  despite extensive use in other malignancies  has played a minor role in the treatment of patients with breast cancer  single agent trials in which etoposide is administered to heavily pretreated patients with metastatic breast cancer have demonstrated a low overall response rate  6 6  of 383 patients   with no convincing evidence for either schedule dependence or a relationship between dose intensity and response  the sole single agent trial in previously untreated patients suggested that the drug has an approximately 15  response rate in untreated patients  combination therapy trials in which etoposide has been combined with either cyclophosphamide  doxorubicin  or cisplatin have not yet convincingly demonstrated superiority over any of these drugs as single agents  although cisplatin plus etoposide appears to be superior to either agent alone  in vitro studies suggest that pretreating hormone sensitive breast cancer cells with estradiol may increase their sensitivity to etoposide induced dna cleavage  this may represent a future direction in the use of etoposide in breast cancer  currently  however  the use of etoposide in breast cancer should be considered investigational  
class4	etoposide in acute leukemia  past experience and future perspectives  etoposide as a single agent is active in relapsed and refractory acute myelogenous leukemia  aml   with complete responses  cr  rates of 10  to 25   the drug has been safely combined with cytarabine  azacytidine  vinca alkaloids  and anthracyclines  inducing remission rates of 20  to 60  in patients with previously treated aml  the experience with etoposide in acute lymphoblastic leukemia is less extensive  but the drug seems to be active in combination with cytarabine or aclacinomycin  in addition  etoposide is combined with cytarabine and anthracyclines for the primary treatment of aml  the response rates thus achieved are comparable with those obtained with standard regimens  a phase i ii trial was initiated to study the efficacy of the nove combination  mitoxantrone  10 mg m2 d  days 1 to 5  plus etoposide  100 mg m2 d for 3  4  or 5 days  in patients with refractory aml  the results showed that extended duration of etoposide administration is associated with higher cr rates  overall  a cr rate of 43  was achieved in 61 patients  a sequential regimen with idac  idarubicin cytarabine  and nove was designed for primary treatment of adult patients with aml  cycles of idac or nove are applied depending on response  the results of the pilot study with this strategy were encouraging with 18 of 20 patients achieving cr  further studies are under way to verify the efficacy of this strategy  
class4	etoposide in leukemia  etoposide  vp16 213  nsc 141540  induces a complete response  cr  in 15  to 25  of previously treated patients with acute nonlymphocytic leukemia  anll  when used as a single agent  etoposide has been used successfully in combination with cytarabine  daunorubicin  and amsacrine for salvage and consolidation therapies  previously untreated anll patients 15 to 70 years of age were randomly assigned to cytarabine  100 mg m2  on days 1 to 7 plus daunorubicin  50 mg m2  on days 1 to 3  7 3  or to the same drugs plus etoposide  75 mg m2  on days 1 to 7  7 3 7   patients achieving a cr received two consolidation courses  5 2  attenuated 7 3 or 5 2 5   among 264 eligible patients  there was a 56  cr rate with 7 3 therapy and a 59  cr rate with 7 3 7 therapy  remission duration was significantly improved with 7 3 7  median  12 months with 7 3 and 18 months with 7 3 7  p   0 01   but survival was not  subset analysis in patients younger than 55 years of age revealed prolonged remission  median  12 months with 7 3 and 27 months with 7 3 7  p   0 01  and survival  median  9 months with 7 3 and 17 months with 7 3 7  p   0 04  with the 7 3 7 regimen  hematologic toxicity was similar for both regimens during induction  but significantly more severe for 7 3 7 during consolidation therapy  etoposide is active in anll and prolongs remission when used in induction therapy  
class4	high dose etoposide and marrow transplantation  etoposide underwent conventional phase i testing in the 1970s  the dose limiting toxicity in these studies was mild myelosuppression  other toxicities were infrequent  if a greater degree of myelosuppression is accepted  higher than standard doses could be given  this approach takes advantage of the steep dose response relationship for most chemotherapeutic agents  including etoposide  as shown in early in vitro and clinical studies  thus  etoposide was considered an ideal agent for further dose escalation studies  given its wide range of clinical antitumor activity at standard doses  steep dose response curve  mild bone marrow suppression  and few nonmyeloid side effects  the high dose etoposide studies that followed used improved and more intensive hematologic supportive care  including  in some trials  autologous marrow transplantation  when etoposide was used as a single agent in these high dose trials  mucositis  and  to a lesser degree  hepatic dysfunction were dose limiting  the maximum tolerated dose  mtd  in this setting was 2 4 to 3 0 g m2  multi agent phase i trials with etoposide and cyclophosphamide  total body irradiation  carmustine  or carboplatin also resulted in dose limiting mucosal toxicity  with liver and lung problems appearing more often than with high dose etoposide alone  the toxicity and mtd can be influenced markedly by the schedule of administration  etoposide as a continuous intravenous infusion can be given at doses of 4 2 g m2  with 200 mg kg cyclophosphamide  with similar toxicity  but without marrow support  the antitumor results in the lymphomas set the stage for treatment of solid tumors  where treatment of patients with  sensitive  relapses had the best outcome  lymphoma patients had an 80  response rate  overall  long term  greater than 2 years  disease free survival was approximately 40   germ cell tumors were also responsive  and the same pattern of sensitive relapses and improvement in responding patients was seen  50  to 75  of patients greater than 1 year   in breast cancer and small cell lung cancer  sclc   high dose etoposide containing regimens were used to intensify standard therapy  the results in these settings were not quite as good  breast cancer  30  disease free survival at 2 years  sclc  10  at 2 years   
class4	the pharmacology of intravenous and oral etoposide  the epipodophyllotoxin derivative etoposide  vp 16  has been in widespread use both alone and in combination chemotherapy for the past decade  it has phase specific cytotoxicity that acts in the last s and g2 phases of the cell cycle  although its mode of action is not certain  it appears to act by causing breaks in dna by interaction with dna topoisomerase ii or by the formation of free radicals  most studies show biexponential decay after the intravenous  iv  administration of etoposide  approximately 30  to 70  of administered etoposide is excreted  with approximately 45  present in the urine  etoposide is available in oral and iv preparations  it is highly schedule dependent  with once daily doses  e g   for 5 to 8 days every 21 days  giving results superior to intermittent administration  the bioavailability of oral etoposide is approximately 50   but its absorption is not linear with increasing dose  e g   greater than 200 mg d  bioavailability decreases   factors influencing the bioavailability of oral etoposide include patient status  concurrent medications  hepatic and renal function  and nausea and vomiting  in numerous clinical trials  etoposide has demonstrated excellent activity against a range of tumors  including small cell lung cancer  sclc   malignant lymphomas  gestational trophoblastic tumors  ewing s and soft tissue sarcomas  and germ cell tumors  with more modest activity in other tumors  e g   non sclc   although few comparative studies have been carried out  available data suggest that oral etoposide administered daily during 5 to 8 days is similar to the iv preparation in range of activity  in a study of 53 elderly patients with sclc treated with etoposide  200 mg d for five times   there was a response rate of 79  and a median survival of 9 5 months  these results were similar to those achieved with more intensive iv regimens  several studies of chronic oral etoposide  50 mg m2 d for 21 times  have been reported recently  responses were observed in sclc and germ cell tumors among patients who had relapsed after standard etoposide containing regimens  these data suggest that etoposide may be a  new  drug when given in this schedule  the high response rates with oral etoposide suggest that oral administration may be substituted for iv administration  this substitution may allow for greater flexibility in chemotherapeutic administration  less hospitalization  and more acceptable toxicity  
class4	chronic oral etoposide  etoposide is an important drug that has been recently incorporated with other agents in the curative treatment of patients with advanced neoplasms  including germ cell tumors  non hodgkin s lymphomas  nhl   and small cell lung cancer  sclc   etoposide demonstrates remarkable schedule dependency  a randomized comparison has shown an impressive survival difference for patients with extensive sclc receiving a 5 day course versus those receiving a 1 day course  because of these and previous clinical and laboratory data  etoposide is now given intravenously or orally in a 3 day to 5 day schedule  it is generally accepted that approximately 50  of the orally administered drug is absorbed  the authors have initiated several etoposide studies using an extended administration schedule  believing that a prolonged schedule may be superior to the standard 3 day to 5 day schedule  this was initially tested in a phase i study  results showed that etoposide  50 mg m2 d  given over 21 days was feasible and was associated with only moderate toxicity  several phase ii studies have been completed or are nearing completion  including studies in patients with sclc  nhl  germ cell tumors  soft tissue sarcoma  renal carcinoma  and ovarian carcinoma  responses have been seen in all of these groups  particularly in patients with sclc  lymphoma  and germ cell tumors  in these groups we saw responses in patients who were clearly resistant to etoposide plus cisplatin given in a standard schedule or in some patients who were resistant to high dose etoposide with bone marrow transplantation  investigators at indiana university medical center who studied oral etoposide in a similar fashion in patients with advanced germ cell tumors and sclc achieved results similar to those reported here  the authors have initiated a number of combination chemotherapy programs using the chronic oral form of etoposide  these include patients with sclc  non small cell lung cancer  and elderly patients with high grade and intermediate forms of nhl  in addition  chronic intravenous oral etoposide is being used in salvage approaches for patients with acute myelocytic leukemia and recurrent resistant intermediate grade and high grade nhl  preliminary pharmacokinetic data suggest that a 50 mg m2 oral dose is highly bioavailable  91  to 96    therefore  during a prolonged oral course at 50 mg m2  many patients maintain a minimum plasma concentration of 1 microgram ml  further studies of multiple dose or continuous infusion etoposide to maintain a potentially critical plasma level are in progress  etoposide administered in this way could represent a  new  drug because many of its features are different  and its activity spectrum may be broader  
class4	the role of etoposide in the treatment of poorly differentiated carcinoma of unknown primary site  patients with poorly differentiated carcinoma  pdc  or poorly differentiated adenocarcinoma  pda  of unknown primary site comprise 25  to 35  of the patients with carcinoma of unknown primary site  some of these patients have neoplasms that are highly responsive to combination chemotherapy  and a minority have potentially curable tumors  between 1978 and 1982  68 patients were treated with combination chemotherapy  most received cisplatin  vinblastine  and bleomycin  pvb  with or without doxorubicin   thirty eight patients  56   responded to treatment  with 15  22   complete responder  cr  and 9  13   long term  disease free survivors  since that time  we have incorporated etoposide into the treatment of these patients because of its synergism with cisplatin and its great activity against several other neoplasms  including germ cell tumors  seventeen patients with pdc of unknown primary site received salvage therapy with etoposide and cisplatin after failing pvb  ten of these patients had partial responses  pr   with a median response duration of 5 months  range  2 to 12 months   thirty two previously untreated patients with pdc received etoposide and cisplatin combinations as initial treatment  eighteen of 30 evaluable patients  60   responded to therapy  and 11 patients  37   had cr  seven patients remain disease free 39 to 63 months after the completion of therapy  etoposide is an active drug in the treatment of pdc of unknown primary site  preliminary results indicate that initial treatment with etoposide and cisplatin combinations produces results equivalent to or superior to those achieved with pvb  
class4	future directions for etoposide therapy  etoposide is an important chemotherapeutic agent in the treatment of selected patients with germ cell tumors  lymphomas  and small cell lung cancer  sclc   its optimal use is continuing to evolve  it is clear that schedule dependency is of critical importance  recently  preliminary studies have suggested that a prolonged schedule of etoposide administration  21 days  may be more effective than the standard 3  to 5 day schedule  results of several phase ii studies show chronic oral etoposide administration induces occasional responses in resistant tumors and higher than expected response rates in patients with germ cell tumors and sclc  preliminary data show nearly 90  etoposide absorption when given in a low dose schedule  50 mg m2 d  for 21 days  these observations indicate that etoposide may be a  new drug  when given in the chronic schedule  further exploration of the schedule dependency of etoposide is indicated  etoposide has recently been proven useful in selected patients with gastric  ovarian  and poorly differentiated carcinoma of unknown primary site  several other drugs are either synergistic or additive and will be explored in combination chemotherapy  the possibility of adding topoisomerase i inhibitors and modulating etoposide s activity by inhibiting drug resistance is now within the realm of human testing  
class4	the clinical pharmacology of etoposide  etoposide  a semisynthetic derivative of podophyllotoxin  is increasingly used to treat cancer  etoposide is a phase specific  cytotoxic drug acting in the late s and early g2 phases of the cell cycle  it appears to cause breaks in dna by either an interaction with dna topoisomerase ii or the formation of free radicals  most studies show a biexponential decay after the intravenous  iv  administration of etoposide  the peak plasma concentrations of drug and the area under the concentration versus time curve  auc  are linearly related to the iv dose  considerable interpatient variability of pharmacokinetic variables exists after iv etoposide  various metabolites of etoposide have been identified  but their detection and quantitation are disputed  approximately 30  to 70  of an etoposide dose is excreted  the bioavailability of oral etoposide is approximately 50   but its absorption is not linear with increasing doses within the range in clinical use  considerable interpatient and intrapatient variability exists in the pharmacokinetics of oral etoposide  there is no evidence of etoposide accumulation after multiple consecutive doses by either the iv or oral route  the exact roles of the liver and kidney in metabolism and excretion of etoposide are uncertain  etoposide has been shown to be a highly schedule dependent drug in clinical studies  this  together with the phase specific action of etoposide and its increasingly widespread use in treating cancer  makes the clinical pharmacology of this drug of great clinical importance  
class4	diagnosis of noninfective cardiac mass lesions by two dimensional echocardiography  comparison of the transthoracic and transesophageal approaches  this study was conducted in 46 patients with cardiac thrombi  15 patients with atrial myxomas  and 32 patients with other cardiac or paracardiac tumors  diagnoses were subsequently proven by surgery  autopsy  computed tomography  magnetic resonance imaging  or angiography in all patients  all patients underwent precordial and transesophageal two dimensional echocardiography to assess the various mass detection rates  atrial myxomas and predominantly left sided cardiac tumors were identified by both echocardiographic techniques with comparable detection rates  left ventricular apical thrombi were detected more frequently by precordial echocardiography  in contrast  transesophageal echocardiography was superior in visualizing left atrial appendage thrombi  small and flat thrombi in the left atrial cavity  thrombi and tumors in the superior vena cava  and masses attached to the right heart and the descending thoracic aorta  these data indicate that transesophageal echocardiography leads to a clinically relevant improvement of the diagnostic potential in patients in whom cardiac masses are suspected or have to be excluded in order to ensure the safety of clinical procedures  
class4	effects of radiation therapy on skeletal growth in childhood  ionizing radiation was used to treat childhood cancer long before the advent of chemotherapy  and it took little time for physicians to appreciate the deleterious effects it had on skeletal growth  the cause of this complication results predominantly from alteration of chondroblastic activity  this may stem directly from irradiation at the epiphyseal plate or indirectly from irradiation of glands that secrete growth mediating hormones  the complication can go far beyond the obvious physical afflictions and extend into the psychologic domain  rendering deeper  more permanent scars  presently  many of these effects are predictable  reducible  and treatable without compromising the cure that so often depends on the use of irradiation  because of the complexities of childhood cancer therapy  strategies aimed at diminishing these effects are challenging  it is imperative that these effects be understood so that they can be reduced in current patients and prevented in future patients  
class4	limb salvage surgery in the treatment of osteosarcoma in skeletally immature individuals  sacrifice of major growth plates during resection and fixed length reconstruction of a limb in a skeletally immature child with osteosarcoma may result in a significant limb length inequality as growth progresses  a limb length discrepancy in the humerus may cause minor cosmetic problems but does not generally result in a significant functional deficit  in the lower extremity  tumors about the knee  including the distal femur and proximal tibia  usually present the dilemma of whether limb salvage by arthrodesis  osteoarticular allograft  or endoprosthetic replacement would result in a significant limb length inequality and whether amputation of the extremity is a preferable procedure  the techniques of rotationplasty and an expandable endoprosthesis have been successfully used for treating skeletally immature patients with osteosarcoma of the distal femur  with regard to survival and function  the results obtained with these innovative methods are favorable compared with those of a high above knee amputation  
class4	the cellular biology of bone tumors  new knowledge in cell and molecular biology has begun to expand the understanding of the biology of osteosarcoma and ewing s sarcoma  studies on osteosarcomas have revealed abnormalities in the growth inhibiting retinoblastoma gene  which may release cells from normal growth control  abnormalities in growth factor production or response tend to inappropriately activate cell growth  tumor cell dna content and cytogenetics may affect the diagnosis and prognostic grouping of osteosarcomas  in ewing s sarcomas  a characteristic translocation between chromosomes 11 and 22 has been identified  this translocation is also found in malignant neuroepitheliomas  a variety of studies point to both neuroectodermal and mesenchymal origins for ewing s sarcomas  applications of new biologic knowledge and technology to clinical problems will lead to significant changes in the diagnosis  and perhaps in the treatment  of these tumors in the coming years  collaborations between community and referral center physicians and scientists are critical for continued progress  
class4	osteoid osteoma of the scapula  a case report and review of the literature  the scapula is a rare location for osteoid osteoma  which in most cases does not involve the flat bones  the en bloc excision in this uncommon location can be problematic since the surgical exposure is difficult  and shoulder joint function can be affected if the lesion is subchondral  in an 18 year old man  an osteoid osteoma was located in the subchondral area of the glenoid  a guided needle biopsy of the nidus resulted in complete healing  this mode of treatment  with proper follow up examination  is acceptable for a benign lesion situated in a problematic location  
class4	autograft versus allograft for benign lesions in children  benign bone lesions in children are often so large in size that there is not an adequate amount of bone available for an autograft to fill the resultant cavity after surgical curettage  this study compared autografts and allografts with respect to the time required and the success of graft incorporation  fifty four patients with 61 lesions were studied  lesions were classified as small volume  less than 60 cc  or large volume  more than 60 cc  and were separated into four groups  small volume autograft  large volume autograft  small volume allograft  and large volume allograft  allografts appeared comparable to autografts when small volume lesions were treated  the healing time was slightly longer for allografts with an average period of 21 months versus 27 months for autografts  autografts were superior to allografts in rate and completeness of healing for solitary large lesions  this increased efficacy presumes a somewhat older child in which an adequate amount of bone is available for an autograft  a young child with multicentric or polyostotic lesions can still achieve successful incorporation with allografts  in this study  38  healed completely and 29  healed partially  allografts have a distinct place in the treatment of benign bone lesions in children  
class4	cryosurgery and acrylic cementation as surgical adjuncts in the treatment of aggressive  benign  bone tumors  analysis of 25 patients below the age of 21  this article reviews the clinical experience with cryosurgery  use of liquid nitrogen  and acrylic cementation  polymethylmethacrylate  pmma  in the treatment of aggressive  benign bone sarcomas and the biologic basis of this technique  the results of 25 patients below the age of 21 treated by cryosurgery  with an average follow up period of 60 8 months  are reported  three approaches to surgical reconstruction were used  group 1  four patients  had cryosurgery with no reconstruction  group 2  13 patients  had bone graft reconstruction alone  and group 3  eight patients  had composite osteosynthesis with internal fixation  bone graft  and or pmma  the overall control rate was 96   one recurrence   the tumor types were giant cell tumor  chondroblastoma  aneurysmal bone cyst  and malignant giant cell tumor  nineteen lesions involved the lower extremity  and six lesions were located in the upper extremity  there were two secondary fractures  8    one local flap necrosis  and one synovial fistula  there were no infections  two epiphyseodeses were performed  the functional results were excellent  83    good  13    and fair  4    the technique of composite osteosynthesis is recommended for all large tumors of the lower extremity  cryosurgical results compare favorably with those obtained by en bloc resection and demonstrate the ability of cryosurgery to eradicate tumors while avoiding the need for extensive resections and reconstructive procedures  
class4	chemotherapy for children with aggressive fibromatosis and langerhans  cell histiocytosis  two disorders involving histologically benign proliferations of fibrous tissue or of histiocytes occur preferentially in children and often require combined management by an orthopedic surgeon and a pediatric oncologist  treatment of young people with aggressive fibromatosis usually begins with wide local excision of the lesion  however  some tumors cannot be completely removed either because of their location or because of the risk of subsequent serious dysfunction  not infrequently  local recurrence supervenes despite previous wide local excision  and sometimes multiple tumors are present  in these situations a trial of multiple agent chemotherapy incorporating vincristine  actinomycin d  and cyclophosphamide may be indicated in an attempt to control the disease  radiation therapy may also be useful  but the relatively high dose  5000 cgy or more  needed in a growing child is at times a less attractive alternative  biopsy of a lytic bone lesion in young patients with langerhans  cell histiocytosis  formerly known as histiocytosis x  is also indicated for initial diagnosis  biopsy and curettage are usually curative in the patient with an isolated lesion  patients with multiple simultaneous or recurrent lesions need chemotherapy if dysfunction of the liver  spleen  or lungs is present  drug therapy may also be beneficial for children with systemic symptoms  this article outlines suggestions for chemotherapeutic treatment in both diseases  
class4	limb reconstruction with vascularized fibular grafts after bone tumor resection  limb salvage operations are being used with increasing frequency for patients with malignant bone tumors  for children  when a biologic reconstruction is desired  the choice is often between conventional and vascularized fibular grafts  an experimental study was performed in dogs to compare the two types of fibular grafts for bridging segmental defects in the radius and ulna  twenty six adult dogs were divided into two groups and studied at intervals of two  three  four  six  and 12 months after transplantation  the conventional grafts healed by creeping substitution i e   they were first partially resorbed before new bone was laid down  in contrast  the vascularized fibulae maintained their normal structure and hypertrophied by subperiosteal new bone formation  the conventional fibulae eventually hypertrophied but much later than the vascularized grafts  the vascularized grafts were stronger at four and six months  between six and 12 months  both grafts remodeled to resemble the size and shape of the forearm bones they were replacing  these experimental results have influenced the treatment of patients  vascularized fibular grafts are ideal for diaphyseal defects greater than 10 cm long  especially in very young children  a poorly vascularized bed  or when bone healing is delayed by chemotherapeutic agents  to maximize hypertrophy  an external fixator is used to immobilize the graft rather than a plate  which acts as a stress shield  
class4	modified van nes rotationplasty in the treatment of malignant neoplasms in the lower extremities of children  a technique of modified van nes rotationplasty has been used since 1981 for limb salvage surgery in children and adolescents with malignant sarcoma of the lower extremity  the original procedure for lesions of the distal femur was further modified and adopted for selected lesions of the proximal femur and tibia  sixteen skeletally immature children form the base of this report  the tumors were located in the distal femur in ten children  the proximal tibia in five and the proximal femur in one  there were no intraoperative complications and postoperative complications included one infection requiring debridement and three minor healing delays  there were no local recurrences  neurovascular compromises  late derotations  or psychologic decompensations  one patient died of metastatic disease and another died of a second malignancy  leukemia   the remaining patients are good  functional  below knee prosthesis users who participate in a number of sporting and athletic activities  the procedure is safe  has a relatively low complication rate  allows for the functional demands of an active  growing child  and accommodates for the future growth of extremities  
class4	ewing s sarcoma  prognostic factors  disease control  and the reemerging role of surgical treatment  advances in the treatment of ewing s sarcoma have been dramatic  present treatment protocols control local disease by radiotherapy  surgery  or both  systemic spread is limited by aggressive multiagent chemotherapy  in patients with localized osseous ewing s sarcoma  five year survival rates now range from 54  to an estimated 74   with late relapse not uncommon  control of the primary lesion is critical to long term survival  several studies now show improved local control and possibly improved survival of patients with surgical treatment of primary osseous ewing s sarcoma  
class4	pulmonary metastases and bone sarcomas  surgical removal of lesions appearing after adjuvant chemotherapy  pulmonary metastasis is the leading cause of death in pediatric patients with bone tumors  multiple thoracotomies for surgical removal of individual lesions are performed at many centers  to explore the efficacy of this procedure and establish guidelines for an appropriate choice of patients  the experience with 43 thoracotomies in 24 children was reviewed  the appearance of first metastasis later than one year after diagnosis  presence of fewer than five nodules  and completeness of surgical resection were favorable predictors of postthoractomy survival  early or multiple metastases  unresectable disease  and hilar  nodal  or pleural lesions conferred an unfavorable prognosis  with careful patient selection  pulmonary metastecotomy is a safe procedure that has few operative or long term complications  it must be emphasized that although surgical removal of pulmonary metastases prolongs survival with good quality of life  the majority of patients with bone sarcomas ultimately succumb to their disease after thoracotomy  follow up time of greater than eight years is necessary to adequately assess the effectiveness of pulmonary resection in eradicating all disease in these patients  
class4	the effect of chemotherapy on growth in the skeletally immature individual  one hundred twenty two children with nonmetastatic osteogenic or ewing s sarcoma were studied to assess the effect of multiagent adjuvant chemotherapy on skeletal growth and final stature  no deviations from the height distributions of a normal population were noted at diagnosis  there was a marked retardation of linear growth during the year of intensive chemotherapy  only 15  of the patients grew at the expected rate during that year  the distribution of nutritional status scores was significantly different at the end of the first year than at baseline  the distribution of ultimate height scores was significantly different than the baseline distribution  the overall final distribution was also significantly different from the normal population expectation  any absolute difference in height  however  is likely to be small  the subgroups that were observed to full adult stature showed mean heights of 162 cm for girls and 176 cm for boys  
class4	cardiac rhabdomyoma  rare cause of fetal death  two cases of nonimmune hydrops fetalis and fetal death associated with cardiac rhabdomyoma are reported  case 1 presented with fetal supraventricular tachycardia  and cardiac rhabdomyoma was accurately diagnosed by fetal echocardiography  autopsy revealed multiple rhabdomyomata involving the right atrial free wall  the sinoatrial node  and the left ventricle  the left circumflex coronary artery was extrinsically compressed by adjacent tumor tissue  causing left ventricular myocardial infarction  case 2 had a unique  pedunculated  ball like rhabdomyoma that almost totally occluded the mitral orifice  the causes of fetal death in patients with cardiac rhabdomyoma are analyzed and the possibility of fetal surgical management is proposed  
class4	99mtc anti cea radioimmunoscintigraphy of lung adenocarcinoma  anti carcinoembryonic antigen radioimmunoscintigraphy  anti cea ris  in colorectal adenocarcinoma has been reported to allow a better estimation of the local tumor extension than other radiologic methods  this study evaluated the clinical feasibility of a 99mtc labeled anti cea monoclonal antibody  bw 431 26  behring institute  frg  in 11 patients for staging of primary adenocarcinoma of the lung  the primary tumor size ranged from 3 to 8 cm with a mean of 4 cm  mediastinal and hilar nodes were present in four patients  intrapulmonary metastases were present in two patients  and pleural and liver metastases were present in one patient each  the cea levels were in the range of 2 to 265 ng ml and elevated  greater than 5 ng ml  in six patients  planar scintigraphy was performed at 6 h and 24 h post injection  pi   analog and digitized images were interpreted by two observers  one patient was imaged twice and experienced serum sickness due to human anti mouse antibodies  hama  after the second study  which showed marked unspecific tracer uptake in liver  spleen  and bone marrow  but no specific uptake by the tumor and was excluded from further analysis  visual interpretation identified the primary tumor clearly in seven patients  no tumor imaging was observed in two patients  two patients were classified as having questionable imaging due to a poor separation of tumor uptake from mediastinal blood pool  the primary tumor could be clearly delineated in both patients after comparison with the chest radiograph  thus  the overall sensitivity for imaging of the primary tumor was 82 percent  the average target background ratio was 1 31     0 17 1 at 6 h pi  and 1 30     0 16 1 at 24 h pi  hilar and mediastinal nodes were correctly suspected in three patients  but the cardiac blood pool hampered a clear interpretation  intrapulmonary and pleural metastases were diagnosed in all cases  the single liver metastasis was missed because of the high unspecific tracer uptake  planar anti cea ris with 99mtc bw 431 26 was superior to computed tomography  ct  in one case with subtotal tumor resection  we summarize that at present  planar anti cea ris with 99mtc bw 431 26 cannot be advised as a routine staging procedure in adenocarcinoma of the lung  but it may be helpful in the detection of residual or recurrent tumor tissue  
class4	pulmonary complications of combination therapy with cyclophosphamide and prednisone  oral cyclophosphamide and prednisone are standard treatment for some neoplasms and necrotizing systemic vasculitis and are advocated with increasing frequency for idiopathic interstitial lung disease  during a 15 month period  we observed four cases of acute respiratory failure from pneumocystis carinii pneumonia  pcp  in patients treated with oral cyclophosphamide and prednisone  one patient each had polyarteritis nodosa  wegener s granulomatosis  bronchiolitis obliterans with organizing pneumonia  and chronic lymphocytic leukemia with red blood cell aplasia  hypoalbuminemia  serum albumin level less than 3 0 g dl  and daily therapy were associated with increased risk for development of pcp  p less than 0 05   none of the patients had leukopenia  less than 3 500 cu mm  or neutropenia  less than 1 000 cumm  at diagnosis  all were negative for the human immunodeficiency virus  patients receiving oral cyclophosphamide and prednisone may be at higher or increasing risk for pcp  a high index of suspicion and aggressive evaluation for opportunistic infection are needed in these patients  consideration for trimethoprim sulfamethoxazole prophylaxis and development of more quantitative measures of immunosuppression are needed  
class4	minute squamous cell carcinoma arising in the wall of a congenital lung cyst  a case of minute squamous cell carcinoma arising in a congenital lung cyst is reported  two aspects of this case were notable  first  we were able to make the diagnosis of squamous cell carcinoma by bronchial lavage at an early stage  second  to our knowledge  this is the first case of probable de novo origin of squamous cell carcinoma in a congenital lung cyst  
class4	complications of general anesthesia for nd yag laser resection of endobronchial tumors  we studied the incidence and mechanisms of cardiovascular complications and postoperative respiratory insufficiency associated with ga and nd yag laser endobronchial tumor resection  the records of 73 patients undergoing 87 procedures were reviewed  preoperative status  anesthetic methods and perioperative complications were analyzed by multiple regression to determine predictors of outcome  twenty three percent of patients had greater than 90 percent mainstem bronchus obstruction  longer serum elimination half life of relaxant drug was significantly correlated with longer duration of mechanical ventilation after neuromuscular blockade reversal  cardiovascular complications were noted in 24 procedures and often required therapeutic intervention  variables predicting cardiovascular complications included longer duration of ga and increasing age  perioperative respiratory and cardiovascular complications are common after ga for nd  yag laser resection  short acting neuromuscular relaxants  careful assessment prior to postoperative extubation  limiting duration of ga and cardiovascular monitoring are recommended when implementing ga for nd  yag laser resection of endobronchial tumors  
class4	zollinger ellison syndrome  relation to helicobacter pylori associated chronic gastritis and gastric acid secretion  since helicobacter pylori infects the gastric mucosa in most patients with chronic duodenal ulcer  infection with this organism has been implicated in the pathogenesis of this common disease  we postulated that if h  pylori is pathogenic in the usual type of duodenal ulcer  it should be less common when duodenal ulcer has another  specific etiology  such as zollinger ellison syndrome  gastric mucosa was compared from 18 patients with proven zollinger ellison syndrome  17 of whom had had duodenal ulcer disease  and 18 controls with chronic duodenal ulcer without such a diagnosis  all subjects  who were matched for age and sex  had undergone elective gastric resections  gastric tissues were stained by hematoxylin eosin and giemsa and were reviewed by an experienced pathologist who was unaware of the diagnosis  the frequency of h  pylori in patients with zollinger ellison syndrome  8 18  was lower than in controls with duodenal ulcer  16 18  p less than 0 02   moreover  chronic antral gastritis scores were higher in patients with duodenal ulcer  p less than 0 01   in zollinger ellison syndrome  peak acid output was lower in patients positive  median 22 meq 30 min  compared to those negative for h  pylori  median 32 meq 30 min  p less than 0 02  but serum gastrin was correspondingly lower in patients positive for h  pylori  p less than 0 05   h  pylori infection appears to be more frequent when duodenal ulceration is not associated with another etiology  such as acid hypersecretion in zollinger ellison syndrome  h  pylori infection in zollinger ellison syndrome may also be associated with decreased gastric acid secretion  
class4	helicobacter pylori and zollinger ellison syndrome  helicobacter pylori  previously campylobacter pylori  is almost invariably associated with chronic duodenal ulcer disease  the relationship between h  pylori infection and duodenal ulcer in zollinger ellison syndrome is unknown  we investigated the frequency of h  pylori infection in zollinger ellison syndrome and also what effect h  pylori infection had on gastric function in patients with zollinger ellison syndrome  h  pylori infection was diagnosed based on a specific serologic  elisa  assay based on high molecular weight cell associated proteins of h  pylori  we studied 20 patients with zollinger ellison syndrome  15 men and 5 women ranging in age from 24 to 71 years  median age 51  six zollinger ellison syndrome patients had h  pylori infection compared to 100 consecutive patients with chronic recurrent duodenal ulcer disease  p less than 0 05   pretreatment basal acid output in zollinger ellison syndrome patients ranged from 7 9 to 95 0 mmol hr  median 35 2  pentagastrin stimulated maximal acid output ranged from 8 5 to 132 mmol hr  median 52 7  acid secretion was lower in the h  pylori infected patients than the uninfected patients  bao 24 5     6 5 vs 45 4     6 6  and mao 44 3     11 8 vs 67 9     10 7  for h  pylori infected vs uninfected patients  respectively   the difference in bao was statistically significant  p less than 0 05   the present results indicate that h  pylori is not a major contributing factor in duodenal ulcer associated with zollinger ellison syndrome  the association of a reduced bao with h  pylori suggests that these findings may be related  
class4	peptic ulcer perforation as the presentation of zollinger ellison syndrome  we examined the characteristics of patients with zollinger ellison syndrome who developed a perforation prior to diagnosis to determine whether any clinical features were useful markers of the syndrome  of 160 patients with zollinger ellison syndrome  perforation occurred prior to the diagnosis being made in 11  7    at surgery  perforations were found in the duodenum in six cases and in the jejunum in five  in no case was tumor identified at emergency surgery  and the diagnosis of zollinger ellison syndrome was made only in the postoperative period when excessive gastric secretions were noted  neither acid output nor serum gastrin concentration were useful predictors for perforation  the patients  six men and five women  were 27 61 years old  median 48  and one had men 1  three patients had no symptoms prior to the perforation  the other eight had symptoms for 1 15 years  with diarrhea occurring in 45  of the cases  following the diagnosis of zollinger ellison syndrome  patients were given medication to control gastric acid hypersecretion  eight patients remained well  but the three patients who had had a partial gastrectomy had a complicated course despite medical therapy  although features of perforation in zollinger ellison syndrome are not specific  jejunal perforation or perforation associated with a history of diarrhea is suggestive of the diagnosis  serum gastrin should be measured in every case and a partial gastrectomy avoided  
class4	partial gastric corpectomy results in hypergastrinemia and development of gastric enterochromaffinlike cell carcinoids in the rat  studies in the rat have shown that partial gastric corpectomy  in which about 75  of the acid producing oxyntic mucosa was removed  leads to markedly reduced acid secretion and a feedback increase in the plasma gastrin levels  ten weeks after operation  the gastric enterochromaffin  ecl  like cell density in the remaining part of the oxyntic mucosa had increased significantly  in the present study  the effects on the gastric ecl cells of lifelong persistent hypergastrinemia induced by partial  75   corpectomy have been investigated  seventy five partially corpectomized rats and 40 control rats were investigated for plasma gastrin and oxyntic mucosal changes in a 124 week study  the partially corpectomized rats showed increased plasma gastrin levels after the operation  the mean increase compared with the controls was almost 10 fold during the entire study  the remaining oxyntic mucosa of the partially corpectomized rats differed from that of control rats in two respects  showing first general hypertrophy and second a marked hyperplasia of argyrophil ecl cells  the degree and incidence of these changes increased towards the end of the study  i e   in the aging rats  an age related increase in ecl cell density occurred spontaneously also in the control rats but to a lesser extent than in the partially corpectomized group  ecl cell carcinoids were found in the oxyntic mucosa of 26 of the 75 partially corpectomized rats  the first carcinoid was found 78 weeks after the beginning of the study  six rats with carcinoids  23   were found before week 104  2 years  and the remainder  20  77    were discovered later  no carcinoid tumor was found in the control rats  it is concluded that lifelong hypergastrinemia induced by partial corpectomy leads to the development of ecl cell carcinoids in the oxyntic mucosa of some rats towards the end of their life span  this observation strongly supports the hypothesis that the gastric ecl cell carcinoids found in rats treated with antisecretory drugs are caused by long standing hypergastrinemia developing secondary to inhibition of gastric acid secretion  
class4	patterns of growth and metastases of induced pancreatic cancer in relation to the prognosis and its clinical implications  to understand high malignancy of pancreatic cancer  the growth and metastatic patterns of pancreatic cancer induced in syrian hamsters were examined  in this model  induced tumors resemble the human disease morphologically  clinically  biologically  and immunologically  in the current study  primary induced cancer and transplants of pancreatic cancer cell line  pc 1  into the sc tissue or pancreas of homologous hosts were used  in the primary induced pancreatic cancer  perineural invasion was the most common path  88    followed by lymphogenic  31   or vascular  2   metastases  inoculation of pc 1 cells into the pancreas resulted in 100  tumor take within 3 weeks  of 19 intrapancreatic allografts  all showed peritoneal invasion  5  26   liver metastases  3  16   lymph node metastases  17  89   perineural invasion  and none vascular invasion  even microscopic tumors were found to metastasize primarily via perineural spaces  it was also demonstrated  for the first time  that cancer cells take this route to reach distant tissues  including the lymph nodes  intraductal spreading occurred in both primary cancers and intrapancreatic allografts either continuously or discontinuously  the patterns of discontinuous intraductal tumor expansion imitated tumor multicentricity  although perineural invasion was the most common feature of primary cancer and intrapancreatic allografts  lymphatic  hepatic  and vascular invasion and metastases usually occurred in advanced cases  environmental factors seem to influence expansion and metastases  as evidenced by differences in growth and in metastatic patterns between sc and intrapancreatic allografts  
class4	granulocytic sarcoma of the colon  granulocytic sarcoma is an extramedullary tumor consisting of immature cells of the granulocytic series known to occur in patients with myelodysplastic syndrome  chronic myelogenous leukemia  or acute myelogenous leukemia  this tumor may involve nodes  cervix  bone and periosteum  and infrequently the small intestine  granulocytic sarcoma rarely occurs in the colon and has not been previously described endoscopically  we encountered a 73 year old man with myelodysplastic syndrome who presented with fever  diarrhea  and abdominal pain  colonoscopic evaluation  focal ulceration  friability  and nodularity  was compatible with crohn s disease  although histology showed a dense myeloid cell infiltrate characteristic of granulocytic sarcoma  in patients with myelodysplastic syndrome or acute or chronic myelogenous leukemia presenting with diarrhea  abdominal pain  and or fever  colonoscopy and biopsy are indicated to determine if the colon is affected by granulocytic sarcoma  
class4	hyperplastic polyps seen at sigmoidoscopy are markers for additional adenomas seen at colonoscopy  asymptomatic individuals undergoing screening flexible sigmoidoscopy were prospectively studied  polyps were found in 185 subjects  the endoscopist recorded an opinion on the polyps  histology based on endoscopic appearance  no polyps were removed at sigmoidoscopy  all subjects with rectosigmoid polyps then underwent colonoscopy and polypectomy  of them  99 subjects  54   had at least one rectosigmoid adenoma  69  37   had only hyperplastic polyps  and 17  9   had other findings  the endoscopists  opinion of the histopathology of polyps at sigmoidoscopy was correct for 61  of the lesions  of subjects with adenomatous rectosigmoid polyps  29  had additional adenomas at more proximal sites  proximal adenomas were found in 28  of patients with hyperplastic rectosigmoid polyps  patients with rectosigmoid hyperplastic polyps had the same risk for additional proximal adenomas as patients with rectosigmoid adenomatous polyps  
class4	carotid artery resection and replacement in patients with head and neck malignant tumors  tumor involvement of the carotid artery with head and neck cancers may be present either simultaneously with the primary lesion or more often appears at a later date following resection of the primary tumor  management of the secondary tumor consists of its resection together with the involved carotid artery with or without carotid artery reconstruction  the authors are convinced that the best chance for cure of patients with advanced head and neck squamous cell cancers involving the carotid artery is radical extirpation with ablative surgery in the form of en block resection of the primary lesion  the secondary tumor  and the involved carotid artery followed by immediate revascularization  this bold approach was carried out in two male patients  48 and 61 years of age  followed by chemotherapy and radiation therapy in one and radiation therapy alone in the other  with excellent results  dermal grafts were placed over the entire length of the arterialized veins to protect them from radiation injury  based on this limited experience and excellent results  we recommend this one stage surgical ablative procedure in well selected patients  however  cooperation between the ent and vascular surgeons  strict adherence to the principles and techniques of vascular surgery  and coverage of the arterialized vein with a dermal graft is absolutely essential  
class4	thrombin stimulates tumor platelet adhesion in vitro and metastasis in vivo  recent studies have revealed a role for platelets and the platelet adhesive proteins  fibronectin and von willebrand factor  vwf  in platelet tumor cell interaction in vitro and metastasis in vivo  the present report documents the effect of thrombin treatment of platelets on this interaction in vitro and in vivo  in vitro  thrombin at 100 1 000 mu ml maximally stimulated the adhesion of six different tumor cell lines from three different species two  to fivefold  as little as 1 10 mu ml was effective  the effect of thrombin was specific  inhibitable by hirudin  dansyl arginine n  3 ethyl 1 5 pentanediyl  amide and unreactive with the inactive thrombin analogue n p tosyl l phenylchloromethylketone thrombin and d phenylalanyl l propyl l arginine chloromethylketone thrombin  ppack thrombin   and required high affinity thrombin receptors  competition with ppack thrombin but not with n p tosyl l lysine chloromethyl ketone thrombin   functionally active thrombin was required on the platelet surface  binding of tumor cells to thrombin activated platelets was inhibitable by agents known to interfere with the platelet gpiib gpiiia integrin  monoclonal antibody 10e5  tetrapeptide rgds and gamma chain fibrinogen decapeptide lggakqagdv  as well as polyclonal antibodies against the platelet adhesive ligands  fibronectin and vwf  in vivo  thrombin at 250 500 mu per animal increased murine pulmonary metastases fourfold with ct26 colon carcinoma cells and 68 413 fold with b16 amelanotic melanoma cells  thus  thrombin amplifies tumor platelet adhesion in vitro two  to fivefold via occupancy of high affinity platelet thrombin receptors  and modulation of gpiib gpiiia adhesion via an rgd dependent mechanism  in vivo  thrombin enhances tumor metastases 4 413 fold with two different tumor cell lines  
class4	the growth inhibition of human breast cancer cells by a novel synthetic progestin involves the induction of transforming growth factor beta  recent experimental work has identified a novel intracellular binding site for the synthetic progestin  gestodene  that appears to be uniquely expressed in human breast cancer cells  gestodene is shown here to inhibit the growth of human breast cancer cells in a dose dependent fashion  but has no effect on endocrine responsive human endometrial cancer cells  gestodene induced a 90 fold increase in the secretion of transforming growth factor beta  tgf beta  by t47d human breast cancer cells  other synthetic progestins had no effect  indicating that this induction is mediated by the novel gestodene binding site and not by the conventional progesterone receptor  furthermore  in four breast cancer cell lines  the extent of induction of tgf beta correlated with intracellular levels of gestodene binding site  no induction of tgf beta was observed with the endometrial cancer line  hecl b  which lacks the gestodene binding site  but which expresses high levels of progesterone receptor  the inhibition of growth of t47d cells by gestodene is partly reversible by a polyclonal antiserum to tgf beta  these data indicate that the growth inhibitory action of gestodene may be mediated in part by an autocrine induction of tgf beta  
class4	coexpression of two fibronectin receptors  vla 4 and vla 5  by immature human erythroblastic precursor cells  human erythroblastic precursor cells adhere to fibronectin  fn  but the exact nature of the receptors mediating this interaction has not been characterized  in this study  we report data showing that immature human erythroblasts express the integrins vla 4 and vla 5 and that both these molecules act as fibronectin receptors on these cells  we have recently demonstrated that adhesion to fn of purified human cfu e and their immediate progeny preproerythroblasts was inhibited by antibodies directed against the human fibronectin receptor  vla 5   here we have extended those results and characterized by immunoprecipitation with specific antibodies the integrins expressed on surface labeled normal human immature erythroblasts  a polyclonal antibody recognizing the common vla beta 1 subunit yielded two polypeptides of 120 and 160 kd  our data further demonstrate that the polypeptide of 160 kd contains alpha subunits corresponding to both alpha 4 and alpha 5  thus  erythroblast lysates prepared in 0 3  chaps and immunoprecipitated with antibodies which specifically recognize the alpha 4 subunit showed a heterodimer with peptides of 120  beta 1  and 160 kd  alpha 4  and the additional peptides of 70 and 80 kd which usually coprecipitate with the alpha 4 chain  on the other hand  specific anti alpha 5 antibodies immunoprecipitated an alpha 5 beta 1 complex with peptides of 120 and 160 kd which under reducing conditions migrated as a single band of 130 kd  similar experiments performed with an erythroleukemic cell line  ku 812  showed that these cells also coexpress both the vla 4 and vla 5 members of the integrin family  furthermore  monoclonal antibodies recognizing the vla alpha 4 chain blocked the adhesion of immature erythroblasts to fn coated surfaces  thus demonstrating that  as vla 5  vla 4 is also a functional fn receptor on these cells  
class4	use of cytoplasmic 5 nucleotidase for differentiating malignant from benign monoclonal gammopathies  bone marrow smears from 15 patients with multiple myeloma  15 patients with monoclonal gammopathy of undetermined significance  mgus   and 15 control subjects were examined for the presence of cytoplasmic 5 nucleotidase  c5nt  in plasma cells  plasma cell positivity for c5nt  mean and 95  confidence interval  in patients with multiple myeloma numbered 46 4   38 0 54 8    in those with mgus it was 15 3   11 1 19 6    and in control subjects it was 1 2   0 3 2 1    these findings indicate that c5nt can be used to differentiate benign from malignant monoclonal gammopathies  
class4	immunohistochemical demonstration of pancreatic secretory trypsin inhibitor in normal and neoplastic colonic mucosa  specimens of normal and neoplastic colonic mucosa from 52 patients were analysed by immunohistochemistry using a monospecific polyclonal antiserum against human pancreatic secretory trypsin inhibitor  psti   in normal colonic mucosa psti was found in the goblet cells in the basal parts of the crypts  in adenomas of tubular  villous  and tubulo villous types psti was also found in the upper parts of the polyps  usually occurring in the regeneration zone  there was a more intense staining reaction in polyps with increased atypia  carcinomas of different types and of various grades of differentiation and of in situ type did not contain psti  these findings indicate that psti could be a marker for adenomatous rather than carcinomatous epithelium in the colon  furthermore  the absence of the inhibitor in malignant cells might facilitate tissue invasion by malignant cells because of deficient protease inhibition  
class4	human papillomavirus in oesophageal squamous cell carcinoma  thirty seven cases of oesophageal squamous cell carcinoma were studied by applying dna slot blot analysis and in situ hybridisation using type specific probes for hpv 6  11  16 and 18  cases of condyloma accuminata  cervical carcinoma  and laryngeal papilloma were used as controls  blocks including areas of invasive carcinoma  intraepithelial neoplasia  and normal epithelium were studied in each case  no hpv genome was detectable in any of the oesophageal cases  it is concluded that these types of hpv do not have an association with oesophageal squamous cell carcinoma  
class4	detection and typing of human papillomavirus using the vira type  in situ  kit  comparison with a conventional dot blot technique  a new commercial kit  vira type  in situ   life technologies  inc   molecular diagnostics division  guithersburg  maryland  usa  for the detection of human papillomavirus  hpv  types 6  11  16  18  31  33 and 35 in routinely processed human anogenital tissue was compared with a conventional dot blot assay for hpv 6  11  16 and 18  both systems use double stranded genomic dna probes for the detection of type specific hpv dna  the probes used on the dot blots were labelled with 32p and visualised autoradiographically  the vira type probes were labelled with biotin and visualised using a streptavidin alkaline phosphatase conjugate with nbt bcip substrate  biopsy specimens from the cervix  vagina  and vulva of 46 women were processed by both methods and compared  the histological diagnoses ranged from benign changes  to dysplasia  and invasive carcinoma  overall  50  of biopsy specimens were positive for hpv dna by dot blot hybridisation  only 39  were positive by vira type in situ hybridisation  three of the specimens positive by the vira type  in situ  kit showed no cross hybridisation and were the same hpv type as the dot blot  a further 13 showed hybridisation  but the showed cross hybridisation  but the to the dot blot results  one biopsy specimen was positive for different hpv types by the two tests and one was positive by vira type and negative by dot blot  six biopsy specimens were negative by vira type but positive by dot blot  it is concluded that the vira type  in situ  kit has a similar specificity but lower sensitivity than the dot blot hybridisation method for the detection of hpv dna  
class4	detection of human papillomavirus type 16 dna in carcinomas of the palatine tonsil  twenty eight tonsillar carcinomas of various histological types were investigated for the presence of epstein barr virus  ebv   cytomegalovirus  cmv   and human papillomavirus  hpv  types 6  11  and 16 by in situ hybridisation using highly stringent procedures  in six cases an autoradiographic signal was obtained in the tumour cell nuclei with the hpv type 16 specific probe  no signal was obtained with any of the other probes  immunohistochemical investigations with mouse monoclonal antibodies directed against the l1 protein of hpv type and a rabbit antiserum that detects common protein determinants of hpv gave negative results  thus indicating latent infection  furthermore  a series of tonsils from controls with comparable age distribution was negative by both in situ hybridisation and immunohistology  these results indicate a possible role for hpv 16 in the aetiology of a proportion of tonsillar carcinomas  
class4	measurement techniques for melanoma  a statistical comparison inter  and intra observer variation in measuring the depth of invasion of malignant melanomas was assessed using three different techniques  eye piece graticule  stage vernier  and projection image analysis  significant variation was found for all methods but was least pronounced with the stage vernier  it is recommended that this should be the preferred technique for routine use  
class4	bone marrow stromal cell changes in haematological malignancies  stromal cell numbers from subjects with no haematological disease and those with acute myeloid leukaemia  aml   chronic granulocytic leukaemia  cgl   acute lymphatic leukaemia  all  and non hodgkin s lymphoma  nhl  were compared to determine their role in malignancy  frozen sections of trephine biopsy specimens from iliac crests were stained for endogenous alkaline phosphatase activity  endogenous acid phosphatase activity  and  using immunocytochemical methods  for endothelial cells  anti factor viii related antigen  and macrophages and related cells  ebm 11   in granulocytic malignancies  whether acute or chronic  alkaline phosphatase positive reticulum cells  al rc  and vascular endothelial cells were generally increased  in lymphoid malignancies  the numbers of al rc were generally reduced  numbers of vascular endothelial cells seemed to be normal in all but reduced in foci of nhl  macrophages are numerous in normal marrow  and their numbers seemed to be normal in granulocytic lesions but were more variable and sometimes reduced in all and nhl  lymphoid malignancies  therefore  have a destructive effect on some stromal elements  granulocytic malignancies are associated with normal or increased numbers of stromal cells  a possible consequence of depleted stromal cells might be slower reconstitution of normal haemopoiesis after treatment  the large numbers in granulocytic malignancies raises the possibility of synergistic stimulation between stromal and neoplastic cells  
class4	cartilage removal prior to skin grafting in the triangular fossa  antihelix  and concha of the ear  skin grafting onto a large area of exposed ear cartilage with irregular contours poses an increased risk of inadequate re establishment of circulation  removal of cartilage not needed for structural support before grafting following mohs surgery on the triangular fossa  antihelix  and concha of the ear decreases the risk of recurrence of the carcinoma  and increases the chances for survival of the graft  
class4	mohs micrographic surgery fixed tissue technique for melanoma of the nose  mohs micrographic surgery  fixed tissue technique  for excision of nasal melanoma provides three important benefits  1  assurance of eradication of the main mass along with its  silent  contiguous outgrowths  2  safe management of non contiguous satellites too small to be visible initially  and 3  safe sparing of maximal amounts of surrounding normal tissues  these benefits are achieved because all incisions are through chemically fixed  killed  tissue  eliminating the danger of disseminating the highly transplantable melanoma cells and permitting the excision of successive layers for microscopic scanning of their undersurfaces by the systematic use of frozen sections  the process is continued to the termination of each ramification  there is no need to remove a wide margin of normal tissue as is customary with conventional surgery  clinically invisible satellites are not moved or disturbed and can be removed safely by the same method if they appear  the reliability of the method is manifested by the 62 5  5 year cure in a series of 10 consecutive patients  all of whom had no local recurrence after micrographic surgery  
class4	razor blade surgery  the razor blade can be a valuable tool in the performance of many minor surgical procedures  it is extremely sharp  flexible  inexpensive  readily available  and easy to use  the technique and specific applications are reviewed and discussed  
class4	fine needle aspiration for diagnosis of intranodal squamous cell carcinoma metastatic from the skin  fine needle aspiration is a useful way to determine the presence of squamous cell carcinoma in enlarged lymph nodes of patients at high risk for metastases  advantages include a high degree of accuracy  outpatient as well as inpatient availability  and negligible potential for seeding of malignant cells  cutaneous oncologists should consider using this technique in patients with lymphadenopathy and a previous history of cutaneous squamous cell carcinoma  
class4	basal cell carcinoma arising in pemphigus vulgaris of the lower eyelid  a 59 year old woman on continuous treatment with corticosteroids and immunosuppressive drugs for pemphigus vulgaris of 14 year s duration presented with an enlarging nodular lesion on the right lower eyelid  the neoplasm  diagnosed as basal cell carcinoma  was excised conserving the lid margin  and eyelid reconstruction was done with a rotated cheek flap  wound healing proceeded without complications in spite of immunosuppressive treatment  and the final cosmetic and functional result was satisfactory  
class4	elevated serum concentrations of ige antibodies to environmental antigens in hiv seropositive male homosexuals  forty five homosexual male subjects with human immunodeficiency virus  hiv  infection  who received care during a 4 month period in an ambulatory center for acquired immunodeficiency syndrome  aids   were classified according to their principal presentation with characteristic secondary infections  cdc group iv c  n   28   cancers  iv d  n   10   or limited or no symptoms  groups ii  iii  iv a  or iv b  n   7   the incidence of allergic rhinitis and conjunctivitis increased after hiv seroconversion by approximately twofold in patients of groups iv c and iv d  the mean serum concentration of ige was significantly higher for group iv c than for the other hiv seropositive groups and for a control group of 45 hiv seronegative homosexual male subjects from the same community who were studied concurrently  more patients in groups iv c and iv d had positive rasts for a panel of environmental antigens than patients in the other hiv seropositive groups and the hiv seronegative control group  patients with aids presenting with typical secondary infections thus have a high frequency of some clinical and laboratory manifestations of allergic diseases  
class4	continuous infusion carboplatin on a 21 day schedule  a phase i and pharmacokinetic study  a phase i study with continuous infusion carboplatin for 21 days every 6 weeks using a venous access port and portable pump was performed over a dose range of 12 to 32 mg m2 d  with increments of 2 mg m2 d  forty four patients received 107 courses  median  two  range  one to nine   world health organization  who  grade iii iv leukopenia and thrombocytopenia occurred in one of seven patients at 30 mg m2 d  and in two of six and four of six patients at 32 mg m2 d  cumulative platelet depression was found at dose levels of 28 mg m2 d or more  median glomerular filtration rate  gfr  and effective renal plasma flow  monitored by radioisotope clearances at doses greater than or equal to 20 mg m2 d  decreased 8 2   p less than  05  and 10 9   p less than  01  after two courses  there was a relationship  r    50  p less than  0002  between the percentage of platelet depression and gfr  no other toxicity was observed  of the 17 patients who were evaluable  one complete response and four partial responses were observed  in addition  six patients had stable disease  pharmacokinetic analysis of total and ultrafiltrable platinum  ufpt  was performed by atomic absorption spectrophotometry  steady state plasma levels for ufpt were reached after 8 hours  these levels could be detected from the 20 mg m2 d dose  during steady state  carboplatin dose and ufpt plasma levels were not correlated  but steady state ufpt and gfr  r     27  p less than  05  were  twenty four percent of total platinum  pt  was present as ufpt during steady state  x   160     10 micrograms l   total body clearance of ufpt exceeded gfr 2 2 times  mean area under the curve  auc  for ufpt during continuous infusion was 4 921 8     301 72 mg min l  for total pt  steady state plasma levels were not reached  total pt plasma levels increased between day 7 and day 21  p less than  0001   there was a significant relation between total pt serum levels day 7  14  and 21 and the drug dose administered  immunohistochemical analysis of dna bound pt in leukocytes showed a linear increase from day 7 to day 14 to day 21  r    97  between dna bound pt and duration of infusion in individual patients  the maximum tolerable dose of carboplatin is 30 mg m2 d for 21 days  total dose 630 mg m2  and is recommended for phase ii studies  
class4	cardiopulmonary resuscitation and the patient with cancer  the records of 114 cancer patients suffering cardiopulmonary arrests  cpa  during a 3 year period at memorial sloan kettering cancer center  mskcc  were retrospectively reviewed to identify variables predicting final outcome in these patients  although 65 7  of the patients were successfully resuscitated  only 12  10 5   were discharged alive from the hospital  median survival after discharge was 150 days  by univariate and multivariate analysis  the only variable predicting the likelihood of a patient s being discharged alive after a cpa was the performance status of the patient at the time of admission to the hospital  thus  a patient spending more than 50  of the time in bed at the time of admission had only a 2 3  chance of being discharged alive after cpa  a thorough discussion of these findings between physicians and patients and their families is strongly recommended at the time of admission to spare cancer patients unnecessary invasive resuscitative procedures  
class4	high survival rate in advanced stage b cell lymphomas and leukemias without cns involvement with a short intensive polychemotherapy  results from the french pediatric oncology society of a randomized trial of 216 children  from april 1984 to december 1987  the french pediatric oncology society  sfop  organized a randomized trial for advanced stage b cell lymphoma without cns involvement to study the possibility of reducing the length of treatment to 4 months  after receiving the same three intensive six drug induction courses based on high dose fractionated cyclophosphamide  high dose methotrexate  hd mtx   and cytarabine in continuous infusion  patients were evaluated for remission  those who achieved complete remission  cr  were randomized between a long arm  five additional courses with two additional drugs  16 weeks of treatment  and a short arm  two additional courses  5 weeks   for patients in partial remission  pr   intensification of treatment was indicated  two hundred sixteen patients were registered  15 stage ii nasopharyngeal and extensive facial tumors  167 stage iii  and 34 stage iv  20 of the latter having more than 25  blast cells in bone marrow  the primary sites of involvement were abdomen in 172  head and neck in 30  thorax in two  and other sites in 12  one hundred sixty seven patients are alive in first cr with a minimum follow up of 18 months  four are lost to follow up  eight patients died from initial treatment failure  14 died from toxicity or deaths unrelated to tumor or treatment  and 27 relapsed  the event free survival  efs   with a median follow up of 38 months  is 78   se 3  for all the patients  73   se 11  for the stage ii patients  80   se 3  for the stage iii patients  and 68   se 8  for the stage iv and acute lymphoblastic leukemia  all  patients  one hundred sixty six patients were randomized  82 in the short arm and 84 in the long arm  efs is  respectively  89  and 87   statistical analysis confirms equivalence of both treatment arms with regard to efs  moreover  morbidity was lower in the short arm  this study confirms the high survival rate obtained in the previous lmb 0281 study without radiotherapy or debulking surgery and demonstrates the effectiveness of short treatment  
class4	hic com  a 2 month intensive chemotherapy regimen for children with stage iii and iv burkitt s lymphoma and b cell acute lymphoblastic leukemia  we designed a protocol that included 2 months of intensive cytoxan  cyclophosphamide  bristol myers co  evansville  in   high dose methotrexate  mtx   high dose cytarabine  ara c   and vincristine  hic com  to improve event free survival  efs  for patients with advanced stage burkitt s lymphoma and b cell acute lymphoblastic leukemia  all   we also wished to test the feasibility of rapidly cycling cytoxan and high dose ara c based on signs of early marrow recovery  twenty patients including 12 with stage iii burkitt s lymphoma and eight with stage iv burkitt s lymphoma or b cell all were entered onto this pilot study  the rate of complete remission was 95   four patients have relapsed  the 2 year actuarial efs was 75   median follow up  37 months   two of the initial five patients developed transverse myelitis  which we believe may have been secondary to the concomitant administration of intrathecal  it  and high dose systemic ara c  we conclude that this short but intensive regimen is highly effective for patients with advanced burkitt s lymphoma and b cell all  efs has improved over previous less intensive regimens  and is comparable to regimens of longer duration  
class4	a phase ii study of combined methotrexate and teniposide infusions prior to reinduction therapy in relapsed childhood acute lymphoblastic leukemia  a pediatric oncology group study  teniposide  vm 26  can increase intracellular methotrexate  mtx  and its polyglutamate derivatives in vitro and thus has the potential to improve the therapeutic index of regimens containing mtx  in this phase ii study  children and adolescents with acute lymphoblastic leukemia  all  in first or second marrow relapse were randomly assigned to receive either simultaneous  n   11  or sequential  n   12  continuous infusions of mtx and vm 26 prior to reinduction  infusions of vm 26 were begun 12 hours after completion of mtx infusion in the sequential group  dosages were individually adjusted to maintain plasma concentration levels of 10 microns for mtx and 15 microns for vm 26  total infusion times were 24 and 72 hours  respectively  significant toxicity in the first six patients who received the scheduled 72 hour vm 26 infusion  including one drug related death  prompted a 50  reduction in infusion duration  the reduced dose was associated with similar but more manageable toxicity  examination of bone marrow aspirates 10 days after therapy was begun showed one complete and two partial marrow remissions  a fourth patient who had an aplastic marrow on day 10 received no further chemotherapy and had a complete remission  cr  documented on day 31  there was no obvious clinical advantage associated with either infusion schedule  although small sample sizes preclude definitive conclusions  the 17  response rate to the mtx vm 26 therapeutic window in patients with refractory disease suggests the need for further investigation to evaluate alternative schedules and concomitant therapy for this drug combination  
class4	comparison of neuropsychologic functioning and clinical indicators of neurotoxicity in long term survivors of childhood leukemia given cranial radiation or parenteral methotrexate  a prospective study  we prospectively compared neuropsychologic functioning and clinical indicators of neurotoxicity in 49 consecutive childhood leukemia patients in long term continuous complete remission  cr  who had received two different regimens of cns prophylaxis by random assignment  twenty three patients were treated with 1 800 cgy cranial radiation and intrathecal methotrexate  rt group  and 26 with parenteral methotrexate only  mtx group   over half of the rt group had somnolence syndrome  and four developed cerebral calcifications late in their clinical course  abnormal electroencephalograms  eegs  were seen in 15 patients in the mtx group  and six had early  transient white matter hypodensities apparent on computed tomographic  ct  scans  mean scores on standard tests of intelligence and academic achievement  administered after remission induction and again at a median of 6 years after treatment cessation  did not differ significantly between the two groups  however  statistically significant decreases in overall and verbal intelligence quotients  iqs  and in arithmetic achievement were found within both treatment groups  sixteen of 26 in the mtx group and 14 of the 23 in the rt group had clinically important decreases  greater than or equal to 15 points  on one or more neuropsychologic measures  these changes did not correlate with findings on ct scans  eegs  or other clinical signs of neurotoxicity  we conclude that 1 800 cgy cranial radiation and parenteral methotrexate  as used in this study  are associated with comparable decreases in neuropsychologic function  
class4	high dose chemoradiotherapy supported by marrow infusions for advanced neuroblastoma  a pediatric oncology group study  published erratum appears in j clin oncol 1991 jun 9 6  1094  we conducted a pilot protocol at seven pediatric oncology group  pog  institutions to examine the feasibility  toxicity  and efficacy of using a common regimen of high dose chemoradiotherapy  hd ct rt  supported by autologous or allogeneic marrow infusions in children with metastatic neuroblastoma  nbl  in first or second remission  during a 57 month period  we accrued 101 patients  we report here results for the 81 who completed treatment at least 2 years ago  the hd ct rt regimen consisted of melphalan 60 mg m2 d for three doses  and total body irradiation  tbi  either 1 5 gy  n   27  or 2 0 gy  n   54  twice daily for six doses  twenty three patients also received irradiation consisting of 1 2 gy twice daily for 10 doses to persisting disease sites  seventy four were given autologous and seven allogeneic marrow  64 autologous marrows being purged immunomagnetically  fifty four children were in first complete  cr  or partial  pr  remission and 27 in second cr or pr  as of october 1  1990  follow up was from 32 to 72 months  forty seven of these 81 children relapsed  10 died of complications  one of unknown cause  and 23 continue in remission  including 21 of the 54 treated in first remission  and 16 who completed treatment more than 3 years ago  the 2 year actuarial event free survival  efs  probabilities are first cr  cr1  32   se 10    first pr  pr1  43   se 9    second cr  cr2  33   se 27    and second pr  pr2  5   se 5    probability of efs correlated with remission number  first better than second  p less than  001   with interval from diagnosis to hd ct rt  greater than 9 months better than less than 9 months  p    055   and with tbi dose  12 gy better than 9 gy  p    031   these encouraging results may partly reflect selection for this treatment of patients with nbl who have a slower disease pace  
class4	relationship of tumor cell ploidy to histologic subtype and treatment outcome in children and adolescents with unresectable rhabdomyosarcoma  published erratum appears in j clin oncol 1991 may 9 5  893  clinical and histopathologic features are often inadequate for accurate prediction of relapse or survival of individual patients with rhabdomyosarcoma  rms   we therefore studied the cellular dna content  ploidy  of rms cells in relation to histology and response to therapy in 37 patients with unresectable tumors  using flow cytometric techniques  we found that about one third of patients had diploid tumor stem lines  regardless of the histologic subtype  in the group with abnormal ploidy  a hyperdiploid classification  1 10 to 1 80 times the dna content of normal diploid cells  was exclusively associated with embryonal histology  p    001   by contrast  near tetraploidy  1 80 to 2 60 times the dna content of normal cells  was strongly associated with alveolar histology  p    001   thus  in these histologic subtypes of rms  abnormal ploidy appears to arise through different mechanisms  tumor cell ploidy had a significant impact on survival that was especially apparent in patients with unresectable  nonmetastatic  group iii  tumors  in this subgroup  hyperdiploidy conferred the best prognosis and diploidy the worst  p less than  0001   none of the eight patients with diploid tumors survived for more than 18 months  tumor cell ploidy was the best predictor of treatment outcome for patients with either embryonal  p less than  001  relative risk  25 5  or alveolar  p    073  relative risk 7 1  rms and contributed significantly after adjustment for disease stage and anatomic site  patients with unresectable diploid rms have an unacceptably high risk of treatment failure  justifying new therapeutic approaches for this distinct subgroup  
class4	fludarabine phosphate  a synthetic purine antimetabolite with significant activity against lymphoid malignancies  fludarabine phosphate is the 2 fluoro  5  monophosphate derivative of vidarabine  ara a  with the advantages of resistance to deamination by adenosine deaminase  ada  and improved solubility  the mechanism of cytotoxic action of the compound appears to involve metabolic conversion to the active triphosphate  fludarabine phosphate has substantial activity against lymphoid malignancies  particularly chronic lymphocytic leukemia  cll  and low grade non hodgkin s lymphoma  nhl   its single agent activity in cll appears at least comparable to those of other conventional combination regimens  its activity in hodgkin s disease  mycosis fungoides  and macroglobulinemia  although suggestive  needs to be further defined and clinical trials are warranted in hairy cell leukemia  prolymphocytic leukemia  and previously untreated myeloma  the compound does not appear active against most common solid tumors  early clinical trials indicated significant myelosuppression and the potential for severe neurotoxicity  toxicity on the currently used low dose schedules includes transient and reversible myelosuppression  nausea and vomiting  diarrhea  somnolence fatigue  and elevations of liver enzymes and or serum creatinine  possible pulmonary toxicity has been suggested in several patients  the currently used low doses of fludarabine phosphate  even with repeated administration  are well tolerated and appear safe with a negligible risk for severe neurotoxicity  based on its single agent activity and tolerability  the food and drug administration recently granted group c designation of the drug for the treatment of patients with refractory cll outside the clinical trials setting  the use of fludarabine phosphate in combination regimens and its impact on the natural history of the lymphoid malignancies is yet to be determined  fludarabine phosphate may well occupy a pivotal role in the management of cll and low grade nhl  
class4	a phase ii clinical trial of carboplatin infusion in high risk acute nonlymphoblastic leukemia  carboplatin  cbdca  is a second generation platinum drug that has been shown to be useful when used as a continuous infusion in treatment of refractory adult leukemia  we report on the effectiveness of continuous infusion cbdca  300 mg m2 d x 5 days  as evaluated in nine patients with secondary acute nonlymphocytic leukemia  anll   seven previous myelodysplastic syndrome and two treatment associated anll   three anll patients in first relapse  six refractory anll  and nine patients with blastic phase of chronic myelogenous leukemia  bp cml   all patients were considered assessable  the response rate was 44   eight complete remissions  crs   four partial remissions  prs    median duration of postchemotherapy neutropenia was 36 days  range  18 to 45   therapy was well tolerated  and toxicity was mainly hematologic and nondose limiting  despite prolonged neutropenia  severe infections were rarely seen  and most patients were managed as outpatients  twelve patients had nausea and vomiting  two had symptomatic hypomagnesemia  and one patient showed reversible ototoxicity  because of substantial antileukemic activity and unusual extrahematologic toxicity  cbdca appears to be an effective second line agent in the treatment of anll and should be considered for upgrading to first line treatment regimens  
class4	fludarabine  a new agent with marked cytoreductive activity in untreated chronic lymphocytic leukemia  thirty three patients with chronic lymphocytic leukemia  cll  with advanced rai stage  iii iv  or progressive rai stage  0 ii  disease were treated with fludarabine as a single agent  eleven patients  33   obtained a complete remission  cr   13  39   a clinical cr with residual nodules as the only evidence of disease  nodular partial remission  pr    and two patients  6   achieved a pr for a total response rate of 79   response was rapid  usually occurring after three to six courses of treatment  the major morbidity was infection  febrile episodes occurred in 13  of the courses  pneumonia 6   minor infection 4   and transient fever of undocumented cause 3    fludarabine appears to be the most cytoreductive single agent so far studied in cll  
class4	cytotoxic chemotherapy induces cell differentiation in small cell lung carcinoma  despite the high response rates resulting from chemotherapy  the majority of small cell lung cancer  sclc  patients relapse with chemoresistant tumors  to analyze the phenotypic changes that are precursors of chemoresistant status  and to investigate the role of chemotherapy in these changes  tumor samples from 20 patients  taken before chemotherapy  etoposide  doxorubicin  and cyclophosphamide  and again at the onset of chemoresistance  after at least three courses of chemotherapy   were compared  the histologic changes were minor in 10 of 20 patients  as shown by an increase in cell size  they were major in 10 of 20 patients  with the appearance of mixed composite tumors in which neuroendocrine  ne   epidermoid  and glandular components were mixed  major changes correlated with a good response to chemotherapy  p    001   ultrastructural studies showed an increase in neurosecretory granules and desmosomes  and a high frequency of multidirectional differentiation  45   when comparison was made with pretherapy samples  10    p less than  01   immunohistochemical  ih  analysis showed an increase in cytokeratin  ck  expression in treated patients  with a different labeling pattern and the expression of higher molecular weight ck  the expression of ne lineage markers  leu 19  sy 38  sl 11 14  remained stable  while that of ne differentiation markers  leu 7  chromogranin  increased in the treated patients  the neuron specific enolase  nse  activity remained stable in treated sclc  large cells with a more differentiated phenotype and proliferative capacity  as shown by ki 67 labeling   appeared to be characteristic of treated and secondary chemoresistant sclc  the acquisition of a more complex phenotype  which correlates with primary response to therapy  implies a drug induced differentiation in sclc  
class4	effectiveness of carboplatin  etoposide  and bleomycin combination chemotherapy in good prognosis metastatic testicular nonseminomatous germ cell tumors  the combination of carboplatin  etoposide  and bleomycin  ceb  was evaluated as initial chemotherapy in 76 patients with good prognosis metastatic nonseminomatous germ cell tumors  nsgct  between 1984 and 1988  the classification of eligible patients included royal marsden hospital  rmh  stages im  iia  iib  iic  iiia  iiib  iv0abcl1  and iv0abl2  four courses of combination chemotherapy were administered in a 21 day cycle  and surgical excision of residual mass was performed in 27 cases  23 laparotomies and four thoracotomies   at the time of analysis  median follow up was 24 months from start of chemotherapy  range  6 to 54 months   the 2 year cause specific survival probability was 98 5   the single cause related mortality being caused by bleomycin pneumonitis  five patients failed ceb chemotherapy  but all have been successfully salvaged with a combination of surgery and intensive chemotherapy  follow up from completion of all treatment being 35 to 44 months  the toxicity of ceb included bone marrow suppression and alopecia in all patients but no significant neurotoxicity or ototoxicity  and minimal renal toxicity  only four  5   patients had a decrease in the glomerular filtration rate greater than 15   in 51  of patients  the hemoglobin fell below 10 g dl  the wbc count nadir was less than 1 500 microl in 11  of treatment cycles and in 16  the platelet nadir fell below 50 000 microl  decreases in the wbc and platelet counts were of very brief duration  only one of 310 ceb cycles was complicated by neutropenic sepsis  and there were no episodes of thrombocytopenic purpura or bleeding  we conclude that the ceb combination represents an effective alternative to cisplatin based chemotherapy in good prognosis nsgct and that the replacement of cisplatin by carboplatin leads to reduced toxicity  
class4	how american oncologists treat breast cancer  an assessment of the influence of clinical trials  the present study was designed to assess the preferred methods of treatment of breast cancer by american oncologists  and the impact of clinical trials on their practice  we mailed 465 questionnaires to surgical  radiation  or medical oncologists  the questionnaire described five hypothetic patients with breast cancer  and respondents were asked to select their preferred treatment for each patient  for primary breast cancer  most physicians would offer the choice of local excision followed by radiation therapy or modified radical mastectomy  about 80  of physicians would prescribe adjuvant chemotherapy for a premenopausal woman with estrogen receptor negative  axillary node negative breast cancer  and for a postmenopausal woman with estrogen receptor negative  node positive disease  this policy was favored by male and female physicians of each specialty  almost all respondents would treat a young woman with inflammatory breast cancer with initial chemotherapy followed by radiation and or surgery  and about 60  would recommend chemotherapy to a postmenopausal patient with estrogen receptor negative disease and minimally symptomatic bone metastases  clinical trials have compared treatment strategies that could be applied to patients described in our questionnaire  preferred treatments for primary breast cancer  and for inflammatory breast cancer are supported by the results of clinical trials  recommendation of adjuvant chemotherapy for node negative breast cancer is not based on a consistent demonstration of improvement in survival  although randomized trials with short follow up have shown delay to recurrence  recommendation of adjuvant chemotherapy for a postmenopausal woman with node positive breast cancer is contrary to the results of large randomized controlled trials  and to a meta analysis   which have shown that this policy does not lead to improved survival  our report suggests that even large randomized clinical trials may have a minimal impact on practice if their results run counter to belief in the value of the treatment  
class4	4 hydroperoxycyclophosphamide purging of breast cancer from the mononuclear cell fraction of bone marrow in patients receiving high dose chemotherapy and autologous marrow support  a phase i trial  we designed an ex vivo bone marrow treatment for breast cancer patients receiving high dose chemotherapy and autologous bone marrow support  abms   using 4 hydroperoxycyclophosphamide  4 hc   an active derivative of cyclophosphamide with known activity against breast cancer  this phase i bone marrow purging trial used ficoll separated mononuclear cells  mnc   devoid of granulocytes and rbcs   as opposed to the buffy coat  twenty five patients with metastatic breast cancer were studied  patients received three cycles of the adriamycin  doxorubicin  adria laboratories  columbus  oh   fluorouracil  and methotrexate  duke afm  regimen  followed by marrow harvest  an mnc fraction of marrow was prepared and treated with 4 hc in concentrations of 20 micrograms ml  four patients   40 micrograms ml  four patients   60 micrograms ml  nine patients   or 80 micrograms ml  eight patients  and cryopreserved  patients then received high dose systemic cyclophosphamide  cisplatin  and carmustine  followed by infusion of the purged marrow  the study end point was marrow engraftment  defined as wbc count greater than 1 000 cells per microliter  at the first three dose levels  20  40  and 60 micrograms ml 4 hc   there was no significant delay in time to engraftment  19  20  and 23 days  respectively  compared with the unpurged historical controls  17 days   at 80 micrograms ml  engraftment was significantly delayed compared with the lower concentrations  p    027   and further escalation of 4 hc was not attempted  a significant correlation was observed between the time of leukocyte engraftment and the 4 hc concentration  p    017   with a methylcellulose based tissue culture assay  we demonstrated a statistically significant correlation between the colony forming unit granulocyte macrophage  cfu gm  content in the purged marrow and the days to engraftment  ninety five percent of patients responded clinically to the entire program  55  of them completely  longer follow up is required to assess the ultimate benefit of intensive therapy on long term survival  
class4	phase i clinical trial with floxuridine and high dose continuous infusion of leucovorin calcium  sixty two patients with metastatic disease were treated with continuous infusion folinic acid  leucovorin calcium  lv  and 2 deoxy 5 fluorouridine  floxuridine  fudr   lv was given by constant intravenous  iv  infusion at 500 mg m2 d  days 1 to 6  while fudr was given by iv push  days 2 to 6  at 3 00 pm daily with doses ranging from 294 to 1 214 mg m2 d  this program was well tolerated with dose limiting toxicities of diarrhea and stomatitis  while hematologic toxicity was minimal  eighty two percent of the assessable patients  46 of 56  had failed at least one chemotherapy regimen  one complete remission lasting 9 months and 10 partial remissions ranging from 5 to 10 months were observed in this heavily pretreated patient population for an overall response rate of 20   these data suggest that the combination therapy with lv and fudr may have clinical use  because of differing patient sensitivity to this drug combination  the recommended dose of fudr for the initial therapy cycle is 500 mg m2 d  days 2 to 6  with subsequent escalation to 900 mg m2 d in those patients without extreme sensitivity  phase ii studies are now in progress with these doses  
class4	effect of dietary alpha linolenic acid on growth  metastasis  fatty acid profile and prostaglandin production of two murine mammary adenocarcinomas  the purpose of this study was to determine whether dietary  n 3  fatty acids would affect mammary tumor growth and metastasis  weanling female balb c mice were fed diets that contained 10  corn oil  co   linseed oil  lo  or a fish oil corn oil mix  fo  for 3 8 wk prior to receiving subcutaneous injections of one of two syngeneic mammary tumor cell types  410 and 410 4   tumor growth was assessed by monitoring mean tumor diameter and tumor weight upon removal  feeding lo  but not fo  reduced the growth  p less than 0 05  of 410 4 mammary tumors compared with growth in those fed co  metastasis data paralleled the tumor growth rate  feeding lo and fo enhanced  p less than 0 005  incorporation of  n 3  fatty acids into tumors  tumor prostaglandin e  pge  production was reduced  p less than 0 005  by lo and fo  compared with co  fo feeding reduced 410 4 tumor pge synthesis more  p less than 0 05  than lo feeding  yet tumor growth was only inhibited by lo  these data suggest an inhibitory effect of dietary linolenic acid  i e   18 3  n 3   on mammary tumor growth and metastasis  however  this effect did not directly correlate with diet induced changes in pge synthesis  
class4	extraoral application of osseointegrated implants  the use of osseointegrated implants to provide support for craniofacial prostheses has provided the clinician with another approach to the treatment of complex craniofacial reconstructive problems  the surgical technique is reviewed and the mayo clinic experience is presented  
class4	central odontogenic fibroma  clinicopathologic features of 19 cases and review of the literature  the odontogenic fibroma is a benign neoplasm infrequently reported in the literature  20 cases   nineteen additional examples are reported  this lesion occurs most frequently in the maxilla anterior to the molars and displays a striking female predilection  on occasion  it may be associated with an unerupted mandibular third molar  histomorphologically  it is not encapsulated  a spectrum of fibrous connective tissue stroma is present  from myxoid to densely hyalinized and from relatively acellular to cellular  calcification may or may not be present  it is distinguished by the presence of sparse cords and islands of inactive odontogenic epithelium  enucleation or surgical curettage is appropriate therapy and recurrence is low  as there appears to be no correlation of histologic pattern with clinical behavior  it seems unnecessary to try to separate the tumor into two variants  
class4	antisecretory and antilesional effect of a new histamine h2 receptor antagonist  it 066  in rats  the effects of a new histamine h2 receptor antagonist  it 066  3 amino 4  4  4  1 piperidinomethyl  2 pyridyloxy  cis 2     butenylamino   3 cyclobutene 1 2 dione hydrochloride   were investigated on the secretagogue induced acid secretion in vivo and in vitro  and on experimental gastric and duodenal lesion in rats  it 066  10 60 micrograms kg  given i v  inhibited histamine stimulated acid secretion dose dependently in gastric lumen perfused rats  and the inhibitory effect was observed for about 12 hr  famotidine  fmd   10 60 micrograms kg i v   also had an antisecretory effect  but the acid secretion recovered to the control level 4 hr after the administration  cold stress plus indomethacin induced lesion was significantly inhibited by it 066 and fmd given i v  30 min before the cold stress plus indomethacin treatment  it 066 given 7 hr before the cold stress plus indomethacin treatment also inhibited lesion formation significantly  but such antilesional effect was not observed with fmd  in the rat isolated gastric mucosal sheet  it 066 inhibited histamine stimulated acid secretion dose dependently and noncompetitively  its action was produced via a unique mechanism  the inhibitory effect of it 066 remained after washing of the mucosa  and became more potent time dependently  the inhibitory effects of fmd and cimetidine were not observed after washing the mucosa  these data suggest that it 066 has a potent and long lasting antisecretory effect in vivo and in vitro  and that these properties are responsible for the long lasting antilesional action  
class4	potent selective inhibition of 7 o methyl ucn 01 against protein kinase c  ucn 01 is a staurosporine related compound that was isolated from the culture broth of streptomyces sp  and shows potent and selective inhibitory activity against protein kinase c  cellular inhibitory activity of ucn 01 against protein kinase c and cytotoxicity of ucn 01 were compared with those of staurosporine  when the mechanism of inhibitory activity was investigated in vitro  ucn 01 as well as staurosporine inhibited the activity of the catalytic domain of protein kinase c  in spite of direct inhibition against the catalytic domain of protein kinase c  cytotoxicity of ucn 01 was much lower than that of staurosporine  in addition  ucn 01 showed more selective inhibitory activity against protein kinase c than did staurosporine because of the sole structural difference at c 7  therefore  a series of 7 o alkyl derivatives of ucn 01 was synthesized and investigated  interestingly  one of the compounds  the beta methoxy derivative  showed 3 fold greater potency and 17 fold more selective inhibitory activity against protein kinase c than did ucn 01  
class4	stimulatory effects of maitotoxin on insulin release in insulinoma hit cells  role of calcium uptake and phosphoinositide breakdown  in hamster insulinoma  hit  cells  maitotoxin  mtx  induces a time dependent and concentration dependent release of insulin that requires the presence of extracellular calcium  the response is nearly completely blocked by cinnarizine and cadmium  but is not inhibited by the l type calcium channel blocker nifedipine or by manganese  mtx induces 45ca  uptake in these cells in a dose dependent mode  and the uptake is blocked with cinnarizine  nifedipine and cadmium  and is partially inhibited by manganese  mtx induces phosphoinositide breakdown in hit cells  and the response is partially blocked by cadmium  but is not affected by nifedipine  cinnarizine or manganese  high concentrations of potassium ions also induce insulin release and calcium uptake in hit cells  both effects of potassium are blocked partially by nifedipine  cadmium and cinnarizine  high concentrations of potassium do not induce phosphoinositide breakdown in hit cells  the results suggest that mtx elicited release of insulin is attained by two mechanisms  1  a nifedipine sensitive action  which results from mtx induced activation of l type calcium channels  which can be mimicked with high potassium concentrations  and 2  a nifedipine insensitive action  which may be initiated by the activation of phosphoinositide breakdown by mtx  such an activation of phospholipase c would result in the formation of 1 4 5 inositol trisphosphate  a release of intracellular calcium and then release of insulin to the extracellular space  cinnarizine is proposed to block both mtx elicited mechanisms  the first by blockade of calcium channels and the second by blocking 1 4 5 inositol trisphosphate induced release of internal calcium  either mechanism alone appears capable of eliciting release of insulin  
class4	improved outcome in childhood acute lymphoblastic leukaemia with reinforced early treatment and rotational combination chemotherapy  to improve outcome in childhood acute lymphoblastic leukaemia  all   a stratified  randomised study of extended intensified chemotherapy was done  358 evaluable patients received remission reinforcement therapy  teniposide  cytarabine  high dose methotrexate  added to a four drug induction regimen  those achieving complete remission were randomised on the basis of risk group assignment to conventional continuation treatment or to four pairs of drugs rotated weekly or every 6 weeks  all patients received intrathecal chemotherapy  higher risk patients also received 1800 cgy cranial irradiation after 1 year of remission  complete remission was induced in 96  of the patients  at median follow up of 40  range 19 73  months  4 year event free survival  se  was 73  4   overall  81  6   in the lower risk group  n   110   and 69  5   in the higher risk group  n   248   outcome within risk groups was not significantly affected by the speed of rotation of drug pairs during continuation treatment  various high risk subgroups had apparently improved responses to this treatment  this intensified chemotherapy may cure 69 77  of children with all  
class4	nd yag laser in the microsurgery of frontobasal meningiomas  forty three patients with big frontobasal meningiomas underwent a microsurgical removal of the tumor  the 1 32 microns nd yag laser has proved useful in this prospective series particularly with the contactless shrinkage of the tumors and the necrotization of the dural and bony attachments  tumor shrinkage was achieved by radiating the tumor surface with the nd yag laser  this technique facilitated the microsurgical dissection and reduced the blood loss by half  the nd yag laser necrotization of the dural and bony attachments reduced the recurrence rate following grade two resections from 20  to zero  the postoperative quality of life was excellent with a complete rehabilitation in 76  of the patients  the use of the 1 32 microns nd yag laser improved significantly the results of microsurgery for frontobasal meningioma  
class4	molecular surgery of the basement membrane by the argon laser  although the argon laser is used successfully to weld a number of different tissues  the underlying chemical and cellular mechanisms for this process are not precisely defined  consequently  a biochemical model has been developed in vitro using the well defined extracellular matrix from the murine engelbreth holm swarm  ehs  sarcoma  control and experimental samples of ehs basement membranes were irradiated with a trimedyne argon laser at 500 3 000 joules cm2 at 0 degrees c  the samples were diluted into cold phosphate buffered saline and allowed to gel at 35 degrees c  the time course of the gelation reaction was followed in a spectrophotometer at 360 nm  irradiation reduced the absorbance 7 5 15  compared to controls and was independent of the dilution over a 10 fold range  gelation was also measured by determining the amount of protein by the bradford assay that could be collected by centrifugation at 10 000g for 10 minutes  argon irradiated samples had 30 40  less protein in the precipitate than the controls  the addition of 5 mm beta mercaptoethanol to the ehs extract blocked the effect of the laser on the gelation reaction  in addition  when gelation was carried out in the absence of calcium and magnesium  there were no differences between laser treated samples and controls  the basement membrane proteins were separated by electrophoresis through polyacrylamide gels under denaturing plus reducing or denaturing and non reducing conditions  no differences in the polypeptide composition were noted between irradiated and control samples using either coomassie  or silver staining techniques  
class4	cancer mortality in workers exposed to 2 3 7 8 tetrachlorodibenzo p dioxin background  in both animal and epidemiologic studies  exposure to dioxin  2 3 7 8 tetrachlorodibenzo p dioxin  or tcdd  has been associated with an increased risk of cancer  methods  we conducted a retrospective cohort study of mortality among the 5172 workers at 12 plants in the united states that produced chemicals contaminated with tcdd  occupational exposure was documented by reviewing job descriptions and by measuring tcdd in serum from a sample of 253 workers  causes of death were taken from death certificates  results  mortality from several cancers previously associated with tcdd  stomach  liver  and nasal cancers  hodgkin s disease  and non hodgkin s lymphoma  was not significantly elevated in this cohort  mortality from soft tissue sarcoma was increased  but not significantly  4 deaths  standardized mortality ratio  smr   338  95 percent confidence interval  92 to 865   in the subcohort of 1520 workers with greater than or equal to 1 year of exposure and greater than or equal to 20 years of latency  however  mortality was significantly increased for soft tissue sarcoma  3 deaths  smr  922  95 percent confidence interval  190 to 2695  and for cancers of the respiratory system  smr  142  95 percent confidence interval  103 to 192   mortality from all cancers combined was slightly but significantly elevated in the overall cohort  smr  115  95 percent confidence interval  102 to 130  and was higher in the subcohort with greater than or equal to 1 year of exposure and greater than or equal to 20 years of latency  smr  146  95 percent confidence interval  121 to 176   conclusions  this study of mortality among workers with occupational exposure to tcdd does not confirm the high relative risks reported for many cancers in previous studies  conclusions about an increase in the risk of soft tissue sarcoma are limited by small numbers and misclassification on death certificates  excess mortality from all cancers combined  cancers of the respiratory tract  and soft tissue sarcoma may result from exposure to tcdd  although we cannot exclude the possible contribution of factors such as smoking and occupational exposure to other chemicals  
class4	prognostic value of immunocytologic detection of bone marrow metastases in neuroblastoma  background  morphologic evaluation of bone marrow for neuroblastoma cells is a routine and important component of clinical staging  specific immunostaining of malignant cells with monoclonal antibodies should be more sensitive  however  and may improve the detection of metastases and provide additional prognostic information  methods  we looked for tumor cells in bone marrow from 197 patients with newly diagnosed neuroblastoma  using immunoperoxidase staining with monoclonal antibodies  immunocytologic analysis  and examination of smears and specimens obtained by trephine biopsy  conventional analysis   results  routine smears and trephine biopsy specimens were positive for tumor cells in 46 percent of the patients  whereas 67 percent were positive on immunocytologic analysis  p less than 0 0001   immunocytologic analysis detected bone marrow metastases in 34 percent of patients considered to have only localized or regional disease  stage i  ii  or iii   it also identified tumor cells that were not detected by conventional analysis in patients with widespread disease  stage iv or ivs   tumor content  as determined by immunocytologic analysis  predicted clinical outcome in relation to the age of the patient at diagnosis  patients with stage ii or iii disease diagnosed after one year of age who did not have occult marrow metastases did well  whereas those with metastases did poorly  p   0 006   patients in whom stage iv disease was diagnosed before they were one year of age did well if bone marrow metastases were few or absent  but had poor survival if the marrow contained more than 0 02 percent tumor cells  p   0 03   conclusions  immunocytologic analysis of bone marrow aspirates is more sensitive than conventional analysis in detecting tumor cells and provides prognostic information  the relations among marrow metastases  age at diagnosis  and clinical outcome illustrate the biologic heterogeneity of neuroblastoma  
class4	neonatal subependymal giant cell astrocytoma associated with tuberous sclerosis  mri  ct  and ultrasound correlation  we describe a term newborn with tuberous sclerosis who presented with a neonatal brain tumor  diagnosed as a subependymal giant cell astrocytoma  we compare the various imaging modalities used in the diagnosis of this tumor  
class4	absence of acetylcholine induced current in epithelial cells from thymus glands and thymomas of myasthenia gravis patients  we investigated the activity of ion channels in epithelial cells from human thymus glands and thymomas kept in short term cell culture by clamping the membrane potential of the cells at  85 mv and determining the membrane current flowing on application of acetylcholine  glycine  or gamma aminobutyric acid  in concentrations of up to 10  3  m  none of the neurotransmitters induced any detectable current  this suggests  1  that there are no acetylcholine receptors  achrs  or other products of the achr gene family having ion channel properties in the membranes of these epithelial cells  and  2  that the alpha bungarotoxin binding protein of thymus and thymoma has no achr like ion channel property  these results support the hypothesis that the cross reacting structures that elicit the anti achr autoimmune response in thymoma associated myasthenia gravis are antigens having only limited homology with the achr  myasthenia gravis not associated with thymoma might have a different pathogenesis  
class4	brain and spinal cord hemorrhage in long term survivors of malignant pediatric brain tumors  a possible late effect of therapy  three children with malignant primary cns tumors treated with craniospinal radiotherapy developed intraparenchymal hemorrhages a median of 5 years following therapy in sites distant from the primary tumor  radical surgical procedures disclosed fresh and old hematoma  gliosis  and necrosis in all 3 patients and an aggregation of abnormal microscopic blood vessels in two  no tumor was found  all 3 patients remain in long term  greater than 10 years  continuous remission  
class4	comparison of myelography with ct follow up versus gadolinium mri for subarachnoid metastatic disease in children  we evaluated 17 children with primary intracranial neoplasms for subarachnoid metastatic disease  samd  using myelography with computed tomographic follow up  myelo   ct  and cerebrospinal fluid  csf  histopathologic examination  as well as magnetic resonance imaging with gadolinium dtpa  mri   gd   between december 1988 and december 1989  there were 12 boys  and the median age was 5 7 years  range  0 8 to 21 8 years   tumor histology included 8 primitive neuroectodermal tumors  pnets   3 ependymomas  2 low grade astrocytomas  1 anaplastic astrocytoma  1 glioblastoma multiforme  1 atypical rhabdoid tumor  and 1 malignant fibrous histiocytoma  thirteen tumors originated in the posterior fossa  2 were supratentorial  and 2 were in the spinal cord  the median interval between the 2 diagnostic tests was 2 days  mri   gd was positive in 11  65    myelo   ct in 8  47    and csf in 5  29   cases  mri   gd was superior in delineating spinal cord nodules and  sugar coating  whereas myelo   ct more readily revealed nerve root sleeve filling defects  there was no case in which myelo   ct was positive that mri   gd did not reveal samd  mri   gd is a safe  noninvasive test that should be used as the initial imaging modality for the presence of samd  
class4	dysgeusia  gustatory sweating  and crocodile tears syndrome induced by a cerebellopontine angle meningioma  facial nerve involvement in cerebellopontine angle tumors  both during their development and after excision  may be expressed in irreversible dysfunction of the parasympathetic pathways  the exact location of the lesion along the efferent nerve fibers can be established through evaluation of the functional level of those organs supplied by the cholinergic motor secretory components  this report deals with a female patient in whom peripheral facial palsy developed shortly after removal of a right cerebellopontine angle meningioma  she had slight facial asymmetry and deafness in the right ear and complained of prandial flush and sweating of the right malar area  occult ipsilateral hyposalivation and hypolacrimation were diagnosed  in patients with seventh and ninth cranial nerve pathoses  evaluation of the end organs that are supplied by their associated autonomous nerve fibers is mandatory to prevent late ocular and oral sequelae  
class4	salivary flow rates in patients with head and neck cancer 0 5 to 25 years after radiotherapy  in this clinical study at the university of texas m  d  anderson cancer center  unstimulated and stimulated salivary flow rates were obtained from 47 patients with head and neck cancer who had received mantle  unilateral facial  or bilateral facial field radiotherapy from 0 5 to 25 years earlier  the magnitude of salivary flow rate reduction compared with a healthy control group was primarily related to the radiation dosage and the amount of salivary gland tissue included in the irradiated fields  flow rates were lower for women in all groups  but these differences were not statistically significant  
class4	intramuscular hemangioma in the oral region  report of three cases  the occurrence of intramuscular hemangioma in an intraoral or perioral localization is rare  and a thorough knowledge of these tumors is necessary for adequate diagnosis and treatment  three cases are presented with discussion  and their histopathology and differential diagnosis are discussed  an adequate primary excision is necessary to avoid recurrence  
class4	human papillomaviruses  pediatric perspectives on a family of multifaceted tumorigenic pathogens as summarized here human papillomaviruses are associated with a wide spectrum of epithelial lesions  ranging from benign warts to invasive carcinomas  they have been difficult to study in part because they have not yet been propagated in tissue culture  fortunately advances in molecular biology have allowed characterization of hpv genomes and identification of some hpv gene functions  in addition to their clinical importance hpvs represent an important tool for exploring virus cell interactions  gene expression  cellular differentiation and cancer  hpv infections are not only common but also difficult to treat and prevent  depending on the hpv type and location  the modes of hpv transmission may involve casual physical contact  sexual contact and perinatal vertical transmission  hpv dna genomes replicate at a low copy number in basal cells and  as most clinicians know  are difficult to eradicate  there is often a long latent period and subclinical infections  and hpv dna can be found in normal tissue adjacent to lesions  hpvs can cause widely disseminated lesions  especially in the immunocompromised host and in epidermodysplasia verruciformis  aside from the rare carcinomas  the most serious life threatening hpv induced illness in children is recurrent respiratory papillomatosis  somewhat surprisingly in malignant lesions hpv dna is also found as fragments incorporated into the cellular genome  unlike retroviruses such as human immunodeficiency virus which integrate into the cellular genome as part of their life cycle  hpv integration is a terminal event for viral replication  such integration may be critical  however  for viral induced abnormal cell growth  perhaps the most important implication of the finding that some anogenital cancers are in part sexually transmitted infectious diseases is that they may be preventable  the data overwhelmingly suggest that avoidance of exposure to hpv via abstinence or monogamy in both partners markedly reduces the risk of cervical cancer  a more realistic goal  however is prevention of hpv transmission by the use of barrier method contraceptives  which may be protective against development of cervical carcinoma  the america association of pediatrics committee on adolescents has outlined the obligation of pediatricians to be actively involved in adolescent education on sexually transmitted diseases  certainly a fundamental knowledge of hpv epidemiology  the risks of hpv related sequelae and prevention of hpv infection are important considerations for adolescent sexuality  although helpful  such awareness alone falls far short of making an impact on sexual behaviors  a significant reduction in hpv infection rates could be achieved only by inundating adolescents at an early age with a highly visible society wide campaign directed at these issues  
class4	the butterfly rash and the malar flush  what diseases do these signs reflect  the butterfly rash and malar flush are common facial manifestations of several disorders  systemic lupus erythematosus may produce a transient rash before any other signs  in pellagra  symmetric keratotic areas on the face are always accompanied by lesions elsewhere on the body  erysipelas produces brawny  fiery red facial lesions  and scarlet fever causes facial eruptions as part of a generalized eruption  lupus vulgaris and lupus pernio produce nodules that may spread in a butterfly pattern  and seborrheic dermatitis has a predilection for the malar prominences and other areas of the face  carcinoid syndrome often causes flushing attacks that vary in duration  and facial flushing that lasts throughout treatment may accompany chemotherapy if the patient has a hypersensitivity reaction  deep red rashes and or lichenoid lesions may be caused by graft versus host disease in a patient undergoing bone marrow transplantation  
class4	analysis of interleukin 2 and various effector cell populations in adoptive immunotherapy of 9l rat gliosarcoma  allogeneic cytotoxic t lymphocytes prevent tumor take  recombinant interleukin 2  ril 2  and various effector cell populations were used for adoptive immunotherapy in the fischer strain 9l rat gliosarcoma model  the in vivo cytotoxicities of nonspecifically activated lymphocytes and specifically activated cytotoxic t lymphocytes  ctls  were assessed in a modified in vivo neutralization  winn  assay  effector cells  10 6   and 9l tumor cells  10 5  were combined with 10 4  units of ril 2 and stereotactically implanted into the right frontal centrum semiovale of the fischer  f344  rat  at 7 and 14 days  additional effector cells  10 6  and ril 2  10 4  units  were administered through the same burr hole  nonspecifically activated splenocytes were lymphokine activated killer  lak  cells  both plastic adherent and nonadherent  whereas specifically activated ctls were either syngeneic  genetically identical  or allogeneic  genetically dissimilar   syngeneic ctls were t lymphocytes from fischer rats primed in vivo with 9l cells and restimulated in vitro  allogeneic ctls were generated by exposing da rat lymphocytes either to irradiated fischer lymph node cells or to 9l fisher tumor cells in vitro  control groups included rats bearing 9l tumor who were untreated  those who received peripheral  i p  or s c   administration of ril 2  or those who received syngeneic unstimulated t lymphocytes and ril 2  for a set of animals given the same inoculum of 9l tumor  significantly improved survival was shown for groups treated with nonadherent or adherent lak cells  p less than or equal to 0 0003   syngeneic ctls  p   0 0327   or allogeneic ctls  p   0 0025  over untreated control animals by using mantel haenzel nonparametric logrank equations  only treatment with allogeneic ctls prevented tumor take  
class4	activation of early events of the mitogenic response by a p2y purinoceptor with covalently bound 3  o  4 benzoyl  benzoyladenosine 5  triphosphate  3  o  4 benzoyl benzoyl atp  bzatp   a photoaffinity analog of atp  was used as a ligand for a p2y purinoceptor  adenine nucleotide receptor  present in intact swiss 3t3 and 3t6 cells and a 431 epidermoid carcinoma cells  photolysis of serum starved cells in the presence of 10 50 microm bzatp  followed by extensive washing to remove unincorporated bzatp  induced the release of arachidonic acid  a trace  less than 0 01   of photoincorporated bzatp was as effective as when 50 microm bzatp or atp was contained in the incubation medium during the assay  photoincorporated bzatp also stimulated the production of prostaglandin e2 and the accumulation of cyclic amp  in previous studies  we demonstrated that these three events are obligatory early steps in a pathway leading to dna synthesis in the above cell lines  the evidence indicated that the purinoceptor activated by extracellular atp or bzatp was linked to a pertussis toxin sensitive gtp binding protein  consistent with these observations  we now find that pertussis toxin inhibits the effect of photoincorporated bzatp on arachidonic acid release  these results indicate that bzatp is an effective agonist for the p2y purinoceptor concerned with stimulation of dna synthesis in 3t3  3t6  and a 431 cells  furthermore  after photolysis it becomes irreversibly associated with intact cells and promotes the activation of early events required for dna synthesis  
class4	human tumor necrosis factor alpha gene regulation by virus and lipopolysaccharide  we have identified a region of the human tumor necrosis factor alpha  tnf alpha  gene promoter that is necessary for maximal constitutive  virus induced  and lipopolysaccharide  lps  induced transcription  this region contains three sites that match an nf kappa b binding site consensus sequence  we show that these three sites specifically bind nf kappa b in vitro  yet each of these sites can be deleted from the tnf alpha promoter with little effect on the induction of the gene by virus or lps  moreover  when multimers of these three sites are placed upstream from a truncated tnf alpha promoter  or a heterologous promoter  an increase in the basal level of transcription is observed that is influenced by sequence context and cell type  however  these multimers are not sufficient for virus or lps induction of either promoter  thus  unlike other virus  and lps inducible promoters that contain nf kappa b binding sites  these sites from the tnf alpha promoter are neither required nor sufficient for virus or lps induction  comparison of the sequence requirements of virus induction of the human tnf alpha gene in mouse l929 and p388d1 cells reveals significant differences  indicating that the sequence requirements for virus induction of the gene are cell type specific  however  the sequences required for virus and lps induction of the gene in a single cell type  p388d1  overlap  
class4	boron neutron capture therapy of intracerebral rat gliosarcomas  the efficacy of boron neutron capture therapy  bnct  for the treatment of intracerebrally implanted rat gliosarcomas was tested  preferential accumulation of 10b in tumors was achieved by continuous infusion of the sulfhydryl borane dimer  na4 10 b24h22s2  at a rate of 45 50 micrograms of 10b per g of body weight per day from day 11 to day 14 after tumor initiation  day 0   this infusion schedule resulted in average blood 10b concentrations of 35 micrograms ml in a group of 12 gliosarcoma bearing rats and 45 micrograms ml in a group of 10 similar gliosarcoma bearing rats treated by bnct  estimated tumor 10b levels in these two groups were 26 and 34 micrograms g  respectively  on day 14  boron treated and non boron treated rats were exposed to 5 0 or 7 5 mw min of radiation from the brookhaven medical research reactor that yielded thermal neutron fluences of approximately 2 0 x 10 12  or approximately 3 0 x 10 12  n cm2  respectively  in the tumors  untreated rats had a median postinitiation survival time of 21 days  reactor radiation alone increased median postinitiation survival time to 26  5 0 mw min  or 28  7 5 mw min  days  the 12 rats that received 5 mw min of bnct had a median postinitiation survival time of 60 days  two of these animals survived greater than 15 months  in the 7 5 mw min group  the median survival time is not calculable since 6 of the 10 animals remain alive greater than 10 months after bnct  the estimated radiation doses to tumors in the two bnct groups were 14 2 and 25 6 gy equivalents  respectively  similar gliosarcoma bearing rats treated with 15 0 or 22 5 gy of 250 kilovolt peak x rays had median survival times of only 26 or 31 days  respectively  after tumor initiation  
class4	identification of transforming growth factor beta family members present in bone inductive protein purified from bovine bone  characterization of the polypeptides present in bone inductive protein extracts from bovine bone has led to the cloning of seven regulatory molecules  six of which are distantly related to transforming growth factor beta  the three human bone morphogenetic proteins  bmps  we describe herein  bmp 5  bmp 6  and bmp 7  show extensive sequence similarity to bmp 2  a molecule that by itself is sufficient to induce de novo bone formation in vivo  the additive or synergistic contribution of these bmp 2 related molecules to the osteogenic activity associated with demineralized bone is strongly implicated by the presence of these growth factors in the most active fractions of highly purified bone extract  
class4	adenovirus 12s e1a gene represses differentiation of f9 teratocarcinoma cells  the f9 teratocarcinoma cell line differentiates in vitro after treatment with retinoic acid and camp and has been a widely used model system for the study of the molecular events that are responsible for cellular commitment and differentiation during early development  previous experiments have suggested intriguing parallels between the control of gene expression during f9 cell differentiation and the regulation of gene expression by adenovirus e1a  transfection of a 12s e1a expressing plasmid into terminally differentiated  nonproliferating f9 cells generates  at high frequency  colonies of dividing cells  each of which expresses e1a  cell lines established from these colonies proliferate in the presence of retinoic acid and have lost the fully differentiated phenotype as characterized by the absence of expression of a series of differentiation specific genes  we conclude that expression of the viral 12s e1a gene product interferes with retinoic acid induced f9 cell differentiation  moreover  the results suggest that the differentiation process  as defined by markers of terminal differentiation  may not be a permanent event but can be reversed by e1a expression  
class4	frequent mutation of the p53 gene in human esophageal cancer  sequence alterations in the p53 gene have been detected in human tumors of the brain  breast  lung  and colon  and it has been proposed that p53 mutations spanning a major portion of the coding region inactivate the tumor suppressor function of this gene  to our knowledge  neither transforming mutations in oncogenes nor mutations in tumor suppressor genes have been reported in human esophageal tumors  we examined four human esophageal carcinoma cell lines and 14 human esophageal squamous cell carcinomas by polymerase chain reaction amplification and direct sequencing for the presence of p53 mutations in exons 5  6  7  8  and 9  two cell lines and five of the tumor specimens contained a mutated allele  one frameshift and six missense mutations   all missense mutations detected occurred at g c base pairs in codons at or adjacent to mutations previously reported in other cancers  the identification of aberrant p53 gene alleles in one third of the tumors we tested suggests that mutations at this locus are common genetic events in the pathogenesis of squamous cell carcinomas of the esophagus  
class4	activation of erythropoietin receptors by friend viral gp55 and by erythropoietin and down modulation by the murine fv 2r resistance gene  the leukemogenic membrane glycoprotein  gp55  encoded by friend spleen focus forming virus appears to bind to erythropoietin receptors  epor  sto stimulate erythroblastosis  li  j  p   d andrea  a d   lodish  h f    baltimore  d   1990  nature  london  343  762 764   to directly compare the effects of gp55 with erythropoietin  epo   we produced retrovirions that encode either gp55  epo  or epor  after infection with epor virus  interleukin 3 dependent da 3 cells bound 125i labeled epo and grew without interleukin 3 in the presence of epo  these latter cells  but not parental da 3 cells  became factor independent after superinfection either with epo virus or with friend spleen focus forming virus  in addition  epo virus caused a disease in mice that mimicked friend erythroleukemia  although fv 2r homozygotes are susceptible to all other retroviral diseases  they are resistant to both epo viral and friend viral erythroleukemias  these results indicate that both gp55 and epo stimulate epor and that the fv 2 gene encodes a protein that controls response to these ligands  however  the fv 2 protein is not epor because the corresponding genes map to opposite ends of mouse chromosome 9  these results have important implications for understanding signal transduction by epor and the role of host genetic variation in controlling susceptibility to an oncogenic protein  
class4	skeletal manifestations of ectopic or inappropriate endocrine and metabolic syndromes  a variety of tumors and nontumorous lesions were used to illustrate some of the biologic  clinical  and pathologic aspects of inappropriate or ectopic endocrine and metabolic syndromes that have musculoskeletal repercussions  it is clear  both from the discussion and case material  that many mechanisms of ectopic endocrine syndromes have yet to be clarified  elaborate techniques are available for hormonal estimations  but their routine use is prohibitively expensive and relatively unrewarding  cells of a given lesion may be functionally heterogeneous or may fail to elaborate active products in substantial amounts  different cells may produce similar peptides  while the same cells can produce more than one  despite these difficulties  recognition of ectopic endocrine syndromes remains crucial to diagnosis and patient management  and thus corroboration or correlation must often rest on a cruder basis  in fact  the clinical significance of basic laboratory data  e g   pth elevation  may vary  as pth may be immunoreactive but biologically inactive  as another example  hypercalcemia associated with myeloma may be variously related to coexistent hyperparathyroidism  renal disease  dehydration  or humoral osteolysis  therefore  roentgenographic evidence of bone destruction or skeletal stigmata of hyperparathyroidism imbues laboratory data with greater significance  paraneoplastic syndromes are of particular concern to the radiologist  as multiple systemic manifestations  occurring either synchronously or metachronously  may suggest the presence of an underlying or unifying lesion or even of a specific type of neoplasm  they may precede detection of neoplasms by months to years and can develop at any time during their course  paraneoplastic syndromes may  furthermore  parallel the course of a lesion and be used as indicators of remission or recurrence  conversely  those unassociated with overt symptoms possess endocrine markers that can reinforce sometimes silent skeletal stigmata  familiarity with representative secretory products influencing the musculoskeletal system per se may often clarify seemingly innocuous and sometimes asymptomatic skeletal findings  alert imagers may  therefore  detect  infer  or suspect particular syndromes when they present in a specific sequence or mosaic  conversely  when apprised of their existence  imagers should know where their related effects may be sought or anticipated  such relationships  sometimes serendipitously discovered  may be valuable assets in clinical diagnosis and patient management in both suspected and unsuspected cases  
class4	adenocarcinoma of the colon and rectum in patients less than 40 years of age  from 1962 to 1988  50 of 801 patients with adenocarcinoma of the colon and rectum treated at the national naval medical center were less than 40 years old  symptoms were present in 47 of the younger patients at presentation  the mean duration of time from the onset of symptoms to diagnosis in this group was 4 9 months  risk factors for carcinoma of the colon and rectum were identified in 14 of 50 patients less than 40 years old  a significantly greater proportion of patients less than 40 years old had stage c disease compared with the older group of patients  42 versus 22 per cent  p   0 014   stage b disease was more common in patients more than 40 years of age  44 8 versus 26 0 per cent  p   0 014   the proportion of patients with stages a and d disease was similar in both age groups  the cumulative survival rate in this group at five and ten years was 43 and 34 per cent  respectively  the five year survival rate in patients less than 40 years old with stage b disease was 76 per cent and with stage c disease  37 per cent  all young patients with stage d disease were dead at 28 months  synchronous and metachronous carcinomas of the colon and rectum were uncommon in patients less than 40 years old  patients less than 40 years of age with carcinoma of the colon and rectum are usually symptomatic and have advanced disease at the time of presentation  survival time for these patients for each stage of disease is similar to the over all population of patients with carcinoma of the colon and rectum  
class4	the oncologic risks of skin preservation at mastectomy when combined with immediate reconstruction of the breast  most oncologic surgeons agree that removal of the nipple  the areola and any recent scar at the site of the biopsy is necessary during a mastectomy for treatment of carcinoma of the breast  there is less agreement about what should be done with the remaining uninvolved mammary skin  its preservation facilitates the performance of immediate reconstruction of the breast and can lead to improved aesthetic results  but many oncologists fear that this practice could lead to an increased incidence of local tumor recurrence  to determine if that fear was justified  87 patients who had undergone unilateral or bilateral mastectomy with immediate reconstruction for treatment of early carcinoma of the breast were studied  preservation of uninvolved skin was used in all instances  all patients had a documented follow up study of 12 months or more  the average follow up time was 23 1 months  one peripheral local recurrence was observed  this 1 2 per cent rate of early local recurrence is lower than that reported from several series using modified radical mastectomy without skin preservation or immediate reconstruction  and suggests that skin preservation does not confer additional risks of local recurrence of carcinoma of the breast in properly selected patients  
class4	prognostic significance of serosal invasion in carcinoma of the stomach  two hundred and seventy seven patients with advanced carcinoma of the stomach invading the serosa were studied with regard to the relationship between the length of the serosal invasion  lsi  and prognosis  with a division made between expanding and infiltrative types of tumors  among patients with expanding types of tumors  five year survival rates were 40 per cent in patients with lsi less than 4 0 centimeters  33 per cent in patients with lsi 4 1 to 6 0 centimeters and 13 0 per cent in patients with lsi more than 6 0 centimeters  among those patients with infiltrative types of tumors  those with less than 2 0 centimeters of lsi had a better prognosis  five year survival rate of 53 per cent   whereas those patients with a lsi more than 2 0 centimeters had a very poor prognosis  five year survival rate of less than 20 per cent  and the significant lsi on prognosis was found to be 2 0 centimeters  involvement of the lymph node and metastasis to the liver were not affected by lsi  whereas the rates of peritoneal dissemination and direct invasion to neighboring organs increased with an increase in lsi  knowledge of these factors facilitates the planning of postoperative treatment  
class4	gastric lymphoma  from 1976 to 1988  35 patients were treated for stage ie and stage iie primary gastric lymphoma  non hodgkin s   pain and weight loss were the predominant symptoms  physical findings were usually absent and 20 per cent of the patients were anemic  the results of gastrointestinal contrast studies suggested a malignant condition in 75 per cent  but findings were not specific for lymphoma  endoscopic findings suggested a malignant process in 85 per cent  but the yield for biopsy was only 60 per cent  of 28 patients undergoing operative exploration  75 per cent were resectable  nine patients received postresectional adjuvant therapy  five had chemotherapy  three  radiotherapy  and one patient  a combination of the two  primary nonsurgical treatment consisted of chemotherapy in 11  radiotherapy in two and combined therapy in one instance  three of five recurrences were successfully treated  the five year survival rate was 65 per cent without significant differences between surgical and nonsurgical regimens  those with tumors smaller than 7 centimeters had a five year survival rate of 100 per cent versus 50 per cent for larger neoplasms  patients more than 60 years of age appeared to have a more favorable course after surgical therapy compared with those who had nonsurgical treatment  we concluded that endoscopy is a most useful  although limited diagnostic study and since no treatment program is obviously superior  the choice of therapy can be individualized accordingly  
class4	effect of closing dead space on incidence of seroma after mastectomy  seromas are a significant cause of morbidity after modified radical mastectomy  the effect of closing dead space by suturing skin flaps to underlying muscle combined with early removal  48 hours postoperatively  of closed suction drains on formation of the seroma was evaluated prospectively in 37 patients  thirty three underwent modified radical mastectomy for invasive carcinoma while four underwent total mastectomy with a level 1 axillary dissection for multifocal intraductal carcinoma  seromas occurred in three  all were minor  two required one aspiration only and one required two aspirations  two were seromas of the lower flap while one was an axillary seroma  except for one patient who had a wound hematoma develop  no other instances of morbidity were noted  closing dead space by suturing skin flaps to underlying muscle combined with early removal of closed suction drains is associated with a low incidence of seroma formation after mastectomy  use of this technique has important economic and clinical implications for patients who had mastectomy  
class4	efficacy of doxazosin in specific hypertensive patient groups  in practice  some of the major problems for the physician who treats hypertension are patients who are resistant to treatment or who have other complicating risk syndromes  therefore the overall efficacy of an antihypertensive agent must include an assessment of effect in patients with serious ancillary problems  in this article  doxazosin is reviewed for its efficacy in the treatment of severe essential hypertension and specific complications or conditions of mild or moderate essential hypertension  namely  left ventricular hypertrophy  hyperlipidemia  noninsulin dependent diabetes mellitus  renal insufficiency  pheochromocytoma  chronic obstructive pulmonary disease  peripheral vascular disease  and smoking  doxazosin is particularly efficacious in many specific subgroups of patients with hypertension  and the results of relevant studies are discussed  
class4	nutritional approach to cancer prevention with emphasis on vitamins  antioxidants  and carotenoids  the main human cancers are associated with complex life style related causative  enhancing  and inhibiting factors  tobacco smoking or chewing exposes humans to genotoxic carcinogens and to promoting substances  likewise  western dietary traditions involve certain carcinogens and promoters  whereas oriental traditions implicate other carcinogens and promoters  importantly  in virtually all situations regular intake of fruits and vegetables appreciably lowers the risk of cancer  this paper reviews the causes of the main human cancers and analyzes the mechanisms of the protective effects of fruits and vegetables  prevention of human cancer requires the definition of optimal levels of recommended daily allowances of micronutrients  
class4	effects of carotenoids in cellular and animal systems  it has been suggested that carotenoid pigments may function as chemopreventive agents for reducing the risk of cancer in humans  part of this suggestion rests on epidemiological evidence  and part rests on work done in cellular and animal systems  in this article  the experimental evidence for carotenoid inhibition of mutagenicity  malignant transformation  tumor formation  and immunoenhancement is reviewed  although a mechanism for these effects cannot yet be identified  it is clear that the overwhelming evidence in these systems would indicate that carotenoids exert an important influence in modulating the actions of carcinogens  
class4	vegetables  fruits  and carotenoids and the risk of cancer  low intake of vegetables  fruits  and carotenoids is consistently associated with increased risk of lung cancer in both prospective and retrospective studies  in addition  low levels of beta carotene in serum or plasma are consistently associated with the subsequent development of lung cancer  the simplest explanation is that beta carotene is protective  since retinol  preformed vitamin a  is not related in a similar manner to lung cancer risk  beta carotene appears to function through a mechanism that does not require conversion into vitamin a  however  the importance of other carotenoids and other constituents of vegetables and fruit has not been adequately explored  both prospective and retrospective studies suggest that vegetable and fruit intake may reduce the risk of cancers of the mouth  pharynx  larynx  esophagus  stomach  colon  rectum  bladder  and cervix  but because of fewer studies and less consistency among studies  the epidemiologic evidence is at present less persuasive than for lung cancer  
class4	prediagnostic serum levels of carotenoids and vitamin e as related to subsequent cancer in washington county  maryland  in 1974 and 1975  serum specimens were collected from 25 802 volunteers in washington county  maryland  the serum was kept frozen at  73 degrees c until the time of assay  prediagnostic samples from 436 cancer cases and 765 matched control subjects have been assayed  nine sites have been studied  colon  rectum  pancreas  lung  melanoma  basal cell of skin  breast  prostate  and bladder  serum beta carotene levels showed a strong protective association with lung cancer  suggestive protective associations with melanoma and bladder cancer  and a suggestive but nonprotective association with rectal cancer  serum vitamin e levels had a protective association with lung cancer  none of the other sites showed impressive associations  low levels of serum lycopene were strongly associated with pancreatic cancer and less strongly associated with cancer of the bladder and rectum  
class4	beta carotene and cancer prevention  the basel study  in 1971 1973 at the third examination of the basel study started in 1959  the major antioxidant vitamins and carotene were measured in the plasma of 2974 men  a subsample and their families were reinvestigated in 1977 79  during the 12 y observation period  1973 85  553 men died  204 of cancer  lung cancer 68  stomach cancer 20  colon cancer 17  all other malignancies 99   we found significantly lower mean carotene levels for all cancer  bronchus cancer  and stomach cancer  all p less than 0 01  compared with the 2421 survivors  the relative risk of subjects with low carotene  less than 0 23 mumol l  was significantly elevated  p less than 0 05  for lung cancer  cox s model   higher risks were noted for all cancer  p less than 0 01  if both carotene and retinol were low  low plasma carotene which is known to reflect carotene intake is in our study associated with increased cancer risk  
class4	vitamin c and cancer prevention  the epidemiologic evidence  epidemiologic evidence of a protective effect of vitamin c for non hormone dependent cancers is strong  of the 46 such studies in which a dietary vitamin c index was calculated  33 found statistically significant protection  with high intake conferring approximately a twofold protective effect compared with low intake  of 29 additional studies that assessed fruit intake  21 found significant protection  for cancers of the esophagus  larynx  oral cavity  and pancreas  evidence for a protective effect of vitamin c or some component in fruit is strong and consistent  for cancers of the stomach  rectum  breast  and cervix there is also strong evidence  several recent lung cancer studies found significant protective effects of vitamin c or of foods that are better sources of vitamin c than of beta carotene  it is likely that ascorbic acid  carotenoids  and other factors in fruits and vegetables act jointly  increased consumption of fruits and vegetables in general should be encouraged  
class4	vitamin e and cancer prevention  some animal experiments and human studies suggest that vitamin e may protect against cancer  serum alpha tocopherol concentration was studied for its prediction of cancer in a cohort of 36 265 adults in finland  during a mean follow up of 8 y  cancer was diagnosed in 766 persons  the levels of serum alpha tocopherol were determined from stored serum samples  at  20 degrees c  taken from these cancer patients and from 1419 matched control subjects  individuals with a low level of alpha tocopherol had about a 1 5 fold risk of cancer compared with those with a higher level  the strength of the association between serum alpha tocopherol level and cancer risk varied for different cancer sites and was strongest for some gastrointestinal cancers and for the combined group of cancers unrelated to smoking  the association was strongest among nonsmoking men and among women with low levels of serum selenium  the findings agree with the hypothesis that dietary vitamin e in some circumstances protects against cancer  
class4	gastric juice ascorbic acid  effects of disease and implications for gastric carcinogenesis  n nitroso compounds  noc  are strongly implicated in the causation of cancer of the stomach and it has been suggested that ascorbic acid might reduce the risk of gastric cancer by preventing their formation within gastric juice  however  until recently there have been no measurements of gastric juice ascorbic acid concentrations  we have measured both gastric juice ascorbic and total vitamin c  ascorbic acid and dehydroascorbic acid   our findings suggest that ascorbic acid is secreted into the gastric lumen so that gastric juice concentrations are often greater than those in plasma  gastric pathology affects this secretion  leading to values in gastric juice that are lower than plasma levels  stimulation of gastric secretion does not raise vitamin c concentrations in individuals whose values are initially low  the role of ascorbic acid in preventing formation of noc and protecting against gastric cancer is discussed in the light of these findings  
class4	potential role of beta carotene in prevention of oral cancer  recent data suggests that retinoids and carotenoids may be effective in reversing a putative  field cancerization  defect in the epithelium at risk for oral cancer  animal experiments have shown that these compounds can inhibit cancer formation  several clinical trials have demonstrated the ability of retinoids to reverse oral leukoplakia  however  toxicities associated with retinoids at the doses used in these studies limits their potential for chemoprevention  because of its lack of toxicity  beta carotene is a very attractive agent for chemoprevention  it suppresses micronuclei in exfoliated oral mucosal cells from subjects at risk for oral cancer and recently has been shown to be active in reversing leukoplakia  another area under investigation is the possibility of preventing second primary tumors in patients cured of their initial cancer who have an increased risk of developing new cancers of the upper acrodigestive tract  
class4	remission of precancerous lesions in the oral cavity of tobacco chewers and maintenance of the protective effect of beta carotene or vitamin a  participants in the intervention trials were fishermen  kerala  india   who chewed tobacco containing betel quids daily before and throughout the study period  frequency of oral leukoplakia  micronuclei in oral mucosal cells  and alterations in nuclear textures were used as endpoints  administration of vitamin a  60 mg wk  for 6 mo resulted in complete remission of leukoplakias in 57  and a reduction of micronucleated cells in 96  of tobacco chewers  beta carotene  2 2 mmol wk  induced remission of leukoplakia in 14 8  and reduction of micronucleated cells in 98   vitamin a completely suppressed and beta carotene suppressed by 50  formation of new leukoplakia within the 6 mo trial period  after withdrawal of vitamin a or beta carotene treatment  oral leukoplakias reappeared  frequency of micronuclei in oral mucosa increased  and nuclear textures reverted to those present before the administration of chemo preventive agents  the protective effect of the original treatment could be maintained for at least 8 additional months by administration of lower doses of vitamin a or beta carotene  
class4	studies evaluating antioxidants and beta carotene as chemopreventives  cancer chemoprevention research takes leads from epidemiologic and laboratory research and develops them through in vitro and in vivo preclinical research and initial human studies into randomized controlled clinical trials  at present  the chemoprevention program is sponsoring 21 human efficacy studies  these trials are testing the potential of agents  beta carotene  folic acid  13 cis retinoic acid  4 hydroxyphenyl retinamide  vitamins c and e  and minerals  as inhibitors of a variety of cancers in humans  colon  lung  esophagus  cervix  bladder  and skin   endpoints in these studies include overall incidence of cancer  incidence of specific cancers  rate of regression or progression of preneoplastic changes  and changes in cellular or biochemical parameters  study participants include volunteers from the general population  populations at high risk for cancer because of occupation  lifestyle  or place of residence  persons with previously treated cancers  and persons with preneoplastic lesions  study designs include single agent randomization  combination of agents and complete factorial designs  
class4	premalignant lesions  role of antioxidant vitamins and beta carotene in risk reduction and prevention of malignant transformation  epidemiological studies have shown that diets rich in one or more antioxidant nutrients may reduce the risk of cancers of the lung  uterine cervix  mouth  and gastrointestinal tract  study of premalignant lesions offers a comparatively expedient approach to identifying and evaluating the efficacy of the cancer chemopreventive components of foods  some recent findings suggest roles for beta carotene and or vitamin c in reversing or reducing the risk of cervical dysplasia and oral leukoplakia  there are some indications that vitamin c and beta carotene may reduce the risk of atrophic gastritis and gastric cancer  additional epidemiological and molecular biology studies and clinical intervention trials using premalignant lesions as the marker of specific cancer risks should become an important component of future research in the area of cancer chemoprevention  
class4	nevus flammeus  discordance in monozygotic twins  nevus flammeus has been described as an inherited vascular anomaly  we report two cases of nevus flammeus  each appearing in one of two monozygotic twins  this finding supports the idea that nevus flammeus results from embryologic mishap rather than genetic transmission  
class4	interaction of chloramphenicol and metabolites with colony stimulating factors  possible role in chloramphenicol induced bone marrow injury  we have recently demonstrated that two chloramphenicol  cap  metabolites known to be produced by intestinal bacteria  dehydro cap  dh cap  and nitrophenylaminopropane  npap   are much more cytotoxic to bone marrow in vitro than cap itself  since colony stimulating factors  csfs  play an essential role in hematopoietic cell growth  toxicity from cap metabolites could also involve interaction with csf or csf producing cells  in the present study  we found that increasing concentrations of rhgm csf or rhg csf completely reversed the inhibitory effect of cap  2 x 10  4  m  on human cfu gm growth and on the growth of kg 1 cells  gm csf also reversed the inhibitory effect of cap on hl 60 cells  inhibition by dh cap  50  at 5 x 10  7  m   nitroso cap  no cap   60  at 5 x 10  6  m  and npap  35  at 10  5  m  was not affected by either csf  in addition to their inhibitory effect on cell growth  dh cap  5 x 10  6  m  and no cap  5 x 10  6  m  inhibited csf production by buffy coat cells 50 70  without affecting cell viability  neither cap nor npap inhibited csf production  it is suggested that the dual toxic inhibitory effect of some intestinal metabolites of cap such as dh cap on hematopoietic cell growth on the one hand  and on csf production on the other  renders them very potent as potential mediators of cap induced aplastic anemia  
class4	kaposi s sarcoma involvement of the bone marrow  kaposi s sarcoma  ks  is a predominantly cutaneous malignancy with several clinical variants  extracutaneous sites of involvement are uncommon in all disease variants except epidemic ks  human immunodeficiency virus related  and the african lymphadenopathic variant  extracutaneous ks usually involves the lymph nodes  gastrointestinal tract  and respiratory tract  the authors report the first description of a patient with classic ks to have bone marrow involvement  two additional patients with ks variants and bone marrow involvement have been described  bone marrow tumor invasion should be considered in patients with ks and hematologic abnormalities  
class4	ethanol causes accelerated g1 arrest in differentiating hl 60 cells  the effects of clinically relevant ethanol concentrations on myeloid differentiation in the hl 60 cell promyelocytic leukemia line have been studied  the exposure of noninduced stem cells to 60 mm ethanol results in an increase in g1 cells  but there is no increase in superoxide production or expression of the mo1 antigen  when hl 60 cells are induced to differentiate along the myeloid line with dimethylsulfoxide  dmso  or retinoic acid  ra   there is a shift to smaller cell size  an increase in g1 cells and acquisition of the ability to produce superoxide as reported previously by several authors  when ethanol is present during differentiation  there are further increases in g1 cells  and increases in the percentage of cells which produce superoxide and express mo1  and decreases in mean cell size and total growth during the incubation period  regrowth experiments after periods of differentiation indicate that the increased g1 arrest seen in the presence of ethanol represents terminal commitment if inducer is present  but in the absence of inducer the increased g1 percentage is readily reversible  examination of rna content by flow cytometry reveals a decrease in both the peak and mean g1 rna content during dmso or ra induced differentiation  these decreases are accentuated by the presence of ethanol  resulting in a higher g1a g1b ratio than in nonexposed cells  these findings indicate that ethanol enhances g1 growth arrest in hl 60 cells exposed to myeloid inducers  partial differentiation occurs during this process  resulting in terminally arrested cells  some of which have undergone fewer postinduction cell divisions than normal and may not be fully competent  
class4	herpes zoster ophthalmicus and iris cysts  herpes zoster ophthalmicus has been associated with numerous complications such as neuropathy  keratitis  anterior uveitis  and neuralgia  to my knowledge  there have been no reports of secondary iris cyst formation  i hereby report the case of a patient who developed an iris cyst during a herpes zoster ophthalmicus infection  
class4	childhood blindness in peru  a survey of childhood blindness in peruvian children was done  although most causes of blindness were due to congenital and hereditary conditions  measles accounted for almost 10  of blindness  with widespread measles immunization  this preventable cause of blindness in children can be eliminated or dramatically reduced  
class4	magnetic resonance imaging and computed tomography in pediatric head and neck masses  fifty three magnetic resonance imaging  mri  and 25 computed tomography  ct  studies of 53 head and neck masses in pediatric patients were reviewed retrospectively  all lesions had pathologic proof except for 2 metastatic and 2 recurrent lesions  which only had prior pathologic confirmation at their primary sites  these included 12 malignant tumors  23 benign tumors  6 inflammatory masses  and 12 congenital lesions  the mri performance ranged predominantly from good to excellent in detection of the lesion and the extent of involvement and in contrast to the surrounding tissue  when ct comparison was available  mri proved to be equal to or better than it in detection of these factors and in preoperative diagnosis  our results suggest that mri should be the method of choice for the initial evaluation of the pediatric head and neck region  especially in those patients requiring multiple examinations  however  ct and mri should be used conjunctively in complicated cases  especially those possibly involving lesions with calcifications or bony involvement  
class4	vertical partial laryngectomy  a critical analysis of local recurrence  the purpose of this study was to evaluate local recurrence following vertical partial laryngectomies in 416 patients with either t1n0m0 or t2n0m0 glottic carcinoma  local failure was reported according to the t stage  the precise tumor location within each stage  the true vocal cord mobility  and the surgical procedure performed  no local recurrences were observed among 42 patients who underwent thyrotomy and cordectomy when the tumor was confined to the middle third of the mobile true vocal cord  local failure occurred in 8 of 111  7 2   patients in whom hemilaryngectomy was performed for tumors confined to one mobile true vocal cord  there was a diverse group of lesions within each t stage that responded differently to the surgical approaches  the differences in the initial recurrence rates are discussed in terms of careful preoperative assessment and choice of surgical technique for early glottic carcinoma  
class4	hemangioma of the temporalis muscle  a rare case of an intramuscular hemangioma of the temporalis muscle is reported  the clinical examination  carotid arteriogram  computed tomographic scan  and aspiration cytology suggested the vascular nature of the tumor  but an exact diagnosis could only be made after histopathologic examination  temporary occlusion of the ipsilateral external carotid artery and subperiosteal dissection permitted complete  wide excision without much bleeding  
class4	undifferentiated carcinomas of salivary glands  undifferentiated carcinomas of salivary glands are those epithelial malignancies whose light optic histopathologic features are not sufficient to place them in other defined classes of carcinoma  they are ultrastructurally heterogeneous and can manifest neuroendocrine differentiation  with or without the latter  the carcinomas are biologically high grade and rank with salivary duct and high grade mucoepidermoid carcinomas in terms of morbidity and mortality  
class4	cholangiocarcinoma complicating primary sclerosing cholangitis  cholangiocarcinoma is more likely to develop in patients with primary sclerosing cholangitis  our aims were to describe the clinical presentation  course  and management of patients afflicted with both cholangiocarcinoma and primary sclerosing cholangitis and to estimate the prevalence of cholangiocarcinoma in patients with primary sclerosing cholangitis  a retrospective analysis was conducted of 30 patients with both primary sclerosing cholangitis and cholangiocarcinoma managed at our institution during an 8 year period  development of cholangiocarcinoma was heralded by rapid clinical deterioration with jaundice  weight loss  and abdominal discomfort  cholangiocarcinoma complicating primary sclerosing cholangitis often was detected at an advanced tumor stage  which precluded effective therapy  and overall median survival was 5 months  earlier recognition and treatment of cholangiocarcinoma in such patients will be necessary to increase survival rates  seventy patients with primary sclerosing cholangitis were followed prospectively in a clinical trial of medical therapy for an average of 30 months  twelve patients died and five were found at autopsy to have cholangiocarcinoma  the potential for cholangiocarcinoma to develop in patients with primary sclerosing cholangitis may indicate that liver transplantation should be considered earlier in the course of the disease  
class4	a clinical pilot study combining surgery with intraoperative pelvic hyperthermochemotherapy to prevent the local recurrence of rectal cancer  intraoperative pelvic hyperthermochemotherapy  iophc  with mitomycin c  mmc  was prescribed for 14 patients with resectable advanced rectal cancer in an attempt to prevent a postoperative local recurrence  immediately after rectal amputation and extended lymphadenectomy  iophc was performed using physiologic saline containing 40 micrograms ml of mmc at 45 5     0 6 c for 90 minutes  with an apparatus devised for iophc  at the end of iophc  the esophageal temperature was 37 2     0 8 c and cooling was not required  antitumor efficacy and complications in the iophc group were compared with findings in 12 rectal cancer patients who underwent surgery only within the same period of time  operation time was not prolonged with iophc treatment  in cytologic examinations of the pelvic lavage just before iophc treatment  viable cancer cells were detected in 6 of the 14 patients but were never detected in the postoperative exudate drained from the pelvic cavity  of the 12 patients in the control group  2 had a local recurrence  while in the iophc group there was no local recurrence for 16 9     9 7 months at this writing  postoperative complications did not differ between the groups  this iophc treatment is a favorable method in eradicating cancer cells for postoperative local recurrence of rectal cancer  
class4	locally recurrent parathyroid neoplasms as a cause for recurrent and persistent primary hyperparathyroidism  between 1982 and 1989  145 patients underwent operations for persistent or recurrent primary hyperparathyroidism  hpt   at re exploration  15 patients  10 3   were found to have locally recurrent parathyroid tumors  11 patients with adenoma and 4 with carcinoma   these 15 patients had 28 previous operations at outside institutions for hpt  patients with locally recurrent hpt secondary to adenoma had a longer disease free interval than patients with locally recurrent carcinoma  at the time of evaluation at the national institutes of health  nih  for recurrent or persistent hpt  each patient was symptomatic and patients with carcinoma had significantly more symptoms and higher serum levels of calcium and parathyroid hormone than patients with adenoma  locally recurrent parathyroid neoplasm was correctly localized by preoperative testing in 14 of 15 patients  these 15 patients underwent 18 reoperations at nih for excision of locally recurrent parathyroid tumors  following the final reoperation  two patients had more than one procedure   each patient had normal serum levels of calcium  in addition each patient remains biochemically cured  based on normal serum calcium level   with a median follow up interval of 21 months  local recurrence of parathyroid adenoma comprises a small but significant proportion of cases of recurrent or persistent hpt and can be indistinguishable from parathyroid carcinoma  findings suggestive of carcinoma include shorter disease free interval  higher serum levels of calcium and parathyroid hormone  and histologic appearance  whether the locally recurrent parathyroid neoplasm is benign or malignant  aggressive surgery can control serum levels of calcium in these patients with acceptable rates of morbidity  
class4	synthesis of type i collagen in healing wounds in humans  to quantify wound healing in surgical patients  samples of wound fluid were collected through a silicone rubber tube for 7 postoperative days and their concentrations of the carboxyterminal propeptide of type i procollagen  picp  and the aminoterminal propeptide of type iii procollagen  piiinp  were measured with specific radioimmunoassays  the mean concentration of picp in would fluid on day 1 was 207     92  sd  micrograms l  and on day 2 908     469 micrograms l  p less than 0 001  signed rank test   on day 7  the mean concentration reached was 380 times higher than that of day 1  79 330     54 151 micrograms l   only one peak of picp antigenicity  corresponding to the intact propeptide as set free during synthesis of type i procollagen  was detected on sephacryl s 300 gel filtration analysis of wound fluid samples  the mean concentration of piiinp was 70     61 micrograms l on day 1  86     88 micrograms l on day 2  and 180     129 micrograms l on day 3  p less than 0 001 when compared with day 1   finally on day 7  a 250 fold concentration  17 812     9839 micrograms l   compared with day 1  was reached  methods described in the present paper allow separate and repetitive quantification of the synthesis of both type i and type iii procollagen during human wound healing  
class4	rupture of a benign mediastinal teratoma into the right pleural cavity  a 27 year old woman with a ruptured mediastinal cystic teratoma had high levels of amylase and carcinoembryonic antigen in cystic fluid  the activity of the amylase is thought to be the most likely cause of the rupture  high levels of carcinoembryonic antigen in pleural fluid are not necessarily indicative of a malignant lesion but may suggest the presence of a ruptured teratoma in patients with mediastinal tumors  
class4	tricuspid valve papillary fibroelastoma  echocardiographic characterization  we report a tricuspid valve papillary fibroelastoma initially detected by transthoracic two dimensional echocardiography and subsequently characterized by transesophageal two dimensional echocardiography  the mass was excised during open heart operation  and the diagnosis was verified grossly and histopathologically  transesophageal echocardiography usually provides images far superior to those from transthoracic echocardiography and may be a useful adjunct for intraoperative localization of intracardiac tumors for excision  
class4	rectus abdominis muscle flap with microvascular anastomoses for repair of recurrent sarcoma  after radical resection of a recurrent leiomyosarcoma  the thoracic wall was stabilized with a gore tex graft  the skin and soft tissue defect was repaired with a large rectus abdominis flap in which the circulation was secured by end to end microvascular anastomosis of the inferior epigastric artery to the internal mammary artery  which had to be cut during tumor removal  
class4	thymoma  results of 241 operated cases clinical and histopathological aspects of 241 thymomas were reviewed  one hundred sixty of the patients with thymoma had myasthenia gravis and 15 had other autoimmune diseases  55  of the thymomas were encapsulated and 45  invasive  operation was radical resection in 87 5  of the patients  subtotal resection with residual tumor in 8 7   and simple biopsy in 3 7   a tumor relapse was observed in 24 patients  10    2  1 5   of 133 with encapsulated thymomas and 22  20 4   of 108 with invasive thymomas  among these patients  a relapse was found in 20 6  of the patients who received radiotherapy postoperatively and in 24 6  who did not  adverse prognostic factors were clinical stage iva  multiple pleural nodes   not feasible resection  for technical reasons   inoperable tumor relapse  and association with one of the following autoimmune diseases  pure red cell aplasia  hypogammaglobulinemia  and lupus erythematosus  conversely  myasthenia gravis is now a curable disease  it contributes to early discovery of associated thymoma  thus allowing a better survival for patients with thymoma who have myasthenia gravis compared with patients with thymoma but without myasthenia gravis  p less than 0 05   postoperative radiotherapy does not seem necessary after removal of encapsulated thymomas  but it is advisable in case of invasive thymomas  regardless of the extent of the resection  
class4	multiple primary bronchogenic carcinomas  treatment and follow up  a second primary bronchogenic carcinoma subsequently developed 8 to 156 months later in 19 patients who underwent curative resection of primary bronchogenic carcinomas  the second primary tumor was treated by surgical resection in 9 patients  3 patients  tumors were considered unresectable  and the remaining 7 patients  despite having potentially resectable tumors  did not undergo resection because of insufficient pulmonary reserve or unwillingness to undergo resection  actuarial life table analysis of survival for the 9 patients who underwent resection showed a median survival time of 110 3 months compared with 19 months for the group with unresected but resectable tumors and 10 5 months for the group with unresectable tumors  there was no operative mortality in the group with resected tumors  we conclude that in patients in whom a second primary carcinoma of the lung develops  surgical resection prolongs survival and can be performed with a low operative mortality  
class4	the impact of physician compliance on screening mammography for older women  screening mammography is underutilized  even for women older than 50 years for whom there is a general consensus that regular annual screening is appropriate and necessary  to evaluate reasons for this underutilization  we studied a random sample of 517 women in los angeles  calif who were older than 50 years  all women were found to be underscreened  especially women older than 65 years  for example  approximately 35  of women 50 to 64 years old and 47  of women aged 65 years and older never had had even one mammogram  analyses revealed that the most important factor that predicted whether a women ever had had a mammogram was whether her physician had talked to her about mammography  women were between four and 12 times more likely  depending on their age group  to have had a mammogram at some time if their physicians discussed it with them  the discussions did not need to be lengthy or complex  these results indicate that physicians need to know that discussing screening mammography with their patients has a major impact on breast cancer screening behaviors  
class4	the relationship of papanicolaou testing and contacts with the medical care system to stage at diagnosis of cervical cancer  the relationship of papanicolaou  pap  testing and physician visits to stage at diagnosis of cervical cancer was assessed by interviews with 149 women with invasive cervical cancer and 214 women with in situ cervical cancer  a significantly smaller percent of study subjects with invasive disease than in situ disease had at least one pap test in the 3 years prior to diagnosis  age  and race adjusted odds ratio  3 38   the two groups did not differ in visits to a physician for other reasons during this period  pap testing decreased with increasing age for both groups  but not physician visits  while 65  percent of the subjects with invasive disease aged between 65 and 79 years had never had a pap test until diagnosis  88  had seen a physician in the preceding 3 years  women with regional or distant invasive disease were least likely to have had pap tests  and  within this group  those aged between 35 and 64 years were also least likely to have seen a physician  strategies for early detection must reflect missed opportunities and the need to bring those not receiving care into the system  
class4	menopausal estrogen replacement therapy and breast cancer we conducted a meta analysis of the literature concerning breast cancer and estrogen replacement therapy  the overall relative risk of breast cancer associated with this therapy was 1 07  however  the variation of the estimated risks among the studies was far greater than could plausibly be explained by chance alone  to explain this variation  we looked at the effects of type  duration  and dosage of treatment  overall  women who took 0 625 mg d or less of conjugated estrogens had a risk of breast cancer that was 1 08 times that of women who did not receive this therapy  95  confidence interval  ci   0 96 to 1 2   the relative risks from these individual studies of low dosage therapy did not differ significantly from each other  women who took 1 25 mg d or more of conjugated estrogens had a breast cancer relative risk of 2 0 or less in all studies  however  the variation in observed risks at this higher dosage was significant  this implies that other risk factors varied among these studies  making it difficult to estimate the overall risk associated with this dosage  the relative risk of breast cancer associated with estrogen replacement therapy among women with a history of benign breast disease was 1 16  95  ci  0 89 to 1 5   the combined results from multiple studies provide strong evidence that menopausal therapy consisting of 0 625 mg d or less of conjugated estrogens does not increase breast cancer risk  
class4	decreased mortality in users of estrogen replacement therapy in a prospective study of 8881 postmenopausal female residents of a retirement community in southern california  we evaluated in detail the relationship between estrogen use and overall mortality  after 7 1 2 years of follow up  there had been 1447 deaths  women with a history of estrogen use had 20  lower age adjusted  all cause mortality than lifetime nonusers  95  confidence interval  0 70 to 0 87   mortality decreased with increasing duration of use and was lower among current users than among women who used estrogens only in the distant past  current users with more than 15 years of estrogen use had a 40  reduction in their overall mortality  among oral estrogen users  relative risks of death could not be distinguished by specific dosages of the oral estrogen taken for the longest time  women who had used estrogen replacement therapy had a reduced mortality from all categories of acute and chronic arteriosclerotic disease and cerebrovascular disease  this group of women had a reduced mortality from cancer  although this reduction was not statistically significant  the mortality from all remaining causes combined was the same in estrogen users and lifetime nonusers  
class4	combined hepatic and vena caval resection with autogenous caval graft replacement  right sided and caudate hepatic lobectomy with resection of the retrohepatic vena cava were performed in a 34 year old woman with recurrent adrenal carcinoma  the vena cava was replaced with a graft constructed from autogenous superficial femoral vein  included herein is a review of the literature detailing the three previously reported cases of combined hepatic and caval resection  to our knowledge  there are no prior reports of the use of an autogenous vein graft in this setting  with surgical and anesthetic techniques  including total vascular exclusion of the liver and venovenous bypass  methods that were developed in large part through experience in liver transplantation  this type of surgery can be performed with a high rate of success  
class4	photodynamic therapy to treat tumors of the extrahepatic biliary ducts  a case report  the poor survival rate of patients with extrahepatic bile duct tumors is well documented  over the course of 4 years  we treated a white woman with diabetes diagnosed with histologically proven adenocarcinoma of the common bile duct with six injections of dihematoporphyrin ether followed by seven photodynamic therapy treatments to the biliary duct  as of july 1989  the patient was still alive  was not jaundiced  and had a karnofsky performance status of 70  no changes occurred in any blood chemistry value from the time of injection to the time of photodynamic therapy  of the transient elevations of some blood chemistry values and the white blood cell count  which occurred within 24 to 48 hours after photodynamic therapy  only those of alanine aminotransferase  aspartate aminotransferase  and amylase were significant  
class4	the changing face of dermatology out patient referrals in the south east of scotland  a study of out patient dermatological services  nhs and private  in the south east of scotland was carried out by medical staff in the department of dermatology in edinburgh during the month of november 1988  the aim was to assess changes in referral patterns and workload compared with the findings of an identical investigation undertaken in november 1981  of particular interest were the possible effects of recent publicity campaigns aimed at increasing public awareness about skin cancer  the medical complement of the dermatology department had changed minimally since 1981 and the population increase in the south east of scotland over the same period was 1 5   during november 1988 1592 new patients and 2037 review patients were seen  this represented an increase of 29 2  and 28 3   respectively  since 1981  the most striking changes in diagnostic groups were a 173  rise in new cases presenting with benign tumours  excluding viral warts  and a 106  increase in new patients with malignant tumours  viral warts and eczema were  as in 1981  the second and third most common diagnostic categories amongst new patients  there was a 98  increase in the number of surgical procedures performed on new patients compared with 1981  we conclude that the substantial increase in numbers of both benign and malignant tumours and the consequent doubling in surgical treatments was due to increased public awareness and concern about skin cancer  
class4	pigmented spindle cell naevus  we report 22 cases of pigmented spindle cell naevus  pscn   the usual appearance of these naevi is that of a heavily pigmented papule found mostly on the legs of young patients  histologically  pscn was characterized by symmetrical proliferation of spindle shaped pigmented melanocytes grouped in large junctional nests  pagetoid spread of single cells in the overlying epidermis was frequently found  in our opinion  pscn is a distinctive benign acquired melanocytic naevus that in the past has been frequently misdiagnosed as atypical spitz naevi or malignant melanoma  
class4	factor xiiia in nodular malignant melanoma and spitz naevi  the distribution of factor xiiia positive dermal dendritic cells was studied in a series of nodular malignant melanomas and compared with that seen in spitz naevi  two patterns of distribution were recognizable   a  diffusely spread through the tumour and  b  located mainly at the periphery of the tumour  these did not correlate with the diagnosis of melanoma or spitz naevus and the distribution appeared to be a function of growth pattern of the tumour  the diffuse pattern was the most common regardless of diagnosis and the distribution of factor xiiia positive cells is the same in malignant melanoma and spitz naevi  
class4	necrolytic migratory erythema  association with neuroendocrine tumour with predominant insulin secretion  we report a case of necrolytic migratory erythema in association with a neuroendocrine tumour producing predominantly insulin  as far as we know this has not been observed before  
class4	angiotropic b cell lymphoma  malignant angioendotheliomatosis   failure of systemic chemotherapy  a 65 year old female with angiotropic b cell lymphoma is reported  despite the absence of systemic involvement on formal staging and the favourable response of the cutaneous lesions to triple systemic chemotherapy with prednisolone  vincristine and cyclophosphamide  postmortem findings showed that death was due to widespread disease dissemination  
class4	donor leukocyte transfusions for treatment of recurrent chronic myelogenous leukemia in marrow transplant patients  three patients with hematologic relapse after bone marrow transplantation for chronic myelogenous leukemia were treated with interferon alpha and transfusion of viable donor buffy coat  all had complete hematologic and cytogenetic remission  which persisted 32 to 91 weeks after treatment  in two patients graft versus host disease developed and was treated by immunosuppression  these results are an example of adoptive immunotherapy without cytoreductive chemotherapy or radiotherapy in human chimeras  
class4	expression of leukocyte alkaline phosphatase gene in normal and leukemic cells  regulation of the transcript by granulocyte colony stimulating factor  the levels of leukocyte alkaline phosphatase  lap  messenger rna  mrna  are evaluated in b and t lymphocytes  monocytes  and polymorphonuclear cells  pmns   and this transcript is found to be present only in pmns  precursors of the myelomonocytic pathway  represented by leukemic cells isolated from several cases of chronic myelogenous leukemia  cml  in its stable and blastic phase and acute myelogenous leukemia  aml   are devoid of lap transcript  these data support the notion that lap is a marker of the granulocyte terminal differentiation  despite the absence of lap mrna in both the myeloid and the lymphoid precursors  nuclear run on experiments show constitutive transcription of the lap gene in leukemic cells obtained from aml  cml  as well as acute lymphoblastic leukemia  all  and b cell chronic lymphocytic leukemia  b cll   in cml and in chronic myelo monocytic leukemia  cmml  pmns  granulocyte colony stimulating factor  g csf  specifically accumulates lap mrna without showing a substantial increase in the rate of transcription of the lap gene  once increased by g csf  lap mrna is very stable  showing a half life of more than 4 hours in the presence of actinomycin d  g csf is suggested to play a pivotal role in the modulation of lap transcript in pmns  
class4	monoclonal antibody to the interferon inducible protein leu 13 triggers aggregation and inhibits proliferation of leukemic b cells  interferon  ifn  alpha inhibits dna synthesis stimulated by low molecular weight b cell growth factor  bcgf  in hairy cells in vitro  suggesting that the therapeutic efficacy of ifn alpha in hairy cell leukemia  hcl  involves growth inhibition of malignant b cells  evidence that the 16 kd cell surface protein leu 13 mediates an antiproliferative signal in t lymphocytes and is ifn inducible in endothelial cells prompted us to examine the expression and functional role of this molecule in leukemic b cells  leu 13 density  determined by flow cytometry  was upregulated in vitro and in vivo by ifn alpha on malignant b cells from patients with hcl  chronic lymphocytic leukemia  and prolymphocytic leukemia  monoclonal anti leu 13 triggered homotypic aggregation of leukemic b cells via an adhesion pathway that was not inhibited by antibodies to leukocyte function associated antigen 1  lfa 1  or intercellular adhesion molecule 1  icam 1   moreover  anti leu 13 potentiated the inhibitory effects of ifn alpha on bcgf stimulated dna synthesis  assessed by  3h  thymidine and  3h  deoxyadenosine incorporation into dna  these results indicate that leu 13 is part of a novel ifn inducible signaling pathway which may modify the growth and adhesive properties of leukemic b cells under physiologic or therapeutic conditions  
class4	granulocyte macrophage colony stimulating factor synergizes with interleukin 6 in supporting the proliferation of human myeloma cells  the role of granulocyte macrophage colony stimulating factor  gm csf  in the growth of multiple myeloma  mm  was investigated in 21 patients with mm  in 17 patients with proliferating myeloma cells in vivo  recombinant gm csf significantly increased the endogenous il 6 mediated spontaneous myeloma cell proliferation occurring in 5 day cultures of tumor cells in vitro  p less than  01   furthermore  gm csf was detected in 5 day culture supernatants of myeloma bone marrow cells  this endogenous gm csf was produced by the myeloma bone marrow microenvironment but not by myeloma cells and contributed to the spontaneous myeloma cell proliferation observed in 5 day cultures  in fact  this proliferation was partially blocked  67   by anti gm csf monoclonal antibodies  the stimulatory effect of rgm csf was mediated through il 6 because it was abrogated by anti il 6 monoclonal antibodies  rgm csf did not reproducibly increase the endogenous il 6 production in short term cultures of bone marrow cells of mm patients  using an il 6 dependent myeloma cell line  xg 1 cell line   rgm csf was shown to act directly on myeloma cells stimulating by twofold their il 6 responsiveness  rgm csf did not induce any il 6 production in xg 1 cells  nor was it able to sustain their growth alone  although no detectable gm csf levels were found in the peripheral or bone marrow blood of mm patients  it is possible that gm csf  produced locally by the tumoral environment  enhances the il 6 responsiveness of myeloma cells in vivo in a way similar to that reported here in vitro  
class4	hybridization protection assay  a rapid  sensitive  and specific method for detection of philadelphia chromosome positive leukemias  the philadelphia  ph1  chromosome is present in greater than 90  of patients with chronic myelogenous leukemia  cml  and in 2  to 20  of those with acute leukemias  for which it is an important prognostic marker too  the chimeric bcr abl mrnas resulting from the translocation encode either a 210 kd or a 190 kd protein  the techniques used to detect ph1 chromosome include karyotyping  southern analysis to demonstrate bcr rearrangement  and polymerase chain reaction to amplify the bcr abl transcripts  however  the routine performance of these methods by clinical laboratories is cumbersome  time consuming  and exposes laboratory personnel to radioisotopes  we describe here the clinical application of a new method  the hybridization protection assay  hpa   which uses chemiluminescent acridinium ester labeled probes in conjunction with pcr for detection of the amplified bcr abl sequences  the method is sensitive  specific  and can reliably distinguish between the transcripts for p190bcr abl and p210bcr abl  in contrast to the 2 days or longer required for conventional hybridization  hpa analysis can be completed in less than 30 minutes  we have successfully used this method to analyze 60 leukemia samples  34 from ph1 negative acute leukemias  6 from ph1 positive acute leukemias  and 20 from cml  with complete correlation  of bcr abl positivity or negativity  with the results of karyotype or southern blot analysis of genomic dna for bcr rearrangement  therefore  the hpa  in conjunction with pcr  appears to provide a rapid and reliable test for the diagnosis of ph1 positivity  
class4	retroviral transformation of cerebral microvascular endothelial cells  macrophage like and microvascular endothelial cell properties  we report that l cell conditioned medium  lcm  transforms porcine cerebral microvascular  pcmv  endothelial cells into cells with macrophage like properties  lcm is known to contain both cytokine s  and the l cell virus  a murine retrovirus found in the l929 cell and lcm  our evidence suggests that both lcm cytokine s  and the l cell virus are involved in this pcmv endothelial cell transformation  criteria for transformation include focus formation  decreased serum requirements for growth  changes in morphology including nonadherence  propagation in suspension culture  and a decreased growth response to stimulation with a known endothelial cell mitogen  macrophage like characteristics of this transformed cell  designated as rvte  include pinocytosis of low density lipoprotein  fc receptor mediated phagocytosis  phagocytosis of bacteria and zymosan  the expression of macrophage enzyme markers  and constitutive production of colony stimulating factor 1  however  the transformed cell retains several properties of the nontransformed cell including the expression of fviii rag and in vitro self organization into capillary like structures  cloning of rvte cells clearly shows that both macrophage like and cerebral microvascular endothelial cell properties are present in the same cell  during self organization  nontransformed cells express morphologic and functional characteristics classically associated with the macrophage  these findings suggest that some brain capillary pathophysiologies could involve macrophage like cerebral microvascular endothelial cells  furthermore  the  reticuloendothelial  phenotypic repertoire expressed by this transformed cerebral microvascular endothelial cell may show that the cerebral capillary endothelial cell in vivo is derived from a hematopoietic and or phagocytic precursor  
class4	consistent involvement of the bcr gene by 9 22 breakpoints in pediatric acute leukemias  to investigate the relationship of bcr abl fusion mrnas with childhood acute lymphoblastic leukemias  all   we examined 27 pediatric philadelphia chromosome  ph1  positive acute leukemias using a reverse polymerase chain reaction  pcr  procedure  in cells from 24 leukemias  single bcr abl pcr products were detected that corresponded to breakpoints in the minor breakpoint cluster region  mbcr in intron 1 of the bcr gene  associated with production of the p190 fusion protein  cells from the three remaining leukemias contained breakpoints in the major breakpoint cluster region  mbcr  as shown by pcr and southern blot analyses  these three leukemias also contained low levels of the mbcr pcr product that may have resulted from alternative splicing of the bcr abl precursor rna  a screen of 35 additional leukemias from patients who failed therapy before day 180  induction failures or early relapses  found one case with unsuccessful cytogenetics to express mbcr abl rna  all four children with mbcr breakpoints had white blood cell levels in excess of 250 000 at presentation  compared with 2 of 24 with mbcr breakpoints  and two had hematologic and clinical features suggestive of chronic myelogenous leukemias  cml  in lymphoid blast crisis  our results indicate that in ph1 positive pediatric leukemias  all 9 22 breakpoints occur in one of the two known breakpoint cluster regions in the bcr gene on chromosome 22  the reverse pcr reliably detected all patients with cytogenetic t 9 22  and is capable of detecting additional ph1 positive leukemias that are missed by standard cytogenetics  furthermore  the mbcr type breakpoint  associated with production of p210  can be seen in childhood leukemias presenting either as clinical all or as apparent lymphoid blast crisis of cml  suggesting that t 9 22  breakpoint locations do not exclusively determine the biologic and clinical features of pediatric ph1 positive all  
class4	synergistic inhibition by verapamil and quinine of p glycoprotein mediated multidrug resistance in a human myeloma cell line model  in an effort to develop a clinically useful approach to overcoming p glycoprotein mediated multidrug resistance  mdr1   we evaluated combined chemosensitization with verapamil and quinine in a multidrug resistant  mdr  human myeloma cell line model  in clonogenic assay  verapamil was used at concentrations from 0 1 to 1 0 micrograms ml  bracketing the plasma levels achieved by oral administration and high dose intravenous  iv  infusion  respectively  the dose of quinine was held constant at 1 0 micrograms ml  a plasma concentration readily achieved by oral administration  at each dose level of verapamil tested  the combination with quinine proved more effective than either drug individually in reversing resistance to doxorubicin and vinblastine and synergistic chemosensitizing interaction was observed  verapamil at 0 1 microgram ml combined with quinine was capable of restoring sensitivity to doxorubicin fully and reduced resistance to vinblastine as effectively as verapamil alone at 1 0 micrograms ml  furthermore  the combination of 1 0 mumol verapamil with 10 mumols quinine increased accumulation and retention of anthracycline in the resistant cells to a greater extent than did either drug individually  p less than  001  and inhibited drug efflux as effectively as verapamil alone at 10 mumols  our findings suggest that combined chemosensitization with verapamil and quinine may prove useful for overcoming mdr1 in patients with drug refractory b cell neoplasms such as multiple myeloma or non hodgkin s lymphomas  
class4	anti cd33 monoclonal antibody and etoposide cytosine arabinoside combinations for the ex vivo purification of bone marrow in acute nonlymphocytic leukemia  pharmacologic and immunologic methods of ex vivo bone marrow  bm  purging for acute nonlymphocytic leukemia  anll  were combined to augment the effect of either method alone  etoposide  vp16  20 to 30 micrograms ml  with or without cytosine arabinoside  ara c  10 mg ml  was used in tandem with the anti cd33 monoclonal antibody  moab   my9  chosen because cd33 is found on the stem cell pool in the majority of patients with anll  the agents were tested singly or sequentially  with a 1 hour incubation of the drugs preceding complement mediated lysis using my9  vp16 combined with ara c killed up to 3 9     0 3 and 5 11     0 4 logs of the human anll cell lines hl60 and k562 at drug concentrations that killed only 1 2     0 1 logs of normal committed granulocyte macrophage stem cells  cfu gm   adding a single exposure of the my9 and complement  c   to the drug treated cells  greater than 5 4 logs of hl60 were killed  similar to other pharmacologic agents  no differential kill for clonagenic leukemic cells  colony forming unit leukemia  cfu l  from patients with anll was seen for drug only treated blasts versus normal cfu granulocyte macrophage  cfu gm   with less than 1 log cfu l kill at drug concentrations that spared 1 log of cfu gm  similarly  only 1 1     0 3 logs of anll cfu l were eliminated using my9 and c   however  with the sequential vp16 ara c    my9   c  treatment  synergy was demonstrated and 2 6     0 3 logs of cfu l were eliminated  because cd33 is also found on the normal cfu gm pool  two stage long term bm cultures were performed to determine pluripotent stem cell elimination by the drug moab purging combination  no difference of cfu gm or bfu e production at 4 to 6 weeks of culture for vp16 ara c  my9   c   or vp16 arac    my9   c  treated cells was seen compared with untreated controls indicating sparing of early progenitor cells  sequential ex vivo treatment of human anll cfu l with vp16 ara c followed by complement mediated lysis using my9 synergistically kills cfu l while sparing early normal hematopoietic progenitor cells  and thus may be a more effective way to purge bm than either alone  
class4	neutrophil function and pyogenic infections in bone marrow transplant recipients  in a consecutive entry trial  the incidence and time course of decreased neutrophil function was assessed in 20 patients treated with allogeneic bone marrow transplantation  bmt   the aim of the study was to assess the prognostic value of low neutrophil function for late pyogenic infections  chemotaxis  superoxide production  and phagocytic bactericidal activity were studied before and 2  6  9  and 12 months after bmt  skin window migration was quantitatively assessed 2 months after bmt  infectious complications were recorded prospectively with preset criteria during 1 year  six of the 20 leukemic patients had defective neutrophil function before bmt  two months after bmt all 10 patients with greater than stage ii graft versus host disease  gvhd   and 6 of 10 patients with less than or equal to stage ii gvhd had at least one decreased function  at this time  patients with subsequent pyogenic infections had lower chemotaxis  p less than  05   phagocytic bactericidal activity  p less than  005   and superoxide production  p less than  025  than those without  defective skin window migration and combined defects were predictive for late pyogenic infections  at 9 months all tests were normal in seven patients surviving without gvhd  in contrast  at 9 months three of three patients  and at 1 year two of three with chronic gvhd had still decreased neutrophil function  in conclusion  neutrophil function is frequently impaired during the first months after bmt  combined neutrophil defects predispose to pyogenic infections and indicate the patient at risk  
class4	flow cytometry for clinical estimation of circulating hematopoietic progenitors for autologous transplantation in cancer patients  optimum methods of harvesting circulating hematopoietic progenitors for autologous transplantation to support myeloablative cancer therapy are still uncertain  mostly because of the lack of an assay for marrow repopulating stem cells  the cfu gm assay  the commonly used indirect indicator of the quality of the graft  is poorly standardized and provides results evaluable only retrospectively  based on the knowledge that hematopoietic progenitors express cd34 and cd33 differentiation antigens  we developed a dual color direct immunofluorescence flow cytometry assay with the aim of replacing the cfu gm assay advantageously  for this purpose  we applied both assays to 157 blood samples obtained daily throughout 20 different recoveries from pancytopenia induced by high dose cyclophosphamide or etoposide cancer therapy with or without recombinant human gm colony stimulating factor  rhgm csf   the appearance of cd34  cells in the circulation indicated that hematopoietic progenitors had increased to more than 500 cfu gm ml  a level clinically adequate for large scale harvest by leukapheresis  total cd34  cells correlated well with cfu gm  r    89   and data could be fitted by a linear regression line described by the equation y   388 3   64 0x  where y   cfu gm ml and x   cd34  cells per microliter  moreover  in a series of six patients treated with myeloablative chemoradiotherapy  early hematopoietic recovery of marrow functions was predicted more accurately by the number of transplanted cd34  cd33  cells than by either total nucleated cells  cfu gm  cd34  cd33  cells  or cd34  cd33  cells  data presented in this article favor clinical use of the cd34 cd33 flow cytometry assay to guide harvesting of circulating hematopoietic progenitors for autologous transplantation and contribute to better understanding of the role played by circulating hematopoietic progenitor cell subsets in marrow recovery after myeloablative cancer therapy  
class4	renal angiomyolipoma  report of 24 cases  a series of 24 patients with renal angiomyolipoma was reviewed  their ages ranged from 10 to 70 years  average 41   four cases were associated with tuberous sclerosis  1 with spinal neurilemmoma  1 with transitional cell carcinoma and another with renal tuberculosis  the presenting symptoms in decreasing frequencies were flank pain  mass  haematuria  fever  syncope and respiratory distress  although it has often been said that angiomyolipomas associated with tuberous sclerosis are small and asymptomatic  all 4 such patients in this study had large symptomatic tumours  before the advent of ct scan and ultrasonography  the pre operative diagnostic rate for cases unassociated with tuberous sclerosis was 10   1 10   with the combined use of these 2 modalities  the diagnostic rate increased to 60   6 10   most patients in this series were treated with nephrectomy  however  equally good outcomes occurred in 2 patients who received partial nephrectomies  pre operative diagnosis now makes it possible to consider more conservative management  
class4	ten cases of transitional cell carcinoma of bladder causing ureteric obstruction  a review was carried out on 10 patients with superficial transitional cell carcinoma of the bladder  ta lesions  that were causing ureteric obstruction  evidence of upper tract obstruction did not necessarily indicate deep invasion  
class4	prostate tumour markers and differentiation grade in prostatic cancer  serum acid phosphatase activity  prostate specific phosphatase and prostate specific antigen were measured in 100 patients with prostatic cancer  the patients were divided according to the differentiation grade into 3 groups  g1  well   g2  moderately  and g3  poorly differentiated  carcinoma  bone metastases were identified by scintigraphy  among the 76 m0 patients the mean levels of all 3 markers were slightly higher in patients with moderately differentiated prostatic carcinoma  among the 24 m1 patients the primary tumour was either g2  18 patients  or g3  6 patients   none had g1 lesions  significantly higher serum acp and pap levels were found in patients with g2 tumours than in those with g3 lesions  it was concluded that the histological differentiation grade of prostatic carcinoma did affect serum levels of prostatic tumour markers  the tendency towards higher levels in the g2 group was noticeable in both non metastatic and metastatic cases despite the limited number of patients in the latter category  in clinical practice this information may be an important additional tool in staging prostatic cancer  
class4	epidermoid cyst  monodermal teratoma  of the testis  we report 14 patients with epidermoid cyst of the testis  monodermal teratoma   in 7 patients  5 treated within the last 5 years  the mass was excised and adjacent testicular tissue was biopsied  seven patients underwent radical inguinal orchiectomy  carcinoma in situ was not detected in any testicular tissue examined  there was no evidence of tumour recurrence in any patient after a mean follow up of 10 years  ultrasonographic appearance was not specific for a diagnosis of epidermoid cyst and exploratory surgery was required in all cases  excision of the tumour and biopsy of adjacent testicular tissue to determine the presence or absence of carcinoma in situ is adequate treatment for this rare testicular neoplasm  
class4	the cancer experience in the framingham heart study cohort  the almost 40 year records of the framingham heart study  fhs  cohort were reviewed to establish the cancer experience of this noninstitutionalized group of white subjects  diagnoses were confirmed from pathology and laboratory reports and clinical notes  age specific incidence rates were compared with connecticut surveillance  epidemiology  and end results  seer  data  among the 5209 subjects  1201 malignancies were confirmed  median age at diagnosis was 69 for men and 65 for women  lung  prostate  skin  and colon accounted for more than half of men s cancers  breast  colon  and skin made up half of the women s  fhs and connecticut seer rates matched closely  with the same primary tumor sites appearing commonly in both groups  thus  the fhs cohort should provide a fair database for analysis of risk factors in cancer incidence  as it has done in cardiovascular diseases  
class4	variability in dna measurements in multiple tumor samples of human colonic carcinoma  the dna ploidy and cell cycle distribution of three separate fresh tissue samples of 60 colorectal adenocarcinomas were analyzed by flow cytometry  dna ploidy was concordant among the three samples in 38 cases  63 3    in the remaining 22 cases  36 6    the dna histograms of two of the three multiple samples were similar  however  the ploidy of the third sample was discordant  no relationship was observed between dukes  stage and histologic grade with concordance or discordance among samples  thus  in about one third of the colonic carcinomas  a single sample showing either a diploid or diploid cycling dna histogram would not detect aneuploid dna patterns  comparison of scrapes and fine needle aspirates of tumors as alternative sampling methods of tumors for dna ploidy analysis indicated a strong association with the tumor ploidy  84  and 96   respectively  only when the ploidy of the multiple samples was concordant  in about 25  of the cases  tumor scrapes and fine needle aspirates did not correlate with the  most abnormal  ploidy observed in one of the three tissue samples  the data suggest that single or even double tissue samples may not show aneuploid dna patterns in a substantial proportion of colorectal cancers  
class4	clear cell carcinoma of the inguinal region arising from endometriosis  the second and third examples of clear cell carcinoma of the inguinal region arising from endometriosis are reported  in one patient a right inguinal mass was excised along with an inguinal lymph node dissection  the tumor recurred in the retroperitoneum and was removed  and postoperative radiation therapy was administered  the patient died of recurrent tumor after 11 years  the other patient was treated by excision of a left inguinal mass and an inguinal lymph node dissection and was alive without recurrence 4 years and 8 months later  
class4	percent tumor necrosis as a predictor of treatment response in canine osteosarcoma  the percent tumor necrosis was determined in 200 dogs with spontaneously occurring osteosarcoma  one hundred dogs had no treatment before amputation or death  one hundred other dogs were treated with either radiation therapy alone  n   23   intraarterial  ia  cisplatin alone  n   16   intravenous  iv  cisplatin alone  n   6   radiation therapy plus ia cisplatin  n   47   or radiation therapy plus iv cisplatin  n   8   eighty nine of these 100 dogs had their tumors resected 3 weeks after the end of therapy  6 weeks after the initiation of therapy  and replaced with a cortical bone allograft  dogs with preoperative treatment were evaluated for local tumor control and time to metastasis  the mean percent tumor necrosis in untreated osteosarcoma was 26 8   the mean percent tumor necrosis for dogs receiving radiation only  ia cisplatin only  and iv cisplatin only was 81 6   49 1  and 23 8   respectively  the mean percent tumor necrosis for dogs receiving radiation therapy plus ia cisplatin or radiation therapy plus iv cisplatin was 83 7  and 78 2   respectively  there was no significant difference between percent tumor necrosis in untreated osteosarcoma compared with those receiving iv cisplatin  but there was a significant increase in percent tumor necrosis with all other treatments  a mathematic model for the effect of cisplatin and radiation dose was developed using multiple regression analysis  the radiation dose calculated to cause at least 80  tumor necrosis was 42 2 gy  95  confidence interval  ci   38 0 to 47 6 gy  when radiation was given alone and 28 1 gy  95  ci  21 3 to 36 6 gy  when radiation was combined with ia cisplatin  areas of viable tumor tended to be most frequent adjacent to the articular cartilage and in the joint capsule  percent tumor necrosis was strongly predictive for local tumor control  28 of 32 dogs with greater than 80  tumor necrosis had local control  and only eight of 29 dogs with less than 79  tumor necrosis had local control  p   0 0047   there was no correlation between percent tumor necrosis and time to metastasis  
class4	usefulness of serum glycoconjugates in precancerous and cancerous diseases of the oral cavity  sera from 47 healthy controls  18 normal individuals with the habit of tobacco chewing  43 patients with oral precancerous  pc  conditions  and 40 patients with oral cancer  oc  were studied for the levels of total sialic acid  tsa   lipid bound sialic acid  lsa   mucoid proteins  and protein bound hexoses  pbh   galactose and mannose   the changes in the glycoconjugate levels were insignificant between the controls and the normal tobacco chewers  all four parameters were significantly elevated in oral pc patients compared with controls  the levels of pbh and lsa showed significant increase in the oral pc patients compared with the normal tobacco chewers  a significant increase was observed in the levels of tsa  lsa  mucoid proteins  and pbh in oc patients compared with controls  normal tobacco chewers  and patients with oral pc  increasing levels of all the biomarkers were found with progression of the malignant disease  elevations in the levels of tsa and lsa were statistically significant in stage iv patients compared with stage iii patients  the patients with metastases had higher levels of the biomarkers than the patients with primary oc  however  elevations only in lsa levels were statistically significant  these results suggest that evaluations of the serum glycoconjugate levels may be useful in diagnosis of the patients with oral pc or oc  in addition to their value in early detection  they can also help in staging of the disease  
class4	a prospective randomized comparison of protracted infusional 5 fluorouracil with or without weekly bolus cisplatin in metastatic colorectal carcinoma  a mid atlantic oncology program study  one hundred eighty four patients with advanced measurable colorectal cancer not previously treated with chemotherapy were entered into a prospective randomized clinical trial by the mid atlantic oncology program  maop  to assess the value of weekly cisplatin  20 mg m2  when added to a protracted schedule of 5 fluorouracil  5 fu  infusion  pif  at 300 mg m2 d for 10 weeks of every 12 weeks  the liver was the primary indicator lesion in approximately 75  of the study group  all tumor measurements required radiographic confirmation  the response rate in the pif alone arm was 35   29 of 83  95  confidence interval  ci   25  to 46   compared with 33   28 of 85  95  ci  23  to 44   for the arm in which weekly cisplatin was added to pif  the median survival times were 11 8 and 11 2 months in the two groups  weekly cisplatin does not appear to add to the effectiveness of pif in colorectal carcinoma  
class4	relationship between histologic features  dna flow cytometry  and clinical behavior of squamous cell carcinomas of the larynx  flow cytometric analysis of dna content was done on 133 primary squamous cell carcinomas of the larynx  overall  76 tumors  57 1   were not diploid  aneuploid or tetraploid   the dna index  di  was calculated and grouped into three levels  fifty seven cases had a di in a range of 1 85 to 2 15  44 diploid and 13 tetraploid   the cases were grouped in relation to ploidy  proliferative index  and the tumor node metastasis  tnm  system  every group was analyzed with respect to survival rate  ploidy was related to histocytologic grade  in well differentiated tumors  g1  survival rates at 48 months were 41 7  in diploid cases and 27 7  in nondiploid ones  relative risk  rr   2 01  95  confidence interval  ci   0 89  4 52   in no cases that underwent surgery  survival rates at 48 months were  respectively  81 8  and 49 2   rr  5 07  95  ci  0 76  33 93   these results suggest that ploidy may be a new independent parameter of prognosis in squamous cell carcinoma of the larynx  this is useful in clinical practice because it allows the clinician to recognize those cases with poorer prognosis among the early tumors at a stage where other prognostic parameters are not yet available  
class4	evaluation of serum ca 125 as a tumor marker in non small cell lung cancer  serum ca 125 levels were evaluated in 130 healthy subjects and 133 patients with untreated pulmonary lesions  these were 33 patients with benign pulmonary conditions and 100 with lung cancer  the mean concentration of ca 125 was higher in patients with lung cancer  37     81 u ml  than in those with nonmalignant disease  4 2     5 7 u ml   p less than 0 01   in the healthy control group ca 125 concentrations were significantly lower  0 63     1 5 u ml   p less than 0 001   in patients with lung cancer the concentration of this tumor marker was related to the tumor node metastasis  tnm  stage  at a cut off value of 15 u ml  ca 125 had a sensitivity of 44   specificity of 100   positive predictive value of 100   and negative predictive value of 65  with respect to healthy subjects  in patients with benign pulmonary conditions  these values were 44   94   94   and 31   respectively  at this cut off value  a correlation between the respectability prognosis and the likelihood of survival 24 months posttreatment was observed  these findings suggest that ca 125 can be used as an adjunctive test in the management of patients with lung cancer patients  
class4	chondrosarcomas of the synovium  chondrosarcoma of the synovium  either primary or secondary to synovial chondromatosis  is rare  ten cases of synovial chondrosarcoma were studied  four from the mayo clinic files and six from the authors  consultation files   two were considered primary  in five cases there was evidence of preexisting synovial chondromatosis  and in the remaining three  there was a suggestion of preexisting disease  several histologic features were found that were helpful to diagnose malignancy  the most important ones were loss of the  clustering  growth pattern typical of synovial chondromatosis  myxoid change in the matrix  areas of necrosis  and spindling at the periphery of chondroid lobules  pulmonary metastasis developed in five of nine patients  three of these patients died  
class4	prognostic value of histopathology in ewing s sarcoma  long term follow up of distal extremity primary tumors  the pathologic material from 56 patients diagnosed initially as ewing s sarcoma of the distal extremity and treated on national cancer institute protocols between 1968 and 1984 was reviewed and correlated with clinical outcome  histologically  the tumors were categorized  based on recent pathologic criteria  into three diagnostic groups   1  typical ewing s sarcoma   2  atypical ewing s sarcoma  and  3  other  predominantly peripheral neuroepithelioma  pn    thirty two patients  57   had typical ewing s  13  23   were atypical  and 11  20   were in the  other  diagnostic category  seven  13   pn  two primitive rhabdomyosarcoma  one primitive sarcoma of bone  and one synovial cell sarcoma   no cases of metastatic neuroblastoma  osteosarcoma  or lymphoma were found  forty five patients had localized disease at diagnosis  11 had metastases  patients with typical ewing s sarcoma were less likely to have metastatic disease at the time of diagnosis  only two of 32 patients with typical ewing s sarcoma had metastases compared with nine of 24 patients in the two other groups  the pattern of relapse was also different in these other groups compared with typical ewing s patients  five patients developed lymph node metastases and two patients developed brain metastases  although the presence of metastatic disease at diagnosis was a strong negative prognostic factor  our histologic grouping was independently prognostic of clinical outcome in patients with localized disease  patients with typical osseous ewing s sarcoma had an improved overall survival  p2   0 03  and patients with other tumors  neither typical nor atypical ewing s sarcoma  had a poorer disease free survival  p2   0 02   since no generally accepted histopathologic prognostic criteria exist for ewing s sarcoma  the potential value of our proposed classification should be evaluated in a larger retrospective and a prospective study  
class4	acinic cell carcinoma  clinicopathologic review  the authors reviewed 90 cases of acinic cell carcinoma treated at the mayo clinic to assess long term follow up and to study features predictive of disease progression  sixty three patients  55 females and 35 males  were seen for primary treatment  27 had recurrent disease when first evaluated  histologically  these tumors were composed of serous acinar cells and intercalated duct type cells  morphologic patterns included solid  microcystic  follicular  and papillary cystic  all patients were followed for at least 10 years or until death  of the primary treatment group  44  had local recurrence  19  had metastasis  and 25  died of disease  disease first recurred locally up to 30 years after presentation and resulted in death after as many as 38 years  poor prognostic features include pain or fixation  gross invasion  microscopic features of desmoplasia  atypia  or increased mitotic activity  and excision as initial treatment  neither morphologic pattern nor cell composition was a predictive feature  
class4	risk factors for cancer of the tongue in uruguay  from 1987 to 1989  a hospital based case control study of cancer of the tongue was conducted in montevideo  uruguay  as part of a large study to investigate a number of risk factors for cancer of the oral cavity  pharynx  and larynx  the study involved interviews with 57 cases and 353 controls and was restricted to men  relative risks  rr  associated with tobacco smoking  alcohol drinking  and selected dietary items were obtained by unconditional logistic regression analysis  users of black tobacco had a rr fourfold higher than users of blond tobacco  and heavy drinkers of alcohol had a rr of 11 6  infrequent consumption of vegetables was associated with a significant rr of 5 3  and heavy drinkers of the local infusion  mate  had a rr of 2 5  it was concluded that black tobacco smoking and alcohol drinking were the strongest risk factors for cancer of the tongue in uruguay  their effects combine according to a multiplicative model  also  infrequent vegetable intake and mate ingestion contribute to the risk of cancer of the tongue  
class4	prognostic factors in yolk sac tumors of the ovary  a clinicopathologic analysis of 29 cases  twenty nine ovarian cancer patients with yolk sac tumors and germ cell tumors with yolk sac tissue as a component of their disease  16 endodermal sinus tumor  11 mixed germ cell tumors  one embryonal carcinoma  and one polyembryoma  were treated with cytoreductive surgery and combination chemotherapy  prognostic factors were investigated in this group  patients with stage i disease had a more favorable prognosis  p less than 0 003  than those with stages ii and iv disease  the difference in prognosis was significant in cases where residual tumor was absent  p less than 0 003  and in cases where ascites was either absent or less than 100 ml in volume  p less than 0 05   endodermal sinus tumor with either an intestinal  p less than 0 05  or microcystic pattern  p less than 0 01  was more common in survivors than in those who died  the age  preoperative serum alpha fetoprotein level  maximum tumor size  and tumor weight had no significant correlation with prognosis  in advanced cases  chemotherapy regimens including cisplatin gave better results than those containing vincristine  dactinomycin  and cyclophosphamide  p less than 0 05   the optimal treatment of yolk sac tumors or tumors with yolk sac tissue as a component of the ovary is discussed in light of these results  
class4	bone sarcomas as second malignant neoplasms following childhood cancer  this study explores the relationship between histologic variants of bone sarcomas and previous therapy in patients in whom an unrelated malignant neoplasm had been diagnosed during childhood  sarcomas of bone were the most common second malignant neoplasm  smn  reported to the late effects study group  a 13 institution consortium consisting of pediatric oncology centers from western europe  canada  and the united states  the authors attempted to relate the histologic subtypes of the 91 bone tumors to clinical factors such as previous therapy and genetic predisposition because morphologic variants have been shown to have biologic significance in other tumors and may have etiologic import  the literature concerning the subtypes of bone tumors  clinical and experimental  is also reviewed  the authors also investigated the effect of several factors on the time interval from the first diagnosis to the smn  i e   the bone sarcoma   anthracyclines significantly shortened the interval by about 3 years  the primary diagnosis also significantly affected the interval  with leukemia lymphomas having the shortest interval and retinoblastoma the longest  the authors could not demonstrate any significant relationship between morphologic characteristics of the osteosarcoma and predisposing conditions  however  lesions diagnosed as chondrosarcoma and malignant fibrous histiocytoma occurred almost exclusively in patients who had received radiation therapy to the site in which the smn developed  
class4	a southwest oncology group study on the use of a human tumor cloning assay for predicting response in patients with ovarian cancer  a total of 211 patients with epithelial ovarian cancer  168 with tumors refractory to prior chemotherapy and 43 with no prior chemotherapy  from 33 different southwest oncology group institutions had their tumors sampled and specimens shipped to two central laboratories for drug sensitivity testing in a human tumor cloning assay  the 168 patients with a prior history of chemotherapy failure  median of four prior chemotherapeutic agents  were treated with the most effective agent s  found in the cloning assay  23 patients   and those patients whose tumors did not form colonies in vitro or did not manifest any sensitivity to agent s  were treated with a clinician s choice of agent s   101 patients   the remaining 44 of the 168 patients were not treated with chemotherapy because of deteriorating performance status or early death  the complete and partial response rate in patients treated according to assay results was 28  versus 11  for the patients treated according to clinician s choice  p   0 03   there was no statistically significant difference in survival between the two options  6 25 versus 7 months  respectively   the 43 patients with no history of prior chemotherapy were all treated with standard combination chemotherapy  and their clinical response was compared with their in vitro sensitivity to the same agents  overall there was a 100  true positive rate and 100  true negative rate for the seven evaluable patients  from these data the authors conclude that use of the human tumor cloning assay may increase the response rate but not the survival for selected patients with advanced chemotherapy refractory ovarian cancer  the study is weakened  however  by the many steps of patient selection necessitated by inadequate tumor colony formation in vitro and the inability to treat all patients  because of early death or a rapid decline in performance status   the assay does appear to be worthy of additional study for predicting response to combination chemotherapy in patients without a prior history of chemotherapy  finally the use of central chemosensitivity testing laboratories is feasible for testing in vitro predictive assays in a cooperative group setting  
class4	yield from total skin examination and effectiveness of skin cancer awareness program  findings in 874 new dermatology patients  the authors reviewed 874 dermatology charts to assess the acceptance rate of total skin examination  tse   incidental skin findings  and patient compliance regarding treatment recommendations  of the 874 new dermatology patients studied  707  80 9   agreed to tse  important incidental findings were found in 151  21 4    these included   1  biopsy specimen confirmed malignant tumors  malignant melanoma  lentigo maligna  and basal cell and squamous cell carcinoma  in 24 of the 707 patients  3 4     2  biopsy specimen confirmed premalignant tumors  actinic keratosis with dysplasia  bowenoid actinic keratosis  bowenoid papulosis  and lentigo with dysplasia  in five  0 7     3  clinically diagnosed premalignant actinic keratosis in 64  9 1     4  biopsy specimen confirmed dysplastic nevi in 17  2 4    and  5  congenital nevi in 41  5 8    only 4 2  of the patients returned for a yearly tse  and only 6 0  were found to follow all recommendations for monthly self examination  yearly professional examination  and sun protection  it is concluded that tse for all new patients  and on a yearly basis for all return patients  is valuable in the detection of many skin conditions and allows skin cancer screening to be done  since patients for the most part do not follow recommendations for at home screening  
class4	achievement of life goals by adult survivors of modern treatment for childhood cancer  to assess the impact of the diagnosis and modern treatment of childhood cancer on achievement of adult goals  the authors evaluated employment  health and life insurance coverage  marriage  divorce  and reproduction in 227 former pediatric cancer patients  each area was evaluated in relation to a common set of disease and demographic factors that included age at follow up  age at diagnosis  gender  marital status  history of disease recurrence  and diagnosis  patients were younger than 20 years of age at diagnosis  and their diagnoses were made between january 1  1960  and december 31  1984  the median age at diagnosis was 11 4 years  and the median age at follow up was 26 6 years  the percentage of unemployed male respondents did not differ from population norms  the percentage of unemployed female respondents  however  was slightly higher than that of the united states population  approximately 11  of the survivors reported some form of employment related discrimination  a level significantly lower than that of prior reports  company offered health insurance was provided to 92 4  of full time and 90 0  of part time employed respondents  life insurance was purchased by 60  of full time employed men and 55  of women  these percentages were lower than those reported for the united states population  twenty four percent of those with life insurance had difficulty obtaining it  fifty eight percent of the subjects were married or lived as married  the percentages of married men and women were significantly lower than united states norms  twenty percent of those who were married or lived as married have divorced or separated or no longer live as married  women aged 20 to 24 years were less likely to marry  and women aged 35 to 44 years had a significantly higher frequency of divorce than similarly aged united states women  in general  the history of childhood cancer did not influence the decision to marry or live as married but was occasionally  20   important in the decision to dissolve a marital relationship  many former patients indicated that their diagnosis and treatment for childhood cancer influenced their decision to have children  the current study suggests that most former pediatric cancer patients achieve adult life goals  additional research is necessary to define those populations at greatest risk of failure to achieve these goals  
class4	two drug therapy in patients with metastatic germ cell tumors  eighty two patients with metastatic germ cell tumors  gct  treated with two drug therapy consisting of etoposide and cisplatin were evaluated for late relapse  good risk gct was defined using memorial sloan kettering cancer center  mskcc  criteria  etoposide was given at 100 mg m2 on days 1 to 5 and cisplatin was given at 20 mg m2 on days 1 to 5  therapy was recycled at 21 days with delays up to 7 days for a leukocyte count of less than 3000 microliters or a platelet count of less than 100 000 microliters  drug doses were not attenuated for myelosuppression  seventy six of 82 evaluable patients achieved a complete response  cr   seventy two patients had a cr to chemotherapy alone  forty six  56   patients had excision of residual abnormalities  11 had teratoma in the resected specimen  31 had necrotic debris or fibrosis  and 4 had a cr after chemotherapy plus complete excision of residual viable gct  six patients had an incomplete response to chemotherapy  one of these patients had unresectable mature teratoma and remains progression free  the median etoposide dose      standard deviation  sd   was 500 mg m2 course      35 mg m2  and the median cisplatin dose      sd  was 100 mg m2 course      6 mg m2   nine patients experienced a relapse at 6 to 17 5 months  two patients with nonseminomatous gct were salvaged by chemotherapy and one patient with seminoma was salvaged by chemotherapy and radiation therapy  the three patients who were salvaged by additional therapy are disease free at 59 to 63 months  seventy one patients  87   remain disease free with a median follow up time of 63 months  range  33 to 92 months   no relapses have occurred beyond 17 5 months  etoposide and cisplatin therapy at these doses and schedule results in durable cr without late relapse  
class4	a study of cyproheptadine in the treatment of metastatic carcinoid tumor and the malignant carcinoid syndrome  sixteen patients with metastatic neuroendocrine tumors and the malignant carcinoid syndrome were treated with cyproheptadine  periactin  merck  sharp   dohme  west point  pa  at maximum tolerable doses that ranged from 12 to 48 mg daily  usual side effects were mild sedation and dry mouth  but three patients found it impossible to sustain treatment due to nausea and vomiting  most patients had significant relief of diarrhea  frequently associated with weight gain  relief of flushing was uncommon  the therapeutic benefit produced by cyproheptadine would appear to be a peripheral effect because 5 hydroxyindoleacetic acid  5 hiaa  excretion in these patients was not reduced  although there have been case reports of objective tumor regression with cyproheptadine therapy  this was not observed in any of these 16 patients  cyproheptadine would appear to be a useful therapeutic tool for the management of diarrhea associated with the malignant carcinoid syndrome  an appropriate initial total daily dose is 0 4 mg kg divided in three fractions with prompt modification to produce minimal and tolerable side effects  
class4	remission induction and continuation therapy in children with their first relapse of acute lymphoid leukemia  a pediatric oncology group study  between january 1979 and april 1983  113 children undergoing their first relapse of acute lymphoid leukemia  all  at any site were registered in pediatric oncology group study 7834  98 were eligible and evaluable  in addition to radiotherapy administered to sites of local relapse  induction consisted of vincristine  doxorubicin  and prednisone  vap  chemotherapy  continuation therapy consisted of triple drug intrathecal therapy and regimens of 6 thioguanine and cytarabine alternating with vincristine  prednisone  cyclophosphamide  and cytarabine  randomization in continuation was between vap pulses or no pulse  regardless of the site of relapse  this report provides long term follow up of these patients  thirty two of 39 children with bone marrow involvement achieved a complete response  cr   only one of these is alive in an unmaintained remission  a child who did not have an initial cr  thirty four of 36 evaluable children with central nervous system involvement as the site of relapse achieved cr  of these ten are alive  eight are in continuing cr  nineteen of 20 boys with testicular relapse achieved cr  of these  14 are still alive and not receiving therapy  although only one half received treatment in compliance with the protocol described  these results illustrate the possibility of cure of patients who have relapsed with all when it is  1  confined to a meningeal or gonadal site and  2  treated vigorously with radiotherapy and a new regimen of systemic chemotherapy  the results reconfirm the need to prevent an initial relapse at any site  
class4	prolonged response to carboplatin in an infant with brain stem glioma  adults and children with brain stem gliomas have a mean survival time of 15 months after radiation therapy  xrt   infants with this tumor present additional complexities for treatment because of possible neurotoxicity of the radiation to the developing brain  we report a 15 month old child with biopsy proven brain stem glioma with clinical and radiographic evidence of disease progression  she was treated with 24 monthly courses of carboplatin without radiation therapy and has had a 39  month response  the clinical response started after 3 months and the radiographic evidence was documented at 10 months by magnetic resonance imaging  the toxicity was minimal  longitudinal neuropsychological assessment demonstrated continued improvement at 36 months post diagnosis but with some motor functioning below expected age levels  cervico medullary astrocytoma in a young patient may be the appropriate clinical setting for future trials of chemotherapy without xrt  
class4	postoperative follow up of patients with early breast cancer  patterns of care among clinical oncologists and a review of the literature  eighty clinical oncologists in the southeastern united states were surveyed to determine their strategies for follow up care after primary treatment of early stage breast cancer  the frequency of use of the history and physical examination  complete blood count  liver function tests  carcinoembryonic antigen levels  chest x ray  skeletal survey  bone scan  liver scan  and mammogram for observing hypothetical low  and high risk patients was assessed  yearly mammograms were recommended by more than 95  of respondents  history and physical examination were the modalities used most often  whereas periodic bone and liver scans were used only in a minority of patients  a review of the literature supported the strategy of the respondents in this survey and further underscored the cost effectiveness of the history and physical examination in detecting recurrence during follow up  based on this survey and supporting literature  recommendations for reasonable yet cost conscious follow up are presented  
class4	imaging of a parapharyngeal hemangiopericytoma  radioimmunoscintigraphy  spect  with indium 111 labeled anti cea antibody  and comparison to digital subtraction angiography  computed tomography  and immunohistochemistry  a 27 year old male patient with a parapharyngeal hemangiopericytoma was investigated radiologically with orthopantomography  computed tomography  and digital subtraction angiography before the operation  because a malignancy was suspected  the patient was imaged with gamma camera using radiolabeled monoclonal anticarcinoembryonal antigen antibody including single photon emission computed tomography  the radioantibody accumulated strongly into the neoplasm  tumor to background ratio was 2 2  samples of the excised tumor were stained immunohistochemically for desmin  vimentin  muscle actin  cytokeratin  cea  carcinoembryonic antigen   and factor viii  they showed that the antibody uptake was of unspecific nature and not due to cea expression in the tumor  
class4	elective radical neck dissection in epidermoid cancer of the head and neck  a retrospective analysis of 853 cases of mouth  pharynx  and larynx cancer  a retrospective analysis of 853 patients with cancer of the mouth  pharynx  and larynx operated on over a 30 year period was performed  four hundred fifty seven of them had a radical neck dissection  rnd  at some point  five hundred ninety patients had no clinically positive nodes  n o  necks at the time of primary treatment  99 of these had elective neck dissection  whereas 95 others had a delayed rnd when nodes became clinically involved  twenty three percent of all n o patients had microscopically involved nodes and less than half of these were among those patients selected for elective rnd  furthermore  58  of those patients who had elective rnd did not have positive nodes  comparative analysis of elective rnd  delayed therapeutic rnd after clinical appearance of nodes  and composite operations for patients with n1 n3 disease indicates little difference in disease free survival when the nodes in the elective rnd were positive microscopically for tumors  56   49  and 47  respectively   it thus seems that elective rnd offers no real advantage over a careful watchful waiting approach in most patients  
class4	results of treating ductal carcinoma in situ of the breast with conservative surgery and radiation therapy  to determine the frequency  pattern  and time course of tumor recurrence in the breast  the outcome of 38 women with ductal carcinoma in situ  dcis  treated with conservative surgery and radiation therapy between 1976 and 1985 was studied  surgery typically consisted of local excision without evaluation of the microscopic margins of resection  the median radiation dose to the tumor site was 6400 cgy  with a median follow up time of 81 months  eight patients  21   have experienced a recurrence in the breast  the time course to recurrence was protracted in some cases  with failures occurring at 17  27  43  63  71  83  92  and 104 months  the 5 year and 8 year actuarial rates of tumor recurrence in the breast were 8  and 27   respectively  seven patients had a recurrence at or near the primary tumor site  four with invasive carcinoma  and one had an invasive recurrence at a site elsewhere in the breast  no clinical or pathologic factor was significantly associated with an increased risk of recurrence  but the number of patients in the study population was small  the authors reached the following conclusions for patients with dcis treated with conservative surgery and radiation therapy without careful mammographic and pathologic evaluation   1  recurrence in the breast may be seen in at least one fifth of the patients   2  recurrence typically occurs at or near the primary site  and  3  recurrence can occur long after treatment  careful mammographic and pathologic assessment may be useful in reducing the local recurrence rate and should be considered essential if patients are considered for conservative surgery and radiation therapy  
class4	surgical management of pericardial effusion in patients with malignancies  comparison of subxiphoid window versus pericardiectomy  there is a lack of consensus regarding optimal surgical management of symptomatic pericardial effusions in patients with malignancies  subxiphoid pericardial window formation  subxiphoid pericardial drainage  has been considered a safe and effective method for diagnostic and therapeutic purposes  to ensure adequate drainage  many surgeons prefer the formation of a larger pericardial window by performing either an anterior thoracotomy or a partial total pericardiectomy  to evaluate the efficacy of these methods for palliation of symptomatic pericardial effusion in patients with malignancy  28 consecutive pericardial surgery cases involving patients with malignancy were retrospectively analyzed  ten patients  group 1  had subxiphoid window formation  whereas 18 patients  group 2  had partial or total pericardiectomy or pericardial window formation by anterior thoracotomy  there was no statistically significant difference  p   0 22  in the survival rates between these two groups  a median survival time of 2 67 months  range  0 43 to 26 6 months  was observed in group 1 versus 1 23 months  range  0 03 to 10 83 months  in group 2  however  a statistically significant difference  p less than or equal to 0 02  in postoperative morbidity was observed between the two groups  67  in group 2 versus 10  in group 1  because of lower morbidity  subxiphoid pericardial window formation is recommended by this study as the preferred surgical method for palliation of symptomatic pericardial effusion in patients with malignancy  
class4	limitation of transcatheter arterial chemoembolization using iodized oil for small hepatocellular carcinoma  a study in resected cases  the radiologic and histologic findings are presented of the resection of 14 small hepatocellular carcinomas  hcc   less than 2 cm in maximum diameter  after transcatheter arterial chemoembolization  tce  using iodized oil  the effect of tce on small hcc depended on the morphologic type of the tumors  when no extracapsular invasion of tumor cells occurred  tce was extremely effective against encapsulated tumors  however  in nine of the 14 resected specimens  viable tumor cells remained in or around the tumor  the authors suggest that small hcc are not always curable with tce alone and that a multi disciplinary approach is necessary for patients with small hcc  
class4	the interferon system in carcinoma of the cervix  effect of radiation and chemotherapy  thirteen patients with advanced carcinoma of the cervix were studied for parameters of the interferon system compared with 40 age matched and sex matched controls  all patients had measurable serum interferon levels  controls did not  all patients had non antibody type interferon inhibitory activity  and controls had none  interferon synthesizing potential was higher in controls than in patients  after successful radiation and chemotherapy  these parameters normalized in the patients  no change was seen in one patient who did not respond to therapy  
class4	immunohistologic detection of the epidermal growth factor receptor in human esophageal squamous cell carcinoma  epidermal growth factor receptor  egf r  expression was studied immunohistologically in 38 patients with esophageal squamous cell carcinoma  the egf r was faintly expressed in basal and parabasal layers of normal esophageal epithelia and in cancer nests of 20 patients  it was strongly expressed in all areas of dysplastic epithelia and in cancer nests of 18 patients  the patients with strongly expressed egf r had lymph node metastases more frequently  and their prognosis was poorer than those with faintly expressed egf r  the egf r expression showed a mosaic pattern in 17 patients and a diffuse pattern in 21 patients  the patients with a mosaic pattern had lymph node metastases more frequently and a worse prognosis than those with a diffuse pattern  expression of egf r in metastatic lymph nodes was similar to that in strongly expressing areas of primary cancers with a mosaic pattern  thus egf r expression may be an important indicator for malignancies of esophageal squamous cell carcinomas because primary cancer cells with strongly expressed egf r metastasize to lymph nodes more frequently  
class4	the value of immunohistochemistry for collagen iv expression in colorectal carcinomas  the dukes  classification has well established prognostic value in colorectal cancer patients  yet  in each dukes  class  the survival of individual patients may vary considerably  recent studies show prognostic significance of genetic alterations in colorectal carcinoma  however  the importance of tumor stromal components noted in the surrounding tissue may have been overlooked by the methods used  therefore  in a longitudinal study of 154 patients with colorectal cancer operated on between 1967 and 1974  the authors determined the influence on prognosis of lymphocytic infiltration and expression of collagen type iv in tumor stroma  also  age  sex  dukes  classification  grade of tumor differentiation  vasoinvasion  and the number of positive lymph nodes were analyzed  follow up was at least 15 years  lymphocytic infiltration and collagen iv expression were scored as mild  moderate  or severe  survival was analyzed by a cox proportional hazards model  the density of lymphocytic invasion showed no significant influence on survival  collagen iv expression analyzed as a single variable was significantly  p   0 038  related to better prognosis in colorectal cancer patients  by multi variate analysis collagen iv expression showed a trend toward better prognosis that was not statistically significant  p   0 12   dukes  classification  p less than 0 001   the presence of vasoinvasion  p   0 009   and lymph node status  p   0 04  significantly influenced survival  in conclusion immunohistochemistry for collagen iv is an important additional staining technique with prognostic value  in addition  collagen iv immunostaining facilitates recognition of vascular invasion by highlighting the basement membrane of vessels  
class4	late effects of treatment for wilms  tumor  a report from the national wilms  tumor study group  the national wilms  tumor study  nwts  was initiated in 1969  one of its objectives was to modulate treatments according to risk factors to minimize the number and severity of treatment related short term and long term iatrogenic complications  the nwts has therefore incorporated a long term follow up study  ltfs  within its framework to monitor late effects  the ltfs is confined to relapse free survivors alive 5 years or longer after initial surgery  and data are collected using specifically designed forms  a total of 787 patients registered on nwts 1 or nwts 2  1969 to 1979  were eligible  of whom 680  86   were available for analysis regarding musculoskeletal  cardiovascular  and neuropsychologic status  and the presence of benign and malignant tumors  patients with early stage disease who were treated with radiation had scoliosis reported  along with other musculoskeletal abnormalities  32 versus 2   nearly seven times as often as did the members of the cohort population who did not undergo radiation  35 of 57 versus 5 of 53  respectively   the difference in cardiovascular problems recorded in survivors who did and did not receive adriamycin  adria laboratories  columbus  oh   2 4 versus 1 1 per 100 person years at risk  had borderline statistical significance  p   0 06   no excess in neuropsychologic events was reported for those given the neurotoxin vincristine  when considering patients with disease of all stages  all 5 second malignant tumors occurred in the 623 patients who underwent radiation  rt patients   benign tumors were also more frequent in rt patients than in those patients who did not undergo radiation  41 of 486 or 8  versus 4 of 194 or 2    continuing study of this unique body of patients is needed  especially for those given adriamycin  because of the known long interval needed for latent cardiomyopathy to become clinically manifest in some patients  
class4	t cell lymphoma and mature nephroblastoma after synchronous bilateral wilms  tumor  a 15 year old boy had lymphoblastic lymphoma of the left tonsil after being treated for bilateral wilms  tumor  bwt  at 7 months of age  in addition  a fully differentiated wilms  tumor was diagnosed in the remaining  partially nephrectomized left kidney  development of second malignancies in patients with a history of bwt  as compared with those with unilateral wilms  tumor  is discussed  a possible explanation for the concurrently diagnosed  fully differentiated wilms  tumor in the remaining left kidney is suggested  
class4	hepatocellular carcinoma as second malignant neoplasms in successfully treated wilms  tumor patients  a national wilms  tumor study report  although rare  second malignant neoplasms  smn  after treatment for wilms  tumor are deadly  a recent national wilms  tumor study  nwts  report identified 15 patients with second malignancies discovered over 14 381 person years of observation  this report described four patients with secondary hepatocellular carcinoma in greater detail  these patients were strikingly similar in that all had right sided tumors and each one had received right upper quadrant irradiation  all patients died shortly after diagnosis of the smn  
class4	a phase ii trial of carboplatin and vinblastine in the treatment of advanced squamous cell carcinoma of the esophagus  cisplatin containing regimens are active in the treatment of esophageal cancer  with response rates of 25  to 35  in advanced disease  carboplatin is less toxic than cisplatin  as a single agent  several responses were seen against esophageal tumors  to better define the role of carboplatin in esophageal cancer  the authors treated 19 chemotherapy naive patients with advanced squamous cell carcinoma of the esophagus with carboplatin and vinblastine  carboplatin  450 mg m2 intravenously  iv  on days 1  29  57  and every 6 weeks thereafter  was given with vinblastine  5 mg m2 iv on day 1 and then every 2 weeks   no major responses were seen  no significant renal toxicity and only mild gastrointestinal toxicity  emesis  diarrhea  were observed  hematologic toxicity was more severe in patients with prior radiation therapy  rt   with three of six patients with prior rt exhibiting grade 4 hematologic toxicity  although generally less toxic than cisplatin containing regimens  carboplatin and vinblastine is also less active in the treatment of squamous cell carcinoma of the esophagus  hematologic toxicity with this regimen was severe in patients who had received prior rt  
class4	a phase ii multi institutional trial of low dose n  phosphonacetyl  l aspartate and high dose 5 fluorouracil as a short term infusion in the treatment of adenocarcinoma of the pancreas  a southwest oncology group study  adenocarcinoma of the pancreas is a highly lethal malignancy and chemotherapy has had little impact on the natural history of this disease  pala  used to potentiate 5 fluorouracil  5 fu   has been shown to have synergy in vivo and in vitro  twenty seven patients were treated with an intravenous push dose of pala  250 mg m2  followed 24 hours later with a 24 hour infusion of 5 fu  2600 mg m2   this regimen was repeated weekly  there was one partial response of 21 eligible patients with an estimated response rate of 5   toxicity was severe with one toxic death and four patients experiencing grade 4 toxicity  5 fluorouracil and pala  given in the schedule described  do not appear to be effective against adenocarcinoma of the pancreas  
class4	a dose intensive regimen of 5 fluorouracil for the treatment of metastatic colorectal carcinoma  5 fluorouracil  5 fu  was delivered in a dose intensive schedule to 23 patients with metastatic or unresectable colorectal carcinoma  the schedule consisted of bolus single dose 5 fu therapy 400 to 500 mg followed by 4 day infusion of 5 fu  600 to 800 mg m2 day  followed by a 17 day to 24 day infusion of 200 to 250 mg m2 day  partial remissions were seen in 22  of all eligible patients  significant toxicity  including mucositis  diarrhea  and hand foot syndrome  necessitated dose reductions in most patients  the authors conclude that 5 fu given in this moderately intensive schedule is associated with a moderate level of response  as easily achieved with more conventional schedules or with 5 fu leucovorin combinations  tumor responsiveness to dose intensive 5 fu regimens may be limited  
class4	neoadjuvant chemotherapy and radical surgery in locally advanced cervical cancer  prognostic factors for response and survival  between january 1986 and september 1988  75 patients with locally advanced cervical carcinoma  international federation of gynecology and obstetrics  figo  stages ib iii  received three courses of neoadjuvant chemotherapy  nac   including cisplatin  bleomycin  and methotrexate  pbm   fifteen percent of patients achieved a complete response  cr  and 68  a partial response  pr   pretreatment characteristics were analyzed for response to nac  significantly lower response rates were found in patients with tumor size more than 5 cm in diameter and bilateral parametrial involvement to the pelvic side wall  none of the biological parameters studied was related to chemoresponsiveness  patients achieving cr or pr had a significantly improved 3 year survival rate compared with those who did not respond  after nac  radical surgery was possible in all responding patients  the median number of lymph nodes removed was 60  a lower than expected incidence of lymph node metastases was detected  none of the clinical and pathologic features considered was significantly correlated with the lymph node status  twelve of the 62 operated patients had disease recurrence  pathologic parametrial involvement and cervical infiltration equal to or deeper than 5 mm were found to be significant prognostic factors for recurrence  a 3 year  disease free survival of 89   73   and 43  for stage ib iia  iib  and iii  respectively  was found  among the operated patients these rates increased to 100   81   and 66  for stage ib iia  iib  and iii  respectively  a prospective randomized trial comparing nac and surgery with radiotherapy alone is in progress  
class4	combined surgical resection and iridium 192 implantation for locally advanced and recurrent desmoid tumors  thirty eight histologically confirmed desmoid tumors were treated with conservative surgical resection and interstitial iridium 192  patients included in this series constituted a poor prognostic group  seventy five percent  75   had previous recurrences of their disease and 50  had tumors 8 cm or greater in size  in addition  16  of the patients had gross residual disease after surgical excision and 79  had positive or close margins of resection  with a median follow up of 5 5 years  the 5 year actuarial in field local control rate was 75  and the overall local control rate was 66   four of the 12 local recurrences developed at the periphery of the implant volume and four patients failed at least 3 cm or more beyond the treated volume  after salvage therapy  the 5 year actuarial local control rate was 95   two patients required amputation for recurrent disease  thirty of 34 patients remain free of disease with an excellent functional result achieved  the authors conclude that surgical resection and postoperative interstitial iridium 192 is effective therapy for patients with desmoid tumors  despite the fact that most patients in this series had bulky  recurrent tumors  excellent long term local control and limb function were achieved  
class4	prognostic factors in the treatment of hepatocellular carcinoma with transcatheter arterial embolization and arterial infusion  from january 1986 to december 1988  a prospective trial of transcatheter arterial treatment was carried out for hepatocellular carcinoma  hcc   two hundred seventy five patients were included  okuda s staging system was employed  patients with stage i and ii hcc were treated by transcatheter arterial embolization  tae  with a gelatin sponge containing an anti cancer agent  protocol 1a   a gelatin sponge and iodized oil mixed with an anti cancer agent  protocol 1b   or iodized oil mixed with an anti cancer agent  protocol 2   patients with stage iii hcc were treated with iodized oil with anti cancer agent  protocol 2   as an exception  patients with an unsuccessful superselective catheterization into the proper hepatic artery by seldinger technique or obstruction of the main trunk of the portal vein were treated with percutaneous transcatheter arterial infusion into the common hepatic artery regardless of stage  protocol 3   tumor type and extension  area of tumor involvement  portal vein involvement  method of treatment  and presence of ascites and icterus were found to be the significant factors for an initial response to therapy  treatment method was the most important factor  respective survival rates at 1 and 2 years were 70 9  and 55 3  for protocol 1a  62 3  and 43 8  for protocol 1b  37 8  and 18 3  for protocol 2  and 16 5  and 0  for protocol 3  many factors proved to significantly influenced prognosis  however  tumor type had the most important prognostic significance followed by afp value  ascites  treatment protocol  and area of tumor involvement  
class4	a report on radiation induced gliomas  radiation induced gliomas are uncommon  with only 73 cases on record to date  the disease that most frequently occasioned radiation therapy has been acute lymphoblastic leukemia  all   three more cases are added here  two after irradiation for all and one after irradiation for tinea capitis  in a review of the relevant literature  the authors stress the possibility that the all glioma and the retinoblastoma glioma links point to syndromes in their own right that may occur without radiation therapy  
class4	second cancer after radiation therapy for cancer of the uterine cervix  radiation induced cancers after radiation therapy for cancer of the uterine cervix were investigated on 11 855 patients including 5725 patients treated with radiation therapy alone  1969 postoperative radiation therapy and 4161 surgery alone  the observed to expected ratios of the second primary cancer was 0 933 for the patients with radiation therapy alone and 1 074 for the patients with postoperative radiation therapy  respectively  no significant increase was observed in the risk of second primary cancers when all sites were combined  however  assessing on site by site basis  significant excess was noted for the rectum cancer  leukemia  and bladder cancer for the radiation therapy group but not for the surgery group  a significant excess of lung cancer was observed in both radiation therapy and surgery groups  which was attributed to some other causative factors  radiation induced cancers were suggested to develop apparently in organs involved in the irradiated field  
class4	evaluation of a simple line width test involving magnetic resonance spectroscopy of plasma in carcinoma of the ovary  magnetic resonance spectroscopic  mrs  measurement of human plasma has been reported as a generally applicable marker for malignancy  patients with malignancy had a mrs line width significantly different from patients with benign diseases or healthy controls  the authors investigated the value of this test in 213 women with ovarian carcinoma  benign pelvic masses  benign nongynecologic diseases  and healthy controls  the mrs measurements were performed on plasma samples at 21 degrees c or 27 degrees c  the line width parameters were obtained by averaging the width at half the height of the methyl and methylene peaks on the resonance spectra  at 27 degrees c using 33 hz as the threshold for an abnormal result  there was a significant correlation between the result of the test and the presence or absence of malignancy  however  the study demonstrates that the specificity  0 44  and positive predictive value  0 42  are too low for the test to be useful in the management of patients with carcinoma of the ovary  at 21 degrees c no correlation between the results of the test and the clinical status of women with carcinoma of the ovary were observed  in 47 patients the test did not predict preoperatively the benign or malignant nature of a pelvic mass  
class4	prostate specific antigen and external beam radiation therapy in prostate cancer  this study of 133 patients with localized prostate cancer  stages a2 to c   treated by external beam radiation therapy  xrt   was undertaken for two reasons   1  to investigate the usefulness of pretreatment serum prostate specific antigen  psa  levels in evaluating patients before xrt  and  2  to investigate post xrt changes in psa values and their likely clinical significance  it was found that pretreatment psa values in patients with localized disease exhibit wide patient to patient variability with a greater than 100 fold difference between the lowest and highest values  although mean psa values were significantly higher in stage c disease  51 patients  mean psa  17 3 ng ml  than in stage a2 disease  31 patients  mean psa  9 0 ng ml   stage b1 disease  23 patients  mean psa  9 1 ng ml   or stage b2 disease  28 patients  mean psa  10 6 ng ml   individual values were of virtually no help in assigning individual patients to a clinical stage  psa levels did not correlate with grade  after xrt  psa values fell significantly and dramatically in virtually all patients  98   by 3 months follow up  mean psa fell from 12 5 to 2 6 ng ml  and median psa fell from 6 6 to 1 9 ng ml  in most patients  psa continued to fall up to 12 months after xrt and then stabilized at 21 months  although psa values fell dramatically after xrt  psa was detectable in the serum of all patients  psa values tended to transiently and mildly elevate during xrt  in a small proportion of patients  rising psa values were observed after 6 months  the full significance of this requires further follow up  of four such patients  one has relapsed  psa is a more sensitive marker of prostatic radiation than prostatic acid phosphatase  
class4	ki 67 immunostaining in human breast tumors and its relationship to prognosis  ki 67 labeling was quantified in 37 nonmalignant breast tissues and in 63 breast carcinomas by counting ten random high power fields each in three section planes  rc  or by evaluation of the area with the highest labeling density  hdc   both procedures proved to be highly correlated  rs   0 94   ki 67 positive fractions of the nonmalignant tissues  mean  2 1  for rc and 4 1  for hdc  were significantly lower as compared with the carcinomas  mean  14 5  for rc and 17 5  for hdc   in carcinomas the ki 67 labeling was significantly associated with pt stage  axillary lymph node status  and tumor grading and inversely related to progesterone receptor status  using the medians of both counting methods  12  for rc and 17  for hdc  as cutoff points  significantly different curves for overall and disease free survival  median follow up  37 months  were obtained  however  cox multivariate analysis failed to demonstrate an independent effect of ki 67 labeling  in contrast  ki 67 reactivity seems to be of independent prognostic value if a higher cutoff level was selected  
class4	a high prevalence of antibody to the hepatitis c virus in patients with hepatocellular carcinoma in japan  in japan  hepatocellular carcinoma  hcc  is one of the most prevalent cancers  with a reported fatality rate showing a consistent and significant increase in the last decade  at most  only 25  of hcc cases are positive for the hepatitis b surface antigen  hbsag   to investigate a potential role for hepatitis c virus  hcv  in the development of hcc  sera from 105 hbsag negative hcc patients were collected from five districts of japan and assayed for antibody to hcv antigen  hcvab   a large number of these patients  76 2   were found to be positive for the hcvab in comparison with the reported prevalence in sera from blood donors  1 1    a history of blood transfusion was found in 39 6  of the cases positive for hcvab  which was significantly different to the lower rate  4 7   observed in hcc patients who were both positive for hbsag and negative for hcvab  p less than 0 001   
class4	a comparison of ho s  international union against cancer  and american joint committee stage classifications for nasopharyngeal carcinoma  five hundred sixty four nasopharyngeal carcinomas  npc   mostly of undifferentiated histologic type  were studied for survival  distant metastasis  and local recurrence  all had computerized tomography of the nasopharynx and skull base  ct np  and fiberoptic nasopharyngoscopy for evaluation of the primary tumor  regional disease was assessed by palpation  a computer data base was formed on presentation  containing all information required for staging according to ho s  the international union against cancer  uicc   and the american joint committee  ajc  classifications  the three were compared for their efficacy in predicting prognosis  ho s classification was superior to the other two because its overall stages differed from one another more significantly in the actuarial survival  asr   disease free survival  dfs   and freedom from distant metastasis  fdm  rates  and its n staging was more accurate in predicting fdm  stages t1 and t2 of uicc ajc were similar in the freedom from local recurrence rate  flr  and should be grouped together  equivalent to ho s t1  a more even patients number distribution among the stages also favored the use of ho s classification  
class4	non hodgkin s lymphoma of the brain after hodgkin s disease  an immunohistochemical study  non hodgkin s lymphoma  nhl  of the central nervous system  cns  is a rarely reported complication of hodgkin s disease  hd   two patients with nhl of the brain after hd were studied by histologic and immunohistochemical methods  both patients were in the second decade  had been treated with radiation and chemotherapy  had experienced a relapse of hd before development of nhl  had no evidence of hd at the time of diagnosis of nhl  and died within 1 year of diagnosis  both brain neoplasms were large cell immunoblastic lymphomas of b cell lineage  patients with hd appear to be at increased risk for nhl of the cns  which may have a poor prognosis  
class4	in situ hybridization for the detection of epstein barr virus in central nervous system lymphomas  epstein barr virus  ebv  has been implicated in the development of lymphomas in immunocompromised patients  to test this hypothesis  26 lymphomas involving the central nervous system  cns   11 primary  15 systemic  were studied for the presence of ebv  in situ hybridization  ish  was performed on formalin fixed  paraffin embedded tissue using a sulfur 35  35s  labeled ebv probe  ebv bamh1 w   the results were interpreted without knowledge of the patients  immunologic status  the ebv sequences were detected in 11 lymphomas  nine of which were mixed or large cell subtypes  review of the clinical information revealed that nine of the 26 lymphomas occurred in immunocompromised patients secondary to renal transplantation  human immunodeficiency virus infection  leukemia  and wiskott aldrich syndrome  the ebv sequences were detected in all nine lymphomas occurring in immunocompromised patients  whereas two of the 17 lymphomas occurring in immunocompetent patients expressed ebv sequences  the authors conclude that the presence of ebv sequences in cns lymphomas is highly correlated with a history of compromised immune status supporting a pathogenetic role of ebv in the development of cns lymphomas in immunocompromised patients  
class4	dna and rna flow cytometric study in multiple myeloma  clinical correlations  flow cytometric studies of cellular dna and rna content using the acridine orange technique were conducted in 81 patients with multiple myeloma  mm   all patients were treated with the m 2 protocol and clinical response was evaluated according to the criteria of the chronic leukemia myeloma task force  aneuploid dna stemlines were found in 38 2  of untreated patients with a median dna index  dna i  of 1 15 in marrow aspirates and 1 22 in biopsy specimens  the median percentage of cells with abnormal dna content was 31 5  aspirates  and 35  biopsy specimens  and a positive correlation with the percentage of bone marrow plasma cells was observed  significantly higher proliferation  s phase  was found in marrow biopsy specimens as compared with marrow aspirates  significantly higher rna content  rna index  rna i   was observed in aneuploid versus diploid patients in biopsy material  there was no difference in response to the memorial hospital m 2 protocol between diploid and aneuploid patients  in patients with dna i greater than 1 15 remission duration was shorter as compared with dna i less than or equal to 1 15  furthermore  no difference in cellular rna content was noted between responders and nonresponders  this study demonstrates no correlation between cellular rna content and response  as previously described for patients treated with vincristine  adriamycin  and dexamethasone  vad   but dna aneuploidy appears to be an adverse prognostic factor in mm patients treated with the m 2 protocol  it also demonstrates that prognostic models for mm are not universal but depend on the chemotherapeutic regimen used  
class4	an immunohistochemical evaluation of progesterone receptor in frozen sections  paraffin sections  and cytologic imprints of breast carcinomas  two monoclonal antibodies to progesterone receptor  pr   jzb39 and kd68  were used for the immunocytochemical visualization of pr in different kinds of breast cancer specimens including  1  cryostat sections of tumors frozen at  80 degrees c   2  paraffin sections of tumors fixed in formalin or in bouin s fixative for varying periods of time at room temperature or at 4 degrees c  and  3  imprints and cryostat sections prepared from the tissue used for frozen section diagnosis and stored at  80 degrees c after fixation in zamboni s solution  sections of conventionally frozen specimens as well as imprints and cryostat sections stored for varying periods of time were stained with the peroxidase antiperoxidase technique  whereas the avidin biotin technique was used for paraffin sections  in all types of specimens the pr immunostaining was localized to the nuclei of carcinoma cells and displayed considerable heterogeneity both in intensity and in distribution of positive cells  close correspondence was found between the different immunohistochemical techniques as well as between immunostaining and steroid binding assays  pr staining was more frequently positive in well differentiated than in moderately or poorly differentiated carcinomas  whereas no meaningful correlation was found between pr staining and extent of the disease  similar results were obtained with the immunostaining of estrogen receptor in the same material using monoclonal antibodies h222 and d75p3 gamma  thus  by choosing the technique that best suits the type of specimen available  it is possible to obtain valid information on the receptor status of any breast carcinoma  regardless of its size and clinical presentation  
class4	a comparative study of histopathology  hormone receptors  peanut lectin binding  ki 67 immunostaining  and nucleolar organizer region associated proteins in human breast cancer  the current study was performed on 71 cases of human female breast cancer and compares the results of five morphologic methods developed for the detection of estrogen receptors  er   progesterone receptors  pgr   lectin peanut agglutinin  pna  binding sites  monoclonal antibody ki 67 immunoreactivity  and the mean number of argyrophilic nucleolar organizer regions  ag nor   all the parameters were evaluated on serial cryostat sections representative of a closely related  if not identical  neoplastic population  a significant positive correlation was found between the occurrence of estrogen  progesterone  and peanut receptors and between ki 67 immunoreactivity  mean number of nor  and mitotic index  furthermore  er  pgr  and pna receptors showed a significant  inverse correlation with ki 67 immunoreactivity  mitotic index  and mean number of ag nor  these results provide further data that support the hypothesis that  1  progesterone and pna receptors are estrogen induced and indicate a metabolic response of the target cells to functioning estrogen receptors   2  the mean number of nor reflects the cell kinetics of the tumor  and  3  metabolic differentiation of neoplastic cells is inversely correlated to the proliferation index  
class4	nucleolar organizer regions in precancerous and cancerous lesions of the bronchus  using a silver staining technique  nucleolar organizer region associated proteins  ag nor  were studied in paraffin sections of five specimens of normal bronchial epithelium  eight of atypical squamous metaplasia  five of carcinoma in situ  and seven of microinvasive squamous cell carcinoma  the mean number of ag nor in the nucleus were normal epithelium 1 2     0 1  mean     sd   atypical squamous metaplasia  borderline lesion  2 2     0 5  carcinoma in situ 3 8     0 6  and microinvasive squamous cell carcinoma 4 8     1 1  there was a highly significant difference between the ag nor numbers in the atypical squamous metaplasia and those in the carcinoma in situ  p less than 0 01   the ag nor staining is a useful technique for the differential diagnosis of difficult borderline lesions in the bronchial epithelium  
class4	differential alpha fetoprotein lectin binding in hepatocellular carcinoma  diagnostic utility at low serum levels  the reactivity of serum alpha fetoprotein  afp  from 20 patients with hepatocellular carcinoma  hcc  with immobilized lentil lectin was examined and found to be significantly greater  39      18   than that of the same protein from seven patients with chronic liver disease  cld  11 2      3 3    seven with fulminant hepatic failure  fhf  10      8 4    and eight normal pregnant women  4 1      2 7    the reactivity with concanavalin a  con a  was also significantly greater for afp from hcc patients  44 5      12 5   than that from fhf patients  7 7      4   and normal pregnant women  5 3      3 3    but not from patients with cld  the reactivity with lentil lectin permitted distinction between those with hcc  31 3      14 1   and those with uncomplicated cld  11 2      8 4   even when the absolute levels of serum afp were in the same range  80 400 ng ml   evaluation of the alterations by lectin binding methodology may be useful in overcoming problems associated with distinguishing between malignant and cld  particularly at moderate serum afp elevations  
class4	insulin secretion and action in patients with pancreatic cancer  the authors investigated insulin secretory capacity and insulin action in 11 preoperative patients with pancreatic carcinoma and 15 age matched and weight matched healthy subjects  c   five patients were classified as diabetic  d   two as impaired glucose tolerant  igt   and four as nondiabetic  nd   postabsorptive serum insulin levels  mean     se  in uu ml  in d  12     2   igt  17     7   and nd  10     2  were comparable  after administration of 100 g of oral glucose  peak insulin achieved in d  60     11  was lower than in igt  101     26  and nd  83     20   whereas peak insulin levels in igt and nd were significantly  p less than 0 05  higher than in c  45     6   comparable insulin response to nonglucose stimuli was documented in all subjects using the slow arginine infusion test with mean serum insulin of 27     4 in d  28     6 in igt  34     10 in nd  and 32     5 in c  in six patients  p  and six controls  insulin action was assessed by the euglycemic hyperinsulinemic clamp technique  with glucose turnover rates estimated by  3 3h glucose infusion  steady state plasma glucose concentrations were maintained at 92     3  p  and 91     1 mg dl  c   after insulin infusion at the rate of 1 0 mu kg min  comparable high physiologic insulin levels were observed in p  73 to 104 uu ml  and in c  81 to 103 uu ml   postabsorptive rates of endogenous glucose appearance  ra  were higher in p  2 86 to 3 02 mg kg min  than in c  1 50 to 2 80 mg kg min   at high physiologic insulin concentrations  negative ra values were documented in all subjects  and complete suppression of ra was assumed  total body glucose use  m  was consistently lower in p  3 90 to 6 40 mg kg min  than in c  6 98 to 10 40 mg kg min   consistent with a state of insulin resistance  patients with pancreatic cancer manifest insulin resistance by virtue of a decrease in total body glucose use  m  and decreased insulin response to glucose due to either inherent beta cell dysfunction or decreased islet cell mass  the latter is not identifiable by histologic morphology  
class4	pancreatic mucinous cystadenocarcinoma with pseudosarcomatous mural nodules  a report of a case with immunohistochemical study  a case of pancreatic mucinous cystadenocarcinoma  pmc  with two pseudosarcomatous mural nodules  pmn  is described  these nodules have not been previously described in this type of tumor  in ovarian mucinous tumors  omt   similar nodules have been reported  the nature of which has been discussed in detail  here the similarity between the tumor described here and ovarian tumors is stressed  the immunohistochemical study carried out disclosed in the nodules strong positive staining for vimentin and moderate positivity for keratin and epithelial membrane antigen  these findings  along with histologic details  favor the epithelial nature of the nodules  it was concluded that the nodules are foci of anaplastic carcinoma with high proliferative cell rate  which could explain the coexpression of vimentin and keratin  
class4	malignant fibrous histiocytoma of soft tissue  a population based epidemiologic and prognostic study of 137 patients  epidemiology and prognosis were analyzed in a consecutive  population based series of 137 patients with malignant fibrous histiocytoma of soft tissue in the extremities and trunk wall  with a complete follow up of minimum 3 years  all but one patient were treated by surgery in 28 cases combined with adjuvant radiotherapy or chemotherapy  the annual incidence was 0 42 10 5   the ratio men to women was 1 1  the median age was 64 years  range  22 to 87 years   the thigh was the most common location  the median size was 6 cm  superficial tumors constituted 43  and were smaller than deep seated tumors  eighty three tumors were storiform pleomorphic  53 were myxoid  and one was of inflammatory type  the myxoid tumors were smaller and more often superficial  the cumulative 5 year survival rate for all patients was 0 7  but differed markedly between the histologic types  it was 1 0 in patients with myxoid tumors and 0 5 in patients with storiform pleomorphic tumors  in the 77 patients with storiform pleomorphic tumors without metastases at presentation  only tumor size larger than 10 cm and tumor necrosis independently impaired survival  the 23 patients who had none of these risk factors had a 5 year survival rate of 0 8  
class4	obesity and body fat distribution and breast cancer prognosis  this study addresses the effect of obesity and body fat distribution on axillary lymph node involvement  tumor size  and estrogen receptor  er  level in breast cancer patients  anthropometric measurements were prospectively obtained on 248 consecutively and newly diagnosed women with invasive breast cancer  the anthropometric measurements evaluated were abdomen  thigh  subscapular  and midaxillary skinfolds  weight  and height  weight and quetelet index  kg m2  were significantly  p   0 001  associated with lymph node involvement in postmenopausal patients  the abdomen thigh skinfold ratio was significantly higher in premenopausal patients  p   0 004  and postmenopausal  p   0 03  without axillary node involvement compared with women with 4  axillary node involvement  the abdomen thigh skinfold was higher  p   0 05  in women with smaller breast cancers  less than 2 0 cm  and higher er levels  weight and quetelet index did not affect tumor size or er level  this study demonstrated that obese postmenopausal women who developed breast cancer tend to have more axillary node involvement than their leaner counterparts  generalized obesity did not affect tumor size or er level  premenopausal and postmenopausal women with upper body fat distribution appear to be a subset of women who have a more favorable prognosis as measured by less lymph node involvement  smaller tumors  and higher levels of er in their tumors  
class4	prognostic implications of tumor diameter in carcinoma of the head of the pancreas  two hundred twenty patients with a carcinoma in the head of the pancreas were divided into three tumor diameter groups  group 1  0 5 to 4 4 cm  n   72   group 2  4 5 to 6 0 cm  n   77   and group 3  6 1 to 15 0 cm  n   71   for these tumor diameter groups a six fold eliminatory curability analysis was performed  of the patients with liver metastases in group 1 the last patient had died at 10 months and in groups 2 and 3 no patients were alive at 18 months after the start of complaints  patients with extrahepatic metastases did not survive 12 months in group 1  16 months in group 2  and 25 months in group 3  the 6  actuarial survival rate for inoperable patients was reached in group 1 after 17 months  in group 2 after 36 months  and in group 3 after 27 months after the start of complaints  for groups 1 through 3 in curable  but not curatively operated patients  the respective 0  actuarial survival rate was reached at 24 months  23 months  and 14 months  the 0  actuarial survival rate in patients with irresectable vessel invasion was reached in group 1 at 33 months  in group 2 at 23 months  and in group 3 at 25 months  the 0  actuarial survival rate in patients with an irresectable tumor was reached at 33 months  31 months  and 27 months after the start of complaints in groups 1  2  and 3  respectively  the 0  actuarial survival rate in curatively operated patients was reached in group 3 after 26 months and in group 2 after 29 months  in group 1 25  of the patients were alive at 36 months after the start of complaints  small tumors were associated with the greatest chance of curative operation and on average had the longest survival  however  small tumors with liver or other metastases carried a worse prognosis than large tumors with liver or other metastases  if tumors were found not to be resectable at the time of operation  the size of the tumor did not appear to affect survival  
class4	is the treatment of metastatic carcinoid tumor with interferon not as successful as suggested  eight patients with metastatic carcinoid tumor  seven of whom had symptoms of the carcinoid syndrome  were treated with either human leukocyte interferon  seven patients  or recombinant alpha interferon  ifn alpha 2b   one patient  at doses of 4 5 to 21 x 10 6  iu weekly for 1 to 21  mean  8 5  months  tumor regression on computed tomography  ct  scan was found in one patient  the ct findings remained unchanged in three  and the tumor progressed in four patients  a clearcut and continuing decrease in urinary levels of 5 hydroxyindoleacetic acid  5 hiaa  was observed in one patient and a transient one in four patients  the symptoms improved in only two of seven patients  four patients had leukopenia develop  which was circumvented by reducing the dose  the authors conclude that interferon therapy of the carcinoid tumor is not as successful as has been suggested in previous reports  
class4	a pilot study of intermediate dose methotrexate and cytosine arabinoside   spread out  or  up front   in continuation therapy for childhood non t  non b acute lymphoblastic leukemia  a pediatric oncology group study  one hundred six children with newly diagnosed non t   non b cell acute lymphoblastic leukemia  all  were treated in a pediatric oncology group  pog  pilot study in which six courses of intermediate dose methotrexate  mtx  and cytosine arabinoside  ara c   1 g m2 each  were added to a  backbone  of standard continuation therapy  the dose and sequence of mtx ara c administration were based on a preclinical model that demonstrated synergism between mtx and ara c  poor risk patients  n   49  were assigned to  up front  therapy  in which the mtx ara c courses were administered during the initial 15 weeks of remission  standard risk patients  n   57  were assigned to  spread out  therapy  in which the mtx ara c courses were interspersed at 12 week intervals within continuation treatment  toxicity after intermediate dose mtx ara c  principally neutropenia and fever  was judged significant but manageable  unexpectedly  the incidence of fever and neutropenia less than 500 mm3 was greater after  spread out  therapy  38   than after  up front  therapy  6    at 4 years  the kaplan meier estimate of event free survival  efs  is 71       7   for standard risk patients and 53       8   for poor risk patients  the results of this pilot study support the use of intermediate dose mtx ara c in additional studies  
class4	multidisciplinary treatment of primary orbital rhabdomyosarcoma  a single institution experience  orbital rhabdomyosarcoma accounts for one fourth of the primary tumors in the head and neck region  modern treatment modalities have led to a 2 year survival rate of about 90  in these patients  however  new therapeutic trials are designed to reduce complications and salvage more than 90  of orbital cases  between 1979 and 1990  12 children affected by primary orbital rhabdomyosarcoma have been diagnosed and treated at the university of naples  ten of them have been uniformly treated by biopsy  followed by immediate radiation and combined chemotherapy  all 12 patients are alive and free of detectable disease  from a minimum of 7 months to a maximum of 123 months after diagnosis  in all children  ocular structures have been spared and the complications observed until now have been few  the above results suggest that the association of immediate radiation therapy and chemotherapy might represent an optimal tool for treatment of orbital rhabdomyosarcoma  
class4	combination therapy for anaplastic giant cell thyroid carcinoma  since 1981  20 patients with anaplastic giant cell carcinoma of the thyroid have been prospectively treated according to a combination regimen of chemotherapy and external beam radiation therapy  two types of chemotherapy were used every 4 weeks  depending on the patient s age  for those younger than 65 years  a combination of doxorubicin  60 mg m2  and cisplatin  90 mg m2  was given  and for older patients mitoxantrone  14 mg m2  was used  radiotherapy was carried out between day 10 and day 20 of the first four cycles of chemotherapy  it delivered 17 5 gy in 7 fractions to the neck and the superior mediastinum  survival exceeding 20 months was observed in three patients  complete neck tumor response was observed in five patients  among whom four had undergone previous operations  no response was seen in distant metastases  which were the cause of death in 14 patients  these treatment modalities are effective in some patients  both in terms of survival and of local control  avoiding death from local invasion  gross tumor resection should be performed whenever possible but should not delay the commencement of this protocol  toxicity was high and remains the main limiting factor  
class4	response rates in relapsed wilms  tumor  a need for new effective agents  three hundred eighty one children with wilms  tumor were treated in the united kingdom children s cancer study group wt1 study  1982 to 1986   seventy one patients had relapses during or after treatment with surgery and chemotherapy  and radiation therapy  depending on stage and histologic characteristics  forty nine patients were evaluable for disease response to second line chemotherapy alone  evaluation of response to chemotherapy was impossible in the remaining patients because either surgery or radiation therapy was used at the time of relapse  with second line combination chemotherapy  which included ifosfamide  etoposide vm26  cisplatin carboplatin  bleomycin  melphalan  and thiotepa  lederle laboratories  pearl river  ny    there were five complete responses and 12 partial responses  in patients with favorable histologic findings  six of nine with stage i  five of ten with stage ii  none of 11 with stage iii  three of 16 with stage iv  and one of five with stage v disease survived  two survivors were treated with chemotherapy alone  the others received combined treatment with chemotherapy  radiation therapy  and or surgery  for those with unfavorable histologic findings of any stage  only two of 20 survived  the authors conclude that  even for patients with localized disease with favorable histologic findings  the  salvage  rate is little more than 50   and for all other stages and histologic findings the likelihood of cure after relapse is remote  there is clearly a need for additional effective chemotherapeutic agents for these patients  
class4	primary treatment of large and massive adult sarcomas with iododeoxyuridine and aggressive hyperfractionated irradiation  for a decade  the authors have experimented with treatment for unresectable adult soft tissue and bony sarcomas  over the last 6 years  they have combined hyperfractionated radiation therapy and intravenous iododeoxyuridine as a radiosensitizer  in regimens designed to minimize toxicity and permit delivery of aggressive radiation therapy  patients with solitary lesions and those with metastasis  38   were treated in the hope of both potential cure in some and durable palliation in others  the most formidable of these cancers have been those that are large or massive  often requiring five or more fields and extensive treatment planning  the authors report results from 36 patients with large unresectable sarcomas  tumors ranging from 5 to 35 cm  average 14 cm  treated with hyperfractionated radiation therapy  with a minimum follow up of 1 year  follow up of 4 or more years  in 50    or follow up until death  overall local control has been 60   with control of 66  of lesions from 5 to 9 cm  63  of those from 10 to 14 cm  63  of those from 15 to 19 cm  and 57  of those greater than 20 to 40 cm  morbidity has been modest  this experience compares favorably with the authors  earlier trials with misonidazole  and toxicity has been reduced considerably  
class4	ultrasound and ultrasound guided fine needle aspiration biopsy of supraclavicular lymph nodes in patients with esophageal carcinoma  the use of ultrasound combined with ultrasound guided fine needle aspiration biopsy  ugfab  of supraclavicular lymph nodes in the pretreatment staging of 37 patients with squamous cell carcinoma of the esophagus is described  all patients underwent computed tomography  ct  scans of the chest and the abdomen and ultrasound of the abdomen and supraclavicular regions  supraclavicular lymph node metastases  stage iv disease according to the tumor nodes metastasis  tnm  classification  were cytologically diagnosed in seven  18 9   of the 37 patients  in two of these patients  no other metastases were found  in the other five patients  ugfab replaced more invasive diagnostic procedures  due to their superficial location  ultrasound and ugfab of the supraclavicular lymph nodes was relatively simple to perform  and contributed to an improved staging of squamous cell carcinoma of the esophagus  
class4	altered protein tyrosine kinase levels in human colon carcinoma  to further understand the molecular mechanisms and the biological indicators of colonic tumorigenesis  the authors examined tyrosine kinase activity in the cytosol and in the particulate fraction of the homogenates of specimens from 20 human colonic carcinomas and compared them with the adjacent normal mucosal tissues  total protein tyrosine kinase activity could be precisely detected using miniphosphocellulose column purification and a synthetic peptide  glu asparagine  asp  alanine  ala  glu tyrosine  tyr  ala ala arginine  arg  arg arg glycine  gly   e11 g1   as an artificial substrate  tyrosine kinase activity of colonic carcinoma and normal mucosa was reduced in the cytosol fraction whereas activity in the particulate fraction was elevated with respect to protein concentration  the average specific activity ratios were 1 95     0 27  normal cytosolic carcinoma cytosolic  and 0 57     0 01  normal particulate carcinoma particulate  for tyrosine kinase activity  cellular distribution    cytosol  of tyrosine kinase activity in normal mucosa and in carcinoma varied from 21 0  to 91 2  and from 7 0  to 61 4   respectively  in nearly all cases the percentage of cytosolic tyrosine kinase activity in carcinoma tissues was lower than in normal tissues  there was no difference due to histologic type or the presence of adenomatous components  a significant decrease of cytosolic tyrosine kinases was correlated with dukes  stage a  with advancing dukes  stage  the average specific activity ratios  normal cytosol carcinoma cytosol  were decreased  this study indicates that colonic carcinogenesis might be associated with alterations in cellular levels of tyrosine kinase activity and that the average specific activity ratio  normal cytosol carcinoma cytosol  had a possible correlation with colonic tumor growth  
class4	watch and wait after careful surgical treatment and staging in well differentiated early ovarian cancer  patients with well differentiated epithelial ovarian cancer stages ia  ib  ic  and iia  figo 1976  were observed after surgical treatment without adjuvant therapy  careful surgical staging was required  and the extent of the staging procedure was assessed in each individual patient  there were 107 patients entered in the study by nine dutch oncology centers  of these 107  21 did not fulfill all of the inlet criteria of the study and were excluded  central pathologic review was performed in the remaining 86 cases  revealing that there was borderline tumor in seven patients  moderately or poorly differentiated tumor in nine patients  and tumor of nonepithelial histologic cell type in one patient  in two cases  no material for histologic review was available  after exclusion of these 19 cases  67 patients were further analyzed  none of these 67 patients was lost during the follow up period that ranged from 19 to 99 months  mean  50 months   tumor recurrence was found in four patients after 11  25  34  and 34 months of follow up  all of whom died shortly after diagnosis of the recurrence without satisfactory response to secondary treatment  for the patients who underwent the most extensive staging procedure  disease free 5 year survival was 100   for the patients who were inaccurately staged  disease free 5 year survival was 88   it was concluded that well differentiated early stage  ia iia  ovarian cancer carries an excellent prognosis after surgical treatment and complete surgical staging  with the possible exception of patients with stage ic disease with malignant peritoneal washings  furthermore  it was considered that the application of more objective and consistent ways of assessing tumor grade should be encouraged  surgical staging should be regarded as the golden standard in defining subsets of low risk patients and should be included and clearly defined in future trials on early ovarian cancer  
class4	immunosuppressive acidic protein in malignant diseases  clinical relevance  the immunosuppressive acidic protein  iap  has been described as a tumor associated marker in some solid tumors and hematologic diseases  to define the clinical relevance the authors determined the serum iap levels in 194 patients with malignancies before initiation of therapy  14 patients with idiopathic thrombocytopenic purpura  itp   28 patients with bacterial pneumonia  and 23 healthy volunteers  immunosuppressive acidic protein was measured by radial immunodiffusion  the mean value of our controls was 405     48 micrograms ml  this is consistent with published data  the mean values for patients with malignancies varied from 554 micrograms ml to 698 micrograms ml  these are only marginally higher than those observed for the controls  in contrast patients with bacterial pneumonia demonstrated significantly elevated values  1038     261 micrograms ml   the authors conclude that iap cannot be used as a diagnostic marker for the malignant diseases examined in this study  
class4	loss of expression of blood group antigen h is associated with cellular invasion and spread of oral squamous cell carcinomas  membrane bound carbohydrates may influence the metastatic behavior of cancer cells  forty two squamous cell carcinomas  scc  of the buccal and maxillary alveolar mucosa were studied retrospectively using a monoclonal antibody  be2  that reacts with blood group h  type 2 chain  structure  h antigen staining within the entire tumor did not correlate with the stage of the tumor  i e   spread of the tumors  however  loss of staining within the most invasive sites of the tumors correlated significantly with the stage of tumor development and histologic grade of malignancy  these findings support the view that features relating to the cells of deeper parts of the carcinomas are very important for the clinical behavior of the tumors  and that loss of h antigen expression is related to the stage of tumor and invasion of carcinoma cells  
class4	novel antigens characteristic of neuroendocrine malignancies  the authors describe the immunochemical detection  biochemical characterization  and tissue distribution of neuroendocrine antigens recognized by three newly developed monoclonal antibodies  moab  obtained after immunization of mice with the variant small cell lung cancer  sclc  cell line nci h82  rnl 1 was reactive with neuroendocrine tissues similar to the sclc cluster 1 moab  known to recognize n cam  antibodies rnl 2 and rnl 3 are directed against different epitopes on the same proteinaceous complex  both moab recognize an intracellularly located  water soluble antigen which has a subunit composition with a protein triplet ranging in molecular weight between 44 and 45 kilodaltons  kd  next to a component of approximately 30 kd  the antibodies rnl 2 and rnl 3 reacted with a subset of neuroendocrine tissues and neuroendocrine neoplasms  in lung cancer both antibodies reacted only with some sclc and carcinoids and not with nonneuroendocrine lung carcinomas  the potential diagnostic applicability of antibodies rnl 1  rnl 2  and rnl 3 is discussed  
class4	ras gene mutations in intraductal papillary neoplasms of the pancreas  analysis in five cases  five intraductal papillary neoplasms of the pancreas were analyzed for the presence of the ras gene mutations  three  60   of the five neoplasms showed point mutations at k ras codon 12  this incidence of the mutations was rather low compared with that found with ordinary pancreatic adenocarcinoma  the presence of the mutations did not correlate with the severity of cellular atypia  but was apparently related to the size of the tumor  the two neoplasms that had no mutations were smaller than the others that had mutations  the analysis suggested that ras gene mutation is not the first genetic alteration of tumor progression  but that it occurs during the development of neoplasms of the pancreas  
class4	osteosarcoma in young children  the clinicopathologic features of osteosarcoma in 12 children younger than 16 years of age treated at the children s hospital and dana farber cancer institute  boston  during a 70 year time period are presented  only one of six children treated before 1972 is a long term survivor  four of six children  67   treated after 1972 are disease free with an average follow up of 8 8 years  the year 1972 marked the onset of use of effective chemotherapy in osteosarcoma  namely  high dose methotrexate and leucovorin rescue  it would appear that the pathologic features and behavior of osteosarcoma in young children is similar to that of osteosarcoma in older children and adolescents  a combination of complete  wide  surgical resection or amputation and aggressive chemotherapy offers the best chance of long term survival  
class4	clinicopathologic characteristics of adenosquamous carcinoma of the lung  fifty six cases of surgically resected adenosquamous carcinoma of the lung were studied clinicopathologically  and their outcome was compared with that of adenocarcinomas and squamous cell carcinomas of the lung  the frequency rate of adenosquamous carcinoma was 2 6  of 2160 primary lung cancers resected in the national cancer center hospital  tokyo  japan   the survival curves of patients with adenosquamous carcinomas  adenocarcinomas  and squamous cell carcinomas indicated that the outcome of adenosquamous carcinoma was poorer than that of adenocarcinomas and squamous cell carcinomas  particularly in stages i and ii  the amount of adenocarcinoma component did not affect the survival rate  although the histologic features of metastatic lymph nodes was somewhat influenced by the histologic type of the primary tumors  the histologic subtype of adenosquamous carcinoma was one of the independent prognostic determinants  
class4	immunohistochemical evaluation of seven monoclonal antibodies for differentiation of pleural mesothelioma from lung adenocarcinoma  a panel of seven monoclonal antibodies including anti vimentin  anti keratin markers ae1 ae3 and eab902  human milk fat globule  hmfg 2   b72 3  anti carcinoembryonic antigen  cea   and anti leu m1 were used for an immunoperoxidase staining assay to determine their value in the differentiation of pleural mesothelioma from lung adenocarcinoma  anti vimentin positively identified 86  of the mesotheliomas and none of the adenocarcinomas  ae1 ae3  eab902  and b72 3 reacted with a high percentage of both mesothelioma and adenocarcinoma specimens  with hmfg 2  both membrane and cytoplasmic staining was observed in 92  of the adenocarcinomas and in 14  of the mesotheliomas  whereas 26  of the mesotheliomas only exhibited membrane staining  eighty percent of the adenocarcinomas and 8  of the mesothelioma tissues stained with anti leu m1  anti cea did not react with any of the 50 mesotheliomas tested but did react with 95  of the lung adenocarcinomas tested  from this study  it was concluded that anti cea and anti leu m1 were the most effective of the seven tumor markers evaluated  and that 100  of the pleural mesothelioma tissues could be correctly differentiated from lung adenocarcinomas using a panel consisting of anti vimentin  hmfg 2  anti cea and anti leu m1 monoclonal antibodies  
class4	fine needle aspiration in hepatocellular carcinoma  combined cytologic and histologic approach  cytologic features of fine needle aspiration  fna  of hepatocellular carcinoma  hcc  have not been well documented  most previous reports described only the the morphologic features of the tumor cells without considering the sinusoidal stroma  cytohistologic correlation on tissue from the same aspirate has rarely been done  this report describes the cytologic patterns of 50 cases of hcc in terms of histologic pattern observed in cell blocks prepared from the same aspiration specimen and classified according to the world health organization  who  classification  tumors were classified according to the predominant pattern  thirty two cases gave the trabecular pattern  smears could be subdivided into a central sinusoidal pattern  23 cases  and a peripheral sinusoidal pattern  nine cases   one case gave the pseudoglandular pattern  seventeen cases gave the compact pattern with inconspicuous sinusoids  in all cases sinusoids were easily recognized in cell block sections  other cytologic features such as intranuclear cytoplasmic inclusions  eosinophilic globules  and bile secretion could be seen in both smears and cell blocks  mallory s hyalin and ground glass inclusions were only recognized in cell blocks  more attention should be paid to the sinusoidal stroma for diagnosis of hcc in fna  cell blocks should be more widely utilized to this effect  cytologic patterns could be classified according to the who histologic classification  
class4	myeloma of the head of the pancreas  a case report  a 45 year old man was diagnosed with multiple myeloma  iga kappa  in 1975  thirteen years later he presented with obstructive jaundice  computed tomography  ct  showed a 6 cm mass in the head of the pancreas  needle aspiration showed myeloma  the jaundice resolved after treatment with radiotherapy  extraosseous involvement by myeloma is frequently found at autopsy but obstructive jaundice from myeloma of the head of the pancreas is quite rare  this atypical complication of myeloma may be related to the patient s long survival  
class4	nonseminomatous germ cell tumor with very high serum human chorionic gonadotropin  most patients with disseminated nonseminomatous germ cell tumor  nsgct  have an excellent prognosis with modern chemotherapy  although certain subgroups with a worse prognosis have been described  one such subgroup includes patients with high serum levels of the tumor marker  human chorionic gonadotropin  hcg   sixteen patients of 104 treated for nsgct at the crc wessex medical oncology unit  southampton  uk  presented with serum hcg greater than 25 000  most of these patients exhibited features of the  choriocarcinoma syndrome  with bulky  rapidly progressive disease  frequent pulmonary  hepatic  and central nervous system complications  and a generally poorer response to standard nsgct chemotherapy  histologic identification of trophoblastic tumor was not made in all patients and is not essential for the diagnosis of the syndrome  indeed  closed biopsy may be contradicted in some circumstances because of the risk of hemorrhage  the nsgct patients with poor prognosis  including patients with the choriocarcinoma syndrome  must be clearly identified in order to improve management and  eventually  cure rates  
class4	recurrent renal cell carcinoma arising in wilms  tumor  a 19 month old black girl had a radical nephrectomy for a wilms  tumor that contained areas of epithelium indistinguishable from renal cell carcinoma  she was treated with chemotherapy but subsequently had pulmonary metastases develop and massive abdominal recurrence  the recurrent tumor was histologically renal cell carcinoma with no identifiable wilms  tumor elements  the child died with recurrent and metastatic tumor 13 months after nephrectomy  pathologic  immunoperoxidase  and flow cytometric studies of this unusual case are presented  
class4	acute respiratory failure and pulmonary thrombosis in leukemic children  acute respiratory failure  arf  in an 11 year old child with pre t acute lymphoblastic leukemia  all  at the beginning of induction therapy was observed  connected with a pulmonary thrombosis and not with an infective origin  a systematic search for this pathology identified six other children with the same pulmonary complication  five of whom where in the early phase of acute nonlymphoblastic leukemia  anll  and one in induction therapy for all in marrow relapse  at the beginning of the symptomatology  all children presented severe hypoxia and hypercapnia  with no or minimal chest radiograph abnormalities and no clear hemodynamic involvement  in all patients the arteriography and nuclear imaging studies confirmed the diagnosis  the causes of the thrombi could be connected with neoplastic emboli after cell lysis and or with the vascular damage resulting from antiblastic therapy  intravenous urokinase treatment and respiratory assistance had been successfully carried out in six of seven children  
class4	pregnancy outcome in hematologic malignancies  by means of a mail questionnaire  information on a series of 56 pregnancies i in 48 women diagnosed with leukemia or lymphoma was collected from ten hospitals  seven patients conceived while receiving treatment for their neoplasms  in 22 patients  the hematologic disease was diagnosed during pregnancy  and the remaining 27 patients became pregnant after completion of the antineoplastic treatment  when a comparison was made of the evolution of these pregnancies to that of pregnancies in a healthy population  no increase in the incidence of complications was observed  64  of the pregnancies went to term  9  resulted in spontaneous abortion  and 5  resulted in premature births  the observed incidence of one major malformation in 56 pregnancies did not differ from the frequency of malformations in the offspring of healthy individuals  there were no fetal losses in six pregnancies in which conception occurred during the first year after chemotherapy  in spite of the inherent limitations derived from the design of this type of study and the type of subject analyzed  the data here support the hypothesis that the cytostatic treatment of hematologic malignancies  if deemed necessary  should not be postponed because of pregnancy  moreover  the authors agree with advice recommending that no antifolic or alkylating agents be used for prolonged periods and that radiotherapy be avoided  especially to those fields involving the pelvic area  
class4	clinical presentation  treatment  and outcome of trilateral retinoblastoma  in this report  three new cases of trilateral retinoblastoma are presented  the clinical presentation  treatment  and outcome of the patients are described and compared with those of 32 cases that have been previously reported in the literature  a positive family history was obtained in 68  of the patients  the mean age at diagnosis of bilateral retinoblastoma was 7 2 months  the mean age at diagnosis of trilateral disease was 39 7 months  resulting in a mean latent interval of 32 6 months  the mean time from diagnosis of trilateral retinoblastoma to death was 6 6 months  and all patients died with spinal metastases  the patients who received no therapy survived an average of 1 3 months after the diagnosis of trilateral disease  the patients who received any form of definitive therapy survived 9 7 months  five patients who had complete or dramatic response to therapy by computed tomography scans had local intracranial tumor present at autopsy  therefore  more aggressive local therapy may be warranted  
class4	the role of infection in the morbidity and mortality of patients with head and neck cancer undergoing multimodality therapy  cancer of the head and neck is a common cancer worldwide  the majority of patients present with locally advanced disease  recently a great deal of improvement has been made in multimodality therapy of this disease  warranting more careful consideration of factors affecting quality of life  disease course  and treatment  infection is clearly a factor  analysis of 662 hospital admissions of 169 head and neck cancer patients was performed  a definite infection was documented in 86 febrile episodes  pneumonia contributed to 40   bacteremia to 13   skin and soft tissue infection to 12   and tracheobronchitis to 10   among the evaluated risk factors  foreign bodies  specifically intravenous  iv  cannulae and gastrostomy tubes  race  performance status  alcohol intake  and nutritional status were statistically significant variables that predicted for or were associated with infection  infection contributed to 44  of the deaths  
class4	factors related to and consequences of weight loss in patients with stomach cancer  the norwegian multicenter experience  norwegian stomach cancer trial  of 1165 patients with stomach cancer included in a national  prospective multicenter study with 51 surgical units participating  information about weight loss before diagnosis was available for 855 patients  73    median weight loss was 5 kg  259 patients  31   experienced no weight loss  by logistic regression analysis the authors found that weight loss increased with age and advancing stages of disease  tnm stage i iv   with decreasing karnofsky index  in lauren s diffuse versus intestinal tumor type  and with tumors located at the cardia esophagus  increasing weight loss reduced the resectability rate significantly  but no association between weight loss and postoperative complication rate was found  the odds ratio for postoperative mortality was 2 5 to 1 for the weight loss group 5 to 10kg versus 0 kg  in conclusion  weight loss reflects a less favorable tumor status  weight loss did not increase postoperative morbidity but did lead weight to a higher death rate after surgery  
class4	intrapericardial infusion of 5 fluorouracil  an unusual complication of a hickman catheter  venous access devices  vad  have become an important tool in the management of patients with cancer  multiple complications can occur as a consequence of insertion of a vad  the authors report a case of a hickman catheter perforating the wall of the superior vena cava into the pericardium  resulting in accidental intrapericardial infusion of 5 fluorouracil  5 fu   pericarditis and cardiac arrhythmias developed  but the patient did not have cardiac tamponade  she recovered from the event without apparent chronic cardiac dysfunction  
class4	zinc and copper in breast cancer  a joint study in northern italy and southern france  the relationship between breast cancer and two trace elements  zinc  zn  and copper  cu   was investigated by means of an hospital based case control study at milan  italy  and montpellier  france   variables concerning dietary intake of zn and cu  in milan  and their blood levels  both in milan and montpellier  were measured  dietary intake  evaluated through a questionnaire of the dietary history type  and blood levels of zn and cu were measured in 261 cases and 261 controls  cu blood level showed a contradictory tendency in the two samples  higher in controls in milan  higher in cases in montpellier   which tended to lessen after adjustment for related variables  no odds ratios  or  in the different quantiles  nor x2 for trend reached statistical significance  a sharp difference was evidenced on the opposite with regard to zn blood values in cases and controls  in both samples zn mean values are significantly higher in cases than in controls  and the difference remains significant in the two samples even after adjustment for related variables  the pooled or computed from the two samples  after adjustment for known risk factors and related variables  reaches in the fourth quartile a value of 9 5  ci  4 9 18 2   dietary intake of the two minerals  measured only in milan sample  showed no difference between cases and controls  but a stronger relationship between dietary and blood zn was evidenced in cases with respect to controls  the authors suggest that the higher zn level in cases might be related with an higher incorporation of zn in cancer cases and that the same mineral might play a possible role in tumor growth promotion  
class4	comparative epidemiology of cancer between the united states and japan  a second look  vital statistics were examined for the years 1955 through 1985 for japanese natives and united states whites to elucidate changes in cancer mortality and related antecedent patterns of life style in these two populations  results show that lung cancer rates are rapidly accelerating among japanese males as a consequence of their prior history of heavy cigarette smoking  oropharyngeal cancer rates are also rising in japan paralleling increases in alcohol and tobacco utilization  as the japanese life style and diet continue to become more  westernized   the rates of malignancies of the breast  ovary  corpus uteri  prostate  pancreas  and colon also continue to rise  nevertheless  the mortality patterns of certain malignancies  viz   laryngeal  esophageal  and urinary bladder cancer  are discrepant with their established risk factor associations  suggesting the existence of other differences in risk factor exposure between the two countries  epidemiologists and health educators need to develop innovative international programs of investigation and health promotion with preventive impact on common malignancies associated with risk factors of life style  
class4	gastrointestinal intraluminal ph in normal subjects and those with colorectal adenoma or carcinoma  recent evidence suggests that the production of colorectal carcinogens is facilitated when the ph of the colonic contents is alkaline  it follows that the colonic intraluminal ph of patients with colorectal neoplasms should be higher than in normal subjects  gastrointestinal ph has been measured in 30 patients with colorectal cancer and 37 patients with benign colorectal adenomas  using a ph sensitive radiotelemetry capsule   these values have been compared with those recorded in 66 normal subjects  no differences in gastrointestinal ph were found and the results did not support the hypothesis that colonic ph plays a role in the aetiology of colorectal neoplasia  
class4	in vitro anticolon antibody production by mucosal or peripheral blood lymphocytes from patients with ulcerative colitis  published erratum appears in gut 1991 apr 32 4  460  serum anticolon antibody and in vitro anti colon antibody production by peripheral blood and mucosal lymphocytes was investigated in patients with ulcerative colitis  the frequency of serum anticolon antibody was 71  in 41 patients with ulcerative colitis  estimated by enzyme linked immunosorbent assay  elisa  using isolated rat colon epithelial cells  this finding confirms our previous report on the frequency of serum anticolon antibody detected by flow cytometry analysis  the estimated frequencies of igg anticolon antibody secreting cells were 1 5 12 5 10 6  cells in the colonic mucosa and 0 1 0 5 10 6  cells in peripheral blood  from patients with ulcerative colitis when epstein barr virus  ebv  was used as a b cell polyclonal activator  poisson analysis of limiting dilution culture showed that about one per 140 igg cells in the colonic mucosa synthesised anticolon antibody  two monoclonal igg antibodies were obtained from ebv transformed anticolon antibody secreting cells by limiting dilution method  one reacted with goblet cells in the intestine  and the other reacted mainly with colonic epithelial cells  these results suggest that heterogeneous anticolon antibodies are present in patients with ulcerative colitis and that colonic mucosa may be the main source of anticolon antibody  local autoimmune reaction might have an important role in causing the inflammation of colonic mucosa in this disease  
class4	rectal mucosal dysplasia in crohn s disease  serial sections of 812 rectal biopsy specimens from 356 crohn s disease patients were analysed for mucosal epithelial dysplasia  dysplasia was found in 18 patients  5    with four showing dysplasia on repeat biopsy specimen  in these 22 biopsy specimens the dysplasia was mild in 13  moderate in nine  and severe in none  subsequently  three patients  17   developed neoplasms including carcinoma in two and an adenomatous polyp in one  in colectomy specimens which showed dysplasia  significantly more dysplastic changes were found in seven patients who underwent colonic resection than in 10 others who underwent operation but had no prior dysplasia  p less than 0 001   thirteen patients still have their rectum in situ and remain at risk of developing colonic cancer  four carcinomas developed in patients with crohn s disease who did not have dysplasia on rectal biopsy specimen  
class4	type ii oestrogen binding sites in human colorectal carcinoma  seven cases of colorectal adenocarcinomas were investigated for the presence of oestrogen receptors and progesterone receptors  the tumours specifically bound oestradiol  this binding almost exclusively resulted from the presence of high numbers of type ii oestrogen binding sites  oestrogen receptors were absent or present at very low concentrations  immunohistochemical investigation of nuclear oestrogen receptors gave negative results  this indicates that antioestrogen receptor antibodies recognise oestrogen receptors but not type ii oestrogen binding sites  the presence of specific type ii oestrogen binding sites and progesterone binding offers further evidence for a potential role for these steroids and their receptors in colorectal carcinoma  
class4	primary lymphoma of the liver  clinical and pathological features of 10 patients  nine out of 10 patients with primary lymphoma of the liver presented in a manner that did not suggest a tumour  the initial diagnoses were chronic active hepatitis in three cases and  granulomatous cholangitis   inflammatory pseudotumour  and anaplastic carcinoma in one case each  moreover  extensive haemorrhagic necrosis in three cases initially suggested the budd chiari syndrome  all the tumours were diffuse non hodgkin s lymphomas like the 50 cases reported previously  but they differed from most of these in that nine were of t cell phenotype  five were pleomorphic small t cell  two t zone  and two t lymphoblastic lymphomas  only one was centrocytic and of b cell lineage  this report extends the range of clinical manifestations  diffuse hepatomegaly without a tumour   histological appearances  resemblance to chronic inflammatory or vascular liver diseases  and phenotype  of t cell lineage  of primary lymphoma of the liver  these features seemed to be related in this series  recognition is important as prognosis remains favourable in appropriately treated cases  although the appearances of the liver biopsy specimens may be difficult to interpret  the destructiveness of the infiltrate is an important clue to the diagnosis  
class4	comparative in situ hybridisation study of juvenile laryngeal papillomatosis in papua new guinea and australia  a comparative study of cases of juvenile laryngeal papillomatosis from papua new guinea  n   3  and brisbane  australia  n   9  was carried out  in situ hybridisation reactions for human papillomavirus  hpv  types 6 and 11 occurred in 11 cases  all three cases from papua new guinea and eight from australia gave positive signals  a negative reaction was observed in one australian case  the intensity of the reaction was strong in seven cases  moderate in one  and weak in three  an equivocal reaction was also noted with probes for types 16 and 18  and types 31  33  and 35 in two cases from australia and one from papua new guinea  it is concluded that as similar staining patterns and intensities occurred in cases from both areas  the aetiology is the same  the equivocal reactions noted in three cases were probably due to cross hybridisation rather than multiple infection  
class4	monoclonal antibody b72 3 in benign breast lesions  it has been suggested that the monoclonal antibody b72 3 may be useful as a diagnostic tool in fine needle aspirates of breast masses because it recognises  tumour associated glycoprotein  tag  72   the antigen was sought in paraffin wax sections of 43 normal and benign breast biopsy specimens  using the avidin biotin complex technique  to assess the extent of its presence in non malignant tissue  strong focal staining was seen in 21  49   cases  in 29 cases of fibrocystic change staining was present in 17  59    all areas of apocrine metaplasia were positive  as well as a few normal ducts and acini and occasional areas of adenosis  focal positivity was present in five out of 12 foci of ductal epithelial hyperplasia and in three out of seven radial scars  staining was absent in two areas of lobular hyperplasia  three areas of sclerosing adenosis  and in a focus of lactational change  focal positivity was also seen in two out of five fibroadenomas and in two out of three intraduct papillomas  five normal subareolar sections and a section of normal lactating breast were negative  it is concluded that b72 3 monoclonal antibody can show focal reactivity with a variety of normal and benign epithelial mammary structures  and it is doubtful that its use would be of any help in differentiating benign from malignant cells in fine needle aspirates  
class4	improved silver staining of nucleolar organiser regions in paraffin wax sections using an inverted incubation technique  published erratum appears in j clin pathol 1991 jun 44 6  528  a new simple modification to the silver staining of nucleolar organiser regions  agnors  was devised which  by performing the incubation with the slide inverted  results in minimal undesirable background staining  a persistent problem  inverted incubation is facilitated by the use of a commercially available plastic coverplate  this technique has several additional advantages over other published staining protocols  in particular  the method is straightforward  fast  and maintains a high degree of contrast between the background and the agnors  
class4	refractory parastomal ulcers  a multidisciplinary approach  chronic parastomal ulcers in patients with ileostomy or colostomy stomas are unusual  previous reports have implicated infections  fistulas  recurrent inflammatory bowel disease  ibd   pyoderma gangrenosum  and trauma  over the past 8 years we have evaluated 10 cases of such refractory parastomal ulcers that occurred at a mean of 11 years after stomal surgery  eight patients had had an ileostomy for ibd while two had undergone colostomy for colon cancer  five patients with ibd were diagnosed as having pyoderma gangrenosum ulcerations  they required systemic treatment for a mean of 25 weeks to effect ulcer healing  the other five patients had either parastomal ulcers on the basis of dermatoses  contact dermatitis  eczema  or bullous pemphigoid  or contact ulcers due to face plate pressure and parastomal dermatitis  these patients received topical treatment with healing of ulcers in a mean of 4 weeks  we conclude that parastomal ulcers occurring in patients without ibd or ibd patients without classic pyoderma gangrenosum require early dermatologic evaluation as they respond relatively quickly to appropriate local therapy  
class4	ileal duplication cyst causing massive bleeding in a child  intestinal duplication is a rare congenital anomaly  nonetheless  it comprises more than half of all alimentary duplication disorders  our case report describes the hemorrhagic sequelae of this entity with surgical and pathologic findings  a review of anatomical classification  embryology  and natural history of duplication cyst follows  differentiating characteristics of duplication cyst versus meckel s diverticulum are outlined  intestinal duplication cyst should be considered in the differential diagnosis of gi bleeding  especially in children  
class4	small bowel obstruction associated with a leiomyomatous uterus  a case report and review of the literature  a 38 year old woman developed small bowel obstruction shortly after a cholecystectomy because of a massively enlarged leiomyomatous uterus  small bowel obstruction is a relatively rare complication from fibroid tumors and results from entrapment of the bowel between serosal pedunculated fibroids  as in this patient   adhesions to infarcted leiomyomas  or from compression of the small bowel by the large mass  large uterine leiomyomas clearly must be considered in the etiology of intestinal obstruction  
class4	cystic mesothelioma of peritoneum  occurrence in a man  we report a case of cystic mesothelioma of the peritoneum in a 54 year old man in whom cystic masses were removed twice by surgery at an interval of 2 years  the patient died of cardiac arrest shortly after the second operation for a concurrent unresectable colonic cancer  the pathogenesis of the disease is uncertain  but we consider it neoplastic of low grade malignancy  
class4	neuromesenchymal hamartoma of the small bowel  we present the case of a long small bowel stricture with pathological features similar to those described as  neuromuscular and vascular hamartoma   showing in addition extensive fatty submucosal infiltration and fibrous intramural nodules  in the controversy about the nature of this disorder  we consider it a separate entity  taking into account that other mesenchymal tissues than the originally described can participate  we propose the alternative term of  neuromesenchymal hamartoma  of the small bowel  
class4	early inappropriate secretion of antidiuretic hormone after trans sphenoidal pituitary adenomectomy  the syndrome of inappropriate secretion of antidiuretic hormone  siadh  is a rare but life threatening complication of trans sphenoidal pituitary adenomectomy  it has previously only been described as a late phenomenon  we report an early presentation within the first week  the pathophysiology  clinical features and treatment are discussed  
class4	marijuana smoking as a possible cause of tongue carcinoma in young patients  a case of t1n0m0 carcinoma of the tongue in a male 23 year old  regular  marijuana smoker is described  hemiglossectomy and complete bilateral neck dissection were carried out  no post operative radiotherapy was given as the resection margins were histologically negative  the tumour recurred one year later in the left cervical region involving the mandible and surgery was again performed  but after three months  neck disease was still evident  the case described case implies the introduction of marijuana as a possible new risk factor in the development of oral cavity tumours  resection of the primary lesion has to be as wide as possible even in t1 cases  due to the aggressive biological behaviour of such tumours in young subjects  
class4	pharyngeal adenocarcinoma with intestinal features  a high grade adenocarcinoma arising primarily in the pharynx of a 67 year old man is presented  a ct scan revealed a tumour mass growing in the pharynx  largely affecting parapharyngeal soft tissues  lymph node metastases were found at clinical presentation  both morphological and immunohistochemical studies displayed similar features to those of intestinal origin  to our knowledge  no previous examples of such neoplasm have been reported at this site  its possible histogenetical origin is discussed  
class4	fourth branchial pouch anomaly  we present an extremely rare case of fourth branchial fistula in a 23 year old male  the characteristic clinical feature was a recurrent left lower neck abscess which did not respond to appropriate medical and surgical therapy  radiography and a computed tomographic scan with contrast material revealed a fistula running from the apex of the left pyriform sinus  internal opening  to the left lower neck abscess  the fistula tract was excised surgically  histological examination of the excised fistula revealed a squamous epithelial lining and subepithelial lymphoid tissue  this pyriform sinus fistula is thought to be of fourth pharyngeal pouch origin  because of its surgical aspects and the histological findings of the excised fistula  
class4	cystic hygroma  massive recurrence in adult life  cystic hygroma is considered a disease of childhood  it may appear for the first time in adult life but recurrence by that stage is rare and may present difficulties in diagnosis due to previous treatment  the authors present a case where early pharmacological intervention may have prevented a potentially life threatening situation  the world literature is also reviewed  
class4	papillary adenocarcinoma of the middle ear  a case of papillary adenocarcinoma of the middle ear is presented  the patient had an unusually short history of otalgia  aural discharge and facial palsy  and  at presentation the tumour was too large for surgical resection to be a feasible option  the management of this rare tumour is discussed and the relevant literature reviewed  
class4	a case of amnesia after excision of the septum pellucidum  tumours of the septum pellucidum  sp  are rare and seldom associated with memory impairment either before or after operation  a patient is described who developed amnesia after transcallosal excision of a tumour of the sp  radiology did not show any major lesion of the brain areas traditionally associated with amnesia  because septal nuclei could have been damaged during surgery their possible role in memory functions is discussed  
class4	trends in female breast cancer in connecticut and the united states  trends for female breast cancer were examined by age  period and cohort for the years 1950 1984 in u s  mortality  connecticut mortality and connecticut incidence  birth cohort patterns were evident for all three sets of data  the results confirm a continuing increase in invasive breast cancer by providing evidence of a strong birth cohort pattern  over a time series of 90 years of birth cohorts  this trend appears to be real for the most part because of the cohort patterns and because there is minimal underdetection in data obtained by autopsy and blind biopsy  secondly  when cohort modeling is applied to breast cancer mortality  there is an indication of a modest decline in recent breast cancer mortality  in the face of an apparent long term increase   which suggests that control of breast cancer mortality may have developed in recent decades  perhaps through earlier detection and improved treatment  finally  in contrast with a prior report  there is little evidence for a clinically important difference in time trend between pre  and postmenopausal breast cancer  
class4	recent life change and large bowel cancer  data from the melbourne colorectal cancer study  in a large  population based  epidemiological study of colorectal cancer  the melbourne colorectal cancer study  several etiological factors were investigated  persons  recent life changes  as well as the degree of upset they experienced as a result of these changes  were included  interviews with 715 histologically confirmed new cases of colorectal cancer occurring over a 12 month period in melbourne  australia  and with 727 age and sex matched community controls were conducted  as one of the methods of assessing any effect of recall bias  179 hospital controls were also investigated  major illness or death of a family member  major family problems and major work problems were found to be significantly more common for cases over the 5 years preceding diagnosis compared to controls  cases also reported being significantly more upset with their recent life changes than did controls  no significant differences in results were found between males and females  or between colon cancer and rectal cancer patients  although the possibility of recall bias  was not completely controlled for in this study  it was probably not an important factor in explaining case control differences  recent life changes  and their perceptions  may have significance in the development of large bowel cancer  
class4	clustering of cancer in families of patients with primary lung cancer  we have previously shown that patients with a positive family history of lung cancer did not exhibit characteristics expected if the familial association was a surrogate for a genetic mechanism which was absent in those without such a history  in this study  we examine the incidence of cancer  all sites  in two groups of families   a  those ascertained through a patient with primary lung cancer  n   359 families  and  b  through a community control subject  n   234   the index subjects were excluded from all incidence data analyses  most families  62 vs 57   reported at least one member with a history of neoplastic disease  patients  families were more likely to have 2 or more affected members  p less than 0 05   to exhibit a multigenerational pattern  33 vs 24   and to have a higher risk of multiple tumours  or   1 5  in the same individual  however  most of the sites with the highest odds ratios  males  vocal cord esophagus 8 3  colon rectum 2 3  lung 1 96  females  pancreas 4 8  vocal cord esophagus 4 1  lung 1 8  are smoking associated although these were not necessarily the most frequently affected sites  in conclusion  these data support an ecogenetic etiology of cancer within families  
class4	spect quantitation of iodine 131 concentration in phantoms and human tumors  the validity of spect measurement of iodine 131  131i  concentration was tested in vitro in phantoms and in vivo by measuring bladder urine concentrations  phantom studies comparing known and spect measured concentrations showed a good correlation for 131i  r   0 98  s e e    20 94 counts voxel  for phantoms of 25 to 127 cc and concentrations of 0 13 to 9 5 microci cc  the in vivo  in vitro correlation of 131i concentrations in the urine was also good  r   0 98  s e e    0 677 microci cc   quantitative spect was used to calculate the effective half life and dosimetry of radioiodine in 12 sites of thyroid carcinoma in seven patients  spect was also used to determine the dosimetry of  131i mibg  metaiodobenzylguanidine  in two patients with carcinoid  two with neuroblastoma  and one with pheochromocytoma  the radiation dose for thyroid carcinoma metastases varied between 6 3 and 276 9 rad mci  the dose from mibg varied between 13 4 and 57 8 rad mci  these results indicate the validity of quantitative spect for in vivo measurement of 131i and the need to measure the concentration of 131i in individual human tumor sites  
class4	management of patients with thyroid carcinoma  application of thallium 201 scintigraphy and magnetic resonance imaging thyroid carcinoma has the ability to concentrate radioiodine  an attribute that can be used both for detection of thyroid cells and for treatment  unfortunately  however  radioiodine uptake is not observed in all patients and a radioiodine scan requires that the patient be rendered hypothyroid for 4 6 wk  in the present study  we analyzed the utility of thallium 201 scanning and the usefulness of magnetic resonance imaging  mri  in the detection of thyroid cancer  nineteen patients with thyroid cancer had a total of 24 radioiodine scans  33 thallium scans  and 10 mri examinations  of the 19 patients in the study  17 had differentiated thyroid carcinoma  in these 17 cases  all paired studies were concordant for the presence  n   7  or absence  n   10  of disease  however  in one case  patient 10   the 201tl studies showed far more extensive disease than was observed on the 131i scan  thyroid cancer was also detected on seven mri studies  in summary  thallium and mri scans are adjunctive techniques to radioiodine scanning that can either confirm the presence of neck bed activity  residual disease or metastatic cancer and may delineate tumor deposits not detected by radioiodine scanning  thallium may be capable of detecting tumor deposits even while a patient remains euthyroid  
class4	indium 111 antimyosin scintigraphy after doxorubicin therapy in patients with advanced breast cancer indium 111 antimyosin  111in antimyosin  scans were performed in 20 women with advanced breast cancer after 10 cycles of chemotherapy consisting of cyclophosphamide  5 fluorouracil and doxorubicin  total cumulative dose of doxorubicin of 500 mg m2   antimyosin uptake in the myocardium was quantified by means of a heart to lung ratio  hlr   antimyosin uptake in the myocardium was observed in 17 20  85   patients  and hlr after chemotherapy was 1 86     0 25  left ventricular ejection fraction  ef  was determined before and after chemotherapy  patients with decreased ef  8 20  40   presented with more intense antimyosin uptake  hlr of 2 11     0 10 versus 1 70     0 16  p   0 01   hlr values correlated with ef values after chemotherapy  r    0 47  p less than 0 05   positive antimyosin studies after chemotherapy including doxorubicin  indicate the presence of myocardial damage in these patients  antimyosin studies are a sensitive method to detect myocyte damage in patients after doxorubicin therapy  
class4	indium labeled anti colorectal carcinoma monoclonal antibody accumulation in non tumored tissue in patients with colorectal carcinoma  indium 111   111in  labeled murine monoclonal antibodies zce 025  against carcinoembryonic antigen  and cyt 103 mab b72 3  against tumor associated glycoprotein   72  have been used to image patients with colorectal cancers with encouraging results  the objectives of this study were to assess the frequency and causes of 111in mab localization in tumor free  benign tissues  thus  scans of 75 patients who have undergone exploratory surgery following radioimmunoscintigraphy with 111in zce 025  n   37  or 111in cyt 103  n   38  were reviewed in conjunction with operative and histopathology reports  localization in non tumored tissues was seen in 10 8  and 13 1   respectively  of patients receiving zce 025 and cyt 103  the most common sites involved were  degenerative joint disease  abdominal aneurysms  postoperative bowel adhesions  and local inflammatory changes secondary to surgery or external irradiation  review of patients  medical history and results of concurrent diagnostic modalities is likely to lessen the false positive rate of 111in labeled mab scan interpretation  
class4	6  18f fluoro l fucose  a possible tracer for assessing glycoconjugate synthesis in tumors with positron emission tomography  the potential of 6  18f fluoro l fucose  6  18f ffuc  for assessing glycoconjugate synthesis in tumors with positron emission tomography  pet  was investigated  using the tissue sampling method with five tumor models  different time radioactivity profiles were found  a nearly constant level in lewis lung carcinoma  3ll  and different clearance patterns in others  rapid clearance in normal tissues resulted in preferable uptake ratios for tumor imaging of brain and pancreas  metabolic studies and the l fucose loading effects on the tissue uptake proved the tracer to be a biochemically active l fucose analog  imaging of the intracranial rat glioma and 3ll in lungs or hepatomas in mice by autoradiography  arg  and intramuscular vx 2 carcinoma in rabbits by pet was demonstrated  using double radionuclide arg  similar distribution images of 6  18f ffuc and 14c l fucose but different tumor to liver uptake ratios were found  a metastasis model seemed to show a higher uptake of both tracers as compared to a primary tumor model  
class4	spect imaging of pediatric brain tumor with hexakis  methoxyisobutylisonitrile  technetium  i   technetium 99m hexamibi  hexakis  methoxyisobutylisonitrile  technetium  i   was developed as a myocardial perfusion agent with biologic properties similar to those of thallium 201  201ti   as 201ti has recently been observed to be of value for the diagnosis of brain tumors when used in conjunction with single photon emission computed tomography  spect  imaging technology  the possibility that the biologic similarity of the two radiopharmaceuticals extended to their affinity for tumors was tested  a 5 yr old female patient with a brain stem astrocytoma showed marked focal uptake of 99mtc hexamibi at the site of tumor recurrence as defined by biopsy and prior 201ti spect study  tumor to normal cortex radioactivity ratios for the 99mtc hexamibi spect study were 132 1 and the spatial resolution of the 99mtc hexamibi images was high  this observation suggests that 99mtc hexamibi merits further study as a potential agent for spect imaging of human brain tumors  
class4	beta camera for static and dynamic imaging of charged particle emitting radionuclides in biologic samples  a detection system based on microchannel plates has been constructed to image charged particles emitted by radionuclides in biomedical samples  this technique has significant advantages over conventional film autoradiography for investigating the distribution of radiolabeled compounds  shorter acquisition times due to the high sensitivity  easier sample handling  direct quantification and the ability to perform dynamic studies  the detector performance shows a spatial resolution of 0 9 mm for carbon 14  14c   0 156 mev   good linearity and homogeneity  the noise level is below 50  cm2 sec   successful imaging with this system has been performed with beta emitters 14c  sulfur 35  35s   iodine 131  131i   yttrium 90  90y   and positron emitters gallium 68  68ga   and fluorine 18  18f   dynamic studies of axonal transport of 35s methionine in a nerve  and static images of 90y labeled monoclonal antibodies in slices of tumors are presented  the system shows promise for rapid quantitative imaging of charged particle emitting radionuclides in small biologic samples  
class4	treatment of childhood angiomatous diseases with recombinant interferon alfa 2a  a heterogeneous group of five patients with progressive  invasive angiomatous diseases including pulmonary hemangiomatosis  angiosarcoma  or massive hemangioma with associated consumptive coagulopathy were treated with interferon alfa 2a for periods of 17 to 33 months  one patient with a large thoracic hemangioma  cardiorespiratory failure  and consumptive coagulopathy died after less than 2 months of treatment  the remaining four patients have shown beneficial responses  including  1  regression of abnormal vessels on pulmonary angiogram and improved exercise tolerance in pulmonary hemangiomatosis  two patients    2  decreased corticosteroid and or platelet transfusion requirements in consumptive coagulopathy  two patients   and  3  decreased size and number of tumor nodules in the one patient with angiosarcoma arising in preexisting angiomatous lesions  responses occurred during periods of 2 to 20 months of treatment  there was no measurable progression of angiomatous lesions in any patient receiving interferon at the therapeutic dose  except possibly in the one who died  each of the four surviving patients had improved linear growth and weight gain during interferon treatment  
class4	renal function in obstructive jaundice in man  cholangiocarcinoma model  renal function with respect to water clearance and renal hemodynamics was studied in 15 patients with obstructive jaundice due to cholangiocarcinoma  the results were compared with those of the control normal subjects  there was no change in renal function in the patients with mild to moderate jaundice  with total serum bilirubin from 8 0 to 15 1 mg dl  increased urinary sodium excretion and decreased free water and negative water clearances were observed in the patients with severe jaundice with total serum bilirubin from 27 0 to 40 4 mg dl and normal serum albumin  renal blood flow was normal  but creatinine clearance was decreased  in severely jaundiced patients with serum bilirubin from 30 5 to 40 1 mg dl and hypoalbuminemia urinary sodium excretion  free water clearance  negative water clearance  renal blood flow and creatinine clearance were decreased  there was salt and water retention in this group  the findings suggest that in severe jaundice there is inhibition of sodium chloride reabsorption in the thick ascending limb of henle s loop  adh and increased hydraulic conductivity of the collecting tubules possibly contribute to decreased free water clearance  in severely jaundiced patients with hypoalbuminemia this salt losing effect is converted to salt retention by increased proximal tubular reabsorption of sodium  
class4	postoperative adjuvant chemotherapy in non small cell lung cancer  prognostic value of dna ploidy and post recurrent survival  eighty six patients with non small cell lung cancer who underwent curative operations were postoperatively randomized to control and adjuvant chemotherapy groups  in the adjuvant chemotherapy group  patients received cisplatin based combination chemotherapy 3 or 4 weeks after operation and the average cycle of chemotherapy was 2 3  from 1 to 6 cycles   in this trial  no evidence of improved survival or delayed recurrence was seen in the treated patients  in multivariate analysis of prognostic variables  the most important factor was the pathological stage of the disease and  second  dna ploidy of the primary tumor  although histology  squamous vs  non squamous cell carcinoma  had a trend to influence the survival  it was not a significant factor  a total of 33 patients had recurrences  17 and 16 patients were in control and adjuvant chemotherapy groups  respectively  postrecurrent survival in the adjuvant chemotherapy group was significantly shorter than that in the control group  as determined by the generalized wilcoxon and log rank tests  median survival time after recurrence in the control and adjuvant therapy groups was 18 5 and 7 5 months  respectively  these results suggest that dna ploidy of primary tumors should be considered as a prognostic factor in future trials of adjuvant therapy  furthermore  analysis of postrecurrent survival in the adjuvant chemotherapy trial  as well as that of overall and disease free survivals should be done  
class4	modified anterior compartment resection  in the majority of patients with soft tissue sarcomas of the anterior compartment of the thigh  it is possible to preserve a small portion of the quadriceps with intact nerve supply without compromising on the radicality of the procedure or the local control rate  the distal one third of the vastus medialis can usually be spared with a long  slender branch providing its innervation  dissection of the femoral nerve below the inguinal ligament and its branch es  to an uninvolved area of the quadricepts the farthest from the location of the tumor is essential  this modified anterior compartment resection improves dramatically the function of the extremity  
class4	leukocyte alkaline phosphatase score in patients with cerebrovascular disease and in patients with primary and metastatic brain tumors  leukocyte alkaline phosphatase  lap  activity in peripheral blood was determined in 54 patients with cerebrovascular disease  cvd   11 patients with primary brain tumor  and 23 patients with metastatic brain tumor  the lap score of the primary brain tumor patients  155     40  was significantly higher  p less than 0 03  than the lap score for cerebrovascular disease patients  96     87   the lap score levels of the metastatic brain tumor patients  251     55  was significantly higher as compared with both the cerebrovascular disease  p less than 0 001  and primary brain tumor groups  p less than 0 001   the lap score could serve as an additional  although non specific  marker to assist in the differentiation between cerebrovascular disease and brain tumors  
class4	dysgerminoma of the ovary  review of 27 cases  twenty seven patients with pure dysgerminoma were seen at the tata memorial hospital  bombay  between january 1980 and december 1984  of the 10 patients in stage i  2 patients underwent a unilateral salpingoophorectomy  uso  and were kept under observation without any adjuvant therapy  while the remaining patients received adjuvant treatment following surgery  all of the 6 patients in stage ii and 4 of 7 in stage iii had total abdominal hysterectomy and bilateral salpingo oophorectomy  tahbso  followed by postoperative radiotherapy  one patient presented in stage iv and 3 patients presented with recurrence after previous definitive treatment undertaken at other institutions  the disease free  as well as the overall survival  at 108 months  for the 24 cases primarily treated at this institution  is 81  and 88  respectively  and  for patients in stages i and ii  100   kaplan meier estimation   the need for controlled clinical trials to devise optimal therapy in the early clinical stages and use of chemotherapy for advanced stages of this highly curable entity are stressed  
class4	renal oncocytoma  long term follow up and flow cytometric dna analysis  we report a retrospective study on the clinicopathologic features and flow cytometric dna analysis of ten renal oncocytomas compared with a control group of ten randomly selected renal cell carcinomas  among the oncocytoma patients  no recurrences or metastases were noted over an average follow up of 6 7 years  range   6 months to 16 years   reproducible  high quality dna histograms were obtained on the paraffin embedded specimens by using our modified flow cytometric procedure  one aneuploid  10   and two hyperdiploid tumors  20   were found in the oncocytoma group  there was no correlation between these abnormal dna histographic patterns and survival or tumor stages  on the contrary  a good correlation was found between tumor grades and dna ploidy in the controls  we conclude that renal oncocytoma is a clinically benign tumor  yet it may exhibit varying degrees of flow cytometric dna abnormalities  which have no predictive value on survival and probably reflect the characteristics of oncocytes rather than its malignant potential  
class4	granular cell neoplasm of the extrahepatic biliary tree  morphological  ultrastructural  and immunohistochemical study and review of the literature  a recent case of a biliary granular cell tumor of the cystic duct prompted a literature review and an extensive pathological examination of the tumor in question  a total of 44 cases have been described mostly in black females  most cases present with biliary symptoms  and simple surgical resection allows complete control of this benign condition  granular cell tumors are most likely derived from neural crest cells  
class4	bilateral malignant phyllodes tumours  we report a rare example of bilateral primary malignant phyllodes tumours  the diagnosis was supported by the identification of a benign epithelial element in each lesion  the case illustrates the typical dimorphic features of malignant phyllodes tumours  a contralateral tumour should not be regarded as metastatic without histological confirmation  
class4	adjuvant  specific  active immunotherapy for resectable squamous cell lung carcinoma  a 5 year survival analysis  in 1976 stewart et al   annals of the new york academy of sciences 277 436 466  reported the effectiveness of adjuvant specific active immunotherapy of lung carcinoma in improving the postoperative survival of stage i lung carcinoma patients in a phase ii study using lung carcinoma associated antigen  taa  and complete freund s adjuvant  cfa   a phase iii study was then designed by the authors to see the effects of specific active immunotherapy compared to the conventional management  no treatment  and to nonspecific immunotherapy  from 1976 to 1981  85 patients with resectable  stages i and ii  squamous cell lung carcinoma were entered into a randomized study  1  control group  2  specific immunotherapy group  three monthly doses of 500 micrograms of taa emulsified with cfa  3  nonspecific immunotherapy group  three monthly doses of cfa emulsified in saline  all the patients in the study received skin tests with 100 micrograms of the same taa used for the immunotherapy  recently  a 5 year follow up of all the patients became available  the life table 5 year survival of group 1 was 34   of group 2 was 75   and of group 3 was 53   the median survivals for the three groups were group 1  38 months  group 2  106 months  and group 3  71 months  the difference was significant at p    007  cox mantel test   
class4	unusual malignant neoplasms of the esophagus  oat cell carcinoma  melanoma  and sarcoma  primary noncarcinomatous malignant neoplasms of the esophagus are uncommon and data concerning treatment and results are sparse  to evaluate the results of therapy in this group  we reviewed the records of 32 patients with primary esophageal malignant tumors of unusual histologic type  thirteen patients  41   had sarcoma  eight  25   melanoma  and 11  34   had oat cell carcinoma  dysphagia was present in 78   25 32  of the patients for a median of 13 weeks before diagnosis  location of the esophageal primary tumor was upper third in four patients  12    middle third in 12  38    and lower third in 16  50    treatment consisted of esophagectomy in 10 of 13 patients with sarcoma  77    seven of eight with melanoma  88    and three of 11 with oat cell carcinoma  27    patients not undergoing resection received chemotherapy or radiation therapy  or both  the 3  and 5 year survival rates were 46  and 23  for sarcoma  median 20 months   13  and 0  for melanoma  median 5 months   and 0  and 0  for oat cell carcinoma  median 5 months   respectively  distant disease was the initial form of recurrence in 73   11 15  of patients undergoing curative therapy  surgical resection appears indicated for localized primary esophageal sarcoma  optimum treatment of primary esophageal melanoma is less clear  but surgical resection may be of benefit in selected patients  esophageal oat cell carcinoma is a systemic disease necessitating systemic therapy with local therapy reserved for palliation of dysphagia  
class4	migration stimulating activity in serum of breast cancer patients  an assay to measure the ability to stimulate migration of fibroblasts into collagen gel was carried out on serum from treated and untreated breast cancer patients and from healthy controls  migration stimulating activity was found in the serum of 10  83   of 12 untreated breast cancer patients immediately before surgical resection of the primary tumour and in 9  75   of them 4 days after resection  in 13  93   of 14 patients 1 13 years after tumour resection who had received adjuvant treatment  and in 2  10   of 20 healthy women matched for age  the migration stimulating activity in cancer patients  serum was indistinguishable from the migration stimulating factor produced in vitro by fetal and cancer patient skin fibroblasts in its behaviour in various biochemical fractionation procedures  the presence of this activity in the serum of treated breast cancer patients clearly distinguishes it from other oncofetal proteins  which all seem to be produced by tumours  
class4	the axilla  not a no go zone many surgeons  particularly in the uk  give inadequate primary treatment to patients with operable breast cancer  for spurious reasons they regard axillary clearance as unnecessarily extensive surgery and rely instead upon total mastectomy or tumour excision and node sampling  with or without postoperative radiotherapy  but it is now clear that relapse free and overall survival can be improved by appropriate adjuvant therapy  thus inadequate exploration of the axilla is doubly unjustified  not only is there the obvious risk of failure to remove nodes that contain metastases  so that some patients are deprived of cure by primary treatment  but the extent of tumour spread will be inadequately assessed in many more patients  with the risk that they may not receive appropriate adjuvant treatment  
class4	nonhomologous chromatid exchange in hereditary and sporadic renal cell carcinomas  for the development of renal cell carcinomas  it has been suggested that a germ line or somatic mutation occurs on one of the homologous chromosomes 3p  and subsequently the other 3p segment is lost  we have examined the karyotype and or the allelic combination on chromosomes 3 and 5 by restriction fragment length polymorphism analysis in normal kidney and tumor samples from 28 renal cell carcinomas that developed in two patients with von hippel lindau disease  we then compared the results to those of sporadic tumors  an unbalanced translocation between chromosome 3p and 5q or other chromosomes was found to be the most common aberration  we developed a model of nonhomologous chromatid exchange involving breakpoint clusters at chromosomes 3p13  3p11 2  5q22  and 8q11 2  subsequent chromatid segregation may result in net loss of the 3p segment either  i  in one step or  ii  after a nondisjunctional loss of the derivative chromosome carrying the 3p segment  this general mechanism could also be implicated to explain genetic changes occurring in other types of solid tumors  
class4	prothymosin alpha antisense oligomers inhibit myeloma cell division  the function of prothymosin alpha has been investigated by using four different antisense oligodeoxyribonucleotides directed at selected regions of its mrna  in every case  when synchronized human myeloma cells were released from stationary phase by incubation in fresh medium containing antisense oligomers  cell division was prevented or inhibited  sense oligomers and random antisense oligomers had no effect  a detailed analysis of synchronized cell populations indicated that sense treated and untreated cells divided approximately 17 hr after growth initiation  whereas cells incubated with antisense oligomer 183  a 16 mer targeted 5 bases downstream of the initiation codon  entered mitosis approximately one cell division late  the failure to divide correlated directly with a deficit in prothymosin alpha and with the continued presence of intact intracellular antisense oligomers over a period of at least 24 hr  because antisense oligomers had no effect either on the timing of the induction of prothymosin alpha mrna upon growth stimulation or on mrna levels seen throughout the cell cycle  we concluded that antisense dna caused specific hybrid arrest of translation  our data suggest that prothymosin alpha is required for cell division  however  there is no evidence that prothymosin alpha directly regulates mitosis  
class4	sequence and functional expression in xenopus oocytes of a human insulinoma and islet potassium channel  regulation of insulin secretion involves the coordinated control of ion channels in the beta cell membrane  we have isolated and characterized cdna and genomic clones encoding a voltage dependent k  channel isoform expressed in human islets and in a human insulinoma  this k  channel isoform  designated hpcn1  with a deduced amino acid sequence of 613 residues  mr   67 097   is related to the shaker family of drosophila k  channels  hpcn1 is homologous to two other human k  channel isoforms we have isolated  hpcn2 and hpcn3  with 55  and 65  amino acid sequence identity  respectively  the electrophysiological characteristics of hpcn1 were determined after microinjection of synthetic rna into xenopus oocytes  two microelectrode voltage clamp recordings of oocytes injected with hpcn1 rna revealed a voltage dependent outward k  current that inactivated slowly with time  outward currents were inhibited by 4 aminopyridine with a ki less than 0 10 mm and were relatively insensitive to tetraethylammonium ion or ba2   a delayed rectifier k  channel such as hpcn1 could restore the resting membrane potential of beta cells after depolarization and thereby contribute to the regulation of insulin secretion  
class4	dimerization of mammalian progesterone receptors occurs in the absence of dna and is related to the release of the 90 kda heat shock protein  in this study we have demonstrated that dimerization of mammalian progesterone receptors  pr  occurs in the absence of dna  a specific immune coisolation assay was performed on extracts of t 47d human breast cancer cells with a monoclonal antibody specific for the full length b form of progesterone receptor  pr b   this resulted in coisolation of significant amounts of truncated form a receptors  pr a   indicating the presence of stable pr a pr b dimers in solution  a positive correlation was observed between the ability of different receptor forms to oligomerize in solution and their ability to bind to specific dna sequences  the ability to form stable pr a pr b oligomers in the absence of dna was also found to correlate with release of 90 kda heat shock protein  hsp90  from the unactivated pr complex  these results support the hypothesis that dimerization in the absence of dna is an important mechanism controlling receptor dna binding function and that hsp90 release may be a key step regulating dimerization  this suggests that hsp90 may function to repress dna binding activity indirectly by blocking receptor dimerization  
class4	pancreatic tumor pathogenesis reflects the causative genetic lesion  transgenic mice in which c myc expression is targeted to pancreatic acinar cells develop mixed acinar ductal pancreatic adenocarcinomas between 2 and 7 months of age  this contrasts with the effect on pancreas of the simian virus 40 tumor antigen or activated ras  which in adult mice causes lesions composed exclusively of acinar like cells  furthermore  during an early stage of myc induced pathology  transformed acinar derived cells appear within islets  suggesting that islet hormones may influence the progression of these exocrine pancreatic tumors  these findings demonstrate that the initial oncogenic alteration can influence the pattern of subsequent tumor pathogenesis and  given that human exocrine pancreatic tumors are predominantly ductal adenocarcinomas  support the suggestion that transformed acinar cells may contribute to the genesis of this serious disease in man  
class4	nosocomial infections due to xanthomonas maltophilia  pseudomonas maltophilia  in patients with cancer  from december 1985 to may 1986  xanthomonas maltophilia  formerly known as pseudomonas maltophilia  was isolated at an increased rate at our institution  52 isolates of x  maltophilia were obtained in cultures of clinical specimens from 38 patients during that time  the records of 35 of these patients form the basis of this study  twelve  71   of the 17 infected and nine  50   of the 18 colonized patients had received or were receiving antimicrobial therapy  eleven of 17 patients  three of seven with septicemia  three of five with pneumonia  three with urinary tract infection  and two with wound infection  responded to antimicrobial therapy  microbiologic studies of the potential environmental sources revealed growth of x  maltophilia in two water faucets and in one water sample from the medical intensive care unit  x  maltophilia is emerging as an important nosocomial pathogen in immunocompromised patients  especially those receiving broad spectrum antimicrobial therapy  
class4	williams  vulvovaginoplasty after supralevator total pelvic exenteration  seven patients had delayed williams  vulvovaginoplasty after supralevator total pelvic exenteration  of the three patients who died of carcinoma of the cervix  at 2  5  and 15 months after vulvovaginoplasty   the first died before having a chance to attempt intercourse  but the other two had reported intercourse on at least two occasions after the reconstruction  one of the patients described the experiences as neither pleasant nor unpleasant but stated that her husband seemed satisfied  the other patient described the experience as satisfactory to both herself and her husband  the remaining four patients are alive with no evidence of recurrent disease at 28  42  56  and 106 months after operation  two of these patients have reported entirely satisfactory sexual relations approximating pre exenteration frequency  but the remaining two have not had sexual relations since surgery  both give the main reason for this as lack of opportunity  the williams  vulvovaginoplasty appears to be a reasonable alternative for vaginal reconstruction in patients who will have and especially who have had exenteration  to improve results  other methods of vaginal reconstruction should continue to be evaluated  
class4	roentgenographic evaluation of the augmented breast  we performed a retrospective study to determine the sensitivity of mammography in detecting breast cancer arising in women with augmented breasts  of eight women with breast implants in whom breast cancer developed  six had mammograms before biopsy  only two of the six cancers were identified mammographically  sensitivity   33    and one of these two was seen only in retrospect  in both cases  the mammographic findings suggested a benign rather than a malignant process  all eight women had a palpable mass and early disease  and all are clinically disease free at present  the sensitivity of mammography in detecting palpable cancers in a control group of women without implants was 92   118 of 128   for tumors of 2 cm or less  the sensitivity was 88   58 of 66   these results suggest that the sensitivity of mammography in detecting breast cancer is decreased when implants are present  further investigations are needed to determine the effects of prostheses on mammographic evaluations  
class4	flexible sigmoidoscopy as a screening procedure in rural patients  in this study of flexible sigmoidoscopy as a screening procedure for rural  impoverished patients  16  of asymptomatic patients who were screened by sigmoidoscopy and 23  of patients with a positive test for fecal occult blood were found to have a polyp or carcinoma  flexible sigmoidoscopy appears to be an important part of the physical examination of patients older than 50  it is a test that can readily be done by primary care physicians in a rural setting  
class4	pancreatic carcinoma in an elderly woman with an organic affective disorder and aids delusion  an elderly woman with symptoms of depression and an aids delusion was found also to have pancreatic carcinoma  i have discussed her case in conjunction with organic affective disorder  the evaluation of depression in the elderly  and suicide in the elderly  
class4	scoring system for the preoperative evaluation of metastatic spine tumor prognosis  an assessment system for the prognosis of metastatic spine tumors was evaluated for 64 cases who had undergone surgery  six parameters were employed in the assessment system  1  the general condition  2  the number of extraspinal bone metastases  3  the number of metastases in the vertebral body  4  metastases to the major internal organs  lungs  liver  kidneys  and brain   5  the primary site of the cancer  and 6  the severity of spinal cord palsy  each parameter ranged from 0 to 2 points  the total score obtained for each patient can be correlated with the prognosis  while being valuable in predicting it  however  the prognosis could not be predicted from a single parameter  in conclusion  an excisional operation should be performed on those cases who scored above 9 points  while a palliative operation is indicated for those who scored under 5 points  
class4	total sacrectomy and reconstruction for huge sacral tumors  the authors carried out successful total sacrectomy in three cases  two with giant cell tumors and one with a chordoma  the anterior and posterior approach is feasible for resecting huge sacral tumors en bloc  but it is important to reconstruct the continuity between the pelvic ring and spinal column using spinal instrumentation and sacral rods or ao plates  as total sacrectomy is a large scale  time consuming  and collaborative operation  two or three teams should be used in relays  both pelvic and spinal surgical techniques are required  post operatively the patient can stand within 3 to 6 months and well planned rehabilitation allows ambulation  in spite of the serious structural and neurologic damage caused  total sacrectomy can be rewarding procedure in terms of improved morbidity and mortality  
class4	transurethral resection versus needle biopsy prior to radical prostatectomy for stage c prostate cancer  influence on progression and survival  previous reports have claimed that transurethral resection of the prostate  turp  preceding definitive radiation therapy for patients with stage c prostate cancer promotes the risk of distant metastasis and increases the mortality rate  a total of 490 patients with pathologic stage c adenocarcinoma of the prostate treated by radical prostatectomy were studied  median time to follow up was 4 6 years  comparison was made between patients who had turp within the six months preceding prostatectomy  n   54  and those who had needle biopsy  n   437  prior to operation  no significant differences were noted in local recurrence of disease  systemic progression of disease  disease free interval  and overall and cause specific survival  even after adjustment for clinical  adjuvant treatment  and pathologic prognostic variables  our data suggest that for patients with pathologic stage c prostate cancer treated by radical surgery  preoperative turp is not associated with unfavorable outcome  
class4	renal cell carcinoma vs  renal oncocytoma  report of a case with overlap features and review of the literature although the salient features of renal oncocytomas and renal cell carcinomas have been discussed in the recent literature  renal masses with features of both entities will present diagnostic difficulty  especially when the cells are diffusely eosinophilic on microscopic examination  a case of a firm  tan  rounded mass replacing the lower pole of the kidney is discussed  the final diagnosis of renal cell carcinoma  granular cell type  was made after multiple sections of the tumor were examined  and after electron microscopy was performed  a thorough search by light microscopy should be made for clear cell foci  necrosis  mitotic activity  and vascular or capsular invasion  features generally accepted as pathognomonic for renal cell carcinoma  cellular and especially nuclear pleomorphism is typically focal or mild in renal oncocytomas  true oncocytic tumors will be packed with mitochondria on electron microscopy  however  granular renal cell carcinomas will contain mitochondria as well as other cellular organelles  lipid  and glycogen  electron microscopy should be performed on tumors suspected of being oncocytomas because eosinophilia on hematoxylin and eosin stain  as demonstrated by this case  is not a predictable measure of mitochondria content  immunoperoxidase staining for vimentin in oncocytomas has recently been shown to be negative  and may offer a method of ruling out oncocytoma in vimentin positive tumors  pending further studies  
class4	perinatal transmission of human papillomavirus  human papillomavirus infection is probably the most prevalent sexually transmitted disease in the united states  in adults  it is associated with condylomata acuminata and with neoplastic changes ranging from dysplasia to carcinoma  infected mothers may transmit human papillomavirus during the perinatal period  affected children face prolonged  difficult treatment for respiratory papillomatosis  prevention of infection remains the best approach  since diagnostic and therapeutic methods are suboptimal  
class4	hepatobiliary manifestations of the acquired immune deficiency syndrome  patients with the acquired immune deficiency syndrome  aids  frequently develop hepatic dysfunction  although hepatic injury may indirectly result from malnutrition  hypotension  administered medications  sepsis  or other conditions  the hepatic injury is frequently due to opportunistic hepatic infection  directly related to aids  infection with mycobacterium avium intracellulare typically occurs in patients with advanced immunocompromise and with systemic symptoms due to widely disseminated infection  in contrast  hepatic tuberculosis often occurs with less advanced immunocompromise  cytomegaloviral infection may produce a hepatitis  cytomegaloviral and cryptosporidial infections have been implicated as causes of acalculous cholecystitis and of a secondary sclerosing cholangitis  about 10 20  of patients with aids have chronic hepatitis b infection  these patients tend to develop minimal hepatic inflammation and necrosis  the clinical findings in patients with hepatic cryptococcal infection are usually due to concomitant extrahepatic infection  hepatic histoplasmosis usually develops as part of a widely disseminated infection with systemic symptoms  hepatic involvement by kaposi s sarcoma is rarely documented ante mortem because an unguided liver biopsy is an insensitive diagnostic procedure  patients with non hodgkin s lymphoma of the liver typically have lymphadenopathy  hepatomegaly  and systemic symptoms  as a pragmatic approach  patients with liver dysfunction and hiv related disease should have a sonographic or computerized tomographic examination of the liver  patients with dilated bile ducts should undergo endoscopic retrograde cholangiopancreatography because opportunistic infection may produce biliary obstruction  patients with a focal hepatic lesion should be considered for a guided liver biopsy  patients with a significantly elevated serum alkaline phosphatase level should be considered for a percutaneous liver biopsy  when performed for these indications  liver biopsy will demonstrate a significant disease involving the liver in about 50  of patients with aids and in about 25  of patients who are hiv seropositive but who are not known to have aids  the clinical impact of a diagnostic biopsy is blunted by a lack of efficacious therapy for many opportunistic infections  
class4	clinical evaluation of plasma abnormal prothrombin  des gamma carboxy prothrombin  in hepatobiliary malignancies and other diseases  des gamma carboxy prothrombin  dcp   a protein induced by vitamin k absence or antagonist ii  pivka ii  was measured in the plasma of patients with primary hepatocellular carcinoma and those with various other hepatobiliary and pancreatic diseases  dcp levels were determined by enzyme immunoassay  e 1023   using an anti dcp monoclonal antibody  forty two of the 91 patients  46 2   with hepatocellular carcinoma had abnormally elevated levels of dcp  whereas only one of the 24 patients with hepatic cirrhosis showed a slight increase  an increase was also observed in some patients with obstructive jaundice  there was no correlation between plasma levels of dcp and those of serum alpha fetoprotein  afp   in most patients with hepatocellular carcinoma  plasma dcp levels normalized after curative surgical resection  plasma dcp levels were not related to the plasma concentration of vitamin k in the patients with hepatocellular carcinoma  plasma dcp determination may be useful in the diagnosis and postoperative monitoring of the response of hepatocellular carcinoma  
class4	spontaneous rupture of hepatocellular carcinoma  a review of 172 japanese cases  the spontaneous rupture of a primary hepatocellular carcinoma  hcc  accounts for 10  mortality of hcc patients in japan  because this problem occurs much less frequently in western countries  it is often difficult for clinicians practicing in such countries to decide upon the best course of action during the crisis accompanying the spontaneous rupture of a hcc  in an effort to advance the general knowledge of this disease and clarify a selection for its treatment  we review 172 cases of spontaneous rupture of a hcc reported in the japanese literature  the chief complaint of the patients was sudden epigastralgia or right hypochondriac pain  abdominal paracentesis was positive in 86  of the patients  liver failure was the cause of death in 42  of the patients  therefore  it is important to evaluate liver reserve quickly  in addition  emergency hemostatic procedures must be implemented to avoid hemorrhagic shock  although two stage hepatectomy was performed in only 12  of the cases  these had the highest survival rates  consequently  this is the procedure of choice for the treatment of spontaneous rupture of a hcc  
class4	endoscopic placement of a foley catheter across a stricture and rectovaginal fistula to perform a barium enema  evaluation of enteric fistulas is often best performed with barium contrast studies  clinical situations that preclude the satisfactory installation of barium decrease the yield of the study  a case is presented of a 59 yr old female with stage iii b cervical carcinoma and a known rectovaginal fistula with an adjacent sigmoid colon stricture  an additional more proximal  enteric fistula was suspected  definitive preoperative knowledge of the existence or absence of this fistula would have shortened the duration of a planned palliative intervention  the rectovaginal fistula and stricture precluded adequate barium and air installation for contrast study  colonoscopy was unsuccessful  we have developed a combined technique in which the endoscopic placement of a semirigid guidewire allowed placement of a foley catheter across the fistula and stricture  successful barium study was performed  intraoperative time and hospital stay were shortened  
class4	epstein barr virus transformation of b lymphocytes from iga nephropathy patients and first degree relatives results in increased immunoglobulin synthesis not restricted to iga  in order to study b cell activation patterns independent of t cell regulation in patients with iga nephropathy  igan   peripheral blood mononuclear cells from 67 patients with igan  15 first degree relatives of patients with familial disease  and 13 normal controls were transformed with epstein barr virus  ebv   culture supernatants of these transformed cells were assayed for levels of igg  iga  and igm  and results obtained on the three populations were compared  ebv transformed cells of igan patients  as well as the population of first degree relatives  secreted significantly elevated levels of all three isotypes as compared with the normal controls  however  in comparing ratios of secreted isotypes  it was determined that more iga relative to igg and igm was synthesized by cells of these two populations as compared with the normal controls  our results imply that  1  the population of b cells susceptible to ebv activation is increased in igan patients   2  this population of  activatable  b lymphocytes is polyclonal and not restricted to the iga class  and  3  even though there may be a primary b cell abnormality in igan  an additional defect s  is probably operative in the pathogenesis  since cells of clinically unaffected relatives behaved in a pattern similar to that of patients  
class4	infiltration of the lower respiratory tract by helper inducer t lymphocytes in htlv 1 associated adult t cell leukemia lymphoma  the human t cell lymphotropic virus type 1  htlv 1  is the causative agent of adult t cell leukemia lymphoma  atll   a disorder in which peripheral blood and multiple organs are infiltrated by malignantly transformed t lymphocytes  we investigated the nature of pulmonary disease in a patient with serologic evidence of htlv 1 infection  in this case  endobronchial biopsy specimens showed infiltration of the bronchial mucosa by pleomorphic cells exhibiting a high degree of nuclear irregularity  these cells were morphologically identical in appearance to malignant cells found in peripheral blood and infiltrating the dermis  expressed the okt4 leu3 phenotype and the receptor for interleukin 2  and  by analogy to gene rearrangement studies on leukemic blood cells  were monoclonal in origin  however  in situ hybridization of endobronchial biopsy specimens with full length htlv 1 probes failed to detect retroviral rna or proviral dna  these studies indicate that t lymphocytic involvement of the lower respiratory tract in htlv 1 associated atll is characterized by expression of a malignant phenotype despite the inability to document actual cellular infection with this retrovirus by a molecular hybridization technique  
class4	aggressive primary gastrointestinal lymphomas  review of 91 patients treated with the lnh 84 regimen  a study of the groupe d etude des lymphomes agressifs  purpose  patients with aggressive primary gastrointestinal lymphoma undergoing the lnh 84 chemotherapy regimen were analyzed to determine the efficacy of intensive combination chemotherapy  the role of surgical debulking in patients treated with combination chemotherapy  and the toxicity associated with each of these modalities  patients and methods  ninety one patients with primary gastrointestinal lymphoma who participated in the prospective multicenter lnh 84 combination chemotherapy trial  total number of patients in trial  737  were analyzed  these 91 patients included 69  76   with diffuse large cell  nine  10   with diffuse mixed  and seven  8   with small noncleaved cell lymphoma  two patients  2   had stage ie  54 patients  59   stage iie  and 35 patients  38   stage iv disease  all patients with stage ie  22 with stage iie  and 18 with stage iv disease had bulky  greater than or equal to 10 cm  tumors  specific sites of gastrointestinal involvement included stomach  47    small bowel  38    ileocecum  14    colon  11    and rectum  7    although surgical resection was attempted in 71 patients  78    only 28  31   had complete tumor excision  all patients received three or four cycles of acvb  defined in text  induction therapy followed by sequential consolidation as previously described  results  responses to treatment in the 91 patients included 71  78   complete remissions  six  7   partial remissions  five  5   nonresponses  and nine  10   deaths  with a median follow up of 3 years  10 patients  14   have had relapses  predicted 4 year disease free survival of complete responders is 85  and predicted 4 year survival of the entire group is 62   in patients with stage ie or iie disease  the complete response  survival  and disease free survival rates were similar in those who underwent complete surgical resection or incomplete or no surgical resection prior to the administration of combination chemotherapy  prognostic factors predicting for survival in the 91 patients with primary gastrointestinal lymphoma were similar to those in the 646 other patients treated with the lnh 84 regimen  conclusions  patients with aggressive gastrointestinal lymphoma treated with intensive chemotherapy have outcomes and prognostic factors comparable to those of patients with similar stage aggressive lymphoma without primary gastrointestinal involvement  surgical resection prior to the administration of combination chemotherapy did not influence the complete response rate  survival rate  or disease free survival rate in this small group of patients  
class4	overexpression of her 2 neu in endometrial cancer is associated with advanced stage disease  prior studies have shown that overexpression of her 2 neu occurs in one third of breast and ovarian cancers and that overexpression is associated with poor prognosis  we used a monoclonal antibody to assess immunohistochemically the level of her 2 neu expression in normal and malignant endometrium  in 24 normal endometrial samples light to moderate  1  to 2   staining for her 2 neu was seen in the glands  and there was no variation in intensity of staining during the menstrual cycle  among 95 endometrial adenocarcinomas  nine  9   were found to have heavier staining for her 2 neu than was seen in normal endometrium  3    high expression of her 2 neu was found in 27  of patients with metastatic disease compared with 4  of patients with disease confined to the uterus  p less than 0 005   high her 2 neu expression also was associated with absence of estrogen receptor  p less than 0 005  and with increased mortality from cancer  further studies are needed to determine the significance of her 2 neu overexpression in endometrial cancer  
class4	a risk benefit analysis of elective bilateral oophorectomy  effect of changes in compliance with estrogen therapy on outcome  a bilateral oophorectomy at the time of elective hysterectomy is often performed to prevent ovarian cancer  the assumption that endogenous estrogen can be easily replaced with supplemental medication fosters the decision for routine oophorectomy  published reports on the use of postmenopausal estrogen indicate that compliance is less than perfect  this fact could affect the overall outcome  decision analysis techniques with markov cohort modeling were used to evaluate the policy of elective bilateral oophorectomy  results from studies judged methodologically sound were combined to determine values representing the influence of estrogen on coronary heart disease  breast cancer  and osteoporotic fracture  the decision tree also explicitly incorporated patient compliance  when compliance with estrogen therapy is assumed to be perfect  oophorectomy yields longer life expectancy than retaining the ovaries  when actual drug taking behavior is considered  retaining the ovaries results in longer survival  this analysis highlights the importance of including the effects of patient compliance with treatment recommendations when the impact of a health policy decision such as prophylactic surgery is assessed  
class4	human immunodeficiency virus induced immunosuppression  a risk factor for human papillomavirus infection  in a group of 92 women with genital condylomata  15  16 3   human immunodeficiency virus positive patients were found  whereas no case was detected in a control group of 100 women  the relative risk was greater than 19 28  human immunodeficiency positive status was associated with other parameters  lower age and parity  major frequency of induced abortions  and sexually transmitted diseases  thus although human immunodeficiency positive status seems to be a true risk factor in relation to the altered immunologic state  an indirect association cannot be discarded  such patients should be screened closely for human papillomavirus infection and cervical cancer  among human immunodeficiency positive women  a more resistant behavior of human papillomavirus associated lesions was detected  recurrence persistence of 41 7  versus 12    a fact that might also be in relation to the immunodepressed status  
class4	the diagnosis of ovarian cancer by pathologists  how often do diagnoses by contributing pathologists agree with a panel of gynecologic pathologists  the cancer and steroid hormone study  a multicenter  population based  case control study of ovarian  breast  and endometrial cancer in women 20 to 54 years of age  permitted the diagnoses of contributing pathologists to be compared with those of a panel of three gynecologic pathologists  a diagnosis of ovarian cancer was made by contributing pathologists on 477 subjects  agreement between the two groups of pathologists was 97  for primary epithelial ovarian cancer and 89  for primary nonepithelial ovarian malignancies  agreement on diagnosis of major cellular subtypes of ovarian malignancy ranged between 73  for endometrioid cancer and 100  for clear cell carcinomas  we conclude that the diagnosis of pathologic features of primary ovarian cancer is highly predictable  nonetheless  diagnosis by histologic type varies sufficiently that a review process should be considered for clinical or investigative decisions involving specific histologic diagnoses of ovarian cancer  
class4	dissection of the cardinal ligament in radical hysterectomy for cervical cancer with emphasis on the lateral ligament  surgical experience with carcinomas of the uterus and rectum has provided new insights into the surgical anatomy of a lamina  which separates the paravesical space from the pararectal space  it has been proved that each of the lamina consists of the cardinal and lateral ligaments and pelvic splanchnic nerves  descending in the following order  the cardinal and lateral ligaments  as a connective stalk  insert into the lateral walls of the uterus and rectum extending from the inner aspect of the pelvic wall  clarification of this structural relationship led to the development of a new procedure for the dissection of the cardinal ligament in radical hysterectomy  while still preserving the lateral ligament  this facilitated systematic dissection of the cardinal and uterosacral ligaments with posterior manipulation  leading to a reduction in blood loss and to prevention of brisk bleeding from the venous plexuses  
class4	angiosarcoma of the uterus  a case report  we are reporting a case of angiosarcoma of the uterus in which the diagnosis was confirmed ultrastructurally by demonstration of weibel palade bodies in the tumor cells  only 10 cases of this entity have been previously documented in the literature  
class4	the elusive colonic malignancy  a need for definitive preoperative localization  colonoscopy with biopsy is the standard of practice for the diagnosis of colonic malignancies  unfortunately  the inability of endoscopy to obtain precise distance measurements from the anal verge can make localization of lesions at operation difficult  for this reason  preoperative barium enema or intraoperative colonoscopy have been advocated to further pinpoint the sites of those lesions not thought to be easily located at operation  five patients are presented in whom malignant lesions of the colon were diagnosed and verified histologically  but were later undetectable at operation or subsequent colonoscopic examinations  four of these patients underwent laparotomy and three received colon resections  none of these patients  tumors were identified during intraoperative colonoscopy  in the resected bowel on pathologic examination  or on follow up colonoscopy  a fifth patient is presented who spontaneously passed a polyp containing invasive adenocarcinoma  but multiple colonoscopic examinations have failed to identify the site of the lesion  to date  none of these tumors have recurred with periods of follow up ranging from 6 months to 2 years  these patients demonstrate a poorly documented and little understood aspect of the behavior of colonic malignancies  i e   the ability to spontaneously regress or slough from the bowel wall  based on these instances  localization of potentially malignant colon lesions is recommended with submucosal dye injections at initial endoscopy or with colonoscopy in the operating room immediately prior to operation  
class4	carotid artery disease in patients with head and neck carcinoma  irradiation has been shown experimentally to cause accelerated development of atherosclerosis in exposed large arteries  however  occurrence of such an entity in carotid arteries of patients after treatment for head and neck carcinoma is unknown  therefore  we reviewed 179 patient charts who had undergone head and neck operations with or without irradiation between 1979 1987  of these 179 patients  107  59 8   were dead at time of follow up  cause of death was unknown in 42  40   patients  in the remainder included  respiratory arrest  33  carcinoma related  18  cardiac  6 pneumonia  7  and trauma  1  average interval from treatment to death was 23 5 months  of the 72 patients known to be alive  follow up was obtained in 52 patients  their average age was 64 9 years  risk factors for atherosclerosis included  male gender  43  smoking  50  hypertension  9  diabetes  4  coronary artery disease  12  and peripheral vascular disease  4  seventy five per cent of these patients received postoperative irradiation  average follow up was 64 5 months  duplex scans were performed on 34 patients  three patients had common or internal carotid stenoses greater than 75 per cent  all of these patients had received irradiation and none of them were symptomatic  seven patients had carotid stenoses between 50 to 75 per cent  five of these had received irradiation  of these five patients  one had a stroke 60 months postoperatively  and one had a tia 36 months postoperatively  the remaining 58 patients  of which 48 had irradiation  had carotid stenoses less than 50 per cent and none were symptomatic  
class4	the pathology of nonpalpable breast cancer  a principal goal of mammographic screening is the early detection of breast cancer  we reviewed records of 125 women who were referred because of nonpalpable  suspicious abnormalities on mammogram  which subsequently proved to be cancer  requiring mammographic localization biopsy and subsequent surgery for therapy  we found that 72  57 6   had invasive tumors  15  12   showed evidence of microinvasion and 38  30 4   were noninvasive  a total of 115 patients had lymphadenectomy as part of their definitive surgery  nine  12 7   of the patients with infiltrating tumors had between one and 10 malignant nodes on histologic section  none of the patients with noninvasive or microinvasive tumors were found to have involved nodes  the mammographic abnormalities which led to biopsy in our series were  calcifications in 74  59 2   patients  mass lesions in 39  31 2    mass lesions with calcifications in 11  8 8    and asymmetry in one  0 8    of the nine patients with nodal metastases  seven  77 8   had a mass with or without calcifications as the indication for biopsy  increasing tumor size was found to correlate with invasive tumors on histopathologic examination and the incidence of lymph node metastases  thirty seven  54 4   of the patients with infiltrating tumors had a tumor size greater than 1 cm  further  seven  77 8   of the nine lymph node positive patients had tumors between 1 and 3 cm in size  of note  however  is that two  22 2   patients with microscopic tumors had involved nodes  the 4 year actuarial survival in patients with infiltrating tumors was 85 2 per cent  while that for patients with noninvasive or microinvasive tumors was 100 per cent  median follow up of 20 months   
class4	intravenous administration of recombinant human granulocyte macrophage colony stimulating factor causes a cutaneous eruption the intravenous administration of recombinant human granulocyte macrophage colony stimulating factor to three patients with leukemia who were receiving marrow aplasia inducing chemotherapy resulted in the development of wide spread erythematous macules and papules  the course of the eruption paralleled the time of infusion of the granulocyte macrophage colony stimulating factor  skin biopsy specimens taken from two of the eruptions displayed characteristic changes consisting of a variable mixture of granulocytes and lymphocytes  increased number and size of dermal macrophages  mild to moderate epidermal exocytosis  intercellular edema  and rare dyskeratotic keratinocytes  immunophenotypic analysis of one specimen was notable for keratinocyte intercellular adhesion molecule 1 expression  administration of the recombinant human cytokine in pharmacologic doses is postulated to induce changes in the immunologic status of the skin  resulting in the expression of a cutaneous eruption  
class4	intraepithelial anchoring fibril components  cultured human keratinocytes and cultured human cervical carcinoma cells  me 180  contained intracellular pools of antigens that reacted with the anchoring fibril antibodies af1 and af2  in keratinocytes  these antigens formed a basement membrane like structure near the apical portions of the cells  using flow cytometric techniques  pretreatment of the me 180 cells with acetone revealed large intracellular pools of antigen  the intracellular epitope was calcium sensitive  some forms of recessive dystrophic epidermolysis bullosa have retention of intracellular portions of the anchoring fibril suggesting a relation of the intracellular anchoring fibril antigens to that disease  
class4	cutaneous manifestations of multiple myeloma  we report the cutaneous manifestations of multiple myeloma  using a retrospective review of 115 patients  records obtained from tumor registry files  five patients were found to have biopsy proved extramedullary plasmacytomas without extension from an underlying bony focus  twelve patients had ecchymoses without thrombocytopenia  two of them had biopsy proved amyloidosis  one patient presented with pyoderma gangrenosum and was subsequently diagnosed with multiple myeloma  the last patient initially presented with what clinically appeared to be leukocytoclastic vasculitis  and  in the course of a standard workup  he was diagnosed with multiple myeloma  these findings are discussed with regard to the current literature on the cutaneous manifestations of multiple myeloma  
class4	familial multiple desmoplastic trichoepitheliomas  a kindred with familial multiple desmoplastic trichoepitheliomas is described  desmoplastic trichoepitheliomas should be added to the group of lesions that indicate an inherited pattern when they occur as multiple primary tumors  the implications for nosologic status and treatment of desmoplastic trichoepitheliomas are considered  
class4	in vivo ultraviolet irradiation of human skin results in profound perturbation of the immune system  relevance to ultraviolet induced skin cancer  published erratum appears in arch dermatol 1991 sep 127 9  1368  ultraviolet exposure of human skin deletes the function of antigen presenting langerhans cells normally resident within the epidermis  langerhans cells are capable of activating t lymphocytes by presenting antigens  such as nickel or tumor antigens  to t lymphocytes  such activated t lymphocytes may be involved in the development of contact dermatitis and the immune surveillance of immunogenic skin cancers  deletion of the function of langerhans cells does not result in abrogated epidermal antigen presentation since ultraviolet irradiation simultaneously induces the appearance of another epidermal antigen presenting cell population that is distinct from the langerhans cell population and seems to induce suppression of the immune response  suppression of the immune response following ultraviolet irradiation in murine models is critical for growth of immunogenic ultraviolet induced skin neoplasm  thus  ultraviolet irradiation of human skin may facilitate the growth of human neoplasms  and the spreading of skin associated infections due to induction of suppressor t cells  
class4	acquired von willebrand s syndrome  therapeutic and diagnostic implications  acquired von willebrand s syndrome is a newly recognized bleeding diathesis thought to be caused by autoantibodies to the von willebrand factor  acquired von willebrand s syndrome has been reported in association with lymphoproliferative disorders and benign monoclonal gammopathies  clinical features and laboratory abnormalities of this disease are similar to congenital von willebrand s disease  but the optimal treatment may differ  we describe a 75 year old man with chronic lymphocytic leukemia and recurrent epistaxis and also discuss the pathogenesis  diagnosis  and treatment of both the congenital and acquired disorders  
class4	cervical rotation flaps for midface resurfacing  the midface has long served as a focus for creativity in surgical reconstruction  full thickness skin grafts  split thickness grafts  and distal flaps have long been used to attempt to reduplicate existing anatomy in this area  recent reconstruction efforts have focused on the creative use of microvascular free flaps for this purpose  this article reports on the use of extensively developed regional rotation flaps as an excellent reconstructive modality for use in this area of the face  the details of surgical incisional planning are given  the nuances of surgical creation of these flaps and their rotation and suspension into place are given  the cases we have done using this technique for the past 3 years are reviewed  our present indications for use of these flaps and their limitations are given  
class4	drug response of head and neck tumors in native state histoculture  we describe a chemosensitivity testing of head and neck tumors  in which a native state histoculture  ie  a three dimensional culture system that maintains important in vivo properties  including tissue architecture  was used  fifteen specimens of head and neck tumors were evaluated for sensitivity to the following drugs  cisplatin  ddp  at concentrations of 1 5  15  and 37 5 micrograms ml  fluorouracil at concentrations of 4 0  40  and 100 micrograms ml  and combinations of cisplatin and fluorouracil in corresponding doses  growth and measurement of drug responses were successfully completed in 10 specimens  five others were contaminated  four of them prior to instituting rigorous antibiotic washes   the results indicated cisplatin sensitivity in five of 10 patients  fluorouracil sensitivity in four of 10 patients  and fluorouracil cisplatin sensitivity in seven of eight patients  our preliminary results indicate that the native state histoculture technique is feasible to test chemosensitivity of head and neck tumors  
class4	ultrasonic morphology of the uterus and ovaries after treatment of invasive mole and gestational choriocarcinoma  ultrasound imaging of the uterus and ovaries was performed on 41 patients after completion of apparently successful cytotoxic chemotherapy for invasive mole and choriocarcinoma  uterine volume was calculated and the echopattern of the uterus and ovaries assessed  forty nine per cent of subjects had an abnormal uterine appearance and 20  had ovarian theca lutein cysts  two patients relapsed on follow up but no predictive ultrasonic features could be established on uterine or ovarian morphology after chemotherapy  
class4	progress and challenges in psychosocial and behavioral research in cancer in the twentieth century  research in the psychosocial and behavioral aspects of cancer has shown steady growth since the 1950s  and its course of development has paralleled the history of medical techniques in treating cancer  table 1 outlines this parallel evolution from the 1850s to the 1960s  the roles of the american cancer society and the national cancer institute  nci  in spearheading and nurturing research in this area are documented  interest in psychooncologic questions can be traced back for centuries to the search for etiologic factors and psychologic variables that would explain individual vulnerability to cancer  the first psychologic studies of cancer patients were reported in 1951 and 1952 from the massachusetts general hospital and memorial sloan kettering cancer center  respectively  the 1970s saw new interest in psychosocial and behavioral research with many issues being addressed for the first time  better care of the terminally ill through more humanistic approaches including better means of pain control  ethical concerns related to patient rights and their status as subjects in experimental protocols  trying to measure quality of life for cancer patients on protocols  seeing the need for multidisciplinary collaborative groups to make up for the absence of formal training in this area  and the need to design valid  accurate measuring scales specific to the symptomology of patients with cancer  table 4 outlines how the 1980s gave increasing recognition and support to the psychosocial dimensions of cancer  this period produced a series of key conferences that examined a broad research and education perspective and produced recommendations that remain a benchmark in regard to instrumentation  conceptual models  pitfalls of psychosocial research  training  and education  and the organization of research efforts  new precision has been added to the field in the past 6 years  studies measuring concurrent psychologic  endocrine  and immune function  use of statistical modeling to incorporate quality of life data as a correction factor in survival data  twist and qaly   and broadened definitions of medical outcome to include functional status  thus allowing advances in psychiatric measurements to help answer questions in cancer  the challenges for the 1990s are identified in a summary in table 9  especially noteworthy is the observation that the comprehensive research needed today cannot be carried out by any one discipline alone  new approaches call for areas of the social sciences formerly inactive in cancer research  e g   anthropology  to contribute the tools and expertise required to address the problems  
class4	advances in data assessment  application to the etiology of nausea reported during chemotherapy  concerns about significance testing  and opportunities in clinical trials  typical inferential statistical procedures  such as the t test and analysis of variance  compare differences in mean values of variables  this approach can sometimes obscure rather than illuminate research data  here we present and discuss alternative data analytic techniques  potential advantages of box plots over conventional t tests for understanding data are shown by comparing the area under high and low frequencies from spectral curves of autonomic changes following chemotherapy treatment  typical t tests provide information regarding statistical significance in terms of the differences in group means  box plots and related exploratory techniques provide information regarding the characteristics of the distributions within the groups as well as examination of potential outliers  multivariate analysis of variance  manova  and other multivariate techniques are commonly used to deal with potentially complex data sets with multiple outcome measures  the potential advantages of visual clustering techniques such as star plots  chernoff faces  and andrew s function plots are demonstrated by examining changes in facial pallor caused by chemotherapy induced nausea and vomiting  typical manova approaches can identify potential differences in mean values between groups  visual clustering approaches do this by graphically presenting complex interrelationships for individual cases  this approach enhances the visual interpretation of potential interactions that would be obscured by simply focusing on overall mean values  preliminary data from a meta analysis on the effect of metoclopramide on chemotherapy induced vomiting demonstrates the potential uses and advantages of this summary technique over simple tabular summaries  we found significant relationships between the effect size of the drug and variables such as the year of study publication and whether the publication was an article or an abstract  while none of these techniques are meant to replace traditional inferential statistics  they offer advantages in terms of data exploration and understanding relationships within data sets that are not clearly addressed by other methods  they are potentially valuable alternatives worthy of exploration  finally  we discuss issues of interim analyses and multiple endpoint assessment for clinical trials  
class4	social environment and social support  research on the relevance of social support to cancer has been plentiful since the first american cancer society workshop on methodological issues in behavioral and psychosocial science  nonetheless  critical shortcomings continue to characterize the attempt empirically to establish such things as the extent to which social support predicts adjustment to cancer diagnosis and treatment  prominent among these is the failure to adequately address large elements of the social structure  such as social class and urbanization  and to investigate how they shape the well being of persons with or at risk for cancer and their caregivers  we recommend that more psychosocial research on the link between social support and cancer be conducted within populations beset by poverty and without adequate access to health care  funding is needed for the training and maintenance of multidisciplinary and multicultural teams of researchers working within community based organizations and hospitals serving the underserved  
class4	social support and the cancer patient  implications for future research and clinical care  this review assesses past progress  current practices  and future needs in research and clinical practice involving the social support needs of cancer patients  a review is given of the various conceptualizations of the social support stress paradigm and of the state of the art of measuring social support  then the current work in the field of social support and cancer is considered and an argument is made for the use of social support measures  which are relevant to the experiences of the cancer patient  potential adaptations of an existing instrument  the duke unc functional social support scale  are demonstrated  and a taxonomy of stages of cancer that would require additional types of social support measures and interventions is outlined  interventions are discussed in terms of the traditional support groups as well as interventions by the oncologist and primary care physician  an argument is made for the inclusion of quality of life or functional measures as outcomes in clinical trials and the care of the cancer patient  finally  the need to address the existential  philosophic  or religious issues surrounding cancer and its treatment is discussed  
class4	needs and recommendations for behavior research in the prevention and early detection of cancer  because life style patterns affect many cancer risks  research on health risk behavior and behavior change is critical to cancer prevention  this report recommends priorities for the next decade of psychosocial research on cancer prevention and detection  the leading priority for future research is to fill gaps in basic knowledge left by the rush to intervention and outcome studies  such research must be theoretically driven and should aim to develop broad principles applicable to diverse health behaviors  studies that include relevant process data on various stages of behavior change are considered more desirable than simple outcome studies  epidemiologic investigations should be expanded to include measures of relevant behaviors  so that their impact on clinical outcomes might be established  more research is needed on lay perception of health risks and on individual and health system barriers to effective cancer prevention and detection  studies that address the needs of minority and underprivileged populations are crucial  funding agencies  narrow categorical mandates impede interdisciplinary research on multiple risk factors and their interactions  these boundaries must be relaxed to promote such approaches  funding agencies should also consider basic research as a long term investment towards the development of effective interventions  
class4	epidemiologic perspectives on life style modification and health promotion in cancer research  the clinical  patient oriented focus of medicine and psychology is contrasted with the epidemiologic  public health  approach in assessing the role of life style factors and health promotion in cancer research  the unifying host agent environment epidemiologic paradigm is applied to contemporary cancer prevention issues  principally smoking cessation and dietary modification  to demonstrate differences in inferences  prevention strategies  and research opportunities  an integration of population based approaches with the dynamics of patient behavior and risks for cancer is especially salient when considering the role of psychosocial stress and personal and social resources  the social epidemiologic perspective  the study of the psychosocial determinants of physical health status  offers one approach for resolving the outlined differences in perspectives and is particularly relevant for understanding the etiology of life style behaviors and how they might be altered  
class4	physiologic and psychobehavioral research in oncology  a major thrust in research in psychosocial oncology is the study of the interaction of psychologic and physiologic variables  this discussion reviews the current status and future directions of such research  areas addressed include pain  nausea and vomiting with chemotherapy  sexuality  effects of cancer on psychologic and neuropsychologic function  impact of psychologic factors on cancer and its treatment  and psychoneuroimmunology  in addition  specific recommendations for strategies to facilitate research in these areas of psychosocial oncology are proposed  
class4	psychoneuroimmunology  implications for oncology  accumulating evidence indicates that the central nervous system  cns  may regulate the activity of the immune system  although the overall significance of the immune system in cancer remains controversial  psychosocial influences on immune function could potentially provide a mechanism to account for some of the reports of an association between psychosocial factors and cancer prognosis  
class4	scientific inquiry in childhood cancer psychosocial research  theoretical  conceptual  and methodologic issues in the investigation and behavioral treatment of procedure related distress  this paper discusses the current status of scientific inquiry in childhood cancer psychosocial research  the investigation and behavioral treatment of procedure related distress serves as a model for illustrating and outlining some of the theoretical  conceptual  and methodologic issues and problems that exist in the area of childhood cancer psychosocial research  specifically  issues related to the process of scientific inquiry  theoretical conceptual modeling  measurement and assessment  and behavioral treatment strategies are discussed  examples of how these issues have been addressed in our investigations of procedure related distress are presented and recommendations for facilitating growth and development in the field of childhood cancer psychosocial research are offered  
class4	quality of life research in oncology  past achievements and future priorities  the status of quality of life research in oncology is assessed  and priorities for future research with regard to conceptual and theoretical developments  focus and content of research  research designs and practical strategies for research implementation  and transferring information to clinical practice and medical policy decision making are identified  there is general agreement that quality of life is a subjective and multidimensional construct  yet comprehensive theoretical models have not been developed and applied fully  we recommend that future research be based on conceptual models that explicate the interrelationships among quality of life domains throughout the stages of cancer care  these models  and the longitudinal research that follows from them  should attend specifically to cross class and cross cultural issues to avoid overgeneralization from theory and research that are based largely on the views of the majority culture  we encourage the inclusion of this theory based quality of life assessment as a standard component of clinical trials  success in this endeavor will require additional standardization of quality of life measures for use across a range of cancer patient populations  including the development of age specific norms and instruments designed to assess the entire family system  
class4	methodologic issues in assessing the quality of life of cancer patients  although quality of life assessments have been employed successfully in descriptive and evaluative studies in oncology  their use in cancer clinical trials has  to date  been limited  a range of issues have impeded the conduct of clinical trial based quality of life investigations  these include  the absence of theoretical models to guide the development of quality of life measures  over reliance on ad hoc approaches to quality of life assessment  and insufficient attention to the practical constraints operating in clinical research settings  of primary importance is the need to develop multidimensional quality of life instruments that are brief and psychometrically robust  it is suggested that future work on instrument development focus on refining currently available generic or cancer specific measures  and on developing new diagnostic specific questionnaire modules  this psychometric work should be guided by appropriate theoretical models of the relationship among health related quality of life domains  although it is widely accepted that the patient represents the most appropriate source of quality of life data  it is suggested that efforts also be directed toward improving the validity and reliability of physician generated assessments of patients  performance status and of treatment toxicities  and toward determining the feasibility of employing family members as proxy raters of the psychologic and social health status of patients who are unwilling or unable to provide such information  additional attention should be paid to the many logistical problems that arise in clinical trial based quality of life investigations  in particular  research designs and data collection procedures should be selected that minimize patient  medical staff  and institutional burden  
class4	quality of life adjusted survival for comparing cancer treatments  a commentary on twist and q twist  in chronic disease situations where treatment comparisons favor no particular therapy  or where definitive outcome requires a considerable follow up period  it is useful to have additional and perhaps intermediate endpoints of relevant clinical significance to compare treatments  one such endpoint is time without symptoms and toxicity  twist  which  together with q twist  attempts to address the quality of life of patients receiving the competing regimens  this paper provides a commentary on these techniques with an emphasis on the problems inherent in implementing q twist  a measure that attempts to incorporate patient value preferences into twist  it is argued that while q twist is intuitively appealing in the clinical setting  there are formidable design and psychometric hurdles that must be overcome to fully operationalize the concept  
class4	progress in psychosocial and behavioral cancer research  the need for enabling strategies  a major component of the second workshop on methodology in behavioral and psychosocial cancer research was a discussion of enabling strategies  that is  strategies by which future goals and needs in the area of psychosocial and behavioral oncology might be accomplished  this report describes and comments on the discussion that took place at a special plenary session at which representatives from four funding agencies  the american cancer society  national cancer institute  national institute of mental health  and national science foundation  presented their views and their agencies  programs for promoting research in psychosocial and behavioral oncology  it is concluded that much progress has been made in the field and that strategies are in place for ensuring continued progress  however  suggestions are also made for new strategies that might accelerate and broaden that progress  
class4	behavioral and psychosocial cancer research  building on the past  preparing for the future  this report identifies five general conclusions that emerged from the second workshop on methodology in behavioral and psychosocial cancer research  these conclusions address diverse topics  including a focus on areas other than methodology  an emphasis on the transfer of technology and knowledge to applied settings  a recognition of the role of basic behavioral research in answering clinical questions  the need to recognize and strengthen ties between the field of behavioral and psychosocial oncology and the basic behavioral and social science fields from which it emerged  and the importance of additional research on minorities and other special populations  it is suggested that meeting the challenges posed in each of these five areas is critical to continued progress in the field  
class4	update  prostate cancer  prostate cancer represents a major health care issue for older men  recent technical advances in imaging  serum markers  and treatment hold great promise  further insight into the natural history and biologic potential of this ubiquitous neoplasm is necessary before we can make rational decisions about early detection and newer treatment approaches  
class4	polycystic ovary syndrome  polycystic ovary syndrome is a disorder of unknown cause characterized by anovulation  hyperandrogenism  and gonadotropin secretory abnormalities producing oligo ovulation or anovulation  hyperinsulinemia and insulin resistance are important features of this syndrome  because other causes of androgen excess may produce similar clinical and biochemical findings  pco remains a diagnosis of exclusion  treatment is directed toward relieving symptoms of hyperandrogenemia in order to stimulate ovulation  correcting obesity  and inducing regular menses to reduce the risk of endometrial cancer  
class4	risk factors for breast cancer  despite the numerous risk factors for the development of breast cancer that have been investigated  only a few demonstrate a clear association with breast cancer development  female gender and increasing age are the most important factors  followed by factors involving a woman s menstrual  reproductive  and family history  the risks related to menstruation and reproduction are probably related to the duration of estrogenic breast stimulation  the relationship of family history and breast cancer risk is unclear  but there may be a true genetic basis  the previous occurrence of breast cancer  invasive or in situ   the presence of proliferative pathological changes  especially with atypia  and the presence of other malignancies  e g   primary ovarian and endometrial cancer  are histological risk factors for the development of new or recurrent breast cancer  radiation exposure  the use of exogenous estrogens  both estrogen replacement therapy and oral contraceptives   diet  especially fat consumption   and alcohol intake may all play a role in cancer risk  certain medications as well as patient demographics may also have a weak association  cigarette smoking  caffeine consumption  and stress presently have little support for an association with breast cancer risk  it should be noted that in only one in four patients can breast cancer be accounted for by the known risk factors  this demonstrates that although presently known risk factors may help in screening for the early detection of breast carcinoma  in its possible prevention by modulation of influenceable factors  and in advising patients about their risks  these factors are merely strong associations with breast cancer incidence and not actual causations  the mechanisms of the development of breast cancer are as yet unknown  
class4	fertility sparing treatment of patients with ovarian cancer  the variety of malignant neoplasms produced by the ovary are legion  each must be considered individually in the young woman with early disease who wishes to preserve her childbearing capability  the risks of conservative surgery are often low  and the patient can be so advised  careful monitoring of this group of patients is essential regardless of the approach  
class4	chromogranin a  posttranslational modifications in secretory granules  the primary structure of chromogranin a indicates multiple domains which might be subject to posttranslational modification  we explored chromogranin a s proteolytic cleavage  glycosylation  and possible intermolecular disulfide links  using biochemical and cell biological approaches  anti chromogranin a region specific immunoblots on chromaffin granules suggested bidirectional endoproteolytic cleavage of chromogranin a  control experiments ruled out artifactual cleavage during granule isolation or lysis  isolation of chromogranin a derived peptides by gel filtration chromatography or sodium dodecyl sulfate polyacrylamide gel electrophoresis  sds page   followed by n terminal amino acid sequencing  established several cleavage sites  including at least two at dibasic sites  secretion of chromogranin a from bovine chromaffin cells did not initiate further cleavage  nor did prolonged exposure of secreted chromogranins to the secretory cells  the chromogranin a cleavage pattern was qualitatively similar in other neuroendocrine tissues  though cleavage was more complete in adrenal medullary than in anterior pituitary hormone storage vesicles  and n terminal fragments of 45 and 55 kilodaltons were more prominent in the hypothalamus  a similar cleavage pattern was seen in human pheochromocytoma granules  as judged by chromogranin a region specific immunoblots  fragment isolation by sds page  and microsequencing  the presence of full length chromogranin a as the core protein of a chromaffin granule soluble proteoglycan was suggested in bovine  but not human  chromaffin granules by glycoprotein staining  chondroitinase abc digestion  chemical deglycosylation  and region specific immunoblotting  human  but not bovine  chromogranin a displayed intermolecular disulfide crosslinks on sds page gels and immunoblotting  these results document diverse structural paths that the chromogranin a molecule may take in endocrine secretory cells after its translation  
class4	comparison of frtl 5 cell growth in vitro with that of xenotransplanted cells and the thyroid of the recipient mouse  the present work was designed to compare in vitro cell growth kinetics with in vivo growth under conditions as similar as possible using labeling with  3h thymidine  to this purpose  frtl 5 cells were cultured as monolayers and as three dimensional spheroids embedded in collagen gels and transplanted simultaneously into nude mice treated with perchlorate and a low iodine diet  the growth of the transplants was compared to that of the thyroids in host mice  in the intact thyroid  the fraction of  3h thymidine labeled follicular cells  flc  24 h labeling  increased sluggishly to a maximum of 10  after 3 weeks of goitrogen exposure  with a subsequent autoregulatory decrease to 3  at 7 weeks  a 4 fold higher flc was found in six adenomas  indicating focal failure of growth restraining mechanisms  in nonconfluent monolayer cultures the flc was as high as 90   even within large individual clusters where cells are in tight mutual contact  solid  highly cellular grafts growing from transplanted monodispersed cells showed an average flc of 20   which is 5 times higher than the flc in the identically stimulated mouse thyroid  in collagen embedded cells  forming three dimensional spheroids  the mean flc decreased from 70  at 1 week in vitro  40  in vivo  to 20  at 3 weeks both in vitro and in vivo  suggesting effective auto regulation of excessive growth in both conditions  however  these flc were again much higher than the 3  flc in simultaneously assessed host thyroids  the difference remained throughout the 45 day period studied  we conclude that frtl 5 cells growing as monolayers and as three dimensional spheroids in vitro or after xenotransplantation in vivo invariably show much higher proliferation rates under comparable environmental conditions than the normal follicular epithelium in the thyroids of host mice  the one exception is the confluent monolayer with near zero growth  while densely packed three dimensional transplants still grow intensively  although growth retarding cell to cell interactions are also clearly operative in growing frtl 5 cells  they are less effective than those dampening the replication rate of the thyrocytes within the monolayer hull of normal follicles  a local failure of these mechanisms  allowing growth rates comparable to those of grafted frtl 5 cells results in adenoma formation in normal thyroids  these observations call for caution in the transfer of in vitro growth studies with frtl 5 cells to in vivo conditions prevailing in the normal thyroid  
class4	regulation of pancreastatin release from a human pancreatic carcinoid cell line in vitro  the objective of these experiments was to investigate the influence of activation of three second messenger systems  protein kinase c  adenylate cyclase camp  and calcium mobilization  on the secretion of pancreastatin  pst  and chromogranin a  cga  by a human pancreatic carcinoid cell line  bon  in tissue culture  stimulation of protein kinase c by a phorbol ester  0 025 7 5 microm  caused a significant dose related release of pst  186     22 4271     228  over controls   treatment of bon cells with graded doses of 8 bromo camp  0 14 3 0 mm  and isobutylmethylxanthine  ibmx  0 01 1 0 mm  also stimulated a dose related release of pst  107     22 284     28 and 16     12 1076     100  over controls  respectively   incubation of bon cells with ionomycin  0 134 13 4 microm  increased the release of pst  102     15 554     21  over controls  in a dose related manner  a combination of ibmx and ionomycin resulted in an additive effect  whereas treatment with a phorbol ester plus ibmx resulted in a synergistic effect on pst release  pretreatment of bon cells with monensin  an agent that prevents processing of precursors to smaller peptides  significantly decreased pst  but not cga  secretion in response to phorbol ester or ionomycin  these findings indicate that protein kinase c  camp  and ca2  mobilization participate in cga and pst secretion  although the observation that secretions of pst and cga in response to theophylline are quantitatively associated  the absence of a quantitative relationship in the release patterns of pst and cga in response to phorbol ester and ionomycin do not support a simple precursor product relationship between cga and pst  the monensin experiments are consistent with the notion that pst is derived from cga in bon cells  
class4	the gonadotropin releasing hormone associated peptide reduces calcium entry in prolactin secreting cells  the precursor molecule to the gnrh contains a peptide named gnrh associated peptide  gap  with prl inhibiting properties  in this work  we have studied the electrophysiological properties and responses to gap of three different types of prl secreting cells  1  the rat tumor cell line gh3  2  normal rat pituitary cells in primary culture  and 3  human prl secreting adenoma cells  using different but complementary techniques we show that gap reduces intracellular ca   levels   ca   i  and inhibits ca   transients in these cells  this reduction of  ca   i results from coordinate actions of gap on k  and ca   conductances and may explain the inhibitory effect of gap on hormonal secretion by prl secreting cells  
class4	regulation of the truncation of luteinizing hormone receptors at the plasma membrane is different in rat and mouse leydig cells  regulation of the truncation of lh receptors was investigated in two types of mouse tumor leydig cells  ma10 and mltc 1   rat testis leydig cells  rtl   and a rat tumor leydig cell  r2c   receptor numbers were measured by binding  125i hcg to the cells cultured in monolayers  addition of 3 3 nm lh for 2 h at 34 c had no detectable effect on binding sites in rtl or r2c cells  but in ma10 and mltc 1 cells it caused a loss in binding sites  the effect on ma10 and mltc 1 cells could be mimicked by inhibiting receptor internalization with 5 mm nan3 and prevented by the addition of protease inhibitors  incubating rtl and r2c cells with protease inhibitors caused a 2  to 3 fold increase in binding sites and a 2  to 3 fold increase in lh  0 033 and 0 33 nm  stimulated camp production  when rtl and ma10 cells were incubated in the presence of  125i hcg  a radioactive protein complex with an approximate mol wt of 80 000 90 000 was released into the incubation medium  we conclude that lh receptors are regulated by proteolysis at the plasma membrane in both mouse and rat leydig cells  furthermore  truncation of the lh receptor in the mouse leydig cells is involved in down regulation  whereas in the rat it is a continuous process  
class4	single cell levels of hypothalamic messenger ribonucleic acid encoding luteinizing hormone releasing hormone in intact  castrated  and hyperprolactinemic male rats  we have examined the changes that occur in neuronal expression of lhrh mrna in response to castration and hyperprolactinemia in male rats  single cell levels of lhrh mrna were determined by quantitative in situ hybridization histochemistry using an 35s labeled synthetic 48 base oligodeoxynucleotide probe and quantitative autoradiography  nine days postcastration  a 10 4 fold increase in mean plasma lh titers was observed which was associated with significantly increased lhrh mrna in rostral hypothalamic neuronal cell bodies  both increases were blocked in rats rendered hyperprolactinemic by the presence of the 7315a prl secreting pituitary tumor  the location and number of neurons expressing lhrh mrna were unchanged  indicating that these differences were attributable to amounts of mrna expressed per neuron  experimental differences occurred in lhrh perikarya situated throughout the rostral hypothalamus from the organum vasculosum of the lamina terminalis to the caudal extent of the medial preoptic nucleus  these results suggest that gonadal steroids and prl are involved  either directly or indirectly  in regulating the biosynthesis of lhrh in the rostral hypothalamus  
class4	breast cancer screening in older women  practices and barriers reported by primary care physicians  annual mammography  in combination with clinical breast examinations  can reduce mortality from breast cancer  however  surveys of both patients and physicians suggest that mammography is underutilized  this study examined whether physicians  reported breast cancer screening practices and barriers to mammography varied with patients  age  data from 576 primary care physicians  internal medicine  family general practice  and obstetrics gynecology  who participated in a mailed statewide survey were analyzed  physicians reported screening elderly women significantly less often than younger women  regardless of family history of breast cancer  with the exception of medical specialty  physicians  demographic and practice characteristics were not associated with reported screening practices  however  physicians  knowledge and beliefs about breast cancer in older women were associated with reported screening practices  when analyzing barriers to ordering mammography  cost to the patient was viewed as a barrier for women of all ages  and pain was viewed as a greater barrier for younger women  otherwise  physicians consistently believed that their elderly patients faced considerably more barriers compared with younger women  further investigation is required to examine why primary care physicians report age related differences in both breast screening and barriers to mammography  
class4	the role of tumor derived cytokines on the immune system of mice bearing a mammary adenocarcinoma  i  induction of regulatory macrophages in normal mice by the in vivo administration of rgm csf  using a dimethylbenzanthracene induced immunogenic nonmetastatic murine mammary adenocarcinoma in balb c mice  our previous work has shown that splenocytes from tumor bearers have reduced responses to both mitogens and ag including tumor associated ag  nk and cytotoxic t cell activities are also reduced in splenocytes of tumor bearers  mac 1 2  macrophages induced in mammary tumor bearers are capable of down regulating lymphocyte responses to mitogens and tumor associated ag by cell to cell contact interaction and increased pge2 production  we have found that the tumor constitutively releases a granulocyte macrophage  gm  csf like factor in vivo and in vitro  which may be responsible for the systemic increase in cells of the macrophage lineage in tumor bearing mice  a tumor cell line established from the in vivo tumor expresses and releases gm csf as shown by northern and western blot analyses  daily i p  injections for 3 wk of 10 000 u of rgm csf into normal mice induces hemopoietic and immunologic alterations similar to those observed in tumor bearers  mac 1  and or mac 2  macrophages can also be detected in the spleens and bone marrow of the mice treated with rgm csf  additionally  splenocytes from rgm csf treated mice have reduced responses to mitogens and their peritoneal exudate cells can cause in vitro down regulation of proliferative responses of lymphocytes from normal mice  the suppression can be partially reversed by the addition of indomethacin to the cultures suggesting that pge2 may contribute to the effect  rgm csf enhances the in vitro release of pge2 by the spleen  bone marrow  and peritoneal cells of normal mice  these data indicate that the high levels of gm csf constitutively produced by the tumor may be responsible for the hemopoietic changes and immunologic alterations observed in tumor bearing mice  
class4	insulin like growth factors are mitogenic for human keratinocytes and a squamous cell carcinoma  normal adult human keratinocytes in monolayer culture and scl 1  a skin derived squamous cell carcinoma cell line  were investigated for the expression of receptors for insulin like growth factors  igf  and insulin  as demonstrated by affinity crosslinking  radiolabeled igf 1  igf 2  and insulin bound specifically to both cell types  each cell expressed type i igf receptors  with affinity for igf 1 greater than igf 2 much greater than insulin  insulin receptors  with highest affinity for insulin  were also present on both cells  however  keratinocytes and scl 1 cells differed in 125i igf 2 binding  125i igf 2 bound to both type i and type ii igf receptors in normal keratinocytes  but bound predominantly to membrane associated igf binding proteins in scl 1  igf 1 was slightly more potent than igf 2 in stimulating growth of both keratinocytes and scl 1 cells  in keratinocytes  concentrations of igf 1 ranging from 5 100 ng ml  and of igf 2 from 50 100 ng ml  resulted in a significant increase in cell number  at the maximum dose of 100 ng ml  either igf 1 or igf 2 caused a 2 3 times increase in cell number  in scl 1 cells  igf 1 was more potent than igf 2 or insulin at lower concentrations  but either igf 1 or igf 2 at the maximal concentration of 333 ng ml stimulated a 4 7 times increase in thymidine incorporation  the stimulatory effect of insulin in scl 1 was 10 50 times less potent than that of the igf  the effect of either igf on scl 1 was completely inhibited by the type i igf receptor antibody alpha ir 3  suggesting that both igfs are mitogenic through the type i igf receptor  insulin action was partially blocked by alpha ir 3  suggesting that insulin can act through both the insulin and type i igf receptors  it thus appears that igf 1 and igf 2 are mitogens for normal and transformed human keratinocytes and that their actions are primarily mediated through the type i igf receptor  whereas insulin is a mitogen through both the igf 1 receptor and the insulin receptor  
class4	inositol phosphate formation in the human squamous cell carcinoma line scc 12 f  studies with bradykinin  the calcium ionophore a23187  and sodium fluoride  the phospholipase c  plc  mediated hydrolysis of membrane phosphoinositides is an important signal transduction pathway coupled to the cell surface receptors for several hormones and growth factors  in addition  plc activity can be modulated by changes in intracellular calcium and activation of gtp binding proteins  in this report  differential activation of plc in the human keratinocyte cell line scc 12f was studied as judged by specific patterns of inositol phosphate formation  several hormones and growth factors previously shown to stimulate plc in a variety of cell types were screened for activity in scc 12f cells  only bradykinin was active  stimulating the plc dependent generation of inositol  1 4 5  triphosphate  ins 1 4 5 p3   ins 1 4 5 p3 was rapidly metabolized to inositol 1 4 biphosphate  ins 1 4 p2  and inositol 1 3 4 5 tetrakisphosphate  ins 1 3 4 5 p4   and subsequently degraded to inositol monophosphates  the response elicited by bradykinin was concentration dependent  ec50 value of 50 nm   suggesting involvement of a specific bradykinin receptor  treatment of these cells with the calcium ionophore a23187 appeared to result in the direct formation of ins 1 4 p2 without ins 1 4 5 p3 as precursor  treatment of the cells with aif4   a putative activator of gtp binding proteins  resulted in the generation of inositol monophosphates as the major metabolites in the absence of detectable ins 1 4 5 p3 formation  taken together  these observations suggest that the plc complex present in scc 12f cells can be differentially activated to yield either ins 1 4 5 p3  ins 1 4 p2  or insp  the observed effects may be due to a direct plc dependent hydrolysis of the appropriate membrane phosphoinositide  
class4	a clonal cd4 positive t cell line established from the blood of a patient with sezary syndrome  the reported inability to establish long term t cell lines from the blood of cutaneous t cell lymphoma patients with circulating neoplastic t cells has hindered the development of an in vitro system to investigate sezary syndrome  we have established a rapidly proliferating t cell line from the peripheral blood of a patient with sezary syndrome  which expresses a mature helper t cell phenotype and contains cytogenetic abnormalities and t cell receptor gene rearrangements identical to those in the patient s blood  the method of establishment and characteristics of this line are described  
class4	scanning acoustic microscopy of neoplastic and inflammatory cutaneous tissue specimens  acoustic microscopy utilizes high frequency ultrasound to generate microscopic images  the current study was designed to examine representative disorders of the skin by use of a reflective scanning acoustic microscope  r sam   and to determine whether the obtainable resolution was sufficient to render a microscopic diagnosis  an olympus uh3 scanning acoustic microscope was utilized with lenses producing burst wave frequencies at 600 and 800 mhz  600 and 800 million cylces sec   cutaneous tissue specimens representing 12 different neoplastic and inflammatory disorders were examined  acoustic images of unstained sections were compared with conventional light microscopic study of sections stained with hematoxylin eosin  in most neoplasms examined  it was possible to make a specific diagnosis primarily from low magnification pattern analysis  although individual cells could be visualized  cytologic atypia was poorly defined  in the inflammatory disorders  a specific diagnosis was possible in all but bullous pemphigoid and lichen planus  because the composition of the inflammatory infiltrate was difficult to determine  the advantages of the r sam include the capability of producing an acoustic profile of the tissue and the future possibility of in situ diagnosis  
class4	t cell subsets with a naive phenotype are selectively decreased in the peripheral blood of patients with mycosis fungoides  peripheral blood lymphocytes of 33 patients with histopathologic confirmation of mycosis fungoides and 27 healthy controls matched for age and sex were analyzed with a panel of monoclonal antibodies using both single and dual color immunofluorescence  patients with mycosis fungoides had a significant reduction in the percentage of circulating t cells with a naive phenotype  i e   cd4 2h4  and cd4 leu8    as well as a significant reduction in the absolute numbers of circulating lymphocytes with the phenotype cd8 leu8  compared to the control cohort  the reduction in circulating naive t cells was found to occur irrespective of stage of disease  duration of disease  or mode of treatment  the depletion of circulating naive t cells may reflect increased conversion to memory t cells in the peripheral blood or skin  
class4	the use of l dopa and carbidopa in metastatic malignant melanoma  a combination of l dopa and carbidopa was given orally to 17 patients with metastatic melanoma  maximum tolerated oral doses were given  up to 4 grams daily  no response was seen in 15 patients evaluable for response  toxicity was considerable  with seven of 17 patients  41   stopping treatment because of unacceptable gastrointestinal toxicity or postural hypotension  contrary to previous anecdotal reports  there was no evidence that l dopa carbidopa treatment resulted in accelerated progression of metastatic melanoma  orally administered l dopa carbidopa is ineffective as therapy for advanced melanoma when maximum tolerated doses are used  
class4	elderly men with histories of heavy drinking  correlates and consequences  recognition that the physical  psychological and social consequences of substance abuse may persist throughout the life span has led to increased study of the impact of lifetime drinking habits on the elderly  we examined the characteristics of elderly men with self reported histories of having ever been heavy drinker  h   in a population based  n   1 155  mean age   73 7 years  longitudinal survey of community dwelling elders  10 4  of the men reported that they had been heavy drinkers at some time during their lives  h  men were younger and less educated than non heavy drinkers  h   or never drinkers  n   mortality was higher among h  men who were current drinkers than among h  or n men  h  men reported more major illnesses  poorer self perceived health status  more physician visits  more depressive symptoms  lower levels of life satisfaction and smaller social networks than did h  or n men  self reported ability to perform activities of daily living and instrumental activities of daily living was poorest among h  men  who also scored the lowest on a mental status examination  thus  a history of having ever been a heavy drinker is predictive of widespread impairments in physical  psychological and social health and functioning among elderly men  
class4	thyroid disease and pregnancy  thyroid disease is common in younger women and may be a factor in reproductive dysfunction  this probably only applies to severe cases of hyper  or hypothyroidism  once adequately treated  neither of these disorders significantly impacts on fertility  the key is to recognize and to treat thyroid disorders in the reproductive age woman before conception  thyroxine therapy and even antithyroid drug therapy should be continued during pregnancy as necessary  pregnancy is a euthyroid state that is normally maintained by complex changes in thyroid physiology  the fetal and neonatal hypothalamic pituitary thyroid system develops independently  but it may be influenced by thyroid disease in the mother  early pregnancy is characterized by an increase in maternal t4 secretion stimulated by hcg and an increase in tbg  resulting in the elevated total serum t4 in pregnancy  the debate continues as to whether maternal t4 is important in early or late fetal brain development  if so  the physiologic changes in thyroid hormone secretion and transport in early pregnancy would help to ensure that a sufficient amount of thyroid hormone was available  there is new evidence in human subjects that substantial maternal t4 can cross the placenta during pregnancy  and this may be particularly important when fetal thyroid function is compromised as a result of congenital hypothyroidism  maternal and fetal neonatal outcomes in pregnancy are adversely affected if severe hypothyroidism is undiagnosed or inadequately treated  thyroid function tests should be obtained during gestation in women taking t4 and appropriate dose adjustments should be made for tsh levels outside a normal range  the tsh receptor blocking antibodies from the mother are a recognized cause of congenital hypothyroidism in the fetus and neonate that can be permanent or transient  if neonatal hypothyroidism is detected through neonatal screening programs  and prompt and adequate t4 replacement therapy is instituted as soon as possible following delivery  subsequent growth and development are usually normal  paradoxically  pregnancy often has a favorable effect on the course of maternal hashimoto s disease  although there is the risk of relapse postpartum  pathophysiologic conditions of hcg secretion such as gestational trophoblastic disease and hyperemesis gravidarum may present as thyrotoxicosis in pregnancy  but the main cause of this syndrome is graves  disease  the mainstay of treatment is antithyroid drugs and either propylthiouracil or methimazole may be used safely  subtotal thyroidectomy  after medical control  is the alternative treatment  but radioiodine ablation is contraindicated  abstract truncated at 400 words   
class4	thyroid disease in the elderly  as people in our society live longer  it is important for clinicians to know more about problems commonly seen in the elderly  thyroid problems are especially important to understand because they do occur with rather high frequency  and their mode of presentation is frequently different from those seen in younger patients  the thyroid gland does undergo certain age related changes in anatomy and physiology  but overall the thyroid is able to produce a normal amount of thyroid hormone throughout the years  hypothyroidism is frequently difficult to diagnose in the elderly  because many of the symptoms of hypothyroidism can easily be confused with symptoms of aging  when hypothyroidism is looked for in large population studies of elderly patients  the incidence varies from 1  to as high as 17   with women being more commonly affected than men  and subclinical hypothyroidism being more common than overt hypothyroidism  virtually all cases of hypothyroidism are due to autoimmune thyroid disease  with most patients having measurable titers of thyroid autoantibodies  the therapy of hypothyroidism is done with extreme caution  as older patients are frequently very sensitive to the effects of excess thyroid hormone  in addition  the metabolism of thyroid hormone slows down with age  making the full replacement dose much less in an older patient than in a younger one  hyperthyroidism is also quite common  occurring in from 0 5  to 3  of all elderly patients  the presentation is frequently atypical  as patients often lack the hyperdynamic symptomatology and instead have a more sedated  apathetic presentation  weight loss and cardiac symptoms frequently predominate  and the presence of a goiter is frequently absent  making the diagnosis less obvious than in a younger patient  therapy is usually radioactive iodine  after an adequate course of antithyroid drugs  to render the patient euthyroid  thyroid nodules do occur with increasing frequency in the elderly  but most of them are not malignant  fine needle aspiration for cytology is very helpful in determining which patients should be referred for surgery  well differentiated cancers do predominate  but their course is frequently less predictable than in younger patients  lymphoma of the thyroid and undifferentiated cancers do occur with increasing frequency in the elderly  multinodular goiter  usually of longstanding  is frequently seen in elderly patients  and thyroid hormone suppressive therapy not only is not indicated but may contribute to exogenous hyperthyroidism  
class4	thyroid cancer  there have been important recent advances in our understanding of the biologic nature of thyroid cancer and in the early diagnosis of the disease  despite these advances  there is still considerable controversy over the management of thyroid cancer  including the extent of surgery  the indications for the use of iodine 131  the effectiveness of thyroid stimulating hormone suppression  and the prediction of outcome  in this review  the current status of the diagnosis and management of the various types of thyroid cancer are carefully reviewed and extensively documented  
class4	the effects of nonthyroid disease and drugs on thyroid function tests  serious nonthyroid illness and caloric deprivation  which so often accompany systemic illness  have diverse and still incompletely understood effects on thyroid hormone economy  we have discussed the pathophysiologic basis for the most common pattern of alterations in routine thyroid function tests  a decreased serum t3 concentration  normal or  in critically ill patients  a low total serum t4 level  and a normal free t4 concentration  another  less frequent pattern  high total and free t4 with a normal serum t3  can be encountered transiently in the acutely ill medical or psychiatric patient  with the recent advent of sensitive assays for tsh and better methods for serum free t4  it is now possible to define more quickly and accurately the thyroid metabolic status of most of these sick patients  the vast majority are euthyroid  certain drugs confound the picture  the most important of these include dopamine and high dose glucocorticoids  both of which suppress tsh secretion from the pituitary and may actually cause a state of central hypothyroidism  other drugs have multiple effects on thyroid hormone indices  e g   amiodarone   knowledge of all of the ways in which systemic illness  starvation  and certain drugs may influence thyroid function tests is crucial in assessing the thyroid status of patients with serious nonthyroid disease  
class4	advances in molecular biology  potential impact on diagnosis and treatment of disorders of the thyroid  advances in molecular biology research continue to have a major impact on clinical medicine  these advances have provided a means to produce proteins previously available in limited supply and allow for the production of novel proteins that are improved agonists or else antagonists with greater specificity for therapeutic targets  newer drug delivery systems should facilitate delivery of these proteins  by combining the capabilities to produce drug targets in acceptable quantities with improved methods for determining the three dimensional structures of these targets  novel organic therapeutic molecules that act on these targets will be designed  gene transfer therapy using genes that express important proteins or that encode  antisense  rnas that inhibit the translation of specific mrnas will soon become a reality  the use of rflps and pcr methodologies promises increased means to diagnose specific genetic diseases and infections  most importantly  molecular biology is helping to understand the mechanisms of disease such that novel diagnostic and therapeutic approaches can be described  these advances are providing an understanding of the mechanisms involved in cancers of the thyroid gland  they have already led to an enhanced understanding of  1  the growth factors that control proliferation of the thyroid gland   2  the potential steps in thyroid nodule and neoplasia development   3  particular mutations that may occur as thyroid cancers develop   4  oncogenes that are expressed in thyroid cancers  and  5  the genetic defects that are responsible for thyroid gland malignancies in the multiple endocrine neoplasia  men  syndromes  with the latter  the rflp technology has already provided an enhanced means to diagnose the disorder  with further progress  enhanced means for diagnosis and treatment should emerge  molecular biology techniques are contributing to an increased understanding of the mechanisms of development of autoimmune thyroid disease as with graves  disease and hashimoto s thyroiditis  the potential role of infections  histocompatibility antigens  thyroid gland and extraglandular antigens  immune modulators  subpopulations of t cells such as suppressor and helper cells  other cells involved in immune responses  and a combination of influences of several different functions on the thyroid gland are being defined  this knowledge should soon suggest improved means for diagnosis and treatment  understanding of the function of the thyroid hormone receptors should have clinical importance  this knowledge suggests a means to develop thyroid hormone antagonists that may be used to more rapidly ameliorate the effects of hyperthyroidism and could be useful in nonthyroidal disorders such as cardiac arrhythmias  abstract truncated at 400 words   
class4	suppression of tumorigenicity in human colon carcinoma cells by introduction of normal chromosome 5 or 18  development of colon carcinomas can be associated with allelic deletions on several chromosomes  including 5q and 18q  the apc gene on 5q and the dcc gene on 18q have been identified as potential tumour suppressor genes  whose suppression contributes to colon carcinogenesis  to investigate the role of genes in these deleted regions  we have now introduced a single normal human chromosome into a human colon carcinoma cell line  cokfu  through microcell hybridization  several clones of hybrid cells containing normal chromosome 5  and others containing normal chromosome 18  were obtained  the morphology of the hybrid cells was markedly altered  the hybrids with chromosome 5 exhibited a closely packed polygonal morphology  and the hybrid cells with chromosome 18 were flattened  the cloning efficiency of the hybrid cells in soft agar was reduced from 0 46 to 0  of that of the parental carcinoma cells  and the tumorigenicity of these hybrid cells in athymic nude mice was completely suppressed  the growth properties of the hybrid cells with chromosome 11 were not substantially changed  these results strongly suggest that the genes on normal chromosome 5 and 18 function as tumour suppressors in colon carcinogenesis  
class4	lack of transmission of the live attenuated varicella vaccine virus to immunocompromised children after immunization of their siblings  the safety of administering the live attenuated oka merck varicella vaccine to the well siblings of children with malignancy was evaluated as a strategy for reducing the risk of household exposure to varicella among immunocompromised children  susceptible well children were eligible for vaccination if the child with malignancy had leukemia  lymphoma  or solid tumor in remission for 3 months or longer  no evidence of vaccine virus transmission was found among 30 children with malignancy whose 37 healthy susceptible siblings were immunized with varicella vaccine  varicella zoster virus was not isolated from the oropharyngeal secretions taken from 17 vaccinees or their 14 immunocompromised siblings  none of the 30 immunocompromised children had vaccine related rashes or showed immunologic evidence of subclinical varicella zoster virus infection based on testing for varicella zoster virus igg antibodies and t lymphocyte proliferation to varicella zoster virus  four healthy vaccinees eventually had mild breakthrough cases of varicella  with transmission to the high risk sibling in 3 cases  however  even in these families  the immunocompromised children had been protected from household exposure varicella for at least 20 months early in the course of their immunosuppressive treatment  
class4	hepatic arterial embolization in cases of extensive celiac arterial stenosis  transarterial hepatic embolization was attempted in 10 and succeeded in nine patients with hepatocellular carcinoma accompanied by extensive celiac arterial stenosis  all catheterization was done through the femoral artery  in six cases  the tip of the catheter  2 5 f ball tip microcatheter in three cases  4 f ball tip supple catheter in three cases  was placed in the proper hepatic artery through the pancreaticoduodenal collaterals  in three cases  a ball tip microcatheter was injected from the guiding catheter  which was placed in a pinhole of the celiac trunk  these techniques involving flow guided ball tip catheters are of great value for hepatic arterial catheterization in cases of extensive celiac arterial stenosis  
class4	malignancy associated with chronic empyema  radiologic assessment  radiologic findings of six cases of malignancy associated with chronic empyema 5 39 years in duration were reviewed  pathologic examination confirmed three b cell non hodgkin lymphomas  one round cell sarcoma  one mesothelioma  and one adenocarcinoma  retrospective findings on plain chest radiographs suggested the occurrence of malignancy  increased radiopacity in the thoracic cavity  soft tissue bulgings and or unsharpness of fat planes in the chest walls  destruction of bone near the empyema  and extensive medial deviation of the calcified pleurae  computed tomography delineated masses with soft tissue attenuation more clearly than radiography in all cases  magnetic resonance images of three cases were informative because empyema cavities were surrounded by low intensity rims  and two of them showed a signal intensity different from that of necrotic tumors  scintigraphy revealed increased uptake of gallium in all cases  ultrasonography was useful for biopsy guidance  every radiologist should know this entity in observation of chest radiographs obtained in patients with chronic empyema  and further radiologic assessment and aggressive biopsy are recommended if malignancy is suspected  
class4	use of gadolinium enhanced mr imaging for differentiating mucoceles from neoplasms in the paranasal sinuses  the purpose of this study was to determine whether additional clinically useful information could be obtained from gadolinium enhanced magnetic resonance  mr  imaging compared with the information obtained from nonenhanced mr imaging and computed tomography  ct   therefore  the authors selected 41 patients  whose results at ct examinations demonstrated a variety of pathologic conditions of the paranasal sinuses  to undergo mr imaging both with and without the use of gadopentetate dimeglumine for contrast enhancement  in 22 of 35 cases of neoplasms and mucoceles occurring separately  the lesions were correctly differentiated by established mr signal criteria alone  however  32 of these 35 cases were accurately differentiated when gadolinium enhanced mr images were obtained  six cases demonstrated co existing neoplasm and mucocele  gadolinium enhanced mr enabled correct differentiation of five of these lesions  while unenhanced mr enabled correct differentiation of three  on the basis of these results  the authors conclude that the use of gadopentetate dimeglumine for contrast enhancement at mr imaging is useful for differentiating mucoceles from neoplasms in the sinonasal tract  
class4	normal and abnormal pituitary glands  gadopentetate dimeglumine enhanced mr imaging  dynamic magnetic resonance  mr  imaging with a 1 5 t superconductive unit was used in the evaluation of nine normal pituitary glands and 10 pituitary adenomas  including four microadenomas and six macroadenomas  seven to 10 images were obtained every 20 30 seconds with use of the spin echo technique after rapid injection of gadopentetate dimeglumine  the earliest contrast material enhancement of normal structures was seen in the infundibulum and posterior lobe of the pituitary gland at 20 seconds  followed by gradual contrast material enhancement of the anterior lobe of the pituitary gland from the junction of the infundibulum to the peripheral portion of the anterior lobe of the pituitary gland within 80 seconds after gadopentetate dimeglumine injection  the peak enhancement of pituitary adenomas occurred at 60 200 seconds  usually after the most marked enhancement of the normal pituitary gland  microadenomas are best visualized at earlier phases of gadopentetate dimeglumine enhanced dynamic imaging  with signal intensity lower than that seen on images of normal pituitary glands  
class4	benign and malignant nodules in cirrhotic livers  distinction based on blood supply  the blood supplies of nodular lesions associated with liver cirrhosis were analyzed in vivo with various imaging modalities  the portal blood supply was evaluated with computed tomography  ct  during arterial portography  ctap   the arterial blood supply was evaluated with hepatic angiography  ct angiography  ct following intraarterial injection of iodized oil  or ultrasound following intraarterial injection of carbon dioxide microbubbles  a total of 84 surgically confirmed hepatocellular carcinomas  hccs   less than or equal to 3 cm  and 25 areas of adenomatous hyperplasia  ah  were included in the study  at ctap  a portal blood supply was seen in 96  of cases of ah and only 6  of hccs  chi 2  p less than  005   in contrast  an arterial supply greater than that of the surrounding liver was verified in 94  of the hccs and only 4  of the cases of ah  chi 2  p less than  005   the blood supply of areas of ah with atypical hepatocytes and the blood supply of well differentiated hccs  edmondson grade 1  tended to be intermediate between that of ah without atypia and that of hcc that was edmondson and steiner grade 2 or greater  evaluation of the blood supply of the nodular lesions associated with liver cirrhosis is considered to be useful in the differential diagnosis and treatment of early stage hcc  
class4	hepatic dynamic sequential ct  section enhancement profiles with a bolus of ionic and nonionic contrast agents  the enhancement characteristics in different portions of the liver during dynamic sequential bolus computed tomography  ct  with iodinated contrast material  dsbct  were prospectively evaluated in 75 patients by using iothalamate meglumine  iopamidol  and iohexol  25 patients received each agent   after baseline noncontrast ct was performed  dsbct was performed with a 180 ml intravenous bolus administered at 2 ml sec  scanning was started 25 seconds after the bolus was initiated  by using a 3 second scan time and rapid cephalocaudal table incrementation  yielding contiguous 8 mm thick sections at a rate of nine sections per minute  on postcontrast images  peak enhancement was 115  for iopamidol and 117  for iohexol  both of which were superior to iothalamate meglumine at 95   p less than  05   after peaking  enhancement then decreased for all three contrast agents  although the decline was more precipitous for iothalamate meglumine  enhancement on the more caudal sections with both iopamidol and iohexol was superior to that with iothalamate meglumine  p less than  05   the data suggest that the enhancement characteristics for the two nonionic agents may be more optimal for detection of focal hepatic lesions than the ionic agent  
class4	linkage of early onset familial breast cancer to chromosome 17q21  human breast cancer is usually caused by genetic alterations of somatic cells of the breast  but occasionally  susceptibility to the disease is inherited  mapping the genes responsible for inherited breast cancer may also allow the identification of early lesions that are critical for the development of breast cancer in the general population  chromosome 17q21 appears to be the locale of a gene for inherited susceptibility to breast cancer in families with early onset disease  genetic analysis yields a lod score  logarithm of the likelihood ratio for linkage  of 5 98 for linkage of breast cancer susceptibility to d17s74 in early onset families and negative lod scores in families with late onset disease  likelihood ratios in favor of linkage heterogeneity among families ranged between 2000 1 and greater than 10 6  1 on the basis of multipoint analysis of four loci in the region  
class4	inheritance of proliferative breast disease in breast cancer kindreds  previous studies have emphasized that genetic susceptibility to breast cancer is rare and is expressed primarily as premenopausal breast cancer  bilateral breast cancer  or both  proliferative breast disease  pbd  is a significant risk factor for the development of breast cancer and appears to be a precursor lesion  pbd and breast cancer were studied in 103 women from 20 kindreds that were selected for the presence of two first degree relatives with breast cancer and in 31 control women  physical examination  screening mammography  and four quadrant fine needle breast aspirates were performed  cytologic analysis of breast aspirates revealed pbd in 35  of clinically normal female first degree relatives of breast cancer cases and in 13  of controls  genetic analysis suggests that genetic susceptibility causes both pbd and breast cancer in these kindreds  this study supports the hypothesis that this susceptibility is responsible for a considerable portion of breast cancer  including unilateral and postmenopausal breast cancer  
class4	detection of ki 67 proliferation rate in breast cancer  correlation with clinical and pathologic features  in situ determination of proliferative activity was performed on 203 breast cancers by use of ki 67 monoclonal antibody and immunohistochemical methods  tumor proliferation rate was analyzed and correlated to tumor size and nodal status  the relationship between ki 67 proliferative activity and nuclear estrogen receptor content was also investigated on adjacent tissue sections  ki 67 values ranged from 1 to 75   with a median value of 10   premenopausal patients had greater ki 67 values  median value  14 1   than postmenopausal ones  median value  9 8    the authors observed no correlation with lymph nodal involvement  whereas a statistically significant relationship with tumor size was found  p less than 0 01   an inverse correlation  spearman s coefficient    0 56  p less than 0 001  was seen between ki 67 values and nuclear estrogen receptor content  these results  similar to those reported for other kinetic measurements  suggest that in situ detection of ki 67 proliferation rate is a useful method for obtaining cell cycle information  follow up studies will be needed to assess an eventual prognostic relevance  
class4	fluorescent cytochemical detection of estrogen and progesterone receptors in breast fine needle aspirates  estrogen and progesterone receptors were studied in fine needle aspiration biopsy specimens of 56 patients with primary  recurrent  or metastatic breast carcinoma  the ligands  17 b estradiol 6 carboxymethyloxine bovine serum albumin fluorescein isothiocyanate  fitc bsa estradiol  and hydroxyprogesterone hemisuccinate bovine serum albumin tetramethyl rhodamine isothiocyanate  tmritc bsa progesterone   were used in the fluorescent cytochemical method  the findings obtained from the aspirated cells with the use of the fluorescent cytochemical technique were compared with results obtained from the cell population of the same tumor after removal with the use of both the fluorescent cytochemical technique and the biochemical dextran coated charcoal  dcc  assay  for the needle aspirates  there was 89  concordance for estrogen receptor and 86  concordance for progesterone receptor between biochemical and cytochemical results  a high degree of correlation was also demonstrated between fine needle aspirates and imprint preparations with the use of the cytochemical technique  this study suggests that the fluorescent cytochemical technique is an effective tool in assessment of estrogen and progesterone receptor content in fine needle aspirates of primary and metastatic breast cancer  the fluorescent cytochemical technique can be performed easily at community hospitals and is well suited for specimens of insufficient size for biochemical assay  
class4	evaluation of in vitro bromodeoxyuridine labeling of breast carcinomas with the use of a commercial kit  the prognostic significance of s phase fraction analyses of breast carcinomas has been reported by several investigators  the cell proliferation kit  amersham corporation  arlington heights  il   which uses in vitro bromodeoxyuridine  brdu  labeling to evaluate cell cycle kinetics without a flow cytometer or radioisotopes  simplifies this assay for the clinical based laboratory by providing standardized reagents and recommended methods  this study was performed to determine whether data derived from its use were comparable to published s phase data from the use of thymidine labeling  brdu  or other methods on breast carcinomas  primary infiltrating ductal carcinomas  n   142  and primary lobular carcinomas  n   6  showed mean and median brdu labeling of 4 63  and 3   1 3  and 1   respectively  with a range of 0 28   benign lesions always had less than 3  brdu uptake  n   21   estrogen receptor  er  and progesterone receptor  pr  status correlated with brdu labeling  p less than 0 05   with the highest s phase fractions in er  and pr negative tumors  correlations between brdu uptake and histologic tumor type or size were observed  significant correlations between brdu uptake and lymph node status  patient age  or histologic tumor grade were not observed  s phase studies of breast carcinomas using other techniques have shown similar data  therefore  the cell proliferation kit appears to be a practical and useful method for in vitro s phase analysis that allows concomitant histologic examination of the same tumor tissue sample  
class4	neuroendocrine carcinoma of the ampulla of vater  a case of absence of somatostatin in a vasoactive intestinal polypeptide   bombesin   and cholecystokinin producing tumor  a 31 year old patient with a clinical picture of obstructive jaundice had surgical treatment  and a primary carcinoid of the ampulla of vater  va  was found  the tumor was studied with light microscopy  immunohistochemistry  and electron microscopy  the neoplasm had histopathologic and cytopathologic features similar to those encountered in typical neuroendocrine neoplasms  it is interesting that immunohistochemical techniques disclosed the presence of vasointestinal polypeptide  cholecystokinin  and bombesin  however  unlike most neuroendocrine neoplasms arising in va  no somatostatin immunoreactive cells were found  
class4	diagnostic value of dna analysis in effusions by flow cytometry and image analysis  a prospective study on 102 patients as compared with cytologic examination one hundred twenty six effusion samples from 102 patients were examined by cytology and flow cytometry  fcm   overall  there was an 84  correlation between cytologic and fcm results  of the 36 malignant cases determined by cytologic examination  fcm revealed an aneuploid peak in 20  56    image analysis  ia  performed on the malignant cytologic cases with a diploid flow pattern detected two additional aneuploid peaks  in addition  fcm indicated three aneuploid cases in which cytologic characteristics were initially interpreted as benign  false negative   aneuploidy was therefore detected in 64  of the malignant effusion specimens by fcm and ia  twenty three of the total of 24 aneuploid cases detected by fcm were associated with malignancy  predictive value   96    the one nonmalignant case was that of hemorrhagic pancreatitis with infected pseudocyst  fcm is an excellent tool when moderate to large numbers of tumor cells are present  whereas use of ia is advantageous for specimens containing smaller numbers of malignant cells because these can be directly analyzed  when an aneuploid peak is present  a diagnosis of malignancy must be suspected  and  if the initial cytologic screen is negative  a critical review of the cytology slides is justified  in those cases with an equivocal atypical cytology report and an abnormal cytometric histogram  additional investigation is warranted  in some malignancies the tumor cells will be diploid  in this study 36   and neither fcm nor ia will add to tumor detection  leaving cytologic examination as the definitive technique  
class4	evolution of in vitro transformation and tumorigenesis of hpv16 and hpv18 immortalized primary cervical epithelial cells  cervical carcinoma develops through a progressive spectrum of premalignant intraepithelial lesions  cin i iii   the majority of which are associated with human papillomavirus  hpv  types 16 and 18  we established hpv16 and hpv18 immortalized human cervical epithelial cell lines and used them as a model to investigate the genesis and progression of cervical malignancy  the cell lines when cultured in vitro in a system mimicking their in vivo environment exhibit cytologic atypia and a variety of defects in morphologic differentiation at early passage compared to their normal counterparts  with increased passage  these alterations progress to more severe grades  histologically similar to cin iii  however only a limited number of the cell lines are tumorigenic  mimicking the epidemiologic evidence on the rate of conversion from premalignant to invasive carcinoma  the observed changes are not associated with alterations of viral dna integration or expression and may reflect specific cellular events or changes in virus host interactions associated with malignant progression  
class4	expression of blood group antigens h 2  le y   and sialylated le a  in human colorectal carcinoma  an immunohistochemical study using double labeling techniques  in this study  double labeling immunohistochemistry was used to gain insight into the coexpression or interrelationship between blood group antigens  bga  that are differentiation antigens in the normal colon  and bga that are sequential moieties in the same synthetic pathway  paired wise sialylated le a  le y  and h 2 le y  was studied  the sialylated le a  and le y  are synthesized from type 1 and type 2 backbones  respectively  in the normal colon  the le y  and sialylated le a  are expressed by cells at the base and surface of the crypt  respectively  representing undifferentiated and differentiated enterocytes  the h 2 is considered oncofetal in nature  and is considered to be the immediate precursor in the synthesis of le y   in individual cancers  sialylated lea and le y  were detected in different cancer cells within the same malignant glands  separately in different glands  and in different subcellular compartments of the same cell  both h 2 and le y  were coexpressed in the same individual cells in 92  of cancers expressing both these bga  in 50  of the cancers  the h 2 and le y  also were expressed separately in different malignant glands within individual tumors  these findings indicate that  in colorectal cancers  differentiation antigens  sialylated le a  and le y   are expressed by different individual cells within the same malignant gland somewhat  recapitulating the normal colon crypt  antigens of different backbones occasionally may be expressed in the same cells but within different subcellular compartments  precursor accumulation is common in cancers  and antigens in the same synthetic pathway are coexpressed in the same cell  the expression of h 2 and le y  in different glands  lack of coexpression  may be explained possibly by aberrant synthesis of le y  by an alternate pathway  
class4	phenotypic relationships of prostatic intraepithelial neoplasia to invasive prostatic carcinoma  thirty one snap frozen human prostate specimens containing examples of benign hyperplasia  prostatic intraepithelial neoplasia  pin   and invasive carcinoma were analyzed using a panel of 24 antibodies and one lectin  twenty seven additional routinely processed radical prostatectomy specimens were studied using selected probes known to work on formalin fixed paraffin embedded material  three probes  anticytokeratin ka4  anti vimentin v9  and the lectin from ulex europaeus  uea 1   demonstrated phenotypic similarities between pin and invasive carcinoma  whereas the luminal cells of normal or hyperplastic prostatic epithelium are minimally reactive with ka4  4   or uea 1  0   and strongly reactive with anti vimentin  91    both the pin and invasive carcinoma are reactive with ka4  89  and 93   respectively  and uea 1  96  and 93   respectively  and minimally reactive with anti vimentin  15  and 0   respectively   the increased ka4 staining was shown to be in part due to detection of cytokeratin 19  by using cytokeratin 19 specific antibodies  4 62 and lp2k  the reasons for the increased expression of this cytokeratin and the decreased expression of vimentin are unclear but seem to indicate a phenotypic relationship between the pin lesions and invasive carcinoma  
class4	tumor secreted vascular permeability factor increases cytosolic ca2  and von willebrand factor release in human endothelial cells  vascular permeability factor  vpf   a tumor secreted heparin binding protein  mr approximately 38 000   is responsible for increased vessel permeability and fluid accumulation associated with tumor growth  vascular permeability factor also promotes the growth of human umbilical vein endothelial cells  ec  and bovine pulmonary ecs in vitro  it is shown for the first time that guinea pig vpf  half maximal and maximal dose approximately 0 4 and 22 pmol l  picomolar   respectively   as well as human vpf  are potent stimuli for human ecs resulting in  ca2  i increases  maximal three  to fourfold  and inositol triphosphate  ip3  formation  unlike the maximal responses to thrombin and histamine  the  ca2  i response to a maximal vpf dose was preceded by a characteristic 10  to 15 second delay  guinea pig vpf also selectively increased  ca2  i in cultured aortic and pulmonary artery ecs  but not aortic smooth muscle cells  human fibroblasts  or neutrophils  affinity purified rabbit antibody  raised to a synthetic peptide representing vpf n terminal amino acids 1 to 24  adsorbed all vessel permeability increasing activity  ec growth promoting activity  and specifically all activity responsible for increasing ec  ca2  i  similar to other mediators that increase  ca2  i in cultured ecs  vpf also induced a 200  increase in von willebrand factor release  together these data indicate that vpf acts directly on ecs and that rapid cellular events in its in vivo in vitro actions are likely to involve phospholipase c activation   ca2  i increase  and von willebrand factor release  
class4	immunoreactivity and receptor expression of insulinlike growth factor i and insulin in human adrenal tumors  an immunohistochemical study of 94 cases  using immunoperoxidase methods  94 human adrenal tumors were examined for evidence of immunoreactivity and receptor expression of insulinlike growth factor i  igf i  and insulin  the frequency of igf i in adrenocortical carcinomas was significantly higher than that in adenomas of the adrenal glands  the adrenocortical carcinomas showed strong intensity of staining for igf i  igf i receptors  and insulin receptors  a significant correlation between immunoreactivity and receptor expression of both igf i and insulin was found only in the adrenocortical carcinomas  the adrenocortical adenomas with cushing s syndrome and pheochromocytomas  more than adrenocortical adenomas with conn s syndrome  also stained strongly for insulin receptors  thus the igf i and insulin probably play a role in the growth of adrenocortical carcinoma tissues  possibly through autocrine mechanisms  the expression of insulin receptors in adrenocortical adenomas in the presence of cushing s syndrome and pheochromocytomas may be associated with functions  
class4	a critical analysis of the largest reported mass fecal occult blood screening program in the united states  fecal occult blood testing for the detection of colon cancer remains controversial  we performed a mass screening program from january 24  1988  to february 19  1988  with intensive media promotion  including 121 minutes of televised air time  a total of 5 000 primary practitioners were notified by mail  hemoccult ii tests were distributed to 156 000 individuals  55 051  35   were returned  ninety five percent of the respondents were informed of the program by television  a total of 3 375 persons  6   tested positive for fecal occult blood  of these  2 469  73   informed the center that they saw their physician to initiate a work up  information from physicians regarding work ups was returned on only 1 356  55   patients  diagnostic tests numbered 2 227  1 6 tests per patient   however  5  had no testing  16  had a repeat hemoccult only  and 35  had neither a barium enema nor colonoscopy performed  thirty six colorectal cancers and 212 polyps were identified  the predictive value  i e   number of cancers per number of patients who tested positive  increased directly by decade  thirty three of 36 patients  92   with cancer underwent either a barium enema or colonoscopy versus only 185 of 438  42   patients with a  negative  work up  cancers found were carcinoma in situ in 10 patients  29    dukes a in 12  35    dukes b in 4  12    and dukes c in 8  24    distant metastases were not found in any participant  thirty six percent of the tumors were located in either the right or transverse colon  we conclude that   1  screening identified early cancers  all were potentially curable and 64  were limited to the bowel wall   2  massive hemoccult distribution was possible over a short interval  but patient and physician compliance was disturbingly low   3  total colonic evaluation is mandatory  since at least 36  of tumors were beyond the reach of the flexible sigmoidoscope   4  many work ups were unnecessary  repeat hemoccults  or inadequate  indicating a need for physician education  
class4	surgical management of nonparasitic cystic liver disease  we report clinical features  surgical management  recurrences  and follow up study of 12 patients with simple hepatic cyst  11 patients with polycystic liver disease  and 19 patients with cystadenoma who were surgically treated over a 25 year period  the median age of patients was 48 years  and 37 women and 5 men were in the series  the most common presenting symptom and physical finding were chronic abdominal pain and tenderness in the right upper quadrant  the most commonly associated disease was polycystic kidney disease  which was an associated finding in 5 of the 11 patients with polycystic liver disease  45    the most valuable diagnostic studies in all groups were computed tomography and ultrasonography  the location of the disease was bilobar in patients with polycystic liver disease  with a right lobe predominance in 18  of patients  the right lobe was also predominant in 83  of patients with simple hepatic cyst and 58  of patients with cystadenoma  of all solitary cystic lesions in the left lobe  75  of them were cystadenomas  of the 66 surgical procedures performed  aspiration was associated with a failure rate of 100   partial excision  a failure rate of 61   and total excision and liver resection  a failure rate of 0   orthotopic liver transplantation was performed in three patients and was associated with two early deaths  partial excision relieved symptoms in three patients  43   with polycystic liver disease  total excision  enucleation  or liver resection with cyst s  is the treatment of choice for non parasitic cystic lesions of the liver  
class4	factors influencing survival after pancreaticoduodenectomy for pancreatic cancer  eighty nine patients with carcinoma of the head of the pancreas underwent pancreaticoduodenectomies  the actuarial 5 year survival for all 89 patients was 19   with a median survival of 11 9 months  the 81 hospital survivors were analyzed in an effort to determine factors influencing long term survival  negative lymph nodes and the absence of blood vessel invasion both favored long term survival  the strongest predictive factor was negative lymph node status with a median survival of 55 8 months  compared with 11 months with lymph nodes involved with tumor  p less than 0 05   blood transfusions were also predictive  with patients receiving two or fewer units having a median survival of 24 7 months  compared with 10 2 months for those receiving three or more units  p less than 0 05   the most important determinant of long term survival after pancreaticoduodenectomy for pancreatic cancer is biology of the tumor  lymph node status  blood vessel invasion   however  performance of the resection  units of blood transfused  also appears to be an important factor influencing survival  
class4	immunophenotyping in the management of gastric lymphoma  primary gastric lymphoma is a rare tumor in which surgical resection plays a major role in improving the response rate and reducing the incidence of bleeding and perforation after chemotherapy  in 17 consecutive patients  the diagnosis of gastric lymphoma was made by immunophenotyping snap frozen endoscopic biopsy specimens  all neoplasms were b cell lymphomas  pan b surface marker antigens were present in all patients  levels of ki 67  a nuclear marker of tumor proliferation  were greater than 45  in two of the four patients who died after progression of their lymphoma  all patients alive had ki 67 levels of less than 30   a lower proliferation index  as measured by ki 67  appears to be associated with better prognosis  ten of 11 patients treated by resection prior to chemotherapy had no complications  immunophenotyping is the key in the differential diagnosis when considering malignant lymphoma with gastric carcinoma and benign conditions such as pseudolymphoma  
class4	implications of peritoneal cytology for staging of early pancreatic cancer  cytologic examination of peritoneal washings was performed in 40 patients with pancreatic ductal adenocarcinoma  35 head  5 body  whose tumors had been selected as potentially resectable by computed tomographic  ct  findings  saline  100 ml  was instilled and aspirated at laparoscopy in 27 patients and at laparotomy in 13  malignant cells were found in the peritoneal washings in 12 of 40 patients  30    29  in cancers of the pancreatic head versus 40  in the body  33  at laparoscopy versus 23  at laparotomy  and in 4 of 8 patients with ascites versus 8 of 32 without ascites  the cytology was positive in 6 of 8 patients  75   who had a prior percutaneous needle biopsy versus 6 of 32  19   of those who did not  p less than 0 01   liver metastases were found in six patients  all with negative cytology  one of 10 pancreatic head cancers with positive cytology was resectable versus 13 of 25 with negative cytology  p less than 0 05   survival was significantly longer in patients with negative cytology  we conclude that  1  pancreatic cancer sheds malignant cells into the peritoneum early and commonly   2  laparoscopic lavage is an effective means of cytologic study   3  ascites is not a precondition for cytologic study  nor does its presence necessarily imply carcinomatosis   4  intraperitoneal spread of cancer cells may be promoted by tumor biopsy   5  cytologic findings provide an additional index of resectability  and  6  cytologic findings appear to correlate with duration of survival  this study shows that even  localized  pancreatic cancer is often not contained and suggests caution with biopsy of potentially curable lesions  
class4	differential diagnosis of sclerosing cholangiocarcinomas of the common hepatic duct  klatskin tumors   although it is recognized that some other lesion may be the cause  a presumptive diagnosis of klatskin tumor is usually made when a focal stenotic lesion of the common hepatic duct is seen on a cholangiogram of a jaundiced patient  biopsy is so often nondiagnostic that decisions about therapy are usually made on the basis of the imaging tests and lack of evidence for some other disease  because the accuracy and consequences of this strategy have never been tested  we contrasted the preoperative diagnosis of klatskin tumor with the final diagnosis in 98 consecutive patients treated from 1985 to 1990  preoperative investigations included ultrasound and computed tomographic scans  percutaneous transhepatic cholangiography  endoscopic retrograde cholangiopancreatography  and angiography  sclerosing cholangiocarcinomas of the bile duct were correctly diagnosed in 68 cases  the final diagnosis was other than a sclerosing adenocarcinoma in 30  31   cases  there were 5 papillary bile duct carcinomas  12 gallbladder carcinomas invading the bile duct  5 metastatic tumors to the bile duct  2 cases of mirizzi syndrome  3 granulomas  and 3 cases of idiopathic benign focal stenosis  patients with papillary adenocarcinomas had an extensive filling defect of the duct  which was often thought to be unresectable  however  four of these five lesions could be completely excised  and the tumor was confined to the duct wall in all four  the outcome of surgical treatment of the other eight patients with benign lesions was good in most cases  these findings demonstrate the pitfalls of assuming that a focal stenosis of the hepatic duct represents a sclerosing adenocarcinoma  the diagnosis is much less specific than is generally thought  so there is considerable opportunity for mismanaging such patients  
class4	high grade dysplasia in the columnar lined esophagus  abnormal columnar lining of the esophagus is a well recognized premalignant condition  the management of patients with high grade dysplasia without evidence of carcinoma remains controversial  esophagectomy is proposed by some investigators  whereas others favor follow up endoscopy and biopsy until microinvasive malignancy is documented  we reviewed our experience with nine patients referred with high grade dysplasia on endoscopic biopsies without evidence of carcinoma  eight patients had the columnar lining extending orad from the cardia  and one patient had heterotopic columnar epithelium in the cervical esophagus  all were white men ranging in age from 19 to 76 years  median  47 years   eight patients underwent esophagectomy with colon interposition  a sleeve resection of the cervical esophagus was done in one patient  multifocal carcinoma was found in three patients  all of whom had severe dysplastic changes throughout the columnar lining  the patient with heterotopic columnar epithelium had microinvasive carcinoma  all four patients with carcinoma had negative nodes and are long term survivors  no carcinoma was found in the resected specimens of the remaining five patients  high grade dysplasia is an important marker of malignancy in patients with a columnar lined esophagus  esophagectomy is indicated in suitable candidates since carcinoma was found in 45  of our patients  
class4	thoracoscopy for the diagnosis of pleural disease  objective  to assess the accuracy and safety of thoracoscopy for the evaluation of pleural disease  design  prospective evaluation of patients referred for thoracoscopy  setting  university hospital specializing in chest diseases  patients  we studied 102 patients with pleural disease  the cause of which had not been determined after initial investigation  including thoracentesis and needle biopsy  eighty six patients had pleural effusion  11 had pleural mass  and 5 had pleural effusion in association with a known primary lung carcinoma  intervention  all patients had thoracoscopy under local anesthesia with mild sedation  visually directed biopsies were done of parietal pleura  measurements  we recorded clinical characteristics  laboratory data  findings and duration of thoracoscopy  and any complications associated with the procedure  hospital and clinic follow up records were reviewed  and patients were contacted by telephone 12 and 24 months after thoracoscopy to assess their health status  main results  one hundred and four thoracoscopies were done in 102 patients  a definitive diagnosis was established in 95 patients  42 had malignant pleural disease and 53 had benign pleural disease  a diagnosis of benign pleural disease using thoracoscopy could not be confirmed in the remaining 7 patients because of insufficient follow up information  overall  thoracoscopy was 96  accurate with a sensitivity of 91   a specificity of 100  and a negative predictive value of 93  for the diagnosis of pleural malignancy  thoracoscopy was well tolerated under local anesthesia and entailed hospitalization for less than 24 hours in most cases  no deaths occurred  although 1 9  of patients had major complications  and 5 5  had minor complications  conclusions  among patients with pleural disease remaining undiagnosed after usual initial investigation  thoracoscopy done under local anesthesia is a rapid  safe  and well tolerated procedure with an excellent diagnostic yield that is equivalent to that of thoracotomy  
class4	late deaths after treatment for childhood cancer  an investigation of 749 deaths occurring among 4082 patients surviving at least five years after the diagnosis of childhood cancer in britain before 1971 has been undertaken  of the 738 with sufficient information the numbers of deaths attributable to the following causes were  recurrent tumour  550  74    a second primary tumour  61  8    a medical condition related to treatment of the tumour  49  7    an traumatic death unrelated to the tumour or its treatment  34  5    finally  any other cause unrelated to the tumour or its treatment  44  6    less than 10  of five year survivors of non hodgkin lymphomas  neuroblastoma  retinoblastoma  wilms  tumour  or a soft tissue sarcoma died of recurrent tumour during the next 15 years  while more than 25  of five year survivors of hodgkin s disease  ependymoma  medulloblastoma  and ewing s tumour died of recurrent tumour during the corresponding period  almost 50  of five year survivors of acute lymphoblastic leukaemia died of recurrent disease during the corresponding 15 years  a large proportion of deaths being due to central nervous system relapse in an era before central nervous system prophylaxis was routinely given  comparison of the mortality observed with that expected from mortality rates in the general population indicated three times the expected number of deaths from non neoplastic causes  five times the expected number of deaths from cardiovascular causes were observed  these were predominantly myocardial infarction and cerebrovascular accidents  there was no evidence of an excess in the number of suicides observed  but there were three times the expected number of deaths from accidents observed after central nervous system tumours  
class4	acute myeloid leukemia and background radiation in an expanded case referent study  a case referent study that investigated possible associations between environmental and occupational exposures and acute myeloid leukemia was performed on 86 cases and 172 referents  all of whom were living  exposure information was obtained through a questionnaire mailed to each subject  an association was found between time spent in concrete buildings at home and work and leukemia morbidity  in addition  extensive x ray examinations that occurred more than 5 y prior to diagnosis were more common among cases than referents  
class4	expression of blood group antigens by normal bronchopulmonary tissues and common forms of pulmonary carcinomas  the expression of abh and lewis antigens has been studied in a series of pulmonary carcinomas  in areas of squamous metaplasia  and in normal adjacent bronchopulmonary tissues by means of a panel of lectins and monoclonal antibodies  all respiratory epithelial cells can express antigens  with the exception of glandular serous cells  the expression of ab antigens is rather homogeneous  while lewis antigens are expressed in a more irregular pattern  alternating positively stained cells with negatively stained cells in the same microscopic field  the expression of blood group antigens allows the identification of residual pneumocytes inside the tumor and the proper classification of some neoplasms  metaplastic areas show a variation in the staining profile when compared with normal tissues and pulmonary carcinomas  the most significant findings are the deletion of a antigen and the strong expression of le antigen  pulmonary carcinomas are composed by a heterogeneous population and tend to express antigens in the more differentiated cases or areas  the most important findings are the deletion of ab antigens and the strong expression of le y  antigen  
class4	expression of abh blood group antigens  ulex europaeus agglutinin i  and type iv collagen in the sinusoids of hepatocellular carcinoma  the expression of blood group antigens  a  b  h  lewis a  and lewis b    ulex europaeus agglutinin i  uea i   factor viii related antigen  and type iv collagen on the sinusoids was examined immunohistochemically in 15 cases of hepatocellular carcinomas  hcc   11 cases of cirrhosis  12 cases of chronic active hepatitis  and in a control sample of 16 normal livers  sinusoidal endothelial cells of hcc characteristically showed a diffuse and strong immunoreactivity to abh blood group antigens in the specimen with a comparable abo blood group  the sinusoidal endothelial cells were also diffusely and strongly positive for uea i receptors  in contrast  in cirrhosis and chronic active hepatitis a few sinusoidal endothelial cells were positive for abh blood group antigens and uea i receptors  in normal livers  only a few sinusoidal endothelial cells were positive for abh blood group antigens and uea 1 receptors  tests for factor viii related antigen and lewis blood group antigens were almost negative on sinusoidal endothelial cells  although type iv collagen was distributed diffusely in the space of disse in these four groups  its expression was strongest in hcc  blood vessels of portal tracts and fibrous septa were positive for abh blood group antigens  uea 1 receptors  factor viii related antigen  and type iv collagen  but negative for lewis blood group antigens  these findings suggest that some sinusoidal endothelial cells undergo  capillarization  in cirrhosis and chronic active hepatitis  and that the majority of sinusoidal endothelial cells of hcc have phenotypic characteristics of capillaries  
class4	null cell adenoma of the pituitary with features of plurihormonality and plurimorphous differentiation  the case of a 35 year old man with pituitary macroadenoma who was complaining of reduced sexual activity is presented  histologic examination showed a chromophobic adenoma corresponding mainly to a null cell adenoma at the ultrastructural level  focal plurihormonality and plurimorphous differentiation of adenoma cells were demonstrated by immunohistochemical and electron microscopic studies  it is suggested that adenomatous null cells represent pluripotent progenitor cells capable of transforming to different hormone producing cell types  the factors accounting for differentiating to various cell populations have yet to be elucidated  
class4	pleomorphic  anaplastic  neuroblastoma in nude mice  two pleomorphic  anaplastic  neuroblastomas  from two children aged 1 and 6 years  were transplanted into nude mice  two noteworthy observations were made  in one case  the transplanted tumor gave rise to a soft tissue sarcoma  moreover  in both cases hepatic metastases were associated with a striking modification of murine hepatocytes  resulting in hyperchromatic and dysplastic nuclei  the latter finding was particularly evident in the hepatic areas surrounding all metastases of pleomorphic  anaplastic  neuroblastoma cells  
class4	glomus tumor of the coccyx  a curable cause of coccygodynia  a 30 year old woman presented with recurrent severe coccygodynia  she underwent exploration for a possible pilonidal sinus and was found to have a precoccygeal glomus tumor that also involved bony trabeculae of the coccyx  to our knowledge  a glomus tumor involving the coccygeal bone has not been previously documented  in view of the relief of this patient s pain following the surgical excision of coccyx and tumor  a causal role is suggested  
class4	malignant mixed tumor  malignant ameloblastoma and fibrosarcoma  of the maxilla  we present a rare case of carcinosarcoma  malignant ameloblastoma and fibrosarcoma  of the left maxilla that developed in a 63 year old japanese man  the tumor recurred repeatedly despite multiple surgical removals  radiotherapy  and chemotherapy and led to progressive cachexia  the patient died after 3 8 years of hospitalization  histopathologic examination revealed that the recurrent tumor was carcinosarcoma  which had progressed from malignant ameloblastoma with fibroma  an autopsy confirmed the diagnosis of malignant mixed tumor with lung metastasis of malignant ameloblastoma and fibrosarcoma  
class4	bone marrow necrosis in leukemic phase follicular lymphoma  bone marrow necrosis has been regarded as a rare entity in specimens obtained from living patients and has been associated with a poor prognosis  it is most commonly found in patients with neoplastic disorders  severe infections  and sickle cell anemia  we present an unusual case of a small cleaved type follicular lymphoma associated with bone marrow necrosis and a leukemic phase occurring in a 55 year old woman  specimens were studied by morphologic  immunohistochemical  cytogenetic  and dna hybridization techniques  
class4	aspergillus terreus endophthalmitis in a patient with chronic lymphocytic leukemia  a 65 year old woman with a 7 year history of chronic lymphocytic leukemia presented with acute visual loss  pain  and redness in her right eye  results of stains and cultures of anterior chamber fluid were negative  neurologic problems  bronchopulmonary pneumonia  recurrent skin lesions  and a low grade fever developed  progressive respiratory distress ensued  and the patient died 1 month after presentation  cultures from antemortem sputum and skin samples were positive for aspergillus terreus  postmortem histologic results showed extensive a terreus invasion of the posterior vitreous  retina  choroid  and anterior optic nerve  this organism was also found in histologic sections from the right adrenal gland  left kidney  thyroid  urinary bladder  right lung  skin  esophagus  sputum  vessels of the myocardium  and brain  to our knowledge  a terreus endophthalmitis has not been reported previously  
class4	response by women aged 65 79 to invitation for screening for breast cancer by mammography  a pilot study  published erratum appears in bmj 1991 jul 27 303 6796  234  objective  to determine whether there is sufficient benefit to be gained by offering screening for breast cancer with mammography to women aged 65 79  who are not normally invited for screening  design  pilot study of women eligible for screening but not for personal invitation  the results of this study were compared with the results of routinely screened younger women  aged 50 64  from the same general practice  setting  one group general practice in south manchester  patients  the 631 women aged 65 79 on the practice list  a total of 42  7   were excluded by the general practitioner  and 22  4   invitation letters were returned by the post office  main outcome measures  response rates to invitation for screening assessed by three indices  crude population coverage ratio  crude invited population coverage ratio  and corrected invited population coverage ratio  results  344 patients aged 65 79  61  of those invited  excluding those who could not be traced  were screened compared with 77  of women aged 50 64  the three response indices were higher for younger women than older  crude population coverage ratio   66 5   crude invited population coverage ratio   69 3   corrected invited population coverage ratio   76 8  for women aged 50 64  compared with 54 5   58 4   and 60 7  respectively for women aged 65 79  all four biopsies done in the older women gave positive results  giving a cancer detection rate of 11 6 1000 compared with 4 1 1000 among younger women  conclusions  these results show that there is a potential for high attendance at routine screening by older women if they are invited in the same way as younger women  if these results are found elsewhere the costs and benefits of screening older women should be reassessed  
class4	the use of cytochemical procedures in the diagnosis and management of acute and chronic myeloid leukemia  the use of wright giemsa stained smears alone for the classification of acute leukemias often proves unsatisfactory  some cases of m1  m5a  m7  and l2 are morphologically similar  in such cases  cytochemical stains can provide an inexpensive and available diagnostic tool  m1 is positive for sbb and mpo  m5a is usually nse positive  whereas sbb and mpo are negative  m7 usually is ana esterase  pas  and ap reactive  and do not stain with sbb  mpo  and anb esterases  the megakaryocytic lineage usually is confirmed by ultrastructural cytochemistry for ppo or immunocytochemistry for platelet glycoproteins and von willebrand factor  pas block positivity and ap dotlike reactivity are suggestive of lymphoid lineage  nse stains are useful in differentiating m2 from m4  morphologic and cytochemical techniques also can suggest the presence of certain chromosomal abnormalities such as t 8 21  and inv 16   which may have an influence on prognosis  because not all cases of acute leukemia are easily subtyped by morphology and cytochemistry  immunophenotyping  karyotyping  and molecular analysis of dna and rna of leukemia cells also may be required to define cell lineage  
class4	leukemias of indeterminant lineage  two biologically and clinically important forms of acute leukemia have been described  evidence suggests that both undifferentiated acute leukemia and many types of hybrid leukemia arise from relatively fewer differentiated cells than do the more straightforward acute leukemias  clinical correlations suggest that patients with these leukemias may have a poorer prognosis  although some findings may be associated with an improved prognosis  more data in which multiple techniques are applied to the same leukemic cells are clearly needed  patients with certain types of hybrid leukemias may be suitable candidates for more aggressive forms of chemotherapy or  possibly  combinations of therapy directed at cells of both lineages  
class4	the role of ras gene mutations in myeloproliferative disorders  mutations in the ras genes frequently are found in myeloproliferative disorders  these abnormalities have prognostic significance in the myelodysplastic syndromes  but their clinical importance in other hematopathic states remains unclear  the study of this gene in leukemic conditions is providing insights into the genetic pathways leading to leukemic progression  
class4	systems used to study the nature of the leukemic cell and predict treatment outcome in patients with myeloproliferative disorders  cell culture techniques have been used to study normal and leukemic hematopoiesis  investigations provided data on the nature of the clonogenic leukemic cell  its patterns of in vitro growth  role of stimulating factors  and effects of chemotherapeutic agents  assay systems developed to study leukemic progenitor cells or self renewal capacity have been useful clinically as predictive indicators of success of remission induction therapy and have allowed testing of drug sensitivity in vitro  alternative approaches using short  and long term suspension cultures have provided systems to evaluate leukemic cells  including nonclonogenic  biochemical  and kinetic events  in vitro systems have been introduced to measure cell cycle events accurately and to identify metabolic mechanisms of drug resistance  the information provided by all of these systems has allowed a more comprehensive and multifocal characterization of the nature of the leukemic process and has better directed our approach to treatment  
class4	myeloproliferative disorders  classification and diagnostic features with special emphasis on chronic myelogenous leukemia and agnogenic myeloid metaplasia  leukocytosis  mild anemia  thrombocytosis  and panhyperplasia in the marrow characterize the early stages of most of the cmpd  whereas extramedullary hematopoiesis  such as in the spleen or liver   peripheral cytopenias  anemia  leukopenia  or thrombocytopenia   and myelofibrosis  with or without osteosclerosis  reflect the changes seen in the later stages  transitions among the different cmpd and termination in acute leukemia or marrow failure also are common  cml often is characterized by leukocytosis and the presence of the entire spectrum of granulocytes  mature and immature  in the blood and marrow  reduced lap  hypercellularity with prominent granulocytic hyperplasia in the marrow  ph chromosome  and bcr abl gene rearrangement  typical features of amm include leukoerythroblastosis  teardrop poikilocytosis  anemia  increased or normal lap  prominent megakaryocytic hyperplasia in the marrow  dyshematopoiesis  and hyperplastic or fibrotic sclerotic marrow  
class4	molecular methods to detect the philadelphia chromosome  the ph1 chromosome has two molecular subtypes  a bcr positive seen in cml and some cases of all  and the bcr negative subtype mainly seen in all  in cml  because of the restriction of chromosome 22 breakpoints to the bcr  southern analysis to detect bcr rearrangements also can be used to detect the ph1 chromosome  in contrast  the translocation breakpoints on the ph1 chromosome are scattered in all  so that other methods such as pfge and pcr are necessary to detect the ph1 chromosome  in both cml and all  use of these methods to detect molecular abnormalities may be superior to cytogenetics in detecting chromosomal abnormalities  southern analysis also can be used in cml to map breakpoint locations within the bcr  this may offer prognostic information as to the length of chronic phase  but there is conflicting information as to the validity of this approach  the modified pcr  using cdna from mrna  can be used to detect the ph1 chromosome and to define which of the molecular subtypes are present  the exquisite sensitivity of this method  which is capable of detecting as little as a single abnormal molecule of rna or dna  makes it suited for the detection of minimal residual disease in both cml and all  this is particularly useful after intensive therapies  such as bone marrow transplantation  whether these low levels of fusion gene expression are of prognostic significance is still unclear  
class4	palliation of malignant esophageal obstruction  progressive dysphagia is common in patients with advanced esophageal carcinoma  multiple nonsurgical techniques are available to provide palliation and improved nutrition  simple dilatation is the oldest technique and newer methods may offer greater efficacy  laser therapy now provides an excellent opportunity to treat obstructing tumors  placement of an esophageal prosthesis may become particularly useful when dilatation must be performed too frequently or has become ineffective or in the patient with an esophageal pulmonary fistula  newer techniques including bicap tumor probe  intracavitary radiotherapy  or absolute alcohol injection offer promise  this review discusses the advantages and disadvantages of these different palliative techniques for patients with the extremely poor prognosis associated with esophageal cancer  
class4	islet cell carcinoma of the pancreas presenting as bleeding from isolated gastric varices  report of a case and review of the literature  gastrointestinal hemorrhage from left sided portal hypertension and gastric varices is an unusual presentation for islet cell carcinoma of the pancreas  islet cell tumors of the pancreas themselves are rare  they present in a variety of ways  those that elaborate functional hormones cause specific neuroendocrine syndromes  nonfunctional tumors characteristically present later with symptoms of metastatic disease or as a result of local enlargement  we present a case of islet cell carcinoma of the pancreas presenting with recurrent gastrointestinal bleeding from gastric varices and review the literature for this rare presentation  we emphasize the importance of a careful initial diagnostic work up that may enable curative surgery  
class4	pancreatic ascites presenting in infancy  with review of the literature  we report a 4 month old boy with massive ascites in whom a diagnosis of pancreatitis was made on a raised ascitic amylase level after two inconclusive laparotomies  he developed a pseudocyst which was managed with repeated percutaneous needle aspirations  nutrition being maintained intravenously  endoscopic retrograde cholangiopancreatography  ercp  demonstrated a congenital intra pancreatic cyst  he thrived after operation drainage for recurrent pseudocyst  but repeat ercp shows that the cyst in the head of the pancreas remains  pancreatic ascites is rare in children and diagnosis is frequently delayed  a third of reported cases in childhood present in the first year of life  a search for the underlying cause should include an ercp to demonstrate abnormalities of the pancreaticobiliary ducts  
class4	significance of anti hbx antibodies in hepatitis b virus infection  serological responses to hepatitis b virus x determinants have been noted in human sera  but conflicting findings concerning the correlation of anti hbx antibodies with different stages of hepatitis b virus infection or pathological sequelae have been reported  using an adenovirus based eukaryotic vector  the 17 kd x protein was efficiently expressed in 293 cells  cellular extracts containing the eukaryotic x protein have been used to screen for anti hbx antibodies by immunoblot analysis in a large panel of sera from patients affected by hepatitis b virus chronic hepatitis  hepatocellular carcinoma and acute viral hepatitis  sera from 32 of 171  19   chronic hepatitis b virus patients were positive for anti hbx antibodies  only one of thirty two  3   hbsag negative  anti hbs anti hbc positive chronic hepatitis serum was anti hbx positive  very few sera from primary hepatocellular carcinoma patients showed positivity for anti hbx  8 of 149 or 5    anti hbx were also detected in 8 of 48  17   acute viral hepatitis patients  in the four cases that were followed up weekly  anti hbx antibodies appeared 3 to 4 wk after the onset of the clinical signs  to compare the x protein expressed in eukaryotic and prokaryotic cells as a substrate for anti hbx antibody detection  171 sera were screened with hbx fusion proteins expressed in escherichia coli  the prokaryotic cell extract test seems to be more sensitive  during the chronic phase of hepatitis b virus infection  the presence of anti hbx antibodies detected with the eukaryotic cell extract correlates with the presence of well established markers of ongoing viral replication  serum hepatitis b virus dna  p less than 0 001  and intrahepatic hbcag expression  p less than 0 001   
class4	point mutation  allelic loss and increased methylation of c ha ras gene in human hepatocellular carcinoma  somatic alterations of the c ha ras gene were examined in 21 japanese patients with hepatocellular carcinoma  restriction endonuclease analysis by double digestion with mspi and hpaii revealed that dnas from two of 21 hepatocellular carcinoma tissues were affected by nucleotide substitution at the twelfth amino acid coding sequence of the c ha ras gene  dnas from cirrhotic noncancerous liver tissue  but not leukocytes  of one of these patients possessed the mutation  whereas dnas from noncirrhotic liver tissue and leukocytes of the other patient did not  in one of the nine patients harboring heterozygosity for c ha ras related bamhi fragments  the loss of one allele was demonstrated as a somatic change not only in dna from the tumor tissue but also in dna from the cirrhotic nontumorous tissue  in two of the 19 patients comparatively examined for digestion patterns of c ha ras locus with hpaii and mspi  extensive methylation was observed as a somatic modification in both dnas from the tumor and the cirrhotic nontumorous tissues  these results thus indicate that the genetic lesions affecting the c ha ras gene do occur in human hepatocellular carcinoma and probably serve as one of the multiple steps in the process of hepatic carcinogenesis  
class4	antibodies in anti hbe positive patient sera bind to an hbe protein expressed on the cell surface of human hepatoma cells  implications for virus clearance  the relevance of the recently described membrane bound form of the hbe protein for the antiviral immune response was examined  the data show that antibodies in anti hbe  but not in anti hbc positive human sera efficiently bind to the membrane expressed hbe  no evidence was obtained that the hbc can reach the cell surface in a form that can be detected with human antibodies  the findings suggest that the decline of virus titer that is usually observed after seroconversion from hbe to anti hbe might be the result of an antibody mediated elimination of infected cells  
class4	increased epidermal growth factor receptors in seborrheic keratoses and acrochordons of patients with the dysplastic nevus syndrome  seborrheic keratoses and acrochordons may change in biologic behavior with pregnancy or during treatment with sex steroids  because epidermal growth factor receptor localization may change in hyperproliferative skin diseases  we compared epidermal growth factor receptor immunolocalization in seborrheic keratoses and acrochordons from women who were or were not pregnant or taking oral sex steroid hormones  epidermal growth factor receptor was further investigated in growing and quiescent seborrheic keratoses and acrochordons from women with and without the dysplastic nevus syndrome  the epidermal growth factor receptor concentration was strikingly elevated in suprabasilar keratinocytes of growing seborrheic keratoses and acrochordons from patients with the dysplastic nevus syndrome who were pregnant or taking sex steroid hormones and less elevated in growing seborrheic keratoses from other patients  in contrast  the epidermal growth factor receptor distribution pattern in acrochordons did not correlate as well with the history of growth of these lesions in normal patients  these data suggest sex steroids may affect epidermal growth factor receptor metabolism in benign epidermal hyperproliferative lesions  particularly in patients with the dysplastic nevus syndrome  
class4	cyclosporine in the treatment of cutaneous t cell lymphoma  we present our observations on the use of cyclosporine in the treatment of three patients with mycosis fungoides and two patients with sezary syndrome  the patients with mycosis fungoides showed mild improvement of short duration  one patient with sezary syndrome had significant improvement during 2 years of treatment  it is unlikely that cyclosporine alone will be sufficient therapy for cutaneous t cell lymphoma  however  lower doses in conjunction with other immunomodulators may minimize potential side effects and lead to longer lasting clinical improvement  
class4	recreational sun exposure in puerto rico  trends and cancer risk awareness  persons who sunbathe or engage in other activities at the beach are exposed to large amounts of uv radiation  four hundred seven adults who visited the beaches of puerto rico were surveyed to determine their knowledge about the risks of sun exposure and to evaluate sunscreen use  the group consisted of 195 year round puerto rican residents and 212 tourists  ninety five percent believed that the sun can cause skin cancer  although only half of the subset who lived all year in puerto rico believed that they personally received enough exposure to be at risk  the majority of the group  83   understood the meaning of the sun protection factor numbers  although 35  used either nothing or a nonscreening oil  half of puerto rican residents rarely or never used sunscreen protection while sunbathing  when sunscreen was used  the most important factor sought was given as sun protection factor  64    followed by a perceived ability to aid in tanning  26    
class4	cutaneous angiolipoleiomyoma  we describe eight cases of cutaneous angiolipoleiomyoma  a rare tumor previously reported only once under the term cutaneous angiomyolipoma  clinically  the tumors were acquired  solitary  asymptomatic nodules that were always acral in location  patients  ages ranged from 33 to 77 years  median 52 6 years   the male female ratio was 7 1  signs of tuberous sclerosis or renal angiomyolipoma were absent in all cases  histologically  the tumors were subcutaneous  well circumscribed  and composed of smooth muscle  vascular spaces  connective tissue  and mature fat  in some tumors the fat was the predominant component  and in others smooth muscle predominated  elastic tissue stains revealed that some blood vessels had developed an elastic lamina whereas other blood vessels lacked it  additional histologic features occasionally observed included vascular thrombi  glomus bodies  and focal mucin deposition  
class4	complete follow up and evaluation of a skin cancer screening in connecticut  on may 21  1988  251 persons were screened for skin cancer in new haven  connecticut  a total body skin examination was performed on 98  of the participants  on the basis of follow up of 93  of persons with positive screens for basal cell carcinoma  squamous cell carcinoma  or bowen s disease  positive predictive values were 43  for basal cell carcinoma  14  for squamous cell carcinoma  and 50  for bowen s disease  in the group with atypical nevi  a person with two or more clinically atypical nevi was 16 times more likely to have histologic confirmation than a person with a single clinically atypical nevus  p   0 003   eighty persons were screened by both a dermatologist and a dermatology nurse  the crude agreement rate for actinic keratoses was 0 62  for atypical nevi  0 53  and for bcc  0 88  both nurses and physicians overdiagnosed in the screening setting  the nurses more so than the physicians  of the 128 persons screened who were advised to seek medical follow up  16 did not do so despite several reminders  their reasons are discussed  
class4	the risk of developing subsequent nonmelanoma skin cancers  data from the southeast arizona skin cancer registry collected during 1985 through june 1988 were used in this study  patients who had a nonmelanoma skin cancer  basal cell or squamous cell carcinoma  removed in 1985 were observed until subsequent nonmelanoma skin cancers developed or until june 30  1988  twelve categories of nonmelanoma skin cancers were developed on the basis of the type of first nonmelanoma skin cancer and type of second  third  and fourth nonmelanoma skin cancers  analyses showed the highest risk of a subsequent nonmelanoma skin cancer developing was within 1 year  36 39    the rate of developing another nonmelanoma skin cancer depended on type  squamous cell carcinoma  100   basal cell carcinoma  44 23  to 83 65    and total risk decreased during the 1277 days of the study  
class4	histologic pattern analysis of basal cell carcinoma  study of a series of 1039 consecutive neoplasms  this study attempts to define histologic patterns in 1039 consecutive cases of basal cell carcinoma and to correlate these patterns with adequacy of margins of surgical excision  five major histologic patterns were identified  nodular  218 cases  21    superficial  181 cases  17    micronodular  151 cases  15    infiltrative  77 cases  7    and morpheic  11 cases  1    a mixed pattern  two or more major histologic patterns  was present in 401 cases  38 5    our study indicates that nodular and superficial basal cell carcinomas can be completely removed by simple surgical excision in a high percentage of cases  93 6  and 96 4   respectively  whereas the micronodular  infiltrative  and morpheic basal cell carcinomas have a higher incidence of positive tumor margins  18 6   26 5   and 33 3   respectively  after excision  mixed patterns that consisted of combinations of the nodular  micronodular  or infiltrative types exhibited a behavior similar to the pattern that resulted in a greater chance of incomplete surgical removal  
class4	treatment of port wine stains during childhood with the flashlamp pumped pulsed dye laser  seventy three patients between the ages of 3 months to 14 years  average age 6 years 2 months  with port wine stains were treated with the flashlamp pumped pulsed dye laser  more than 75  lightening was achieved with an average of 2 5 treatments in 33 patients  45    50  to 74  lightening after an average of 1 7 treatments in 31  42    26  to 49  lightening after 2 treatments in 5  7    and less than 25  lightening after 1 treatment in 4  5    the overall average lightening after one treatment was 53   the percentage of lightening increased as the number of treatments increased  three patients had 100  clearance of the port wine stain  patients aged between 3 months and 6 years  44 patients  had a better response after the first treatment  55  lightening  than did patients aged between 7 and 14 years  29 patients with a 48  lightening  p   0 027   complications included cutaneous depressions in four patients  hyperpigmentation in 16 patients  and hypopigmentation in three patients  all complications were transient and disappeared completely  
class4	induction of dna fragmentation in chronic b lymphocytic leukemia cells  chronic lymphocytic leukemia of b cell type  b cll  is a neoplastic disorder characterized by the accumulation of small resting lymphocytes in the periphery  the phenotype of these cells suggests that they are  frozen  at an early stage of maturation  glucocorticoid hormones are commonly used to treat patients with b cll  resulting in a reduction in the peripheral lymphocyte count by an undefined mechanism  here we report that glucocorticoids stimulate dna fragmentation characteristic of a suicide process known as apoptosis or programmed cell death  pcd  in suspensions of cells from patients with b cll  the effects can be mimicked by ca2  ionophore and involve a sustained increase in the cytosolic ca2  concentration  specific antibodies binding to membrane associated igm on the leukemic cells can also induce pcd by a similar mechanism  phorbol esters block dna fragmentation and cell killing in response to all of the agents  suggesting that activation of protein kinase c desensitizes the cells to pcd  targeting the b cll cells with antibodies that induce an unbalanced  sustained ca2  increase may therefore represent a rational strategy for the destruction of leukemic cells  
class4	transforming growth factor beta induced inhibition of t cell function  susceptibility difference in t cells of various phenotypes and functions and its relevance to immunosuppression in the tumor bearing state  the present study investigates the nature of humoral component s  generated in tumor bearing hosts to induce immune dysfunction of t cells  cell free ascitic fluid and culture supernatant  sn  were obtained from the ascites and cultures allowing mh134 hepatoma cells to grow  these ascites and sn samples were tested for their abilities to influence the generation of ctl responses to tnp and alloantigens  the generation of the anti tnp ctl responses that require self h 2 restricted cd4  th cells was markedly suppressed by addition of the ascites or sn under conditions in which these samples did not inhibit anti allo ctl responses capable of using alternate pathways of allo restricted cd4  and cd8  th  the activation of cd8  ctl precursors and ctl activity were also resistant to the ascites or sn  the ascites  or sn induced suppressive effect to which cd4  th were most susceptible was found to be mediated by transforming growth factor beta  tgf beta  activity  because  1  the tgf beta activity was detected in the mh134 ascites and culture sn  2  the suppression of cd4  th function required for anti tnp ctl responses was almost completely prevented by addition of anti tgf beta antibody to cultures and  3  rtgf beta also induced similar patterns of immunosuppression to those observed by ascites or sn  these results indicate that tgf beta produced by tumor cells induces deleterious effects on t cell  especially on the cd4  th subset  and provide an explanation for the molecular mechanism underlying the previously observed cd4  th selective suppression in the tumor bearing state  
class4	expression of vhiii associated cross reactive idiotype on human b lymphocytes  association with staphylococcal protein a binding and staphylococcus aureus cowan i stimulation  it has been demonstrated that staphylococcal protein a  spa  has an  alternative  binding site with specificity for human ig h chain v region of the vhiii subgroup  because the major mitogenic component of staphylococcus aureus cowan i  sac  is spa  it is possible that sac stimulates a subpopulation of b cells expressing ig of the vhiii h chain subgroup  in the present study  we have investigated further the relationship between spa binding and the expression of vhi  or vhiii associated cross reactive idiotype  cri  on the surface of tonsillar b lymphocytes enriched for the expression or nonexpression of the cri  and we examined the ig secreted by cell lines established from these populations of b cells by ebv transformation  the vhiii cri  d12  enriched population yielded 21 cell lines  with 67  of them secreting spa reactive ig  in contrast  only 6   1 of 16  of vhi cri expressing lines secreted spa reactive ig  the cri negative b cell population yielded 54 cell lines  of which 20  secreted spa reactive ig  as might be anticipated because a majority of vhiii ig  b cells will be cri   sac stimulation of cri  and cri  populations showed preferential stimulation of the d12 population  these data support the proposal that sac stimulation of human b cells is mediated through binding of spa by its alternative binding site to igv regions of the vhiii subgroup  
class4	intraperitoneal cisplatin and cytarabine in the treatment of refractory or recurrent ovarian carcinoma preclinical evaluation has suggested impressive concentration dependent cytotoxic synergy between cisplatin and cytarabine in ovarian carcinoma  to further evaluate the clinical relevance of these observations  39 patients with refractory or recurrent ovarian carcinoma were entered onto a phase ii trial of intraperitoneal  ip  cisplatin  100 to 105 mg m2 per course  plus cytarabine  600 to 900 mg per course   treatment was administered over 2 or 3 days for a maximum of five monthly courses  followed by surgical reevaluation in patients without clinical evidence of disease  the 3 day regimen was discontinued secondary to the development of severe thrombocytopenia  five of 12 courses platelets decreased to less than 50 000 mm3   additional toxicities included abdominal pain  moderate to severe at some time during therapy in 46  of patients   fever without evidence of infection  44    and bacterial peritonitis  10    three patients declined surgical reassessment  fourteen of 36  39   95  confidence interval  ci   23  to 55   assessable patients demonstrated surgically defined responses  including 12 of 23  52   95  ci  32  to 72   patients with tumor nodules less than 1 cm in diameter and only two of 13  15   95  ci  0  to 34   patients with any lesion greater than 1 cm  there were seven  30   95  ci  11  to 49   surgically defined complete responses  crs  in patients with less than 1 cm disease and none in patients with larger tumor nodules  ip cisplatin cytarabine results in a high surgically defined response rate in patients with minimal residual ovarian carcinoma  but activity is low in patients with bulky intraabdominal disease  
class4	prognostic variables in patients with diffuse large cell lymphoma treated with macop b  one hundred twenty six patients with diffuse large cell lymphoma were treated with methotrexate with leucovorin  doxorubicin  cyclophosphamide  vincristine  prednisone  and bleomycin  macop b  between april 1981 and june 1986  univariate and multivariate analyses were performed using overall survival as of september 1989 as the end point  four independent negative predictors of survival were identified  presence of b symptoms  more than two involved lymph node sites  more than one extranodal site  variables related to tumor burden   and age older than 60  a variable related to the patient s ability to tolerate treatment  each variable contributed the same relative risk of dying and  accordingly  this simple predictive formula was developed empirically   4 n  x 30   the approximate percentage of chance of survival at 5 years   n  is the number of predictive variables present  the same four predictors were also found to be significant by multivariate analysis when only those patients achieving a complete response were analyzed  
class4	discordant bone marrow involvement in diffuse large cell lymphoma  a distinct clinical pathologic entity associated with a continuous risk of relapse  from 1975 to 1988  50 patients with lymph node biopsy documented diffuse large cell lymphoma  dlcl  presented with bone marrow involvement  twenty four patients  48   had large cell lymphoma  lcl  in the bone marrow and were compared with 19  38   patients who had small cleaved cell lymphoma  sccl  in the marrow  additionally  seven patients  14   had mixed small  and large cell lymphoma  ml  in the marrow  patients who had lcl marrow involvement were younger  p less than  02  and more frequently had elevated lactic dehydrogenase  ldh  levels  p less than  001   high tumor burden  p less than  01   and more sites of extranodal disease  p less than  05  than those with sccl in the marrow  the complete response  cr  rate to multiagent chemotherapy was 16 7  in the lcl group and 89 4  in the sccl group  p less than  001   one third of the patients with lcl in the marrow developed cns involvement  compared with only one patient in the sccl group  p    06   overall 5 year survival was 79  in patients with sccl marrow involvement  compared with only 12  in patients with lcl in the marrow  p    002   despite a high cr rate  patients with marrow involved by sccl were at a high continuous risk of relapse with only a 30  failure free survival at 5 years  we conclude that bone marrow involvement with lcl predicts for extremely poor prognosis with low response rate and short survival  patients with sccl in the bone marrow have a high rate of cr and a high rate of 5 year survival  however  there is a high risk of late relapse  and only 15  are in a continuous remission at 8 years  
class4	a comparison of induction and maintenance therapy for acute nonlymphocytic leukemia in childhood  results of a pediatric oncology group study  two hundred fifty six children with previously untreated acute nonlymphocytic leukemia  anll  were evaluated on a pediatric oncology group  pog  phase iii randomized trial of both induction and continuation chemotherapies  induction therapy compared vincristine  cytarabine  and dexamethasone  vadx  with daunorubicin  cytarabine  and thioguanine  dat   the complete remission  cr  rate using dat was superior  82  v 61   p    02   postremission therapy consisted of either  standard  two cycle therapy or a more intensive four cycle regimen given for 2 years  overall  there was no difference in outcome for patients randomized to either continuation regimen  the overall complete continuous remission rate  ccr  for the  best  induction continuation therapy combination at 2 years was  50  se    06   at 3 years was  35   04   and at 4 years was  34   05   analysis of selected clinical and laboratory parameters demonstrated differences in induction responses favoring dat induction but did not impact eventual disease free survival  there were two subgroups of patients who responded better to four cycle continuation therapy  these were patients with french american british  fab  m1 m2  2 year ccr was  20 v  44  p    01  and patients older than 10 years at diagnosis   32 v  62  p    004   
class4	influence of chemotherapy administration on monocyte activation by liposomal muramyl tripeptide phosphatidylethanolamine in children with osteosarcoma  the purpose of these studies was to determine whether chemotherapy interfered with the ability of peripheral blood monocytes from patients with osteosarcoma to respond to the liposome encapsulated activating agent muramyl tripeptide phosphatidylethanolamine  l mtp pe   this was done in preparation of designing an adjuvant therapy protocol that includes l mtp pe combined with chemotherapy postoperatively for the treatment of primary osteosarcoma  the majority of patients who fail current adjuvant chemotherapy do so while on chemotherapy  therefore  we believe it is important to combine l mtp pe with chemotherapy early in the treatment course rather than waiting until all chemotherapy cycles are completed  the tumoricidal properties of monocytes from patients with osteosarcoma could be activated by l mtp pe to levels equal to or greater than those expressed by normal control monocytes  no intrinsic monocyte defect could be demonstrated  single agent chemotherapy consisting of cisplatin  cpd   high dose methotrexate  mtx   cytoxan  ctx  cyclophosphamide  bristol myers co  evansville  in   or adriamycin  adr  doxorubicin  adria laboratories  columbus  oh  did not interfere with this activation process  there was even a suggestion of enhanced activation potential following the administration of adr  however  when both adr and ctx were administered together on the same day  profound suppression in monocyte activation was observed  this suppressed function returned to normal by 3 weeks postcombination therapy  we therefore conclude that l mtp pe can be combined with adr  cpd  mtx  or ctx as single agents but recommend that adr plus l mtp pe is the most effective combination  by contrast  we discourage the use of l mtp pe when adr and ctx are given together  
class4	venous and arterial thrombosis in patients who received adjuvant therapy for breast cancer  the records of 2 673 patients randomized according to seven consecutive eastern cooperative oncology group  ecog  studies of adjuvant therapy for breast cancer were reviewed for the occurrence of vascular complications  all protocols opened and closed between june 1977 and july 1987  the objectives of the present study were  1  to compare the frequency of vascular complications among patients who received adjuvant therapy for breast cancer with patients on observation  and  2  to estimate the contribution of chemotherapy and hormonal therapy to the occurrence of venous and arterial thrombi  the frequency of thrombosis  both venous and arterial combined  was 5 4  among patients who received adjuvant therapy and was 1 6  among patients on observation  p    0002   premenopausal patients who received chemotherapy and tamoxifen had significantly more venous complications than those who received chemotherapy without tamoxifen  2 8  v 0 8   p    03   postmenopausal patients who received tamoxifen and chemotherapy had significantly more venous thrombi than those who received tamoxifen alone  8 0  v 2 3   p    03  or those who were observed  8 0  v 0 4   p less than  0001   premenopausal patients who received tamoxifen and chemotherapy had a 1 6  frequency of arterial thrombosis  significantly more than patients who received chemotherapy alone  1 6  v 0 0   p    004   the frequency of arterial thrombosis among postmenopausal patients was not significantly correlated with adjuvant therapy  in conclusion  patients who received adjuvant therapy for breast cancer had a 5 4  frequency of thromboembolic complications  significantly more than those who were observed  the combination of chemotherapy and tamoxifen was associated with more venous and arterial thromboembolic complications than chemotherapy alone in premenopausal patients and with more venous thrombi than tamoxifen alone among postmenopausal patients  
class4	epirubicin at two dose levels with prednisolone as treatment for advanced breast cancer  the results of a randomized trial  two hundred eleven patients with advanced breast cancer were randomized to receive either epirubicin  e  50 mg m2 and prednisolone  lep  or e 100 mg m2 and prednisolone  hep   the intended treatment consisted of 16 courses of lep or eight courses of hep given at 3 weekly intervals  reasons for stopping treatment early included progressive disease  stable disease without symptomatic improvement  or severe toxicity deemed intolerable by either the patient or physician  toxicity was recorded at 3 weekly and response at 9 weekly intervals using the world health organization  who  criteria of response and toxicity  two hundred nine patients were eligible for analysis  98  of whom have been followed for more than a year  one hundred four patients received lep and 105 hep  significantly worse myelosuppression  alopecia  nausea and vomiting  and mucositis were seen in the high dose arm  p less than or equal to  001   more patients in the lep arm stopped treatment before the fourth course than in the hep arm  and the commonest reason for stopping was progressive disease  a similar median number of courses was given in each arm  there was a significantly higher response in the hep arm  hep   complete response  cr    partial response  pr    41   lep   cr   pr   23    despite this  no statistically significant differences was seen in overall survival or progression free interval  the median survival for hep and lep was 44 and 46 weeks  respectively  
class4	a prospective randomized trial comparing epirubicin monochemotherapy to two fluorouracil  cyclophosphamide  and epirubicin regimens differing in epirubicin dose in advanced breast cancer patients  the french epirubicin study group the french epirubicin study group carried out a randomized trial comparing epirubicin alone 75 mg m2 with fluorouracil  5fu  500 mg m2  cyclophosphamide 500 mg m2  and epirubicin 50 mg m2  fec 50  and 5fu 500 mg m2  cyclophosphamide 500 mg m2  and epirubicin 75 mg m2  fec 75  as first treatment for advanced breast cancer patients  patients were stratified according to whether or not there were bone metastases only  four hundred twelve patients entered this trial  378 were assessable for tolerability and 365 for efficacy  the overall response rates were comparable between fec 50  44 6   and fec 75  44 7    but both were better than the epirubicin alone  30 6    p    04 and p    0006  respectively   the complete response rate was better in fec 75  15 5   than in fec 50  7    p    025  or epirubicin  4    p    002   similar results were obtained in the group of patients without bone only metastases  no difference in the three treatments was observed in the patients with bone metastases only  mean durations of response were similar in the three groups  being 412 days  440 days  and 350 days for fec 50  fec 75  and epirubicin  respectively  patients without previous adjuvant chemotherapy fared better than those with previous treatment  without anthracyclines   tolerability was fair in the three groups  overall  the epirubicin alone group showed better tolerance than the two other groups  which did not differ significantly  time to progression and survival were not different among the three groups  but more early relapses occurred in the epirubicin and fec 50 groups  survival seemed to be better during the first 8 months in the fec 75 group  and the survival difference between the epirubicin group and the fec 75 group was of borderline significance  no difference in survival was observed between epirubicin  and fec 50 group patients  even though the response rate was significantly worse in the monochemotherapy group  
class4	intrapleural cisplatin and cytarabine in the management of malignant pleural effusions  a lung cancer study group trial  malignant pleural effusions are a common and significant problem in patients with advanced malignancies  pleurodesis with tetracycline or other sclerosing agents is the usual treatment for malignant pleural effusions  in contrast to this approach  intrapleural chemotherapy has the potential advantage of treating the underlying malignancy in addition to controlling the effusion  intracavitary cisplatin based chemotherapy  which is cytotoxic rather than sclerosing  has proven safe and effective via the intraperitoneal route in ovarian cancer and malignant mesothelioma  there has been little previous experience  however  with intrapleural cisplatin based chemotherapy  as part of a planned series of trials in malignant mesothelioma  the lung cancer study group first evaluated intrapleural cisplatin and cytarabine in patients with malignant pleural effusions from a variety of solid tumors  from april 1986 to november 1987  46 patients with cytologically proven  symptomatic  and previously untreated malignant pleural effusions were entered on study  a single dose of cisplatin 100 mg m2 plus cytarabine 1 200 mg was instilled into the pleural space via a chest tube  which was then immediately removed  patients were evaluated for toxicity and response at 24 hours  1  2  and 3 weeks  and then monthly  no recurrence of the effusion was considered a complete response  cr   partial response  pr  was defined as a 75  or greater decrease in the amount of the effusion on serial chest radiographs  one patient experienced reversible grade 4 renal toxicity  four patients had grade 3 hematologic toxicity  and five patients had grade 3 cardiopulmonary toxicity  the overall response rate  cr plus pr  at 3 weeks was 49   18 of 37 patients   the median length of response was 9 months for a cr and 5 1 months for a pr  the outcome of this trial was sufficiently encouraging that this regimen has been incorporated into subsequent trials for malignant pleural mesothelioma  
class4	when is a prognostic factor useful  a guide for the perplexed  traditionally  a number of variables have been used to predict outcome in patients with early stage breast cancer  these tests are simple to perform and relatively inexpensive  recently  a number of new factors  eg  tumor proliferative index  nuclear dna content  and amplification or overexpression of growth promoting genes or oncogenes have been identified as potential predictors of outcome in patients with breast cancer  there is now increasing pressure to introduce such tests into routine clinical practice  how does a clinical practitioner identify which test  or group of tests  best predicts adverse outcome and whether any more clinically useful information is provided than with the use of more traditional factors alone  the aim of a prognostic test in breast cancer is to predict which patients are destined to develop a recurrence of cancer and those who are not  the prognostic usefulness of a test can be expressed in terms of relative risk  rr   which is the ratio of the risk of breast cancer recurrence in patients who test positive to the risk in those who test negative  methodologic guidelines that should be satisfied by a study evaluating the predictive ability of a test include the following   1  was an inception cohort assembled   2  was the referral pattern described   3  were laboratory and clinical outcomes assessed in a blinded fashion   4  was complete follow up achieved   5  was adjustment for extraneous prognostic factors carried out   6  were appropriate statistical methods used  an approach is suggested to help the clinician choose the test  or combination of tests  likely to discriminate between  high   and  low risk  patients in his her own practice  the decision regarding what particular threshold value  risk  defined by a prognostic test  or series of tests  warrants adjuvant therapy for an individual patient is a complex one but should be based on a clear presentation of the risks and benefits to the patient  
class4	endoscopic ventricular fenestration using a  saline torch   the fiberoptic endoscope has never gained popularity among neurosurgeons although it is ideally suited for navigating within the cerebral ventricles  recent advances in optics and miniaturization make the application of endoscopy in neurosurgery more practical  the authors report eight children who underwent ventriculoscopic fenestration of symptomatic loculated cerebrospinal fluid  csf  collections  these csf collections were either isolated ventricular cysts or trapped lateral ventricles secondary to obstruction at the foramen of monro  cyst wall dissection was carried out with a  saline torch  dissector which was introduced through a working channel in the ventriculoscope  the torch was used to coagulate vessels and to sculpt large windows in cyst walls or in the septum pellucidum  ventriculoscope guided cyst fenestration can be performed safely and easily under direct vision  the technique may permit simplification of shunt systems in some patients and elimination of shunts in others  
class4	intracranial arachnoid cysts in children  a comparison of the effects of fenestration and shunting  the best operative intervention for children with arachnoid cysts remains the subject of controversy  recent reports stress that craniotomy for cyst fenestration is associated with a low incidence of morbidity and mortality and may leave the child shunt independent  the cases of 40 pediatric patients with arachnoid cysts treated between 1978 and 1989 are reported  five children with mild symptoms and small cysts that remained stable on follow up studies have not required surgical intervention  of 15 patients with cysts initially treated by fenestration  10  67   showed no clinical or radiographic improvement postoperatively and have undergone cyst peritoneal  eight patients  or ventriculoperitoneal  vp  shunting  one patient   or revision of a vp shunt placed for hydrocephalus before cyst fenestration  one patient   two other patients with existing vp shunts required no further procedures  thus  only three  20   of 15 patients initially treated by fenestration remain shunt independent after a median follow up period of 8 years  the 20 other patients were initially treated by cysts shunting and all improved postoperatively  shunt revision has been necessary in six  30   of these 20 patients because of cysts recurrence  cyst location influenced the success of shunt treatment  none of the seven middle cranial fossa cysts treated by shunting have required revision  but results with cysts in other locations were less favorable  in all locations  though  shunting was more successful than fenestration  it is concluded that cyst peritoneal or cyst vp shunting is the procedure of choice for arachnoid cysts in most locations  including those in the middle cranial fossa  
class4	multiple adenomas of the human pituitary  a retrospective autopsy study with clinical implications  in a review of autopsy material from two centers  20 pituitary glands were found containing multiple adenomas  in total  44 adenomas were identified histologically  16 glands contained double tumors and in four glands triple adenomas were found  size was measured in 30 tumors  all of which were microadenomas  thirty four adenomas were located in the lateral wings and 10 lay in the median wedge  forty one tumors were chromophobic and three were basophilic  immunocytochemical analysis of the 44 tumors demonstrated the presence of prolactin in 11  adrenocorticotropic hormone in three  growth hormone in one  and alpha subunit as well as follicle stimulating hormone and luteinizing hormone in one  of the 20 patients studied  there were 11 men and nine women  with an average age of 69 years  all patients died from various nonendocrine causes  with the exception of one patient who appeared mildly acromegalic  no correlation was observed between pituitary morphology and clinical data  this study found a 10 4  frequency of adenomas in pituitaries studied randomly at autopsy  multiple tumors were encountered in 0 9  of cases  despite its low frequency  adenoma multiplicity may underlie surgical failure in cases in which one adenoma is removed and the other is left behind  
class4	an epithelial cyst in the cerebellopontine angle  case report  a case of a benign epithelial cyst in the posterior cranial fossa is described  it had the unique histological feature of a double layered cuboidal epithelial lining  detailed immunohistochemical and electron microscopic studies supported an endodermal origin  the differential diagnosis and the histogenesis of epithelial cysts in the central nervous system are discussed  
class4	accessory arm  dysraphism or disparity  case report  the case of a 3 month old infant with an accessory third arm is reported  the extra appendage was attached at the midcervical region and was associated with posterior cervical dysraphism and a cervical cord lipoma  possible theories of origin are examined  
class4	l methionine uptake by human cerebral cortex  maturation from infancy to old age age associated changes in amino acid transport from blood to normal frontal cortex were studied using positron emission tomography  pet   seventeen patients  1 8 71 yr  were injected intravenously with tracer doses of  11c  l methionine and a baseline pet scan was obtained  to assess competitive inhibition of  11c l methionine uptake  patients received either oral l phenylalanine or an i v  infusion of amino acids 1 hr before a second pet study  uptake of  11c l methionine by frontal cortex decreased seven fold between 1 8 and 71 yr  r    0 71  p less than 0 05   blood to brain transfer of  11c l methionine  at 4 5 yr  exceeded mean adult values by more than five fold  competitive inhibition reduced l methionine uptake in all patients older than 4 6 yr  these developmental changes parallel findings in animals  the neutral amino acid transport system may modulate human brain amino acid levels to meet changing developmental metabolic needs  
class4	long term follow up in toxic solitary autonomous thyroid nodules treated with radioactive iodine the long term effects of radioiodine treatment on thyroid function in patients with a toxic solitary autonomous thyroid nodule were evaluated  fifty two patients received a therapeutic dose of 20 mci of iodine 131  131i   duration of follow up was 10     4 yr  follow up data included a biochemical evaluation of thyroid function  the failure rate  recurrent hyperthyroidism  was 2   the incidence of hypothyroidism was 6  and was not related to the dose per gram of nodular tissue  oral administration of 20 mci of radioiodine is a simple and highly effective method for the treatment of patients with a toxic autonomous thyroid nodule  the risk of development of hypothyroidism is low if extranodular uptake of 131i is prevented  this can be achieved by not treating euthyroid patients  by no longer using injections of exogenous thyroid stimulating hormone in the diagnostic work up of the patients and by always performing radioiodine imaging shortly before treatment  
class4	vasculitis as a paraneoplastic syndrome  report of 11 cases and review of the literature  in a study of 222 patients with vasculitis  we identified 11 who had an associated neoplasia  seven had hematological neoplasia and 4 had solid malignant tumors  in 4 patients vasculitis gave the first evidence of the neoplasia or of its recurrence  nine of our patients had cutaneous vasculitis  the other 2 had vasculitis involving the intestine and resulted in acute abdomens  these 2 patients needed prednisone treatment for the vasculitis  neoplasia should be considered in patients with vasculitis without an apparent cause  
class4	systemic toxic effects associated with high dose verapamil infusion and chemotherapy administration  aside from its more conventional uses as a cardiovascular drug  the calcium channel blocker verapamil has recently been added to chemotherapeutic regimens to reduce drug resistance in b cell and other neoplasms that express the p glycoprotein  we recently treated patients with continuous infusion verapamil  0 15 mg kg per hour to 0 60 mg kg per hour  over a 5 day period in combination with continuous infusion vincristine and doxorubicin plus oral dexamethasone  seventy one courses involving 35 hospitalized patients were prospectively studied for cardiovascular and other side effects  cardiovascular side effects were observed most frequently and consisted of first degree heart block  hypotension  sinus bradycardia  and junctional rhythms  we observed higher degree heart block  but the qrs interval remained narrow and the ventricular escape rate remained relatively normal  effects on mean arterial pressure  heart rate  and pr interval were both time and dose related  severe  symptomatic congestive heart failure was rarely observed  the most common noncardiovascular side effects were constipation  peripheral edema  and weight gain  all systemic toxic effects observed were easily treated or disappeared with either temporary or permanent discontinuation of the verapamil infusion or by a decrease in the dose of verapamil  we conclude that the cardiovascular side effects associated with continuous  high dose intravenous verapamil therapy are significant and dose limiting but are rapidly reversible  less cardiotoxic chemosensitizers are needed to reverse multidrug resistance in cancer  
class4	clinical relevance of immunohistochemical detection of multidrug resistance p glycoprotein in breast carcinoma in 20 women with breast carcinoma  17 of whom had locally advanced cancer and 3 of whom had confirmed metastases  the expression of p glycoprotein was evaluated before the start of a chemotherapy regimen that included multidrug resistance related drugs  with the use of the c494 monoclonal antibody in an avidin biotin immunoperoxidase technique  p glycoprotein was detected in 17 of 20 tumor samples  results were expressed in a semiquantitative manner  taking into account the number of positive tumor cells  n index  and the specific staining intensity  i index   the 17 patients with nonmetastatic cancer were followed from the first cycle of chemotherapy to cancer recurrence  subsequent to six cycles of chemotherapy  all of these patients except one were rendered clinically disease free through surgery and or radiation  the end point was defined as either local regional recurrence or metastasis  strong p glycoprotein positive staining in a majority of tumor cells  the n  i  phenotype  was significantly correlated with no initial response to chemotherapy  p less than  02  and with a shorter progression free survival  p less than  02   thus  the pretreatment evaluation of p glycoprotein expression may be of prognostic value in patients with locally advanced breast cancer  
class4	effect of interleukin 1 beta on metastasis formation in different tumor systems  experiments were done to determine the effect of interleukin 1 beta  il 1 beta  on metastasis formation in different tumor systems  intravenous administration of 1 microgram of human recombinant il 1 beta given 1 hour before tumor cell injection augmented lung colony formation  experimental metastases  by the human a375 melanoma variants  the human ht 29m colon carcinoma  the sn12 k1 renal carcinoma in nude mice  the murine b16 melanoma variants  and the murine uv 2237m fibrosarcoma in syngeneic recipients  the same treatment did not induce lung colony formation by a human rectal carcinoma  hcc p2988  or by a murine reticulum cell sarcoma  m5076   both of which are not metastatic to the lung  spontaneous metastases were studied in c57bl 6 mice bearing the b16 bl6 melanoma  metastatic to the lung  in their footpad and the m5076 reticulum cell sarcoma  metastatic to the liver  subcutaneously  daily intraperitoneal treatment with 1 microgram of il 1 beta increased lung and liver metastases  these findings indicate that treatment of mice with il 1 beta can increase the number of artificial or spontaneous metastases and that this effect is not limited to a single tumor type or to a specific organ  
class4	phase i clinical and pharmacokinetic trial of flavone acetic acid  flavone acetic acid is a synthetic benzopyrone derivative with an unknown mechanism of action  thirty eight patients  30 men and 8 women  were treated once a week for 4 weeks every 5 weeks with doses of flavone acetic acid ranging from 0 33 to 12 5 g m2  at doses less than or equal to 3 9 g m2  the drug was administered intravenously over 1 hour  at doses greater than or equal to 5 28 g m2  the infusion period was lengthened to 6 hours  treatment of all patients included hydration before and after treatment and alkalization to maintain urine ph at greater than or equal to 6 5  a dose limiting toxic effect was hypotension at 10 g m2  pharmacokinetic studies revealed linear behavior in the eight patients studied  beginning at 3 9 g m2  peak plasma levels ranged from 125 to 630 micrograms ml  with a mean terminal half life of 22 4 hours  immunologic monitoring was performed in three patients at 10 g m2  a transient increase in cd16  and or leu 19 positive cells was noted in all three patients  in one patient  this increase correlated with a 10 fold increase in k562 cell killing  there were no objective tumor responses seen in this trial  the recommended phase ii dose on this schedule is 8 g m2  further studies to elucidate the drug s mechanism of action and to define its immunologic properties are recommended  
class4	tumor suppressor genes  new prospects for cancer research  cancer is thought to arise from the accumulation of several genetic mutations in a single cell  until recently  the only tumorigenic mutations that have been studied in detail are those that activate oncogenes  the discovery of tumor suppressor genes  for which inactivating mutations elicit tumorigenesis  has added a new dimension to our understanding of neoplasia  the retinoblastoma susceptibility gene rb is the prototype tumor suppressor gene and has been shown to suppress the transformed phenotype for several different cancers  additional studies have revealed other tumor suppressor genes that may operate in a variety of tissues through a variety of mechanisms  these mechanisms may regulate the choice between cellular proliferation and differentiation and appear to involve such processes as the initiation of dna replication  regulation of expression of certain genes  intercellular communication and adhesion  and the transduction of external signals to intracellular effectors  the elucidation of these mechanisms will enhance our understanding of both oncogenesis and the fundamental operations of the cell  
class4	phase i and imaging trial of indium 111 labeled anti epidermal growth factor receptor monoclonal antibody 225 in patients with squamous cell lung carcinoma murine monoclonal antibody  mab  225  igg1  against the epidermal growth factor  egf  receptor competitively blocks egf binding and inhibits egf induced activation of receptor tyrosine kinase and cell proliferation  the effect of mab 225 was studied in a phase i trial in patients with inoperable squamous cell carcinoma of the lung  which invariably expresses high levels of egf receptors  groups of three patients received total doses of mab 225 ranging from 1 mg to 300 mg  except at the lowest dose  each infusion included 4 mg of indium 111  111in  labeled mab 225  no toxicity was observed  tumors were imaged in all patients who received doses of 20 mg or greater  presumed metastases greater than or equal to 1 cm in diameter were imaged with doses of 40 mg or greater  single photon emission computed tomography could be carried out at the 120 mg and 300 mg doses and significantly improved tumor visualization  all patients produced anti murine antibodies  we conclude that treatment with an mab that inhibits egf receptor function is safe at the doses and schedule studied  111in labeled mab images squamous cell lung carcinoma  tumor uptake of the labeled mab is dose dependent  further studies are warranted to explore the potential therapeutic efficacy of anti egf receptor mabs and other agents that act in a comparable manner  
class4	stress response protein  srp 27  determination in primary human breast carcinomas  clinical  histologic  and prognostic correlations expression of an estrogen regulated protein known as the 27 000 d heat shock or stress response protein  srp 27  was evaluated in human breast carcinomas and established breast cancer cell lines  results obtained by northern and western blot analyses and immunohistochemical methods were concordant  immunohistochemical assessment of srp 27 expression in 300 breast carcinomas  with median patient follow up of 8 years  was performed  twenty six percent of lymph node negative and 45  of lymph node positive tumors were overexpressors  univariate analysis demonstrated significant correlations between srp 27 overexpression and estrogen receptor  er  content  ps2 protein expression  nodal metastases  advanced t stage  lymphatic vascular invasion  and a shorter disease free survival period  but not a shorter overall survival  for the study population as a whole  regression tree analysis showed that srp 27 expression was an independent prognostic indicator for disease free survival only in patients with one to three positive lymph nodes  the cox proportional hazards model confirmed the independent prognostic significance of nodal involvement  t stage  and er content but failed to recognize srp 27 overexpression as a significant independent parameter predictive of patient outcome in the patient population as a whole  the observed associations between srp 27 overexpression and more aggressive tumors suggest a biologic role for srp 27 in human breast carcinomas  
class4	therapeutic advantage of hypoxic cells in tumors  a theoretical study the presence of hypoxic cells in solid tumors has long been considered a problem in cancer treatment  particularly for radiation therapy but also for treatment with some anticancer drugs  three general strategies are being actively explored to overcome the problem  oxygenating the tumor  sensitizing the hypoxic cells to radiation  or chemotherapy   or killing the hypoxic cells  with a hypoxic cell cytotoxin   in the present study  we have examined the impact of each of these three strategies on a standard radiation therapy regimen  30 doses of 2 gy   using either of two major assumptions  full reoxygenation or no reoxygenation of the tumor cells  we demonstrate that a hypoxic cell cytotoxin can produce a level of tumor cell killing higher  by several orders of magnitude  than that produced by full oxygenation of a tumor or by use of an optimum hypoxic cell radiosensitizer  provided the cytotoxin kills more than approximately 50  of the hypoxic cells each time it is given  the only assumption that makes a difference is whether reoxygenation occurs  in the worst case  ie  no reoxygenation   the hypoxic cell cytotoxin performs only as well as an optimum radiosensitizer  the analysis shows that hypoxic cells in tumors can be a major therapeutic advantage  therefore  we recommend that research efforts be concentrated on development of superior hypoxic cell cytotoxins rather than improved hypoxic cell radiosensitizers and that  in parallel  emphasis be placed on development of agents to increase hypoxia  
class4	brief intensive chemotherapy for metastatic non small cell lung cancer  a phase ii study of the weekly code regimen  fifty three patients  17 with stage iiib and 36 with stage iv non small cell lung cancer  were given code  cisplatin  vincristine  doxorubicin  and etoposide  plus antibiotic prophylaxis and an antiemetic regimen in an intensive chemotherapy program emphasizing weekly treatment and a planned brief duration  9 12 weeks   for 45 of these patients  the code program also included antifungal prophylaxis and supportive corticosteroids  of the total study population  33 patients  62   responded to treatment  including five  9   with complete response  the median survival for the entire group was 42 weeks  55 weeks for those with stage iiib and 39 weeks for those with stage iv   more than 40  were alive at 1 year  comparison of granulocyte counts of patients receiving prednisone with those of the subgroup to whom no corticosteroids were given showed less granulocytopenia for those receiving prednisone  use of prednisone thus allowed improved delivery of myelosuppressive drugs  code was halted in nine patients because of disease progression  although more constitutional side effects are associated with weekly chemotherapy than with standard chemotherapy  only 12 of the remaining 44 patients  27   failed to receive at least 9 weeks of treatment  serious toxicity was uncommon  there were no treatment related deaths and only three episodes of neutropenia with fever  code is a novel treatment for non small cell lung cancer that this pilot study provided entirely in an outpatient setting over a 9 12 week period with an acceptable incidence of toxicity and a promising level of efficacy  additional testing and comparison with other regimens or supportive care alone are warranted  
class4	analysis of alterations in the retinoblastoma gene and tumor grade in bone and soft tissue sarcomas  we examined 43 sporadic bone and soft tissue sarcomas for molecular genetic alterations affecting the retinoblastoma susceptibility gene rb 1  also known as rb1   the gene was altered in 6 of 14 sporadic osteosarcomas and in 5 of 29 other bone and soft tissue sarcomas  rb 1 messenger rna  mrna  transcripts were detected in normal tissues and benign lipomas  but they were absent or altered in each of the 19 sarcomas we examined  to examine the association of deletions in the rb 1 gene with tumor grade  we correlated the dna alterations in the rb 1 gene with clinical data for 36 patients  the rb 1 gene was altered in 40  of high grade bone and soft tissue tumors  but not in low grade bone tumors and in only one low grade  soft tissue sarcoma  overall  10 of 25 high grade sarcomas had detectable alterations of the rb 1 gene compared with only 1 of 11 low grade tumors  
class4	diffusion and binding of monoclonal antibody tnt 1 in multicellular tumor spheroids  tumor spheroids of ht 29 human colon adenocarcinoma and a375 melanoma were established to investigate the uptake and clearance kinetics of tnt 1  a monoclonal antibody that targets necrotic cells of tumors  our data reveal that there was rapid uptake of tnt 1 and its f ab  2 fragment in both spheroid models  whereas an antibody of irrelevant specificity  lym 1  and its f ab  2 fragment bound poorly to the spheroids  unlike previously reported monoclonal antibodies to tumor cell surface antigens  tnt 1 showed 1  a linear uptake that increased over time without saturation in tumor spheroids and 2  an unexpected uptake by a subpopulation of cells in the viable outer rim of the spheroids  these preclinical studies provide important information concerning the therapeutic potential of tnt monoclonal antibodies for the treatment of cancer and micrometastases  
class4	management of primary nonrenal parenchymal malignancies with vena caval thrombus  we report our experience with the management of 7 primary nonrenal parenchymal malignancies with vena caval tumor thrombus  included are 3 cases of adrenal cortical carcinoma and 1 each of transitional cell carcinoma  embryonal cell testicular carcinoma  pheochromocytoma and primary small cell carcinoma of the lung with metastases to the kidney  surgical treatment and followup are presented  as well as a review of the literature  an aggressive surgical approach is warranted because prolonged survivals free of disease are possible  
class4	the incidence and prognostic significance of humoral hypercalcemia in renal cell carcinoma  this retrospective study was conducted to evaluate the incidence and prognostic significance of humoral hypercalcemia in 218 renal cell carcinoma patients during the last 20 years  of 218 patients 20  9 2   were hypercalcemic  with serum calcium levels ranging from 10 7 to 16 0 mg  dl  the respective incidence of humoral hypercalcemia was 3  in patients with stage i  5 9  with stage ii  14 1  with stage iii and 18 9  with stage iv disease without bone metastasis  the survival curves between the hypercalcemic and eucalcemic groups among stages i to iii cancer patients showed no statistical significance  p greater than 0 05   the survival curve deteriorated significantly in stage iv cancer patients with humoral hypercalcemia  p less than 0 005   with a median survival of 45 0     39 7 days versus 286 4     27 6 days in eucalcemic patients  no specific correlation was found between pathological cell type and humoral hypercalcemia  
class4	uptake of 2 deoxy  2  18f  fluoro d glucose in bladder cancer  animal localization and initial patient positron emission tomography  an orthotopically transplanted  locally metastasizing rat bladder tumor model was developed to evaluate the extent of uptake of fluoro deoxy glucose  fdg  in bladder cancer  significant uptake of fdg in localized bladder tumors in rats was shown  with an average tumor to blood ratio of 39 at 2 hours after intravenous fdg administration  metastases  3 nodal and 1 peritoneal  also showed significant uptake of fdg  with an average metastasis to blood ratio of 21 7  and tumor involved to normal lymph node ratio of 5 3  because fdg is excreted in the urine  urinary fdg potentially could prevent the use of fdg positron emission tomography  fdg pet  scanning for localized bladder cancer  bladder lavage successfully reduced the retention of fdg in the normal rat bladder  with an estimated uptake ratio of tumor to normal bladder of 13 1 after 5 ml  saline irrigation  based on these data  we performed an fdg pet scan of a patient with biopsy proved recurrent intravesical bladder cancer after radiation therapy  computerized tomography  ct  of the pelvis showed abnormalities consistent with radiation scarring and extravesical tumor  due to the scarring  the extent of tumor growth could not be determined  the patient also had pulmonary opacities seen on chest radiography  the fdg pet scan of this patient showed significant extravesical uptake in the pelvis  confirming the abnormality noted on ct  good images of the clinically apparent metastases in the chest also were obtained  these preliminary data indicate that fdg pet imaging of bladder cancer is feasible and it may provide new information for the diagnosis and staging of patients with bladder cancer  
class4	post chemotherapy tumor residuals in patients with advanced nonseminomatous testicular cancer  is it necessary to resect all residual masses  a total of 15 patients with advanced nonseminomatous testicular cancer underwent 2 sequential operations  4 in 1 patient  to remove residual masses after cisplatin based combination chemotherapy  all patients had normal human chorionic gonadotropin and alpha fetoprotein levels but persistent radiographic masses after chemotherapy  the operations included retroperitoneal lymph node dissection in 13 patients  thoracotomy in 15  hepatic resection in 3 and craniotomy in 1  histological comparison of the specimens resected during post chemotherapy operations 1 and 2 demonstrated different patterns in 7 of 15 patients  of these 7 patients 4 had less favorable pathological features in the specimen removed during the second procedure  residual malignant tumor or mature teratoma was found in at least 1 site in 12 of the 15 patients and only 3 had complete necrosis or fibrosis in both specimens examined  these data indicate the favorable impact of excising all post chemotherapy tumor residuals in patients with advanced nonseminomatous testicular cancer  however  in patients with no teratomatous elements in the testicular tumor and complete necrosis or fibrosis in the initial post chemotherapy operation specimen the probability of complete necrosis or fibrosis in remaining tumors appears to be high  
class4	predicting radionuclide bone scan findings in patients with newly diagnosed  untreated prostate cancer  prostate specific antigen is superior to all other clinical parameters  presently  the standard staging evaluation of prostate cancer includes digital rectal examination  measurement of serum tumor markers and a radionuclide bone scan  to evaluate the ability of local clinical stage  tumor grade  serum acid phosphatase  serum prostatic acid phosphatase  pap  and serum prostate specific antigen  psa  to predict bone scan findings  a retrospective review of 521 randomly chosen patients  mean age 70 years  range 44 to 92 years  with newly diagnosed  untreated prostate cancer was performed  local clinical stage  tumor grade  acid phosphatase  pap and psa all correlated positively with bone scan findings  p less than 0 0001   using receiver operating characteristic curves  however  psa had the best over all correlation with bone scan results  the median serum psa concentration in patients with a positive bone scan was 158 0 ng  ml   whereas men with a negative bone scan had a median serum psa level of 11 3 ng  ml   p less than 0 0001   using multivariate logistic regression analysis  local clinical stage  tumor grade  acid phosphatase and pap were evaluated in combination with psa to assess whether these parameters increased the ability of psa alone to predict bone scan findings  none of these clinical parameters  irrespective of the combination used  contributed appreciably to the predictive power of psa alone  a probability plot with 95  confidence intervals was constructed that allows the practicing urologist to estimate on an individual basis the probability of a positive bone scan for any given serum psa value  the most significant finding of this study  however  was the negative predictive value of a low serum psa concentration for bone scan findings  in 306 men with a serum psa level of 20 ng  ml  or less only 1  psa 18 2 ng  ml   had a positive bone scan  negative predictive value 99 7    this finding would suggest that a staging radionuclide bone scan in a previously untreated prostate cancer patient with a low serum psa concentration may not be necessary  
class4	the distribution of residual cancer in radical prostatectomy specimens in stage a prostate cancer  to assess the volume and distribution of residual cancer after transurethral resection of the prostate in stage a cancer patients 42 step sectioned radical prostatectomy specimens were examined  and the volume  location  grade and extracapsular extension of the residual tumor were recorded  a total of 13 patients had stage a1 tumors  5  or less tumor in the transurethral resection specimen and a gleason sum of 7 or less  and 29 had stage a2 disease  residual cancer was present in the radical prostatectomy specimen in 41 patients  98   with a mean volume of 1 28 cc  the location of residual cancer  that is multifocal  76    peripheral  81   and distal to the verumontanum  66    makes complete removal or even identification of residual tumor  restaging  by repeat transurethral resection improbable  of the stage a1 cancer patients 4  30   had more than 1 cc residual tumor volume  extracapsular extension or seminal vesicle invasion  on the other hand  14 of the stage a2 cancer patients  48   had less than 1 cc residual tumor completely confined to the gland  foci of residual cancer were found in the transition zone in 67  and in the peripheral zone in 90  of the patients  the grade of the residual peripheral zone cancer was significantly higher than that of the transition zone cancer in the same gland  p   0 0004   eight of 13 instances of extracapsular extension and all 5 of seminal vesicle invasion were directly attributable to peripheral zone cancer  these observations imply that the greatest threat to patients with stage a prostate cancer may be a separate  associated cancer in the peripheral zone rather than the primary transition zone cancer incidentally removed at transurethral resection  
class4	multifocal  synchronous inverted papillomas involving the ureter  inverted papillomas involving the upper urinary tract remain a rarely diagnosed phenomenon  a case of bilateral ureteral inverted papillomas is presented  the treatment and diagnosis of this lesion remain a challenge  
class4	pelvic lipomatosis associated with cystitis glandularis and adenocarcinoma of the bladder  pelvic lipomatosis is a rare condition characterized by an overgrowth of normal fat in the perivesical and perirectal spaces  cystitis glandularis  cystica or follicularis has been observed in 75  of the patients with pelvic lipomatosis  although cystitis glandularis is widely regarded as premalignant few reports have documented its transition to adenocarcinoma  we describe a 41 year old man with pelvic lipomatosis in whom primary adenocarcinoma of the bladder developed 6 years after a histological diagnosis of cystitis cystica and glandularis was established  to our knowledge this is the second case reported of pelvic lipomatosis associated with proliferative cystitis and adenocarcinoma of the bladder  indicating that intestinal metaplasia of the urothelium may be a precursor of malignancy in these patients  
class4	locally recurrent endometrioid adenocarcinoma of the prostate after radical prostatectomy  endometrioid carcinoma of the prostate is considered a variant of classical prostatic ductal carcinoma  endometrioid carcinoma variant often has the unique clinical presentation of gross hematuria  the propensity of this tumor to spread within the urothelium makes local failure of curative therapy commonplace  we present 2 representative cases with a review of followup surveillance procedures and treatment options for the local recurrence once identified  
class4	effect of suramin on human prostate cancer cells in vitro  suramin  a polyanionic compound with known antiparasitic activity  has been shown to be adrenocorticolytic in primates and to have clinical efficacy in the treatment of patients with metastatic prostate cancer refractory to conventional hormonal manipulation  to better characterize the activity of suramin on prostate cancer biology  we studied the effect of the drug on plasma adrenal androgens of patients and on the human prostate adenocarcinoma cell lines pc 3  du 145 and lncap fgc  five cancer patients treated with suramin had an approximate 40  decline in circulating androstenedione  dehydroepiandrosterone and dehydroepiandrosterone sulfate levels  the drug inhibited the colony formation in two of the three cell lines at concentrations clinically achievable in humans without excessive drug related toxicity  the presence of suramin 300 micrograms  ml  partially inhibited the growth stimulatory effect of testosterone and basic fibroblast growth factor  but not that of epidermal growth factor  the cellular concentration of suramin following exposure to a single dose increases linearly over time in each of the cell lines with lncap fgc accumulating the highest levels of the drug  cellular levels of suramin  not androgen or growth factor sensitivity  correlated with the sensitivity to the drug  the concentrations of prostatic acid phosphatase and prostatic specific antigen released by lncap fgc cells in cell culture medium declined in the presence of increasing levels of suramin in a manner which exceeded the decrease in cell number  we conclude that suramin  aside from decreasing circulating androgens through its adrenocorticolytic effect  is also capable exerting a direct inhibitory effect on cell proliferation of prostate cancer cells  and interfere at a cellular level with the growth stimulatory effects of exogenous testosterone and basic fibroblast growth factor  
class4	influence of age and endocrine factors on the volume of benign prostatic hyperplasia  to determine whether endocrine factors influence the volume of benign prostatic hyperplasia  bph   23 hormonal factors were measured in the serum of 64 men ages 42 to 71 years with low volume prostatic cancer and these levels were correlated with the volume of benign hyperplastic tissue in their radical prostatectomy specimens  with age there was a significant increase in the volume of bph  also with age there was a significant decrease in the serum levels of free testosterone  androstenedione  dehydroepiandronsterone  dha   dehydroepiandronsterone sulphate  dha s   delta 5 androstenediol  and 17 hydroxypregnenolone  and a significant increase in sex hormone binding globulin  shbg   lh  and fsh  when bph volume and hormone levels were corrected for age  bph volume correlated positively with free testosterone  estradiol  and estriol  these data indicate that with age patients with larger volumes of bph have higher serum androgen and estrogen levels suggesting that serum androgen and estrogen levels may be factors in the persistent stimulation of bph with age  if so  therapeutic attempts at lowering plasma testosterone levels  reducing estrogen levels  or blocking androgenic stimulation through other mechanisms may interfere with the progression of bph with age  conversely  the fact that androgen production declines gradually with age may explain the observation that only 20 to 30  of men who live to age 80 require surgical treatment for urinary obstruction from bph  
class4	expression of c erbb 2 gene product in urinary bladder cancer  expression of the c erbb 2 gene product and the epidermal growth factor receptor  egf r  was investigated in 54 cases of human bladder cancer immunohistologically and by western blot analysis  for detection of the c erbb 2 product  two specific antibodies  a rabbit polyclonal antibody directed to the intracellular domain and a murine monoclonal antibody recognizing an epitope in the extracellular domain  were used  seventeen cases of bladder cancer were stained by the anti c erbb 2 polyclonal antibody  while 20 cases were stained by the monoclonal antibody  with good correlation on both stainings  p less than 0 01   there were four c erbb 2 positive cases in 26 g1 tumors  four in 15 g2 tumors  and nine in 13 g3 tumors  there were also eight erbb 2 positive cases in nine muscle invasive tumors  nine of 45 superficial tumors  four of five with lymph node metastasis  and seven of 14 without metastasis  as revealed by staining with the polyclonal antibody  thus  the c erbb 2 gene product was more frequently expressed in high grade tumors  p less than 0 01   in high stage tumors  p less than 0 01   and nodal metastatic tumors  n s  by chi square test   twenty two of the 54 tumors were stained by an anti egf r monoclonal antibody  528 igg  the expression of egf r was independent of histological grading  tumor stage  and nodal status  and no correlation was observed between expression of the c erbb 2 product and egf r  the c erbb 2 product may be applicable as a tumor marker for evaluation of malignant potential  invasiveness  and probably metastatic potential of human bladder cancer  
class4	follicular thyroid cancer treated at the mayo clinic  1946 through 1970  initial manifestations  pathologic findings  therapy  and outcome we retrospectively analyzed the outcome of all patients who received their primary treatment for follicular thyroid cancer at the mayo clinic between 1946 and 1970  the diagnosis was confirmed by reexamination of preserved tissue specimens  the 57 female and 43 male patients  mean age  53 years  underwent follow up for a maximum of 32 years  mean  17 4 years   all patients were treated surgically  and total removal of primary tumor was thought to have been accomplished in all but three  only 2 of the 88 patients without distant metastatic lesions at the time of initial diagnosis underwent ablation of the thyroid remnant  at the conclusion of the study  52 patients had died  thyroid cancer being the cause of death in 19  on the basis of univariate survival analysis  age more than 50 years  tumor size that exceeded 3 9 cm  higher tumor grade  presence of marked vascular invasion  adjacent tissue invasion  and distant metastatic involvement at the time of initial diagnosis were associated with increased cancer mortality  multivariate analysis  by cox proportional hazards model   however  identified only age greater than 50 years  marked vascular invasion  and metastatic disease at the time of diagnosis to be independent predictors of follicular thyroid cancer related mortality  patients with two or more of these predictors were classified as being high risk  these patients had 5  and 20 year survival rates of 47  and 8   respectively  the corresponding survival data for the low risk group were 99  at 5 years and 86  at 20 years  the identification of these risk groups may facilitate a more rational approach to treatment of follicular thyroid cancer  
class4	paraneoplastic brachial plexopathy in a patient with hodgkin s disease  we describe a case of inflammatory brachial plexopathy that occurred in the context of a mild  diffuse sensorimotor peripheral neuropathy associated with hodgkin s disease  clinical  electrophysiologic  and pathologic studies helped distinguish this disorder from other causes of brachial plexopathy in patients with cancer  treatment with corticosteroids seemed beneficial in this patient  we suggest that this may be another type of paraneoplastic condition associated with hodgkin s disease  
class4	longitudinal study of women with negative cervical smears according to endocervical status a longitudinal study of 20 222 women who received negative cervical smear reports in 1987 showed that the incidence of definite or equivocal cervical intraepithelial neoplasia  cin  was not significantly different between those whose first smear lacked an endocervical component and those whose smear included an endocervical component  the incidence of definite cytological evidence of cin was significantly lower in women whose first smear did not include an endocervical component  it is concluded that women whose smears are reported as negative but lack an endocervical component should not be rescreened any earlier than women with negative smears that include an endocervical component  
class4	chromogranin a storage and secretion  sensitivity and specificity for the diagnosis of pheochromocytoma  chromogranin a  co stored and co released with catecholamines from adrenal medullary and sympathetic neuronal vesicles  is elevated in the plasma of patients with pheochromocytoma  the usefulness of the hormone in the differential diagnosis of hypertension is examined  an elevated level of chromogranin a had comparable diagnostic sensitivity  83   24 29  to  but greater diagnostic specificity  96   86 90  than the level of plasma catecholamines when subjects with pheochromocytoma  n   29  were evaluated in comparison to several reference groups  including normotensive controls  n   49   subjects with essential hypertension  n   28   subjects with renovascular hypertension  n   5   and subjects with primary aldosteronism  n   3   subjects with signs or symptoms suggesting pheochromocytoma  but in whom the diagnosis was ultimately ruled out  n   5  had normal plasma levels of chromogranin a  a modest rise in chromogranin a in those with essential hypertension  and correlation of chromogranin a with diastolic blood pressure in normotensive patients and patients with essential hypertension did not impair the diagnostic usefulness of chromogranin a for pheochromocytoma  renal failure was associated with an elevated plasma chromogranin a independently of blood pressure  plasma chromogranin a correlated with tumor mass  tumor chromogranin a content  tumor norepinephrine content  and urinary vanillylmandelic acid excretion  it did not correlate with plasma or urinary catecholamines  nor with blood pressure in patients with pheochromocytoma  plasma chromogranin a levels did not differ in subjects with pheochromocytoma when stratified by age  sex  tumor location  or tumor pathology  several drugs used in the diagnosis or treatment of pheochromocytoma  clonidine  metoprolol  phentolamine  and tyramine  had little effect on plasma chromogranin a concentration  within the pheochromocytoma  chromogranin a was localized along with catecholamines to the soluble core of chromaffin granules  where it accounted for 18     5  of vesicle soluble protein  we conclude that 1  chromogranin a emerges along with catecholamines from pheochromocytoma chromaffin granules  2  plasma chromogranin a is a sensitive and specific diagnostic tool in evaluation of actual or suspected pheochromocytoma  3  plasma chromogranin a predicts pheochromocytoma tumor size and overall catecholamine production  and 4  drugs commonly employed in the diagnosis or treatment of pheochromocytoma have little effect on plasma chromogranin a level  preserving the usefulness of chromogranin a in evaluating pheochromocytoma  thus  measurement of chromogranin a provides a useful adjunct to the diagnosis of pheochromocytoma  
class4	a simplified diagnostic approach to pheochromocytoma  a review of the literature and report of one institution s experience  pheochromocytoma is an unusual but potentially devastating tumor  although a high index of suspicion is necessary  the likelihood of a pheochromocytoma is lower in the absence of the typical symptoms and findings  nonetheless  screening must be broadened to include patients with a lower risk of the disease  such as those with resistant or labile hypertension who are minimally symptomatic  extensive diagnostic evaluations should be reserved for those whose clinical or laboratory findings are more suggestive  symptoms in a group of patients in whom a pheochromocytoma was seriously considered but excluded overlap symptoms in patients with a pheochromocytoma  certain symptoms are useful  flushing to suggest a non pheochromocytoma illness  visual symptoms  flank pain  and pallor to suggest that a pheochromocytoma is more likely  combinations of symptoms can be of value  2 or more symptoms from the triad of headache  palpitations  and diaphoresis were present in the majority of pheochromocytoma patients  but in a smaller number of non pheochromocytoma patients  the presence of the entire triad is more specific  but less sensitive  new hypertension  or hypertension associated with unexplained orthostatic hypotension  are suggestive of an underlying pheochromocytoma  twenty four hour urine studies are consistently abnormal in patients with a pheochromocytoma  but are also elevated in a significant proportion of non pheochromocytoma patients  values greater then 1 5 2 fold above the upper limit of normal are very suggestive that a pheochromocytoma is present  and warrant a more intensive subsequent evaluation  imaging studies are reliable in the diagnosis of pheochromocytoma  and can help to confirm or exclude the disease  patients with a higher clinical likelihood and any elevated urinary testing  or with a lower clinical likelihood and persistently and or significantly elevated urinary testing  should have imaging studies performed  this combination of clinical screening  24 hour urinary testing  and imaging studies is a useful and reliable approach to patients suspected of harboring a pheochromocytoma  
class4	diagnostic relevance of clonal cytogenetic aberrations in malignant soft tissue tumors  background  malignant soft tissue tumors often present substantial diagnostic challenges  chromosome aberrations that might be diagnostic have been identified in some types of soft tissue tumors  but the overall frequency and diagnostic relevance of these aberrations have not been established  methods  we attempted to determine the karyotypes of a series of 62 consecutive  unselected malignant spindle cell or small round cell soft tissue tumors  from 46 adults and 16 children  after direct harvesting of cells or short term culture  all tumors were examined independently by immunohistochemical staining in addition to routine light microscopical evaluation  and all but two tumors were examined by electron microscopy  results  metaphases were obtained from 61 of the 62 tumors  and clonal chromosome aberrations were identified in 55  89 percent   in the six tumors that yielded metaphases but lacked apparent clonal aberrations  the normal metaphases were found to originate from non neoplastic stromal elements within the tumor specimens  thus  all tumors in which karyotyping was successful contained clonal chromosome aberrations  forty of 62 tumors  65 percent  contained clonal chromosome aberrations that either suggested or confirmed a specific diagnosis  in 15 of these tumors  24 percent of all tumors   the aberrations were important in establishing the final diagnosis  cytogenetic analyses were particularly informative about small round cell tumors from children  8 of 14 round cell tumors contained diagnostically important chromosome aberrations  using the combined approaches of light and electron microscopy  immunohistochemistry  and cytogenetics  we established an unambiguous diagnosis for 60 of 62 tumors  conclusions  cytogenetic analyses reveal clonal chromosome aberrations in virtually all malignant soft tissue tumors  these clonal chromosome aberrations  particularly in small round cell tumors in children  often have diagnostic relevance  
class4	pretreatment neuropsychological status and associated factors in children with primary brain tumors  we report on the neuropsychological status of 31 children with primary brain tumors who underwent assessment before receiving therapy  overall  the children performed within normal limits in all test areas  the exception was the group with anterior hemispheric tumors who demonstrated deficits in executive cognitive functions  also  when compared according to tumor type  children with midline tumors and hydrocephalus performed more poorly than others on measures of intelligence  executive abilities  visual motor skills  and fine motor functions  although one half to two thirds of the children with supratentorial midline and infratentorial tumors had cranial nerve  oculomotor  or cerebellar deficits  only the latter were associated with specific neuropsychological deficits  poorer performance on fine motor and visual motor tests   age did not appear to be a factor in these children s neuropsychological test performances  
class4	observations on the pathophysiology of nelson s syndrome  a report of three cases  nelson s syndrome is generally regarded as an unusual sequela of primary bilateral adrenalectomy when performed for cushing s disease  it is classically defined by cutaneous hyperpigmentation  considerably elevated adrenocorticotropic hormone  acth  levels  and an enlarged sella turcica  in this report  we present three cases initially treated by transsphenoidal sellar exploration for cushing s disease  in two of these cases  remission of hypercortisolism did not occur after the initial pituitary exploration  a microadenomectomy was performed in one case and  in the other  no microadenoma was found  in both  nelson s syndrome occurred after adrenalectomy  a second transsphenoidal operation and radiotherapy were required to control tumor growth  in another case  transsphenoidal adenomectomy of an acth secreting tumor initially led to a remission of hypercortisolism for 4 years  but recurrent cushing s disease necessitated adrenalectomy  and again nelson s syndrome occurred  the documentation of a pre existing acth secreting basophilic pituitary microadenoma before adrenalectomy  as seen in two of our cases  has not been previously reported  and these observations of  non classical  courses have major implications for the pathophysiology of nelson s syndrome  
class4	myeloma manifesting as a large jugular tumor  case report  the authors report a case of cranial plasmacytoma with multiple myelomas and palsy of the lower cranial nerves  the osteolytic lesion adjacent to the jugular foramen was demonstrated by an angiogram to be exceedingly hypervascular  with arteriovenous shunting resembling that seen in paragangliomas  forty five cases of cranial and intracranial plasmacytoma from the literature were reviewed  the findings indicate that a cranial plasmacytoma commonly appears to be a hypervascular tumor  whereas most dural tumors or intraparenchymal tumors have poor vascularity  
class4	giant intradiploic epidermoid tumor of the occipital bone  case report  the authors describe a case of a giant intradiploic epidermoid cyst of the occipital bone with an intracranial extension in the posterior fossa and no signs of neurological involvement  the lesion started as a painless lump under the scalp  roentgenographic and computed tomographic findings led to a correct diagnosis  and the complete removal of the cyst was accomplished  despite its large size  the total removal of these cysts is associated with a good prognosis  
class4	neurinoma in the cavernous sinus  report of two cases  two cases of trigeminal neurinoma located solely in the cavernous sinus are reported  preoperatively  magnetic resonance imaging provided the accurate localization of the lesions  allowing precise planning of the surgical approach  that is  a subtemporal lateral approach and a pterional superior approach  respectively  the neurinomas inside the cavernous sinus were removed successfully  and the patients developed no new neurological deficits except for anesthesia in the 1st division of the trigeminal nerve  the characteristic magnetic resonance imaging findings of trigeminal neurinoma in the cavernous sinus are presented  and the different surgical approaches are discussed  
class4	spinal cord hemangioblastoma with subarachnoid hemorrhage  a case of subarachnoid hemorrhage caused by a cervical hemangioblastoma is presented  the clinical picture was indistinguishable from that of a subarachnoid hemorrhage from an intracranial lesion  the diagnosis was established by angiography and water soluble contrast myelography followed by cervical computed tomographic scan  at surgery  the tumor was completely removed  and no neurological deficit was observed after the operation  
class4	 moustache  appearance in craniopharyngiomas  unique magnetic resonance imaging and computed tomographic findings of perifocal edema  this report describes two cases of craniopharyngioma with perifocal edema  in both patients  computed tomography and magnetic resonance imaging  mri  revealed that the tumors occupied the suprasellar cistern  invaginated the floor of the 3rd ventricle and were tightly adherent to the ventricular walls  the intraventricular portions of the tumors were cystic  containing protein rich fluid as suggested by mri and confirmed by operative findings  there was perifocal edema in the hypothalamus adjacent to the intraventricular tumor  the optic tracts  and the posterior limbs of the internal capsules  resembling the shape of a moustache on axial computed tomographic and mri scans  the perifocal edema subsided after treatment of the intraventricular tumor by surgical resection or radiation therapy  the  moustache  appearance seems a unique  characteristic feature of perifocal edema  which is observed infrequently with certain craniopharyngiomas  
class4	prognostic factors in stage ib squamous cervical cancer patients with low risk for recurrence  about one half of cervical cancer patients whose tumors recur after radical surgery have negative lymph nodes and clear resection margins  we evaluated 95 patients with squamous cell tumors who underwent radical hysterectomy and pelvic lymphadenectomy between january 1975 and december 1985 and who were thought to be at low risk for recurrence to see whether other clinical or histopathologic factors were predictive of tumor recurrence  detailed retrospective record review and complete pathology review were accomplished for each case  the 5 year actuarial survival rate was 89   nine patients developed recurrent disease  9 5    of whom eight died  several clinical features were evaluated as possible prognostic factors  patient age  p    26   patient race  p    60   cervical diameter  p    24   extent of gross cervical involvement  p    36   and presence of contact bleeding  p    82   histopathologic features were examined  depth of invasion  p    31   number of mitoses  p    42   character of the tumor stromal border  p    15   histologic differentiation  p    02   lymph vascular space invasion  p    56   and width of tumor  p    23   depth of invasion did correlate with increasing tumor width  p less than  001   once node  and margin positive patients are excluded  differentiation may be the only feature useful in identifying patients at risk for recurrence  because almost one half of our patients had poorly differentiated tumors  sole use of this feature as a criterion for adjuvant therapy would have resulted in overtreatment of low risk patients  
class4	familial ovarian cancer in israeli jewish women  among 310 women with ovarian cancer of epithelial origin  eight ovarian cancer prone families were identified  accounting for 24 cases  five first degree relatives underwent prophylactic oophorectomy  and early ovarian carcinoma was diagnosed in one of them  familial aggregation of ovarian cancer occurs in the israeli jewish population  
class4	serial ca 125 levels during chemotherapy for metastatic or recurrent endometrial cancer  the purpose of this study was to evaluate the role of serial ca 125 in monitoring disease status during chemotherapy in women with metastatic or recurrent endometrial cancer  ca 125 was measured in 21 women receiving cisplatin  etoposide  and adriamycin for a total of 275 courses of chemotherapy  median eight   eight of ten patients had elevated pre therapy ca 125 levels  median 233 u ml   ca 125 became and or remained negative in all 20 women with responding or stable disease and was elevated in all nine patients who relapsed  the median level at the time of relapse was 56 u ml  levels were elevated before clinical relapse in five of nine patients  56    serial ca 125 may aid in the management of women receiving chemotherapy for advanced or recurrent endometrial cancer  
class4	estrogen replacement therapy  is previously treated cancer a contraindication  the benefits of estrogen replacement therapy in preventing vasomotor symptoms  osteoporosis  and cardiovascular disease are well documented  although estrogen is said to be contraindicated in patients successfully treated for endometrial and breast cancer  there are no data to substantiate this admonition  experience suggests that it can be used safely in patients treated previously for endometrial cancer  although there is little or no experience with estrogen use in the woman treated previously for breast cancer  circumstantial evidence suggests that it is not contraindicated in all such cases  informed consent  patient desires  and risk benefit considerations must enter into the decision to use estrogen in these patients  
class4	cone cerclage in pregnancy  we report a technique of cone cerclage and the results and outcome in 17 patients who required a diagnostic cone biopsy in pregnancy  the mean age of the patients was 30 6 years  range 21 41   the mean gestational age was 18 8 weeks  range 10 32  at the time of the procedure  there were no major complications and hemorrhage was not a significant problem  there were no second trimester abortions  two patients required beta sympathomimetics to suppress uterine activity for longer than 24 hours after the procedure  six patients had invasive carcinoma  nine had cervical intraepithelial neoplasia  cin  iii  and two had cin ii  in 14 cases  the endocervical and ectocervical margins were negative  two patients with cin and one with multifocal microinvasion had positive margins  cone cerclage is a safe and easy method for performing diagnostic cervical conization during pregnancy  
class4	identification of a cdna encoding a second putative prohormone convertase related to pc2 in att20 cells and islets of langerhans  pc2 and furin are two recently identified members of a class of mammalian proteins homologous to the yeast precursor processing protease kex2 and the bacterial subtillisins  we have used the polymerase chain reaction to identify and clone a cdna  pc3  from the mouse att20 anterior pituitary cell line that represents an additional member of this growing family of mammalian proteases  pc3 encodes a 753 residue protein that begins with a signal peptide and contains a 292 residue domain closely related to the catalytic modules of pc2  furin  and kex2  within this region 58   65   and 50  of the amino acids of pc3 are identical to those of the aligned pc2  furin  and kex2 sequences  respectively  and the catalytically important asp  his  and ser residues are all conserved  on northern blots  pc3 hybridizes to two transcripts of 3 and 5 kilobases  tissue distribution studies indicate that both pc2 and pc3 are expressed in a variety of neuroendocrine tissues  including pancreatic islets and brain  but are not expressed in liver  kidney  skeletal muscle  and spleen  the high degree of similarity of pc3  pc2  and furin suggests that they are all members of a superfamily of mammalian proteases that are involved in the processing of prohormones and or other protein precursors  in contrast to furin  pc3  like pc2  lacks a hydrophobic transmembrane anchor  but it has a potential c terminal amphipathic helical segment similar to the putative membrane anchor of carboxypeptidase h  these and other differences suggest that these proteins carry out compartmentalized proteolysis within cells  such as processing within regulated versus constitutive secretory pathways  
class4	queuine  a trna anticodon wobble base  maintains the proliferative and pluripotent potential of hl 60 cells in the presence of the differentiating agent 6 thioguanine  6 thioguanine  6 tg  induced differentiation of hypoxanthine phosphoribosyltransferase  imp  pyrophosphate phosphoribosyltransferase  ec 2 4 2 8  deficient hl 60 cells is characterized by 2 days of growth  after which morphological differentiation proceeds  addition of the trna wobble base queuine  in the presence of 6 tg  maintains the proliferative capability of the cells  the ability of 6 tg to induce differentiation correlates with c myc mrna down regulation  but queuine has no effect on this parameter  treatment with 6 tg for 2 3 days commits hl 60 cells to granulocytic differentiation  and  once committed  these cells do not respond to the monocytic inducer phorbol 12 myristate 13 acetate  nonetheless  when cells are treated with queuine and 6 tg  they maintain the promyelocytic morphology and are capable of being induced down the monocytic pathway by phorbol 12 myristate 13 acetate as indicated by stabilization of c fms mrna and cell adherence  in the absence of queuine  phorbol 12 myristate 13 acetate is incapable of inducing monocytic markers in the 6 tg treated cells  the data presented indicate that 6 tg induced differentiation of hl 60 cells is a trna facilitated event and that the trna wobble base queuine is capable of maintaining both the proliferative and pluripotent potential of the cells  
class4	progression of human papillomavirus type 18 immortalized human keratinocytes to a malignant phenotype  we have developed a model system for progression of human epithelial cells to malignancy  using a human papillomavirus type 18  hpv 18  immortalized human keratinocyte cell line  cells of cell line fep 1811 were nontumorigenic in athymic mice through at least 12 passages in culture  but after 32 passages were weakly tumorigenic  producing tumors that regressed  after 62 passages they produced invasive squamous cell carcinomas that grew progressively  the progression to malignancy was associated with an increase in the efficiency of forming colonies in soft agar and with altered differentiation properties  in an organotypic culture system  fep 1811 cells at passages 12 and 32 exhibited features typical of premalignant intraepithelial neoplasia in vivo  and cells at passage 68 exhibited features consistent with squamous cell carcinomas  no change in copy number of the transfected hpv 18 genome or in the level of expression of the viral transforming gene products e6 and e7 was detected between tumorigenic and nontumorigenic cells  cytogenetic analysis of cells at early  middle  and late passage levels and cells cultured from tumors revealed that several chromosomal abnormalities segregated with the tumorigenic cell populations  
class4	vascularized full thickness parietal bone grafts in maxillofacial reconstruction  the role of the galea and superficial temporal vessels  reconstruction of bony structures of the face is always a problem as big as the defect and the function that must be replaced  everything from simple grafts to sophisticated distant bone flaps has been used  based on the studies of cutting et al   psillakis et al   and casanova et al   we have developed the full thickness galeoparietal bone flap  initially for mandibular reconstruction  but of great use for all maxillofacial reconstructions  from july of 1987 to december of 1988  14 patients have been operated on  the experience with this flap is shown in four patients as follows  primary reconstruction of a mandible as a result of ameloblastoma  secondary reconstruction of a mandible with associated old fractures and malalignment of segments  bilateral malar reconstruction in a patient with treacher collins syndrome  and severe sequelae of an already treated romberg case  small variations could be made to best accommodate the technique used to the defect we were treating  some technical details  the experience  the results  and possible sequelae or complications are also discussed  
class4	metastatic melanoma to the facial nerve  isolated metastatic malignant melanoma to the facial nerve has never been reported  this presentation illustrates a primary melanoma of the helix of the ear that was treated by excisional biopsy and then wedge resection in 1983  the primary melanoma was clark s level iv and 1 3 mm in thickness  in 1985  a facial paresis slowly developed  there was no gross evidence of recurrent melanoma in the ear or neck  but ct scan showed a mass in the region of the stylo mastoid foramen  a reoperation of the primary site revealed metastatic melanoma in the facial nerve  expanding it to approximately 10 times its normal size  a composite resection was done for the melanoma  and the paralyzed face was immediately rehabilitated by a masseter muscle transfer  the patient received 6000 rads to this area postoperatively and has remained free of disease to date  having returned to his profession as a dentist  a detailed study of all the specimens indicated that this represented a primary metastasis to the facial nerve  
class4	an evaluation of the distinction of ectopic and pituitary acth dependent cushing s syndrome by clinical features  biochemical tests and radiological findings  the efficiency of various laboratory and radiological investigations in the differentiation of ectopic from pituitary dependent cushing s syndrome was studied  based on findings in 23 patients with verified cushing s disease and seven patients with the ectopic acth syndrome  clinical features strongly favouring the ectopic type were male sex and history for less than 18 months  basal biochemical features strongly indicating the ectopic syndrome included plasma k  less than 3 0 mmol l and hco3 greater than 30 mmol l  serum cortisol at 9 a m  or midnight of greater than 800 nmol l  urine free cortisol greater than 1300 nmol 24 hours  plasma acth greater than 100 ng l  in the high dose dexamethasone suppression test  suppression by less than 50 per cent of 9 a m  serum cortisol  urine free cortisol or 17 oxogenic steroids was usually indicative of an ectopic source of acth  a mean suppressed value of greater than 450 nmol l for the 9 a m  and midnight cortisol combined occurred in all of those with the ectopic syndrome  but in none of the 23 patients with cushing s disease  for urine free cortisol  a mean suppressed value of less than 1000 nmol 24 hours was found in all patients with cushing s disease  but in none of those in the ectopic group  in the metyrapone test  there was an increase of less than or equal to 3 fold in 11 deoxycortisol at 24 hours in patients with ectopic acth  the increase was greater than 3 fold in all but one of the patients with cushing s disease  failure to respond to either dexamethasone or metyrapone was found in only one of the patients with cushing s disease  patient 16   in the ectopic group  all patients except patient d failed to respond to either test  it is concluded that patients presenting with clinically obvious cushing s syndrome along with measurable plasma acth can be reliably divided by conventional tests into those that are driven from the pituitary and those driven by ectopic acth  
class4	clinical features and natural history of von hippel lindau disease the clinical features  age at onset and survival of 152 patients with von hippel lindau disease were studied  mean age at onset was 26 3 years and 97 per cent of patients had presented by aged 60 years  retinal angioma was the first manifestation in 65 patients  43 per cent   followed by cerebellar haemangioblastoma  n   60  39 per cent  and renal cell carcinoma  n   15  10 per cent   overall  89 patients  59 per cent  developed a cerebellar haemangioblastoma  89  59 per cent  a retinal angioma  43  28 per cent  renal cell carcinoma  20  13 per cent  spinal haemangioblastoma and 11  7 per cent  a phaeochromocytoma  renal  pancreatic and epididymal cysts were frequent findings but their exact incidence was not accurately assessed  mean age at diagnosis of renal cell carcinoma  44 0     10 9 years  was significantly older than that for cerebellar haemangioblastoma  29 0     10 0 years  and retinal angioma  25 4     12 7 years   the probability of a patient with von hippel lindan disease developing a cerebellar haemangioblastoma  retinal angioma or renal cell carcinoma by age 60 years was 0 84  0 7 and 0 69  respectively  a comprehensive screening protocol for affected patients and at risk relatives is presented  based on detailed analysis of age at onset data for each of the major complications  median actuarial survival was 49 years  with renal cell carcinoma the leading cause of death  
class4	genetic mechanisms of tumor suppression by the human p53 gene  mutations of the gene encoding p53  a 53 kilodalton cellular protein  are found frequently in human tumor cells  suggesting a crucial role for this gene in human oncogenesis  to model the stepwise mutation or loss of both p53 alleles during tumorigenesis  a human osteosarcoma cell line  saos 2  was used that completely lacked endogenous p53  single copies of exogenous p53 genes were then introduced by infecting cells with recombinant retroviruses containing either point mutated or wild type versions of the p53 cdna sequence  expression of wild type p53 suppressed the neoplastic phenotype of saos 2 cells  whereas expression of mutated p53 conferred a limited growth advantage to cells in the absence of wild type p53  wild type p53 was phenotypically dominant to mutated p53 in a two allele configuration  these results suggest that  as with the retinoblastoma gene  mutation of both alleles of the p53 gene is essential for its role in oncogenesis  
class4	reoperation for colorectal carcinoma  in the management of the patient with intra abdominal recurrence of colorectal carcinoma  surgery remains the primary mode of therapy when cure or significant palliation is anticipated  appreciation of the importance of close follow up after primary resection coupled with improved diagnostic modalities has allowed the surgeon not only to detect earlier recurrence but also to select the patients most likely to benefit from resection of recurrent disease  improved surgical techniques with resultant decreases in the rates of morbidity and mortality have allowed safe hepatic resection of metastatic disease  in selected patients  this procedure produces 5 year survival rates approaching 50   although a clear consensus has not been reached  most studies agree that positive prognostic indicators include absence of extrahepatic disease  a small number of intrahepatic lesions  a low cea level  and a better dukes stage of the primary  likewise  in the patient with recurrent disease locally  surgery provides the only means of cure and also plays a significant role in palliation  aggressive resection with generous surgical margins in patients with contained disease may yield 5 year survival rates approaching 35   in patients with unresectable disease and even in those with carcinomatosis  palliation can be obtained by surgical therapy  judgment is necessary in treating these patients both preoperatively and intraoperatively  surgical intervention for obstruction  perforation  or other anatomic or physiological compromise is often indicated and can improve the quality of life of the patient with intra abdominal recurrence  
class4	treatment of renal cell carcinoma by extracorporeal partial nephrectomy and autotransplantation using splenic vascular anastomosis  a patient with large left lower pole renal cell carcinoma in a solitary kidney is presented  the patient was treated by partial nephrectomy and autotransplantation using splenic arterial and venous anastomoses  the potential for reducing operative morbidity compared with autotransplantation to the iliac fossa is discussed  
class4	a prospective study of double diagnosis of nonpalpable lesions of the breast  approximately three fourths of open biopsies of the breast performed for mammographically detected suspicious lesions are shown histologically to be benign  under the narrow conditions described herein  stereotaxic fine needle aspiration  fna  can identify these lesions with an accuracy of more than 90 per cent and a false negative rate of 5 per cent  in an effort to reduce this failure rate  the mammographic appearance and stereotaxic fna results of these lesions each were given scores on a scale of zero  benign  to five  malignant   to derive an over all risk score prospectively applied to 264 suspicious occult lesions of the breast prior to open  biopsy  while all 264 lesions could be assigned a mammographic score  adequate tissue for assignment of a cytologic score could be obtained from 150 lesions  of the 150 evaluable lesions  53 were malignant and 97 were benign  historically  with a total score of two as the threshold for open biopsy  21 of 150  14 per cent  were proved to be benign  with no false negative findings  if the total threshold score mandating an open biopsy was raised to four  the comparable figures were 61 of 150  40 per cent  benign lesions and two false negative instances of carcinoma in situ  provided adequate tissue is aspirated for cytologic examination  we conclude that this algorithm has practical value in the management of nonpalpable lesions of the breast in that it can reliably identify a fraction of the benign lesions and spare these patients an operation  
class4	simple technique for long term central venous access in the patient with thrombocytopenic carcinoma  a technique for the insertion of a central venous access device in the patient with thrombocytopenia is described  using the seldinger technique  a wire is placed into the internal jugular vein  a catheter tunneled from the anterior part of the chest is inserted through a peel away sheath into the central venous system  the incision is then closed  
class4	the merkel cell and associated neoplasms in the eyelids and periocular region  merkel cells are clear oval cells in the epidermis and outer root sheaths of hair follicles  which are probably of epithelial origin  share ultrastructural features with neuroendocrine cells  and are found in association with touch receptors  in the eyelid  they occur singly in the epidermis and external root sheaths of hairs and eyelashes  and in specialized touch spots alternating with eyelashes  their typical electron microscopical and antigenic features include dense core granules  intranuclear rodlets  spinous processes  and a positive reaction for specific cytokeratins  epithelial membrane antigen  neuron specific enolase  chromogranin and synaptophysin  merkel cell carcinoma probably develops from precursor cells which give rise to keratinocytes and merkel cells  and nearly one out of ten merkel cell carcinomas occur in the eyelid and periocular region  they tend to be bulging lesions near the lid margin of elderly patients  reddish in color  and erythematous with telangiectatic vessels  the diagnosis is based on the frequent presence of neurofilaments and paranuclear aggregates of intermediate filaments in addition to features typical of normal merkel cells  the tumor often mimics lymphoma or undifferentiated carcinoma and frequently invades lymphatic vessels  one third of merkel cell carcinomas recur  almost two thirds give rise to regional node metastases  and up to one half metastasize widely and result in death  initial treatment should be prompt and aggressive  with wide resection and routine postoperative irradiation  although metastatic lesions often respond to radiation therapy and cytostatic drugs  these treatments are mainly of palliative value  
class4	chest wall involvement by lung cancer  computed tomographic detection and results of operation  the aim of this prospective study was to evaluate   1  the role of computed tomographic scanning in predicting chest wall invasion by peripheral lung cancer and  2  the results of operation according to the depth of chest wall involvement and other potential indicators of long term survival  one hundred twelve patients with non small cell lung cancer adjacent to the pleural surface who underwent computed tomographic scanning and subsequent thoracotomy were entered into this study  tumor invasion was confined to the visceral pleura in 53 patients  to the parietal pleura in 18 patients  and to intercostal muscles in 25 patients  invasion extended beyond this layer in 16 patients  the computed tomographic criteria for chest wall invasion were  1  obliteration of the extrapleural fat plane   2  the length of the tumor pleura contact   3  the ratio between the tumor pleura contact and the tumor diameter   4  the angle of the tumor with the pleura   5  a mass involving the chest wall  and  6  rib destruction  the computed tomographic criteria 1 and 3 were significantly related to pathologic findings  sensitivity was 85  for criterion 1 and 83  for criterion 3  specificity being 87  and 80   respectively  long term survival of patients with t3 disease critically depended on the lymph node state and completeness of resection  the adenocarcinoma cell type and the t4 category were unfavorable prognostic factors  the depth of chest wall invasion did not affect survival  except for extensive rib and soft tissue infiltration  en bloc resection yielded better results than discontinuous resection  
class4	esophageal malignancies  is preoperative radiotherapy the way to go  during the period 1969 to 1988  68 patients with esophageal malignancy were subjected to preoperative radiotherapy consisting of 30 gy over 3 weeks followed by esophagectomy after a wait of 2 weeks  sixty two of 68 patients  91   were followed up retrospectively  5 year survival rate  17 2   10 year survival rate  4 8    radiosensitivity of the tumor was graded by a radiation effect scoring method devised by us  and this was found to correlate with long term prognosis  p   0 05   radiotherapy  sterilized  malignant involvement of adventitia and draining lymph nodes in 8 patients and thereby converted  palliative  into potentially  curative  resections with a mean survival of 57 2 months in this group of patients  preoperative radiotherapy was found to increase the survival  decrease the incidence of residual tumor at the resected stump  reduce the incidence of local recurrence  and increase the resectability rate  
class4	response to chemotherapy does not predict survival after resection of sarcomatous pulmonary metastases  between 1979 and 1988  26 patients with pulmonary metastases from adult soft tissue sarcomas were treated with adriamycin  doxorubicin hydrochloride   cytoxan  cyclophosphamide   and dtic before metastasectomy  thirty eight thoracotomies were performed with postoperative complications in 5 patients  5 38  13 2   and one postoperative death  1 38  2 6    two patients had benign lesions at thoracotomy and were excluded from further survival analysis  the median survival of the remaining 24 patients after thoracotomy was 18 5     5 9 months  and the actuarial 5 year survival was 22   five patients  5 24  21   achieved a clinically complete response with preoperative chemotherapy  but all had recurrence in the lung and underwent resection of pulmonary metastases  seven patients  7 24  29   achieved a partial response and had residual disease resected at thoracotomy  twelve patients  12 24  50   showed either no change or disease progression while receiving chemotherapy and were referred for resection  postthoracotomy disease free survival and postthoracotomy overall survival did not differ significantly between the three groups  one patient in the group showing no change or progression of disease while receiving chemotherapy is alive without recurrence 57 months after initial pulmonary metastasectomy  chemotherapy can be used for the initial treatment of pulmonary metastases from adult soft tissue sarcomas  however  survival after resection of pulmonary metastases cannot be accurately predicted based on the clinical response to preoperative chemotherapy  
class4	aggressive surgical intervention in n2 non small cell cancer of the lung  an aggressive attitude toward surgical treatment was taken in patients with n2 non small cell lung cancer in the past 10 years  computed tomographic scanning was employed in the diagnosis of n2 disease  and had a true positive rate of 57   among patients with n2 disease detected by computed tomographic scanning  surgical intervention was attempted except for those with unresectable disease  of 190 patients with clinical n2 disease  115 underwent surgical exploration  9 patients had only an exploratory thoracotomy  53 patients underwent a curative operation  and 53 had a noncurative operation  the overall 5 year survival rate of these patients was 16  and that of curatively resected patients was 20   there were 47 patients whose n2 disease was not recognized before operation  the 5 year survival rate of this group was 20  overall and 33  in curatively resected cases  the overall 5 year survival rate of patients with n2 disease who underwent resection  106 with clinical n2 disease and 47 with clinically unrecognized n2 disease  was 17   and that of the 84 patients undergoing curative operations was 24   an aggressive attitude toward surgical intervention can be advocated for patients with n2 disease on the basis of our present results  
class4	nephrotic syndrome complicating adenocarcinoma of the lung with resolution after resection  nephrotic syndrome is an uncommon complication of lung cancer  we present a case in which adenocarcinoma was complicated by the nephrotic syndrome  which resolved after resection of the cancer  
class4	surgical strategy for early gastric cancer  the diagnostic and therapeutic options in early gastric cancer are reviewed  in japan  the rate of detection of early gastric cancers has increased so that minute gastric cancers can now be identified as a result of advances in diagnostic methods  the results of histopathological staging of a large number of resected specimens have led to three surgical options based on size and depth of the primary lesion  namely classical r2 resection  radical resection with limited lymphadenectomy and endoscopic surgery  
class4	adrenal insufficiency in the cancer patient  implications for the surgeon  aspects of acute and chronic adrenal insufficiency of interest to surgeons who treat cancer patients are reviewed  clinical features and the management of both primary and secondary types are considered with reference to classification  aetiology  diagnosis and treatment  specifically considered are the management of patients with addison s disease and metastases  prompt recognition and treatment of adrenal insufficiency can avert potentially life threatening situations  
class4	adjuvant chemotherapy with 5 fluorouracil  vincristine and ccnu for patients with dukes  c colorectal cancer  the swedish gastrointestinal tumour adjuvant therapy group  a prospective controlled randomized trial testing adjuvant postoperative combination chemotherapy  5 fluorouracil  lomustine  ccnu  and vincristine  versus no adjuvant therapy in patients operated on for dukes  c colorectal cancer is reported  in total 334 patients aged less than 70 years were recruited  205 patients with colonic and 99 with rectal cancer  but there were three protocol violations and these cases are excluded from further consideration  twenty seven patients had a limited resection of their cancer  after 5 years  follow up there was no significant difference in the tumour free survival rate or in the survival rate between the treated and control groups  twenty nine of the 147 patients who started chemotherapy discontinued this treatment because of side effects  mainly from the gastrointestinal tract  in 30 patients treatment was discontinued because of recurrent disease  the conclusion is that systemic administration of combination chemotherapy for colorectal cancer after operation is not worthwhile in routine clinical practice  
class4	value of retesting subjects with a positive hemoccult in screening for colorectal cancer  within a prospective randomized screening study for early detection of colorectal cancer with rehydrated hemoccult ii test  the possibility of increasing the specificity of the test by retesting patients with an initially positive hemoccult ii test was investigated  of those offered the test 3561  62 6 per cent  returned it and it was positive in 210 cases  5 9 per cent   the repeat test was performed by 184 patients and was positive in 68  1 9 per cent   all those with a positive initial test had rectosigmoidoscopy to 60 cm and a double contrast enema  a carcinoma was found in one in seven patients with a positive retest but in only one in 100 patients with a negative retest  p less than 0 001   the specificity of the test was  therefore  increased from 95 per cent to 98 per cent and the sensitivity was unchanged  rescreening was offered at a later date and increased numbers were available  7147 patients returned the test and 369  5 2 per cent  were positive  the test was repeated in 360 patients and 118  1 7 per cent  were positive  a colorectal neoplasm was found in one in three of those with a positive repeat test  compared with one in seven of those with a negative repeat test  in conclusion  screening for early detection of colorectal cancer with a rehydrated hemoccult ii test may be followed by investigation of only those patients with a positive retest  such a procedure will reduce the work load by 60 per cent without reducing sensitivity  
class4	epidermal growth factor receptor expression in colorectal cancer  epidermal growth factor  egf  receptor expression was estimated in 50 invasive human colorectal cancers using immunohistochemistry and the degree of expression was quantified from integrated optical density measurements on the stained sections  all tumours stained positively  but dukes  c tumours exhibited significantly higher levels of receptor than either dukes  a or b tumours  in addition  histologically high grade cancers expressed receptors more strongly than those of low grade  it is concluded that a high egf receptor concentration is associated with poor prognostic factors in colorectal malignancy  
class4	risk of cancer death in first degree relatives of patients with hereditary non polyposis cancer syndrome  lynch type ii   a study of 130 kindreds in the united kingdom  to estimate the relative risks of cancer in first degree relatives of index patients  130 pedigrees of dominantly inherited lynch type ii cancer family syndrome have been analysed  the risk of death from all causes was significantly increased in women over 45 years of age and the overall liability to cancer in women was greater than for men  a sevenfold increase in risk of colon cancer was found in both sexes  in female relatives the risk of breast cancer was increased fivefold and lifetime risk of breast cancer was 1 in 3 7  a screening programme based on estimated risks could be offered to first degree relatives of index patients with lynch type ii cancer family syndrome  
class4	levamisole and 5 fluorouracil therapy for resected colon cancer  a new indication  objective  to evaluate the benefits and risks of postoperative treatment with levamisole plus 5 fluorouracil  5 fu  in patients with colon cancer  design  computerized searches of medline and cancerlit were performed  and the reference list of each retrieved article was checked  only randomized trials of therapy with levamisole alone or combined with 5 fu for colon cancer without distant metastases were included  the studies were then evaluated with the use of four criteria  results  we reviewed six randomized trials  of which three satisfied our criteria  two studies demonstrated a significant improvement in the survival rate with levamisole plus 5 fu among patients with colon cancer and pathologically confirmed metastases to adjacent lymph nodes  dukes  stage c   a subgroup analysis in another study demonstrated a similar benefit  the toxic effects of the drugs were generally mild  the three other studies showed no difference in survival rates between the treatment groups  however  the samples were too small to detect a clinically or statistically important difference  conclusions  because many patients with colon cancer will suffer a relapse we recommend that they be offered the opportunity to participate in clinical trials of adjuvant therapy  for those with stage c disease not entering a clinical trial levamisole plus 5 fu is appropriate adjuvant therapy  
class4	macrophage colony stimulating factor activity in malignant pleural effusions  its augmentation by intrapleural interleukin 2 infusions  the activity of endogenous colony stimulating factor  csf  in malignant pleural effusions of lung cancer patients before and during daily intrapleural infusions of recombinant interleukin 2  il 2  was measured quantitatively by colony forming bioassay and radioimmunoassay  ria   before therapy  malignant pleural effusions had various levels of csf activities  and this csf activity was neutralized almost completely by anti m csf antibody  ria also showed that the effusions contained various amounts of m csf  daily intrapleural infusion of recombinant il 2 caused significant increase in the csf activities and m csf levels in pleural effusions  these results indicate that in vivo treatment with il 2 induces production of endogenous m csf  
class4	catecholamine induced cardiomyopathy in multiple endocrine neoplasia  a histologic  ultrastructural  and biochemical study  a catecholamine induced dilated cardiomyopathy is reported in a patient with multiple endocrine neoplasia  type 3  a histologic and ultrastructural study has been undertaken in cardiac biopsy samples  together with determination of myocardial ca   and cellular membrane fatty acids  contraction band necrosis of cardiocytes with supercontraction of sarcomeres progressing to myofibrolysis and increased levels of myocardial ca   have been found as morphologic and biochemical abnormalities  respectively  no lipoperoxidation of cellular membranes or an alpha adrenergic mediated reduction of coronary supply could be recognized in the study  we indicate a receptor mediated intracellular ca   overload as the main abnormality responsible for myocardial impairment  
class4	atopy and primary lung cancer  histology and sex distribution  atopy  defined as the ability to develop ige antibodies to commonly encountered allergens under conditions of normal exposure  has an inherited component with pleiotropic effects  an inverse relationship between the occurrence of atopy  allergy related diseases  and cancers at specific sites has been reported  the familial association of primary lung cancer is most evident among women  nonsmokers  and those with adenocarcinomas  in order to determine whether the relationship between a lower prevalence of atopy among patients with lung cancer compared to control subjects was consistent between histologic cell types  we used seven common allergens to allergy prick skin test 209 community control subjects  46 women   109 cases with primary squamous cell carcinoma of the lung  25 women   and 67 patients with primary adenocarcinomas of the lung  23 women   we have confirmed earlier reports of an inverse relationship between atopy and lung cancer risk  in analyses focusing on sex and histologic cell type  we found that women with adenocarcinomas were an exception and were as likely to be atopic as control subjects  the evidence does not support a protective role for atopy among these women  
class4	the acute and insidious onset of pulmonary metastatic transitional cell carcinoma  transitional cell carcinoma is a common urologic neoplasm  although pulmonary metastases from this tumor are often not appreciated clinically  they are frequently documented in autopsy studies  therefore  the clinical recognition of this condition can be problematic  to illustrate this point  we present three patients with progressive unexplained dyspnea and histories of transitional cell carcinoma  since ineffective and possibly detrimental therapeutic approaches may be initiated  a high index of suspicion for pulmonary metastatic embolization must be maintained  early histologic identification of these metastatic emboli and initiation of effective chemotherapy may prove beneficial for improved quality of life  
class4	retinoid modulation of insulin like growth factor binding proteins and inhibition of breast carcinoma proliferation  retinoids induce cellular differentiation and inhibit cellular proliferation  proliferation of human breast carcinoma cells in vitro is markedly inhibited by these compounds  on the other hand  insulin like growth factors  igfs  and their receptors seem to be involved in the growth of certain breast carcinoma cells by autocrine or paracrine effects  since the effects of both igf i and igf ii may be modulated by specific binding proteins  igf bps  we examined the possibility that one mechanism by which retinoic acid may inhibit cancer growth is by an alteration in these bps  thereby blocking igf s growth effect  retinoic acid  ra  1 microm  completely blocked the effect of igf i  50 ng ml  on enhancing proliferation of mcf 7 cells in culture  this effect of ra was not associated with any significant change in specific igf i binding sites on these cells  ra induced a 3 fold increase in igf binding activity in conditioned medium  measured using a polyethylene glycol immunoglobulin precipitation assay and a charcoal absorption assay  this increase was associated with the appearance of 42  and 46 kda igf bps on ligand blotting  the effect of ra on these igf bps was time and concentration dependent  in contrast  during some experiments the 27  and 36 kda bps actually decreased  these findings support the hypothesis that ra may inhibit the growth of certain breast carcinoma cells by increasing the secretion of certain igf bps  which could directly modulate the growth effect of igfs  
class4	reviewing the unicystic ameloblastoma  report of two cases  classification of ameloblastoma into solid  multicystic  unicystic  and peripheral types based on clinical appearance and effects has gained recent recognition  the unicystic ameloblastoma is a less encountered variant of the ameloblastoma  it appears more frequently in the second or third decade with no sexual or racial predilection  it is almost exclusively encountered asymptomatically in the posterior mandible  the following report of two cases discusses the pathophysiology  demographics  histology  and prognosis of the unicystic ameloblastoma  
class4	a multicentre follow up study of 1152 patients with myasthenia gravis in italy  a multicentre retrospective study was carried out on the characteristics and course of myasthenia gravis  mg  in italy  data from 1152 patients  fairly representative of the myasthenic population seeking medical advice  were analysed for diagnostic criteria  clinical aspects and therapeutic approaches  mean follow up was 4 9 years  the disease was correctly diagnosed within 2 years of the onset in 80  of cases  onset of symptoms peaked in the second and third decade in females and fell between 20 and 59 years in males  at first observation 87  of the patients had generalized mg  maximal worsening was observed within 3 years in 77  of patients  at the last follow up  35  of cases were symptom free  pharmacological remission 24   remission without treatment 11    the more severe the disease at the first observation and at the maximal worsening of symptoms  the lower was the proportion of remissions  steroids were given in 54  and immunosuppressants in 18   thymectomy was performed in 72   mostly in women  younger than age 40  and with generalized mg  thymectomy seemed to improve the course of the disease  mostly in patients operated on shortly after diagnosis and those with generalized mild to moderate disease and with a normally involuted thymus  mg was lethal in 4  of patients  principally men  older than 40  in grade 3 or worse at first observation  with a short history of disease  and with thymona  
class4	oculo bulbar myasthenic symptoms as the sole sign of tumour involving or compressing the brain stem  four patients with tumours involving or compressing the brain stem are described whose initial clinical symptoms of fluctuating paresis of the external ocular muscles and or the pharyngeal muscles without other neurological deficits led to the primary diagnosis of focal myasthenia  the combination of an unusual clinical pattern  involvement of muscles of only one ocular nerve or severe dysphagia dysarthria without extension of the myasthenic symptoms  should lead to further investigation to exclude other reasons of a focal myasthenic syndrome such as a brain stem tumour  
class4	primary intracerebral sarcoma in childhood  case report with electron microscope study  a case of a primary intracerebral sarcoma is described in a 5 year old girl  histology and immunohistochemistry excluded the diagnosis of a leiomyosarcoma  a malignant haemangiopericytoma or a fibrosarcoma  electron microscopical findings indicated that the origin of the sarcoma was in the pia mater  
class4	evaluation of the serum level of immunosuppressive substance in oral cancer patients  the serum level of immunosuppressive substance  is  was studied in 40 patients with primary oral cancer and in 79 patients without cancer  its usefulness was evaluated as a parameter for monitoring therapy as well as recurrence of the tumors  mean values for serum is in patients with cancer and patients without were 687     284 micrograms ml and 464     153 micrograms ml  respectively  normal healthy controls had a mean value of 431     105 micrograms ml  with the cutoff value set at 641 micrograms ml  mean  2 sd   patients without cancer who had a severe infectious disease showed conspicuously high serum is levels  and these values were closely correlated with their c reactive protein values  the positive rate of is increased in all patients with oral cancer was 58   the mean level of serum is in cancer patients was significantly higher than that of the controls  p less than  01   and the level was found to be more elevated as the stage of the disease advanced  stage i to iii  48   stage iv  68    histologic analysis of the tumor cells in patients with squamous cell carcinoma  scc  showed that the mean serum is level of those who had poorly differentiated scc was much higher  937     181 micrograms ml  than that of patients with well differentiated scc  616     159 micrograms ml   patients who had recurrent or metastatic cancer  or those who died from the cancer exhibited marked elevation of the serum is levels  whereas patients who remained free of cancer in the follow up period showed significantly lower serum is levels  the rise and fall of the serum is level was closely correlated with the disease progression and or remission  these data strongly suggest that serum is is a useful parameter for monitoring the disease stage as well as the effect of therapy on patients with oral cancer  
class4	vulvar paget s disease  is immunocytochemistry helpful in assessing the surgical margins  from january 1977 to december 1988  19 patients with biopsy proven paget s disease of the vulva underwent simple or radical vulvectomy at the university of miami jackson memorial medical center  all vulvectomy specimens were evaluated immunocytochemically for the expression of carcinoembryonic antigen  cea   epithelial membrane antigen  ema  and low molecular weight keratins 8 and 18  lmk   both in areas containing neoplastic cells and in histologically negative surgical margins  neoplastic paget s cells stained positively for cea in all cases  they were positive for ema and lmk in 18 and 17 cases  respectively  in all eight cases with underlying in situ or invasive carcinomas  cea  ema and lmk were localized in the underlying tumors as well  none of the histologically proven negative margins reacted for cea  ema or lmk on immunocytochemistry  cea appears to be a valuable immunocytochemical marker for extramammary paget s disease  ema and lmk are also expressed by the majority of such cases  none of these markers  however  is of added value in identifying paget s cells in surgical margins if those margins appear negative on routine hematoxylin and eosin staining  
class4	immunohistochemical investigations of estrogen receptors in normal and neoplastic squamous epithelium of the vulva  atrophic disease of the vulvar epithelium can be treated with steroids  but carcinoma of the vulva cannot be influenced with any hormone therapy  seventy one vulvar specimens were tested for estrogen receptor  er  content by means of immunohistochemistry  slight er staining was found in nonkeratinizing squamous epithelium in 17 of 22 cases  a weak er reaction in the basal and parabasal layers was found in only 2 of 17 specimens of keratinizing squamous epithelium  however  no er was found in any neoplastic tissue of the vulva or the adjacent stroma  the loss of er in neoplastic cells could explain the clinical experience that antihormonal treatment of vulvar carcinomas produces no appreciable improvement  
class4	granular cell tumors of the vulva  granular cell tumor  gct   although nearly ubiquitous  is seen infrequently in the vulva  a review of the surgical pathology files from grady memorial hospital  atlanta  georgia  from 1983 through 1987 identified eight cases of vulvar gct  five of the eight patients had more than one skin and soft tissue lesion  two of the five had biopsy proven multicentric gct with a unique clinical course  one of the patients was a 32 year old woman with multiple vulvar  lingual  laryngeal  bronchial and pulmonary gct  necessitating multiple excisions and ultimately pneumonectomy  the second patient had multiple gcts in the vulva and inguinal area and finally in both lungs  resulting in her death at age 39  no dependable microscopic features could be identified to distinguish benign gct from its more aggressive variant  however  feulgen dna histomorphometry demonstrated aneuploidy in the patient with apparent lung metastases  whereas the tumors from patients with a benign course as well as from the patient with multiorgan involvement were diploid  in three of five patients who could be interviewed there was a history of soft tissue tumors in members of the family  the multifocal nature and possible familial component of gct need to be explored further  
class4	periurethral colonic type polyp simulating urethral caruncle  a case report  a 50 year old  black woman presented with a 1 cm  polypoid lesion on the posterior edge of the urethral meatus that had the gross appearance of a urethral caruncle  the histologic features  however  revealed a superficially ulcerated lesion composed of colonic type mucosal glands with focal regenerative atypia in response to inflammation  a similar histologic pattern is also found in so called solitary rectal ulcer syndrome and inflammatory cloacogenic polyps arising in the anorectal area  based upon an english language literature review  this case appears to be the second reported one of an intestinal type polyp in this location  the patient had no further problems after excisional biopsy  
class4	vulvar condylomas and squamous vestibular micropapilloma  differences in appearance and response to treatment  a study of 37 women with typical condylomas and so called squamous micropapilloma was undertaken to determine their response to systemic interferon and or podophyllin treatment  thirty lesions were classified as condylomas and 9 as squamous micropapillomas  two women had both lesions  twenty six  87   of 30 condylomas responded  whereas only 1  11   of the 9 cases of micropapillomatosis showed a partial response  p less than  001  to podophyllin and or interferon  twenty six biopsies from condylomas in which sufficient dna was available for analysis contained human papillomavirus  hpv  dna sequences that hybridized to an hpv 6   16 probe mix under nonstringent conditions  in contrast  hpv dna sequences could not be detected in any of the nine cases of micropapillomatosis  immunoperoxidase studies performed on these lesions failed to demonstrate viral capsid antigen  thus  despite certain similarities in the clinical presentation and microscopic features of condylomas and squamous micropapillomas  it is not clear at present whether micropapillomas are hpv related lesions  
class4	vulvar intraepithelial neoplasia  a clinicopathologic study of 60 cases  sixty cases of vulvar intraepithelial neoplasia  vin  were analyzed clinicopathologically  24 vin i  9 vin ii  27 vin iii   the ages of the patients ranged from 21 to 83 years  mean  53 7   colposcopic examinations showed the presence of white areas in 29 cases  red areas in 9  acetowhite areas in 6 and other alterations in 13  one third of the lesions were multifocal  pruritus and burning were present in 65  of the cases  fifty one percent of the cases showed histologic changes suggestive of human papillomavirus  hpv  infection  the mean age of those patients was significantly lower than that of patients without hpv infection  in 15 cases of vin  hpv dna testing was performed with southern blot hybridization  in three  20   of those specimens hpv 16 episomal dna was identified  epithelial alterations surrounding the areas of vin were found in 24 cases  40   23 squamous cellular hyperplasias and 1 lichen sclerosus  different types of treatment were performed according to the different grades of vin  medical therapy  diathermocoagulation  local excision  hemivulvectomy and total vulvectomy  follow up was possible in 52 cases  with a mean of 33 months  range  3 98   two cases of vin i showed progression of disease over 12 24 months  
class4	multimodality therapy for advanced and recurrent vulvar squamous cell carcinoma  a pilot project  from 1985 to 1989 eight women with advanced or recurrent vulvar carcinoma were treated at the women s cancer center of the university of minnesota hospital and clinic  each received a combination of 5 fluorouracil  mitomycin c and cisplatin during radiotherapy  five of the eight women who underwent posttreatment radical vulvectomy had acceptable operative morbidity  six patients experienced a complete clinical response  of them  one had microscopic residual disease in the surgical specimen  one patient with recurrent vulvar carcinoma experienced progression of disease on therapy  one death was attributable to chemotherapy toxicity  and two patients died of intercurrent disease  the overall survival rate at 27 months was 33   this multimodality approach to the treatment of advanced vulvar carcinoma should be considered when designing a therapeutic approach to treating extensive or resistant vulvar carcinoma  
class4	value of four models for selecting patients for local excision of invasive squamous cell carcinoma of the vulva  for 75 women with squamous cell carcinoma of the vulva who underwent radical vulvectomy and inguinofemoral lymphadenectomy  the authors assessed the efficacy of four models for selecting patients who could have been treated adequately with local excision of the tumor  each of the three models proposed by andreasson and nyboe covered 25  of the patients  none of whom had groin metastases or died of cancer  local recurrence in the vulva occurred in 10   a model suggested by the international society for the study of vulvar disease covered almost 10  of the patients  one of seven patients had groin metastases  none died of cancer  and one of seven developed local recurrence in the vulva  the criteria of the clinically best suited model are tumor not situated on the clitoris and less than 4 cm in diameter  with only slight hyperchromasia  this model ought to be tested in a randomized study  
class4	the 1989 presidential address  international society for the study of vulvar disease  major changes in the terminology for vulvar disease have taken place in the past 20 years under the influence of the members of the international society for the study of vulvar disease  major terminology changes have been made for vulvar nonneoplastic disorders  vulvar intraepithelial neoplasia and superficially invasive squamous cell carcinoma  
class4	decreased local toxicity with subcutaneous diamorphine  heroin   a preliminary report  we report the cases of 5 patients who developed severe local toxicity during the subcutaneous administration of morphine sulphate and hydromorphone hydrochloride  all patients required site changes more frequently than once every 24 h due to redness  swelling  or pain while receiving morphine or hydromorphone  all patients showed prolongation in the duration of sites of infusion once an equianalgesic dose of diamorphine hydrochloride  heroin  was started  no change in pain control or systemic toxicity was detected with diamorphine  these findings suggest that diamorphine could be a useful alternative for patients who develop severe toxicity to subcutaneous morphine or hydromorphone  
class4	literacy and laryngectomy  how should one treat head and neck cancer in patients who cannot read or write  the entire population of otolaryngologists and radiation oncologists  n   192  in active practice in the state of north carolina were surveyed to assess their level of awareness of illiteracy among adults in the united states and to determine whether these physicians consider illiteracy in the treatment decision process for patients with head and neck cancer  excluding respondents who did not treat patients with head and neck cancer and physicians practicing outside of the state of north carolina  the response rate was 115 of 182  or 63   only 26  of respondents were able to estimate correctly the prevalence of illiteracy in the us adult population  forty one percent of respondents  however  stated that they did consider their patient s ability to read and or write before making treatment recommendations for head and neck cancer  this survey and accompanying literature review suggest that physicians perceive illiteracy as a problem that may have a significant impact on patients with head and neck cancer  but lack the data needed to enable them to quantify the effect of illiteracy on treatment outcome  the study reported is the first step in examining ways in which illiteracy might negatively affect patient outcomes  
class4	paratesticular myxoma  an unusual benign intrascrotal neoplasm  we have presented a case of paratesticular myxoma and have described the clinical history  findings on light microscopy and immunohistochemistry  and possible pathogenesis  although primary paratesticular myxoma is a rare lesion  it should be considered in the differential diagnosis of intrascrotal mesenchymal tumors  
class4	wernicke korsakoff syndrome complicating t cell lymphoma  unusual or unrecognized  malnutrition rather than alcohol abuse is the common element in most cases of wks  our report may be the first to identify both the clinical and neuropathologic features of the syndrome in a patient with t cell lymphoma  the coincidence of these two illnesses underscores a need to consider wernicke s encephalopathy in debilitated individuals with malignancy or other chronic illnesses  highlights an atypical presentation of acute wernicke s encephalopathy  and demonstrats the precipitation of that syndrome by glucose feeding  attention to a patient s nutritional status and the liberal use of thiamine may prompt early recognition of the syndrome or prevent it entirely  
class4	astroblastoma  electron microscopy and immunohistochemical findings  case report  the clinical  histological  immunohistochemical  and electron microscopic features of a cerebral astroblastoma are reported  the patient is a young woman with a superficial parietal tumor  macroscopic findings include a well delineated superficial nodule with a hard central core  histological study disclosed a predominantly papillary tumor with hyalinized vessels  tumor cells were scarcely positive with immunohistochemical stain for glial fibrillary acidic protein  extensive and diffusely positive with vimentin and neuron specific enolase  and intensely positive with s 100 and epithelial membrane antigen in the papillary areas  ultrastructural study showed abundant intermediate filaments forming bundles in tumoral cytoplasms  membrane junctions  and external laminae when cells were in contact with collagen fibers  based on immunohistochemical and ultrastructural characteristics  we believe that the filaments seen in tumor cells are mainly vimentin filaments  these peculiar immunohistochemical patterns in a glioma may aid in the histological diagnosis of this rare tumor type  
class4	intramedullary spinal cord germinoma  case report  a case of intramedullary spinal cord germinoma within the conus medullaris  with lumbago and pain in the lower extremities  is presented  the intramedullary spinal cord germinoma was determined by a biopsy specimen  after local irradiation of 50 gy  the tumor markedly decreased in size and clinical symptoms disappeared  
class4	glossopharyngeal schwannoma  review of five cases and the literature  glossopharyngeal schwannomas are rare tumors in spite of the fact that acoustic schwannomas account for 8  10  of intracranial tumors  there have been 23 reported cases in the literature  this report of five cases is the largest series of these tumors  the presentation  radiological workup  operation  and long term postoperative results will be presented  along with a review of the literature  
class4	infarct of the conus medullaris simulating a spinal cord tumor  case report  a 71 year old woman had the sudden onset of a neurogenic bladder and a stepwise increase in paraparesis that left her unable to stand or walk  magnetic resonance imaging showed what appeared to be a tumor in the conus medullaris  after laminectomy  the lesion was localized by ultrasound examination  and a biopsy was performed  the deficits remained unchanged postoperatively  microscopic examination of the biopsy specimen showed necrosis and pathologic changes consistent with infarction of the conus medullaris  an anomalous arterial supply of the conus medullaris is the most likely cause of this unusual problem  the patient gradually regained her ability to walk  but the neurogenic bladder persists  
class4	ganglioneuroma of the spinal cord  this report describes a 2 year old boy who harbored an intramedullary ganglioneuroma involving almost the entire length of the spinal cord  the terminology  pathology  and neurobiological behavior of this tumor is discussed  
class4	mammography and early breast cancer detection  screening mammography has been shown to reduce breast cancer mortality  both film screen mammography and xeromammography are highly sensitive and specific  mammography accreditation programs assure physicians and patients that a facility provides mammography of the highest quality  using the lowest possible radiation dose  mammographic signs of early cancer include a small mass  calcifications  architectural distortion and a neodensity  dense tissue may result in a false negative examination even when a cancer is palpable  with adverse effects if biopsy is delayed  
class4	genetic analysis of breast cancer in the cancer and steroid hormone study  the familial risk of breast cancer is investigated in a large population based  case control study conducted by the centers for disease control  the data set is based on 4 730 histologically confirmed breast cancer cases aged 20 to 54 years and on 4 688 controls who were frequency matched to cases on the basis of both geographic region and 5 year categories of age  and it includes family histories  obtained through interviews of cases and controls  of breast cancer in mothers and sisters  segregation analysis and goodness of fit tests of genetic models provide evidence for the existence of a rare autosomal dominant allele  q    0033  leading to increased susceptibility to breast cancer  the effect of genotype on the risk of breast cancer is shown to be a function of a woman s age  although  compared with noncarriers  carriers of the allele appear to be at greater risk at all ages  the ratio of age specific risks is greatest at young ages and declines steadily thereafter  the proportion of cases predicted to carry the allele is highest  36   among cases aged 20 29 years  this proportion gradually decreases to 1  among cases aged 80 years or older  the cumulative lifetime risk of breast cancer for women who carry the susceptibility allele is predicted to be high  approximately 92   while the cumulative lifetime risk for noncarriers is estimated to be approximately 10   
class4	contributions of the zollinger ellison syndrome  the salient contributions of the zollinger ellison syndrome have made it unique  no pancreatic endocrine tumor described before  insulinoma  or subsequently  glucagonoma  somatostatinoma  vipoma  pancreatic polypeptidoma  has been the topic of such a variety of studies  or has been such an inspiration and rich source of new ideas for investigation and ultimate improvement in patient care  
class4	historical review of pancreaticoduodenectomy  the performance of pancreaticoduodenectomy by whipple in 1935 demonstrated that the operation was feasible technically and compatible with reasonable function after recovery  from the mid  to late 1940s until the last 10 years  the procedure was condemned by many because of its associated mortality and morbidity  for reasons that are not clear  the risk of pancreaticoduodenectomy in the last 10 years has fallen to less than 10  and in several centers  less than 5   postoperative complications have been reduced and blood transfusions are unnecessary in an increasing number of patients  furthermore  a normal productive life without the need for medication and with no digestive disorder is expected  seventy one percent of patients are able to return to their preoperative occupation  
class4	carcinoma of the ductus choledochus  a retrospective review of patients treated for carcinoma of the common bile duct has demonstrated improvement in diagnostic capabilities  leading to earlier management by resectional therapy  the ability to resect these tumors is directly translatable to improved long term survival  efforts to obtain proof of malignancy prior to resection are often frustrated by the inability to obtain adequate representative tissue for frozen section  choledochoscopic biopsies and incisional biopsies have given the highest yield of positive diagnoses  in experienced hands  a program of fewer preoperative tests with emphasis on early operation  diagnosis  and definitive treatment may be more cost effective in the management of patients with common bile duct cancer  
class4	germfree animals and technics in surgical research  germfree animals have been reared to a size  weight  and age permitting the performance of major surgical procedures and the pursuit of a variety of surgical research problems  germfree dogs have been maintained in the isolator system through three generations  indicating that life  reproduction  and growth are all possible in the absence of microbial contamination  the value of the germfree approach to surgical problems has been utilized in studies of a variety of gastrointestinal problems  shock  cancer  immunology  burns  wound healing  and in direct patient application  patients have been maintained in isolator environments for prevention of infection  for operative procedures  for treatment of extensive burns  and for management of immune suppressed individuals  we conclude that germfree animals and germfree technics provide a valuable addition to the armamentarium of the surgeon in both research and clinical applications  
class4	vascular lesions of the intestines  this article reviews the pathology  pathophysiology  diagnosis  and treatment of vascular lesions of the intestine as a cause of gastrointestinal bleeding  in addition  a modified system for classifying such lesions  based on the author s personal experience with such lesions  is presented  
class4	the effects of midazolam on cerebral blood flow and oxygen consumption  interaction with nitrous oxide in patients undergoing craniotomy for supratentorial cerebral tumours  cerebral blood flow and the cerebral metabolic rate of oxygen were measured in 30 patients during craniotomy for supratentorial cerebral tumours by a modification of the kety schmidt technique using xenon 133 intravenously  anaesthesia was induced with midazolam 0 3 mg kg  fentanyl and pancuronium  and maintained with midazolam as a continuous infusion  fentanyl  pancuronium and nitrous oxide in oxygen or oxygen in air  the concentration of midazolam in the blood of 10 patients was about 300 ng litre during two measurements  the patients  lungs were ventilated with n2o in oxygen  the concentration of midazolam in the blood of another 10 patients was doubled to about 600 ng litre during the second flow measurement  the patients  lungs were ventilated with n2o o2  the concentration of midazolam in the blood of the third group of 10 patients was doubled to 600 ng litre during the second flow measurement  the patients  lungs were ventilated with oxygen in air  no relationship was found between the dose of midazolam and cerebral blood flow or oxygen consumption  nitrous oxide in combination with midazolam also had no effect on these variables  
class4	pregnancy associated with gorlin s syndrome  a pregnant woman with gorlin s syndrome presented for the removal of malignant ovarian tumours  the main problem encountered by the anaesthetists was an unexpected increase in arterial blood pressure  this was most probably associated with surgical manipulation of the ovaries with an increase in prorenin renin production  
class4	cellular and molecular basis of the asbestos related diseases  asbestosis is an inflammatory and fibrotic process of the alveolar structures mediated  at least in part  by cytokines released by  activated  alveolar macrophages  the process of phagocytosis and  activation  of alveolar macrophages is poorly understood  are all macrophages activated or only subpopulations  which cytokines are up regulated  how does the local milieu modulate profibrotic and antifibrotic mediators  is protein release accompanied by up regulation of gene transcription  is there an ordered sequence of cytokine activity  what roles do neutrophils and lymphocytes play  how can disease progression best be quantified absent further exposure  answers to these questions are important to direct rational strategies at interdicting the fibrotic process  the question of cancer and asbestos is more vexing  the processes of inflammation  fibrosis  and carcinogenesis appear to be closely intertwined  for example  proto oncogenes such as c sis  pdgf b chain  are up regulated in activated alveolar macrophages from fibrotic lungs  these and possibly others may play an important role in asbestos carcinogenesis  second  asbestos can transfect dna into cells  furthermore  dna can adhere to asbestos fibers  and these fibers are capable of direct transmigration into cells  the questions of the mechanisms of cigarette smoke cocarcinogenicity and latency remain  lastly  if the bronchial epithelium is highly metaplastic throughout from cigarette smoking  what triggers a single  or several  nidus of cells to transform into carcinoma  malignant mesothelioma poses the most challenging questions because of association with brief asbestos exposure by history  mesothelial cells are susceptible to minute environmental manipulations  and changes occur after exposure to all fiber types  yet epidemiologic studies point toward long amphiboles as having greater mesothelioma risk  to test this hypothesis  experimental data must be generated differentiating tumorigenesis risk from short  chrysotile fibers that can migrate to the parietal pleura from the associations of long amphiboles persisting in lung tissue  despite the future decreasing numbers of clinical cases of asbestos related disease  solving the important mechanistic questions remaining will contribute significantly to our understanding of fibrosis and cancer  
class4	reversed helper suppressor t lymphocyte ratio in bronchoalveolar lavage fluid from patients with breast cancer and pneumocystis carinii pneumonia  pneumocystis pneumonia  pcp  usually occurs in patients with hematologic malignancies and acquired immunodeficiency syndrome  aids   patients with solid tumors represent a very small fraction of the reported cases of pcp  over an 18 month period  pcp was diagnosed in three patients who had received radiation and chemotherapy for breast cancer  in all three patients  there was no serologic or clinical evidence of aids  direct staining of bronchoalveolar lavage fluid  bal  revealed pneumocystis carinii  and cellular analysis of bal revealed an increased percentage of lymphocytes with reversed helper inducer suppressor cytotoxic t cell  cd4 cd8  ratio  because decreased cd4 cd8 ratio in bal is commonly accepted as findings consistent with hypersensitivity pneumonitis and aids  we conclude that similar findings in patients without aids are not specific for hypersensitivity pneumonitis  and p  carinii should be ruled out in the appropriate clinical setting  
class4	capillary hemangiomas and treatment with the flash lamp pumped pulsed dye laser strawberry  or capillary  hemangiomas are common vascular neoplasms  with an incidence of approximately 2 6  in neonates  they usually develop in the first few weeks of life  so that between 1 month and 1 year the incidence rises to between 8 7  and 10 1   these lesions may grow quite large in the first year of life  and they may ulcerate or obstruct a vital organ or function  the great majority will spontaneously regress after the first year of life  parents are often alarmed at the sight of these hemangiomas and need reassurance that the great majority will regress spontaneously  treatments such as cryosurgery  irradiation  radium instillation  corticosteroid therapy  or surgical excision are often ineffective or cause significant morbidity  we describe 10 children with capillary hemangiomas treated with the flash lamp pumped pulsed dye laser  the patients ranged in age from 7 weeks to 5 5 years at the beginning of laser therapy  the patients underwent 3 1     1  mean     sd  laser treatments  with a mean regression of the lesions of 69 9      4 5   all patients demonstrated some diminution in the size and color of their hemangiomas after the treatments  and there were no ill effects  such as ulceration  hemorrhage  infection  or scarring  there was no evidence of hyperpigmentation or hypopigmentation  pulsed dye laser therapy should be considered as an option in the treatment of capillary hemangiomas  preferably prior to their full evolution  it is also a useful therapeutic approach in those hemangiomas that are slow to regress in older children  
class4	effectiveness of radiotherapy with radical neck dissection in cancers of the head and neck  a retrospective analysis of 457 radical neck dissections performed over a 30 year period for cancers of the oral cavity  pharynx  and larynx was carried out  two hundred thirteen patients underwent radiotherapy to the primary cancer site and or to the neck  of these  164 underwent perioperative adjuvant radiotherapy and 24 underwent definitive radiation for cure and were followed up by salvage surgery  thus  188 patients received radiotherapy for nonrecurrent disease  twenty five additional patients underwent radiation for surgical failure following radical neck dissection  the goal of the study was to determine whether radiotherapy altered the course or end result of the disease  the t and n stage at onset of disease was similar for the radiotherapy and nonradiotherapy groups  preoperative radiotherapy was effective in down staging the disease at the primary site and  to a lesser extent  in the lymph nodes  but had limited impact on survival  failure to control the disease in the neck occurred in 60  32   of the 188 patients who received radiotherapy for primary disease  recurrence rates were lower in the combined therapy group than in the surgical group of patients with n2 and n3 stages of disease  the 3 year disease free survival was 45   this was no better than the 63  survival rate in patients who did not receive radiotherapy  although survival was better in the combined therapy group for patients with n3 stage of disease  the worst results were in those patients who were irradiated for surgical failure  14  survival   the 24 patients who required salvage radical neck dissection following failure of definitive radiotherapy for cure had a 42  survival  
class4	the epithelial changes associated with squamous cell carcinoma of the vulva  a review of the clinical  histological and viral findings in 78 women  seventy eight excised specimens of squamous cell carcinoma of the vulva were reviewed retrospectively for the presence of lichen sclerosus or vulvar intraepithelial neoplasia  vin  at sites proximal to the tumour or more distant  lichen sclerosus was evident in 61  and vin alone in 31   vin iii  differentiated  was associated with over 50  of the specimens with lichen sclerosus  hpv 16 was found in six of the 11 vin lesions  investigated but in none of the six with lichen sclerosus  
class4	decalcification of a choroidal osteoma  a 56 year old man presented with a clearly defined orange tumour in the posterior pole of his left eye  a choroidal osteoma was suspected  and ultrasonography confirmed the diagnosis  fluorescein angiography demonstrated subretinal neovascularisation on the nasal edge of the tumour  which was treated with krypton laser photocoagulation twice  recurrent subretinal neovascularisation occurred one year later and was not amenable to treatment  three years after the patient first presented  thinning of the tumour was noted on follow up examination  during the next 15 months the tumour completely disappeared  leaving an area of retinal pigment epithelial and choroidal atrophy  total decalcification of the choroidal osteoma was demonstrated by ultrasonography  
class4	translocation  9 22  is associated with extremely poor prognosis in intensively treated children with acute lymphoblastic leukemia  the prognostic implications of t 9 22  q34 q11  were assessed at a median follow up of 3 5 years in 434 children receiving intensive treatment for acute lymphoblastic leukemia  all   four year event free and overall survivals were 81  and 88   respectively  in 419 children lacking t 9 22   but were 0  and 20   respectively  in 15 children with t 9 22   p less than  001   poor outcome for children with t 9 22  positive all was particularly notable because we have reported improved survival in other historically poor prognosis all cytogenetic categories when treated with similarly intensive therapy  we recommend that very intensive treatment approaches  including bone marrow transplantation in first remission  be considered for all children with t 9 22  positive all  
class4	clinical characteristics and treatment outcome of childhood acute lymphoblastic leukemia with the t 4 11  q21 q23   a collaborative study of 40 cases  the t 4 11  q21 q23  chromosomal abnormality was identified in 40  2   of 1 986 children with newly diagnosed acute lymphoblastic leukemia  all   this translocation was associated with female sex  63    age less than 1 year  60    hyperleukocytosis  median leukocyte count  156 5 x 10 9  l   cd10  cd19  b precursor cell immunophenotype  and myeloid associated antigen  cd15  expression  63    nearly all cases had at least some cd24  blast cells  the cd10  cd15  cd19  cd24   phenotype was found in 20 of the 32 t 4 11  cases tested  none of the 40 cases had the cytogenetic finding of hyperdiploidy greater than 50  which is a favorable prognostic feature  for clinical comparison  the t 4 11  cases were divided into three groups according to age at diagnosis  less than 1 year  n   24   1 to 9 years  n   8   and greater than or equal to 10 years  n   8   compared with older patients  infants were more likely to have initial central nervous system leukemia  p    05  and less likely to have pre b cell all  p    05   complete continuous remission has been maintained in only 7 of 24 infants and 2 of 8 patients aged greater than or equal to 10 years  in contrast to 7 of 8 children in the intermediate age group  p    048   these findings suggest that the t 4 11  is an adverse prognostic feature in these two age groups  
class4	human immunodeficiency virus infection of megakaryocytic cells  the human immunodeficiency virus  hiv  is capable of infecting certain cells of hematopoietic lineage  particularly monocyte macrophages and t lymphocytes  recently  the possibility that cells of megakaryocytic lineage are susceptible to hiv infection has been raised  we have characterized infection of the permanent megakaryocytic cell line cmk by hiv in vitro  cmk cells were easily infected by hiv type 2  hiv 2   producing significant amounts of virus in culture  infection appeared to be mediated by the cd4 surface antigen on cmk cells  three different strains of hiv 1 were able to minimally infect cmk cells  suggesting there may be isolates of hiv tropic for megakaryocytes  infection of cmk cells led to downregulation of the cd4 surface antigen but no discernable change in expression of megakaryocyte associated proteins glycoprotein ib and glycoprotein iib iiia  these observations support the likelihood that megakaryocytes are susceptible to hiv infection  and cell lines of megakaryocytic origin may provide a useful model to study effects of the retrovirus on megakaryocyte function  
class4	characterization of an interleukin 6 mediated autocrine growth loop in the human multiple myeloma cell line  u266  it has been reported recently that freshly isolated human myeloma cell cultures proliferate in response to added interleukin 6  il 6   endogenous levels of il 6 found in the same cultures suggested that an autocrine growth loop may contribute to cell growth  however  the lack of homogenous cell populations in primary myeloma cultures has made it difficult to distinguish between paracrine and autocrine growth mechanisms  to precisely address the autocrine growth issue we have evaluated the growth of the human myeloma cell line  u266  we have found that a neutralizing anti il 6 monoclonal antibody can inhibit u266 proliferation  furthermore  the addition of il 6 antisense oligonucleotides also inhibits u266 proliferation  these effects are reversed by adding il 6  suggesting the presence of an autocrine loop  using bioassays with two different il 6 dependent cell lines  we were able to detect il 6 in concentrated u266 supernatants  il 6 mrna was detected by polymerase chain reaction amplification of cdna  cell cycle parameter analysis shows that il 6 acts to release a block in g1  taken together these results present conclusive evidence for il 6 mediated autocrine growth in the u266 human myeloma cell line  
class4	t cell translocation gene 1  ttg 1  encodes a nuclear protein normally expressed in neural lineage cells  we previously identified and cloned t cell translocation gene 1  ttg 1   a putative zinc finger protein  as a result of its deregulated expression in a t cell acute lymphoblastic leukemia cell line  rpmi 8402  with a t 11 14  p15 q11   we have now characterized its genomic organization and identified the major transcriptional start site to lie within an initiator like motif  ttg 1 is normally expressed in mouse brain and not in thymus  the mouse neuroblastoma cell line  n2a  also expresses ttg 1  antibodies raised against a trpe ttg 1 fusion protein precipitate an 18 kd nuclear protein from metabolically labeled 8402 cells  immunofluorescence of n2a cells shows a nuclear pattern  the two potential zinc finger domains in ttg 1 are highly homologous to similar regions in lin 11  mec 3  and lsl 1  this data suggests that ttg 1 may be involved in gene regulation  
class4	fine needle aspiration evaluation of lymphoproliferative lesions in human immunodeficiency virus positive patients  a multiparameter approach  forty six fine needle aspirates of lymphoproliferative lesions from 31 human immunodeficiency virus  hiv  positive patients were reviewed using cytomorphologic  immunocytochemical  flow cytometric  fcm   cytogenetic  and molecular studies  there were 29 lymphomas  15 small non cleaved cell  sncl   11 large cell  lcl   one small lymphocytic  and two hodgkin s   14 reactive hyperplasias  and three  atypical lymphoid proliferations   the reactive hyperplasias were characteristically polymorphic and polyclonal lymphoid populations  six of seven were diploid on fcm  the seventh was hypodiploid  higher proliferative indices  mean  11 6   and higher rna indices  mean  1 2  characterized this subgroup compared with published reactive lymphoid hyperplasias from patients without hiv positivity  aspirates of sncl showed monotonous populations of intermediate sized cells except in one patient where a giant cell syncytial variant occurred  nine of 13 sncl aspirates showed light chain restriction  jh rearrangement revealed b cell lineage in one aspirate in which immunocytochemical study was negative for kappa  lambda  b1  and leu 4  nine of 12 sncl were diploid  the mean proliferative index was 25 6  and the mean rna index 2 3  chromosomal translocations involving the c myc locus were demonstrated in five of seven sncl aspirates karyotyped  five of eight lcl showed light chain restriction the remaining three showed null cell phenotype  large cell lymphomas were diploid on tetraploid with the mean proliferative index of 22 0  and mean rna index of 2 2  one of two lcl aspirates karyotyped demonstrated c myc translocation  despite the multiparameter approach  a definitive diagnosis could not be reached in three aspirates  
class4	juvenile  embryonal and alveolar  rhabdomyosarcoma of the head and neck in adults  a clinical  pathologic  and immunohistochemical study of 12 cases  sites in the head and neck region  orbit  nasopharynx  nasal cavity  etc   are among the most frequent locations for juvenile  embryonal and alveolar  rhabdomyosarcomas in patients younger than 15 years  however  comparable neoplasms in adults are very uncommon  a clinicopathologic and immunohistochemical study of 12 juvenile rhabdomyosarcomas in patients between the ages of 18 and 36 years is presented  there was a female male ratio of 2 1  the orbit with or without contiguous paranasal sinus involvement  nasal cavity  sphenoid sinus  middle ear  and soft tissues of the neck and preauricular region were the primary sites  seven tumors involved a parameningeal site and eight cases were alveolar rhabdomyosarcomas which together contributed to the adverse outcome  only two patients were long term  disease free survivors  six patients have died of tumor and two others are alive with persistent disease  immunohistochemical study in 11 cases demonstrated reactivity for vimentin and muscle specific actin  hhf 35  and desmin in ten cases  juvenile rhabdomyosarcoma rarely presents in the head and neck of adults but should be considered in the differential diagnosis of a small cell neoplasm in patients during the third and fourth decades of life  
class4	thymic carcinoma  a clinicopathologic study of 60 cases  the clinicopathologic features of 60 patients with thymic carcinoma were studied  patients ranged in age from 10 to 76 years  mean  46   of whom 24 were females and 36 were males  overall survival at 1  3  and 5 years was 56 6   40   and 33 3   respectively  the following morphologic features were correlated with survival  type of tumor margins  presence or absence of a lobular growth pattern  nuclear atypia  necrosis  mitotic activity  and histologic tumor type and grade  eighty eight percent of patients with poorly circumscribed infiltrating neoplasms died of their tumors as compared with 16 6  of patients with well circumscribed neoplasms  p less than 0 0000   of patients whose tumors had mitotic counts exceeding 10 10 high power fields  hpf   84 3  died  as compared with 21 4  of patients with lower mitotic counts  p less than 0 0000   of patients whose tumors showed lack of lobular growth pattern  91 6  died  as compared with 29  of those whose tumors had a lobular growth pattern  p less than 0 0000   finally  84 6  of patients whose tumors displayed a high grade histology  lymphoepithelioma like carcinoma  small cell neuroendocrine carcinoma  clear cell carcinoma  sarcomatid carcinoma  and anaplastic undifferentiated carcinoma  died of tumor  as compared with 0  of patients whose tumors were of low grade histology  well differentiated squamous carcinoma  mucoepidermoid carcinoma  and basaloid carcinoma   p less than 0 0000   evaluation of the various treatment modalities used to treat these patients did not yield any statistically significant correlations with survival  two clinically distinct groups of patients were identified  one after a relatively favorable clinical course with long survival  and one after a rapidly fatal outcome  the morphologic features of the tumors in these patients correlated well with their clinical behavior  histologic type  and the grade to which it was assigned  constituted the most reliable and important predictor of prognosis  
class4	a comparative analysis of three different techniques for the detection of breast cancer cells in bone marrow  three different methods  morphologic  immunocytochemic  and fluorescence activated cell sorter  fc  analysis  were compared with respect to their efficiency in detecting breast cancer cells in bone marrow  in the first series of experiments  the three techniques were compared using bone marrow cells artificially mixed with a known amount of breast cancer cells  whereas in a second series bone marrow from breast cancer patients with bone metastases were used  the following results were obtained  when mixtures of the first series were analyzed  fc analysis detected from 1  to 10  of breast cancer cells in bone marrow  0 2  was a border line value   the morphologic method detected from 0 05  to 10   and the immunocytochemic method  which was clearly superior  detected breast cancer cells in all mixtures  from 0 00025  to 10    it was noted that  with both the morphologic and immunocytochemic methods  the percentage of breast cancer cells detected was 2 to 360 times higher than the percentage of added cells  and enrichment was inversely proportional to the percentage of added cells  this result could be a result of different separation of cells during centrifugation due to the different density of breast cancer cells  the superiority of the immunocytochemic method was confirmed in the second series of experiments  
class4	microinvasive carcinoma of the uterine cervix  international federation of gynecology and obstetrics stage ia   in 1985 the international federation of gynecology and obstetrics  figo  subdivided stage ia cervical cancer and specified metric criteria to demarcate stage ia from stage ib  early stromal invasion  stage ia1  denotes the first invasive protrusions of a carcinoma in situ into the stroma  microcarcinomas  stage ia2  are small cancers a number of orders of magnitude larger than stage ia1 lesions and with a maximum depth of invasion of 5 mm and a maximum horizontal spread of 7 mm  larger lesions are classified as stage ib  this study reviews 486 patients previously classified as having stage ia disease  this yielded 344 stage ia1 and 101 stage ia2 lesions  41 cancers were reclassified as stage ib  three hundred nine  89  and 38 patients were followed for greater than or equal to 5 years  one  0 3   patient with stage ia1 disease re presented with stage iib disease 12 years after conization  five  5 6   patients with stage ia2 lesions developed invasive recurrences  three died  none of the 38 patients reclassified as having a stage ib lesion  including 16 who were treated conservatively  developed a recurrence  the figo classification is not a guideline for treatment  stage ia1 lesions can be treated conservatively  but treatment in stage ia2 must be individualized  risk factors such as vascular space involvement and confluency are of high sensitivity but low specificity  
class4	leiomyosarcoma of bone  a clinicopathologic  immunohistochemical  and ultrastructural study of five cases  the authors identified five leiomyosarcomas  lms  in a review of 13 nonmatrix producing spindle cell sarcomas of bone  only two were initially recognized as lms  the others had been diagnosed as malignant fibrous histiocytoma  two  and fibrosarcoma  one   the patients  four of whom were women  ranged in age from 32 to 70 years  sites included proximal humerus  two   distal femur  two   and rib  one   all tumors presented with clinical and radiographic features consistent with a diagnosis of primary bone neoplasms  although one probably represented a solitary metastasis from a primary uterine lms  radiographs showed lytic bone destruction with a moth eaten appearance  and three cases had soft tissue extension  histologically  all tumors showed broad  interlacing fascicles of spindle cells with pleomorphic nuclei  frequent mitoses  and necrosis  two cases had a focal storiform pattern and bizarre multinucleated cells  and two other cases had focally prominent osteoclast like giant cells  extensive immunoreactivity for muscle actin was seen in all cases and for desmin in three  in each case  electron microscopy showed definite smooth muscle differentiation including cytoplasmic filaments with densities  at this writing  two patients are free of disease  including the patient with a presumed metastasis   one is alive with locally recurrent disease  and two are dead of disease  experience suggests that lms of bone is a distinct clinicopathologic entity that may be more common than previously recognized  application of immunohistochemistry and electron microscopy to nonmatrix producing bone sarcomas should facilitate diagnosis of additional cases  
class4	clinical characteristics and treatment outcome of children with acute lymphocytic leukemia and down s syndrome  a pediatric oncology group study  of 2947 children with acute lymphocytic leukemia  all   treated during three consecutive studies of the pediatric oncology group  1974 1986   52  1 8   had down s syndrome  ds   comparison of clinical and laboratory characteristics showed no significant differences in leukocyte count  racial distribution  sex ratio  platelet count  incidence of mediastinal mass  lymphadenopathy or hepatosplenomegaly  or percentage of blood or bone marrow blasts for children with all with or without down s syndrome  ds all or nds all  respectively   however  children with ds all were slightly older at the time of presentation and had higher hemoglobin values  the relative frequency of each major immunophenotype  early pre b  pre b  t  or b  was also comparable for patients with or without ds  for this report  treatment regimens were categorized as either conventional  no consolidation therapy  or intensive  cox regression analysis revealed that the presence of ds  a higher leukocyte count  black race  or age older than 10 years was independently associated with a poorer event free survival  efs  for children treated with conventional chemotherapy  however  for the cohort of children who received intensive chemotherapy  ds was no longer an independent risk factor  in fact  event free survival  efs  was markedly improved to a level comparable with that observed in the children diagnosed as having nds all  on the other hand  serious toxicity  requiring interruption of treatment  was significantly more frequent in the intensively treated children with ds compared with similarly treated patients with nds all  although deaths resulting from toxicity occurred infrequently  
class4	idiopathic hypereosinophilic syndrome terminating as disseminated t cell lymphoma  the authors describe a case of idiopathic hypereosinophilic syndrome  hes  terminated as a t cell lymphoma in a 3 year old girl  the clinical course was chronic and characterized by chronic eczema  persistent peripheral blood eosinophilia  organomegaly  interstitial lung change  and pericarditis  postmortem examination demonstrated a disseminated t cell lymphoma involving the inguinal lymph node  liver  lung  and kidney  the findings of the current case suggest a possibility that certain abnormalities in this case of idiopathic hes per se may have triggered the development of malignant lymphoma  and it may represent a transition of idiopathic hes into a t cell lymphoma  other possible sequences are discussed  the development of t cell malignancy in idiopathic hes in a girl is quite an unusual presentation  
class4	hypersensitivity reactions to epipodophyllotoxins in children with acute lymphoblastic leukemia  the incidence  clinical characteristics  and outcome of hypersensitivity reactions to teniposide  vm 26   etoposide  vp 16   or both were determined in 108 children with acute lymphoblastic leukemia  all  treated with a contemporary regimen of intensive multiagent chemotherapy  fifty  46   of the 108 patients had one or more hypersensitivity reactions  the risk of any child having an initial reaction over the cumulative dose range studied was 52   95  confidence limits  41  and 63   for vm 26  compared with 34   95  confidence limits  24  and 44   for vp 16  the risk of having an initial reaction to vm 26 or vp 16 was clearly related to the cumulative dose  this risk peaked at 1500 to 2000 mg m2 for vm 26 and at 2000 3000 mg m2 for vp 16  all reactions were type 1 reactions according to the gell and coombs classification  characterized by urticaria  angioedema  flushing  rashes  or hypotension  and 86  of reactions were of grade 1 or 2 severity according to standard criteria  there was no evidence of increasing clinical severity on repeated rechallenge with premedication  and no deaths occurred  the findings suggested that hypersensitivity reactions to epipodophyllotoxins in children with all are more common than previously reported  but only rarely constitute dose limiting toxicity  
class4	malignant glandular triton tumor  a case of left brachial plexus related malignant peripheral nerve sheath tumor showing neoplastic  glandular  and rhabdomyoblastic elements in a 39 year old chinese man is reported  the authors suggested that this tumor be termed a malignant glandular triton tumor in view of the presence of the adenocarcinomatous component  the patient had extensive local recurrence comprising mainly the schwann spindle cells within a year after complete piecemeal removal and died 15 months later after the initial presentation  the natural behavior of this tumor  as in other reported cases of malignant triton tumor  is extremely aggressive  unlike malignant schwannoma or glandular malignant schwannoma  the histogenesis of this tumor is likely to be from primitive neural crest cells  schwann s cell precursors  or metaplastic malignant schwann s cells  
class4	the long term effects of radiation therapy on patients with ovarian dysgerminoma  a retrospective chart review and questionnaire study was undertaken to look at the long term effects of radiation therapy in ovarian dysgerminoma patients  forty three patients and 55 controls responded to a questionnaire that detailed bowel  bladder  thyroid  menstrual  reproductive  sexual  and growth function  statistically significant differences in the number of bowel movements were noticed when comparing patients with controls  the authors noticed no significant differences between cases and controls in bladder function  no thyroid disorders were attributable to mediastinal radiation therapy  most patients with intact uteri bleed monthly on hormonal replacement  three patients with a remaining ovary and uterus resumed menstrual function after substantial doses of abdominopelvic radiation therapy  no patients have conceived  the authors noticed a slight increase in dyspareunia in the treated group  but most patients were satisfied with their sexual function  one premenarchal patient exhibited a growth disorder  
class4	expectant management of localized prostatic cancer  seventy five patients with clinical stage b histologically proven prostatic cancer accumulated over a 40 year period and receiving no therapy for at least 1 year after histologic diagnosis were retrospectively reviewed  twenty nine patients had stage b1 lesions  37 had b2  and nine had b3 lesions  median follow up for these patients was 124  120  and 96 months  respectively  five ultimately received pelvic lymph node dissection with iodine 125 implantation  23 had transurethral resection of the prostate  and 18 had endocrine therapy  of those tumors which progressed  18 of 19  95   b1  26 of 29  90   b2  and four of four  100   b3 lesions demonstrated local progression first  six of 29  21   b1  17 of 37  46   b2  and two of nine  22   b3 tumors developed recognized distant metastasis  actuarial survival at 15 years was 67   39   and 63  for patients with b1  b2  and b3 lesions  respectively  these data indicate the varied and potentially protracted course of patients with clinical stage b prostatic cancer  
class4	psychosocial adjustment in women with breast cancer  there is a plethora of studies investigating psychosocial adjustment in women with breast cancer  its correlates  clinical course  and prognosis  these studies have been conducted with varying degrees of methodologic rigor  an assessment has been made of the quality of this existing evidence to identify from the best evidence the factors which predict the adjustment status of women with breast cancer  studies have been reviewed  using methodologic standards for the critical appraisal of studies on prognosis  developed by sackett and colleagues in the department of clinical epidemiology and biostatistics at mcmaster university  hamilton  ontario  canada   few of the studies investigating psychosocial adjustment of women with breast cancer meet all of the criteria for reviewing studies of clinical course and prognosis  this review focuses the direction and methodologic rigor required in future investigations  in particular  studies are needed that employ prospective designs and that deliberately measure or control for the extraneous prognostic variables that may affect adjustment  future investigations need to incorporate adequate precision in measurement so that measures of the psychosocial variables are objective  reliable  and valid  
class4	prognosis of pregnancy associated breast cancer  the survival of patients with pregnancy associated  pa  breast cancer is difficult to predict for two reasons  the combination is very rare  and the natural history of breast cancer that is not associated with pregnancy is intricate and varies among individuals  valid data collection and analysis is problematic given that studies gather patients over many years  the charts of 56 women with stages i  ii  and iii breast cancer  who were pregnant or within 1 year postpartum at the time of breast cancer diagnosis between 1960 and 1980  were analyzed  patients with pa breast cancer were compared to nonpregnant women of comparable ages  who were treated at the same hospital  by the same physicians  and during the same period  four patients were lost before 5 year follow up  and one patient before 10 year follow up  these five patients had distant metastases at the time they were lost to follow up  and are considered to have died within that time  across stages  patients with pa breast cancer have survival not significantly different from those patients with non pregnancy associated  non pa  breast cancer  
class4	patient controlled analgesic administration  a comparison of steady state morphine infusions with bolus doses  the authors have shown previously that bone marrow transplant  bmt  patients who self administered bolus doses of morphine gained equal oral mucositis pain relief while using less drug compared with similar patients receiving morphine by staff controlled continuous infusion  in a follow up study they compared the efficacy and side effects of morphine in two groups of marrow transplant patients who controlled their own analgesic administration either by conventional bolus dose  patient controlled analgesia  pca  or by adjusting the rate of continuous morphine infusion to increase or decrease their plasma morphine concentration  patients controlling their morphine infusion rates  pharmacokinetically based patient controlled analgesia  pkpca  group  obtained more relief from oral mucositis pain than did patients using conventional pca  patients in the pkpca group used more morphine than pca patients and achieved superior pain relief without significant increases in side effects  e g   nausea  mood changes  sedation   the authors conclude that pkpca improves the management of prolonged  severe pain in marrow transplant patients and that this approach to patient controlled analgesia may be useful in other types of persistent pain  
class4	combination hormonal therapy with tamoxifen plus fluoxymesterone versus tamoxifen alone in postmenopausal women with metastatic breast cancer  an updated analysis  a randomized trial was performed to determine if therapy with tamoxifen  tam  plus fluoxymesterone  flu  was more efficacious than tam alone for postmenopausal women with metastatic breast cancer  patients failing tam could subsequently receive flu  the dose of both drugs was 10 mg orally twice daily  objective responses were seen in 50 of 119  42   tam patients and 64 of 119  54   tam plus flu patients  two sided p   0 07   time to disease progression was better for tam plus flu  medians  11 6 versus 6 5 months  cox model  p   0 03   duration of response and survival were similar in the two treatment arms  among 97 patients with estrogen receptor  er  of 10 or greater and 65 years of age or older  there were highly significant advantages for treatment with tam plus flu in both response rate and time to progression  of particular note is that in this patient group tam plus flu showed a survival advantage  cox model  p   0 05   although these data require confirmation in a prospective randomized trial  they suggest that there is a substantive therapeutic advantage for tam plus flu over tam alone in elderly women with er of 10 fmol or greater  
class4	cisplatin  continuous infusion 5 fluorouracil  and intermediate dose methotrexate in the treatment of unresectable non small cell carcinoma of the lung  forty one patients with unresectable non small cell carcinoma of the lung  nsccl  were treated with cisplatin 20 mg m2 d for 5 days as a daily bolus injection  5 fluorouracil 800 mg m2 d by continuous infusion for 5 days  and intermediate dose methotrexate 200 mg m2 on days 15 and 22 of a 28 day cycle  pfm   one complete and 23 partial responses were observed  yielding an overall response rate of 60   there was no significant difference in response rates based on histologic subtype or extent of disease  locally unresectable versus metastatic   median duration of response was 6 months  and the median survival of all patients was 10 months  two patients with unresectable disease at presentation became resectable after chemotherapy and remain disease free at 46  and 53  months  toxicity was modest  with oral mucositis the major adverse effect  clinically important neutropenia was uncommon  pfm is an active regimen in nsccl and deserves further study in the  neoadjuvant  setting  
class4	multimodality cisplatin treatment in nonresectable alpha fetoprotein positive hepatoma  twenty eight patients with alpha fetoprotein positive  afp   nonresectable hepatoma have been enrolled in a new multimodality phase i  ii program  induction therapy consisted of 50 mg m2 intravenous cisplatin followed by 2100 cgy irradiation to the tumor volume in seven fractions over 10 days  hepatic arterial infusion of 50 mg m2 cisplatin  ia cddp  was then administered at monthly intervals  twenty one patients have completed induction and at least two cycles of ia cddp  twelve month cumulative survival was 52  for all 28 patients and 69  for the 21 patients completing induction and ia cddp  median survival has not yet been reached  response rate  complete and partial  was 36  overall and 48  among the 21 patients who completed treatment  the improved survival of the present series of patients as well as the minimal hematologic toxicity suggests possible further integration of new modalities for therapy  
class4	ultrasound guided hepatic cryosurgery in the treatment of metastatic colon carcinoma  preliminary results  cryosurgery  the in situ freezing of cancer  has been proposed in the past as a possible treatment for unresectable hepatic tumors  its advantage lies in the fact that it is a very focal treatment sacrificing less normal tissue than surgical resection  allowing treatment of multiple lobes  because cryosurgery does not affect large vessels  tumors in difficult locations  such as adjacent to the inferior vena cava  ivc   can be treated  with the use of intraoperative ultrasound to place the cryoprobes and monitor the freezing process  18 patients with unresectable metastatic colon carcinoma confined to the liver were treated  of the 18 patients treated  4  22   are in complete remission as determined by computed tomography  ct  scans and carcinoembryonic antigen  cea  levels  with a mean follow up of 28 8 months  four patients  22   were not adequately treated at the time of cryosurgery  the number of lesions frozen in each patient ranged from 1 to 12  with a mean of 6 lesions  fourteen patients had bilobar disease  three patients had previous right lobectomies with recurrences in their remaining left lobes prior to cryosurgery  and one patient had unilobar disease  mean survival of the 14 cases with recurrence was 21 4 months  with 2 of the 14 still alive  ultrasound guided hepatic cryosurgery appears to be an effective treatment for metastatic colon carcinoma to the liver that is unresectable  including patients with bilobar and multiple lesions   these preliminary results indicate that the procedure warrants further study  
class4	sphincter preservation in rectal cancer by local excision and postoperative radiation therapy  the authors report the preliminary results of 14 patients with localized  mobile  resectable rectal cancer treated with local excision and postoperative radiation therapy  rt   all had negative surgical resection margins and two received 5 fluorouracil  5 fu   the median follow up was 29 months  4 43 months   the 3 year actuarial survival was 88   the incidence of local failure was 7   only site of failure  and 21   component of failure   the incidence of local failure increased with t stage  t1  0 3  0    t2  1 7  14    and t3  2 4  50    and tumor size  greater than 3 cm  33   versus less than or equal to 3 cm  0    three patients developed local failure at 6  15  and 21 months  three underwent a salvage abdominoperineal resection and were locally controlled at 2 and 28 months following salvage surgery  one patient underwent an abdominoperineal resection for a clinically presumed local failure  however  no tumor was found in the specimen  therefore  the 13 patients who either were initially locally controlled or underwent salvage or nonsalvage surgery had no evidence of disease in the pelvis at the time of last follow up  local excision and postoperative rt may be an alternative to standard surgery in selected cases  however  additional follow up and more experience are needed in order to determine if this approach will ultimately have local control and survival rates similar to those of a low anterior resection or an abdominoperineal resection  
class4	combined chemotherapy and radiation therapy in advanced inoperable squamous cell carcinoma of the head and neck  the final report of a randomized trial  between 1983 and 1986  the national institute for cancer research in genoa and affiliated institutions conducted a randomized study to compare two different ways of combining chemotherapy  ct  and radiation therapy  rt   one hundred sixteen patients were randomized to receive neoadjuvant ct followed by definitive rt  treatment arm a  or alternating ct and rt  in treatment arm a  rt consisted of 70 gy to the involved areas and 50 gy to the uninvolved neck at 2 gy fraction  five fractions per week  in treatment arm b  rt consisted of 60 gy to involved areas and 50 gy to the uninvolved neck in three courses of 20 gy each  2 gy fraction  ten fractions 2 weeks alternated with four courses of ct  ct consisted of vinblastine 6 mg m2 intravenously followed 6 hours later by bleomycin 30 iu intramuscularly  day 1  methotrexate 200 mg intravenously  day 2  leucovorin rescue  day 3  ct was repeated every 2 weeks up to four courses  the same ct was used in both treatment arms of the study  fifty five patients were entered in treatment arm a and 61 in treatment arm b  complete responses were 7 48 and 19 57 in treatment arms a and b  respectively  p less than 0 03   four year progression free survival was 4  in treatment arm a and 12  in treatment arm b  p less than 0 02   and four year survival was 10  in a and 22  in b  p less than 0 02   mucosal tolerance was significantly worse in treatment arm b  p less than 0 00004   the subgroup analysis shows the major improvement of alternating ct and rt in patients with the worst prognostic characteristics  
class4	treatment of advanced neuroblastoma with i 131 meta iodobenzylguanidine  from february 1986 to december 1988  31 children with advanced pretreated neuroblastoma were treated with 131 i meta iodobenzylguanidine  131 mibg   thirteen children had been resistant to first line therapy  three had suffered a local relapse  and fourteen had suffered a disseminated relapse without over bone marrow infiltration  one child was treated initially because of resistance to first line therapy  and subsequently for a local relapse  a total of 72 courses of 131 mibg was administered  with doses ranging from 2 8 to 6 0 gbq  median  3 7 gbq   one child received five courses  two four courses  13 three courses  four two courses  and 12 one course of 131 mibg  the most common toxic effect was thrombocytopenia  with a platelet level of less than 50 000 cmm occurring after 19 of 60 evaluable courses  a leukocyte count less than 1000 cmm was seen only once  there were six major responses  two complete  lasting 4 to 9 months  and two minor responses lasting longer than 38 and 44 months  responses were seen more commonly in children whose only lesion was a residual primary tumor and in children who had not been pretreated who experienced disseminated relapse  further studies of the role of 131 i meta iodobenzylguanidine in treatment of neuroblastoma are needed  
class4	plasma cell granuloma of the nasal cavity treated by radiation therapy  plasma cell granuloma is a rare  benign tumor most commonly found in the lungs in patients younger than 30 years  although presentation has been reported at a number of other anatomic sites  this report is the first of plasma cell granuloma of the nasal cavity  the tumor was initially resected  but progression was seen at 1 month follow up  because further surgery to completely eradicate the tumor would have been extensive and disfiguring  40 gy external beam radiation was given in 20 fractions using a three field wedge technique  most recent clinical follow up at 27 months showed local control  surgery remains the treatment of choice for plasma cell granuloma when the disease can be completely resected  however  irradiation can also be effective in patients with recurrent or inoperable local disease  
class4	surgical treatment of extramammary paget s disease  a report of six cases and a reexamination of mohs micrographic surgery compared with conventional surgical excision  extramammary paget s disease  empd  is a rare cutaneous malignancy  usually on the genitalia  that almost always extends beyond clinically apparent margins  recurrences after standard methods of surgical excision are notoriously frequent  effective treatment with mohs micrographic surgery was first reported in 1979  it has since been suggested this malignancy may be multifocal  and reports of recurrences after resection with micrographic surgery have appeared  the authors report six cases treated with mohs surgery  two of which recurred  they also present data on 42 additional cases obtained from a written survey of members of the american college of mohs micrographic surgery and comparison cases selected from the literature  the recurrence rate after micrographic surgery appears to be at least as low as that after conventional surgical excision with vertical frozen section or paraffin section margin control  mohs micrographic surgery allows for maximal tissue sparing of critical anatomic structures and is performed under local anesthesia as an outpatient  because of this  it may be superior to conventional surgical excision  a scheme for management of this malignancy is presented  surgeons should be aware radical excision is not needed for most cases of extramammary paget s disease and very long term patient follow up is required  
class4	flow cytometric dna analysis of hepatocellular carcinoma  the prognostic value of nuclear dna content was studied retrospectively using flow cytometry in 203 cases of resected hepatocellular carcinoma  the occurrence of dna aneuploidy  which was detected in 50  of patients  correlated significantly with tumor size and the presence of vascular invasion or intrahepatic metastasis  overall  patients with dna aneuploid tumors had a significantly worse prognosis than those with dna diploid tumors  p less than 0 001  and  also in subdivided groups by tumor size  p less than 0 01   among dna aneuploid patients  the survival times were significantly shorter for patients with a low dna index  less than 1 5  than for those with a high dna index  greater than or equal to 1 5   p less than 0 05   in a cox multivariate analysis  nuclear dna content provided significant prognostic value  p   0 008   as did vascular invasion  p   0 001  and intrahepatic metastasis  p   0 005   these results indicated that nuclear dna content has an important prognostic value in hepatocellular carcinoma  
class4	predictors of physician nonadherence to chemotherapy regimens  physician nonadherence to cancer treatment regimens may diminish treatment efficacy and compromise clinical research  the influence of clinical  demographic  and psychosocial patient characteristics on physician adherence to breast cancer chemotherapy was investigated  as was the role of the clinician s attitudes concerning the chemotherapy  one hundred seven women recently diagnosed with breast cancer were followed for 26 weeks of treatment  fifty six  52   of the patients experienced unjustified modification for at least one chemotherapeutic agent  stepwise multiple regression revealed independent contributions of increased patient age  treatment setting  clinic versus academic or community private practice   and stage of disease to physician nonadherence  regimen complexity  delay in seeking treatment  and presence of psychiatric disorder did not contribute  in general  to unjustified regimen modifications  patient psychological and psychiatric factors  however  did influence prescribing behavior for vincristine  physician awareness of factors contributing to unnecessary treatment modifications may reduce the frequency of such behaviors  
class4	complete remission in refractory anaplastic adult wilms  tumor treated with cisplatin and etoposide  a 61 year old woman underwent a left radical nephrectomy for stage ii anaplastic wilm s tumor  she received no adjuvant therapy  one year later computerized tomography  ct  of the abdomen revealed a mass in the left renal fossa and retroperitoneal adenopathy  a ct guided needle biopsy was nondiagnostic  the patient had progressive disease after treatment with dactinomycin  doxorubicin  and vincristine  but achieved a complete response after treatment with cisplatin and etoposide  the therapy of wilms  tumor in adults is discussed  
class4	platelet factor 4 mrna expression in cells from a patient with megakaryoblastic crisis of chronic myelogenous leukemia  a 61 year old man with philadelphia chromosome positive chronic myelogenous leukemia developed megakaryoblastic leukemia  in the blast phase  his blast cells showed undifferentiated megakaryoblastic characteristics with no alpha granules or demarcation membranes but with detectable platelet peroxidase  ppo  activity and surface glycoprotein  gp  iib iiia  the patient has remained reasonably well for at least 12 months after blastic crisis  and 6 mercaptopurine alone has been effective in controlling leukocytosis and megakaryoblast proliferation  the expression of mrna for platelet specific proteins  such as gpiib and platelet factor 4  pf4   was studied in the patient s blast cells by the northern blot analysis  both gpiib and pf4 mrna were detected in the blast cells  cytoplasmic maturation occurs later than the synthesis of the surface gp during megakaryocyte maturation  therefore  pf4 mrna expression should be a marker of mature megakaryoblasts  the pf4 mrna expression in megakaryoblastic leukemia may indicate that a patient will have long survival and a good response to chemotherapy  
class4	differentiation in embryonal neuroepithelial tumors of the central nervous system  ninety six embryonal neuroectodermal tumors were studied histologically and immunohistologically with a panel of antibodies including glial  neuronal  epithelial  mesodermal  and myelin markers  in 71 tumors there was glial and neuronal differentiation and expression both of an s  photoreceptor  antigen and vimentin  in five tumors there was only glial differentiation and in 20 tumors only neuronal differentiation  no reactivity for myelin and epithelial markers was found  histologic and immunohistologic findings identified various degrees of differentiation in different tumors  which was bipolar  glial and neuronal  in most tumors and unipolar in the remainder  the authors suggest that their findings may be the result of normal or aberrant oncogenic differentiation  agreeing with the nomenclature of the world health organization classification for these tumors with and the inclusion of a category for ependymoblastoma  
class4	expression of class i and ii human leukocyte antigens by thyrocytes and lymphocytic infiltration on human thyroid tumors  an immunofluorescence study  surgical thyroid sections from 30 papillary carcinomas  pc   six medullary carcinomas  mc   three anaplastic carcinomas  ac   two follicular carcinomas  fc   and 16 adenomas  ad  were examined with an indirect immunofluorescence technique employing different monoclonal antibodies to evaluate the expression of human leukocyte antigen  hla  a  b  c  class i  and dr  dp  dq  class ii  by thyrocytes  together with the phenotype and distribution of inflammatory cells  ten pc and four fc were also investigated for the presence of intercellular adhesion molecule 1  icam 1   in situ deposits of immunocomplexes and circulating thyroid autoantibodies were also evaluated  an increased expression of class i antigens was found in all pc and fc  in 33  of mc and ac  and in 31  of ad  an anomalous expression of class ii antigens was observed in 70  of pc  in 50  of fc  in 33  of ac  in 19  of ad  and in none of the mc  expression of dp or dq was revealed only in a portion of the dr positive glands  a reduction of microsomal autoantigen expression was found  no icam 1 positive thyrocytes were detected  a moderate t lymphocytic infiltrate was noticed only in pc  where it was correlated with dr and dp and or dq coexpression  b cells and natural killer cells were virtually absent  the authors speculate that the weak class ii antigens expression  together with the partial or complete loss in microsomal autoantigen and the absence of icam 1 by thyrocytes  may account for the limited engagement of immunocompetent cells observed in thyroid tumors  
class4	immunohistologic evaluation of parathyroid hormone related protein in human lung cancer and normal tissue with newly developed monoclonal antibody  with a newly developed monoclonal anti pthrp antibody  4b3  the immunohistochemical localization of the parathyroid hormone related protein  pthrp  was studied on the formalin fixed and paraffin embedded sections of normal human tissues and various subtypes of lung cancer  among normal epithelial tissues  keratinocytes in squamous epithelia  transitional and bronchial epithelia with squamous metaplasia  meningoepithelial cells  and mammary ductal cells with lactating changes showed positive immunoreactivity  also  among endocrine tissues  cells in the parathyroid gland  pancreatic islets  adrenal cortex  pituitary gland  and testis were sporadically positive for pthrp  these distribution patterns suggested that in a physiologic condition  pthrp was closely related to keratinization and local secretion and or the metabolism of calcium in specifically differentiated tissues  in lung cancer  however  pthrp was detected in all cases of well differentiated and moderately differentiated squamous cell carcinoma and in most cases of small cell carcinoma  irrespective of the patients  serum calcium level  however  pthrp was not detected in two of five cases of poorly differentiated squamous cell carcinoma and in all cases of adenocarcinoma  consequently  it was found that pthrp was commonly produced by squamous cell carcinomas of the differentiated type  and that humoral hypercalcemia of malignancy could be induced when the pthrp transgressed the homeostatic mechanisms  
class4	expression of the macrophage colony stimulating factor and its receptor in gynecologic malignancies  recently  hematopoietic growth factors have been implicated in protean nonhematopoietic processes  in the current study  expression of macrophage colony stimulating factor  m csf  and its receptor  the c fms proto oncogene  was investigated in 42 samples of gynecologic tissues  there were 15 samples of normal ovarian and uterine tissue or benign conditions of these organs  11 samples of primary ovarian cancer tissue  seven samples of metastatic ovarian cancer tissue  and nine samples of primary endometrial cancer tissue  steady state transcript levels were assessed by northern blot analysis  macrophage colony stimulating factor  m csf  expression was not observed in any of the specimens of benign abnormalities or of normal organs  c fms expression was detected in two of 15  13   of these specimens  albeit at very low levels  in contrast  14  78   of 18 ovarian tumor specimens  and five  55   of nine endometrial tumor specimens expressed m csf  similarly  16  89   of 18 ovarian tumor specimens and six  67   of nine endometrial tumor specimens expressed c fms  most positive malignant tissues  19  86   of 22  showed coexpression of m csf and c fms  of interest  m csf and c fms mrna were detected in tumor  but not in adjacent normal tissue  furthermore  m csf and c fms transcripts were produced by all metastatic tumors  including two cases in which the corresponding primary tumor from the same patient was negative  because m csf mediates its effects by binding to its receptor  the increased levels of both these gene products in gynecologic malignancies suggest that an interaction between m csf and c fms may participate in the development of ovarian and endometrial carcinomas and especially in progression to the metastatic state  
class4	genotypic analyses of richter s syndrome  the authors report the immunogenotype of two cases of richter s syndrome  the immunoglobulin gene rearrangement pattern obtained on southern blot analysis was found in both cases to be the same in leukemic blood cells and in the tissue involved by the lymphoma  the beta chain and gamma chain t cell receptor gene rearrangement pattern exhibited a germ line configuration in the peripheral blood cells and in the lymph node in case 2  whereas in case 1 the lymph node had a gene rearrangement in the beta chain  as well as in the gamma chain t cell receptor  and the leukemic cells from bone marrow were found to be in a germ line configuration for t cell receptors  beta and gamma chains   
class4	advances in medical imaging for cancer diagnosis and treatment  over the last several decades  significant  new eyes  have been developed that improve the diagnosis  treatment  planning  and monitoring of human cancer  computer tomography  ct   magnetic resonance imaging  mri  and spectroscopy  mrs   single photon emission computed tomography  spect   and positron emission tomography  pet   innovative advances in both morphologic and functional imaging have led to a dramatic improvement in our ability to diagnose and monitor human cancer  frequently  anatomic detail can be demonstrated in ways that exceed views at surgery  and functional biochemical imaging is being used to show the metabolic activity and receptor status of normal and pathologic states  in vivo functional and biochemical studies differentiate normal from neoplastic or nonviable tissue  and make it possible to measure progression or regression of the disease  because physiologic changes often precede morphologic findings in many disease processes  the use of in vivo biochemical probes can demonstrate disease before anatomic abnormalities become evident  gross changes in anatomy are no longer adequate endpoints for therapy protocols  today  using physiologic imaging  we can evaluate the response to treatment within hours of administration of therapy  adjuvant metabolic tumor imaging studies provide complimentary information to morphologic evaluation of human cancers that will ultimately lead to better patient care  
class4	prostate cancer  transrectal ultrasound and pathology comparison  a preliminary study of outer gland  peripheral and central zones  and inner gland  transition zone  cancer  a study was conducted to compare results of transrectal ultrasound with pathologic findings on 116 patients who underwent radical prostatectomy for treatment of prostate cancer  in 96   111 of 116   transrectal ultrasound guided biopsies of a hypoechoic lesion proved cancer  seven patients had known stage a cancer  one patient had cancer detected by palpation and not detected by ultrasound  cancers in the outer gland  peripheral and central zones  were compared with cancers in the inner gland  transition zone  by both ultrasound and pathology  forty eight percent  52 of 108  of cancers originating in the outer gland showed extraprostatic extension  stage c disease   the primary sites of tumor escape from the outer gland were the prostatic capsule  38    anterior fibromuscular stroma  5    seminal vesicle  18    the base of the gland at the neurovascular bundle  21    and the apex  31    twenty two percent  17 of 54  of cancers originating in the inner gland  transition zone  showed extraprostatic extension  stage c disease   the primary sites of tumor escape from the inner gland were the anterior fibromuscular stroma  6   and apex  11    both histologic and biologic differences between outer and inner gland cancers were found when tumor size was controlled  gleason scores were significantly different for inner and outer gland cancers  with mean scores of 6 2     1 6 and 7 4     0 9  respectively  an odds ratio of 8 6 confirmed the increased risk of extraprostatic extension for outer gland cancer  outer gland cancers showed increased aggressive behavior of both histologic and biologic nature  the difference in biologic aggressiveness of outer and inner gland cancers has definite implications for treatment options  use of other diagnostic parameters  such as dna ploidy  may help to determine which cancers to treat and when to treat them  this may have more relevance for cancers originating in the inner gland  strategic transrectal ultrasound guided biopsy affords accurate tumor mapping and staging when modes of internal spread and escape of cancer from both outer and inner gland are known  thus  transrectal ultrasound may be our  window of observation  through which additional research may explain the histologic and biologic discrepancies between outer and inner gland cancers  
class4	the natural history of colorectal cancer  opportunities for intervention  there is now a better understanding of the natural history of colorectal cancer  which has provided a basis for intervention to influence outcome  the possible interventions include earlier detection of colorectal cancer  removal of premalignant adenomas  demonstration of the mucosal field defect that precedes neoplasia to evaluate baseline risk and its change with dietary modification  and identification of inherited and dietary risk factors  five controlled trials evaluating early detection of colorectal cancer with fecal occult blood testing have enrolled more than 309 000 patients  early stage cancers with improved survival has been observed  but data on mortality reduction have not as yet been reported  studies of patients with adenomas have demonstrated high synchronous and metachronous rates as a basis for complete colon evaluation initially and a surveillance follow up program  hyperproliferation and lack of normal differentiation have been observed as a field defect in the colon preceding neoplasia  inherited factors have recently been shown to be important in a larger proportion of individuals destined to develop colorectal adenomas and cancer  these observations of the natural history of colorectal cancer have provided new opportunities for the application of radiologic and endoscopic techniques in diagnosis and surveillance  each examination has its merit  further research is needed to answer many critical questions that have been raised regarding the impact of these interventions  
class4	imaging techniques in the diagnosis of carcinoma of the colon  the variability in the published results for colonoscopy and barium enema examinations is confusing  with both  optimum results are dependent on meticulous preparation  technical excellence  and operator proficiency  it is a mistake to place colonoscopy and the barium enema in competitive positions  the two methods ideally complement one another in the evaluation of high risk individuals  including those with positive hemoccult tests  the exclusion of significant pathology by the double contrast enema can be relied on and is less costly to the patient  detection of abnormalities by a barium enema should  when necessary  be followed by colonoscopic verification and or biopsy  when used in this sequence  the procedures provide a cost effective approach to the early detection and control of cancer  it is estimated that observance of the acs guidelines can reduce mortality rates by 30   
class4	imaging bone tumors in the 1990s  progress in bone tumor management has occurred as a result of cooperation among surgeons  oncologists  pathologists  and radiologists  during the 1990s radiologists will contribute to care of patients with bone tumors in major ways  tumor detection and preliminary diagnosis will be accomplished by radiography  tumor local extent will be assessed by magnetic resonance imaging  mri  and to a lesser degree by computed tomography  ct   distant spread of malignancy will be documented by radionuclide scintigraphy  skeleton  and by ct  lungs   the combined estimate of local extent and distant spread will assure adequate staging before definitive management decisions  preoperative closed percutaneous biopsy for histologic diagnosis will be accomplished on an outpatient basis under fluoroscopic or ct guidance  arteriography will be employed for delivery of local chemotherapy  some combination of arteriography  mri  and mr spectroscopy will be used to evaluate tumor response  after limb salvage surgery  mri will sequentially assess the tumor bed  bone scintigraphy and ct will detect skeletal and pulmonary metastases  the radiologist s role will undergo continuous redefinition  
class4	primary neoplasms of the hollow organs of the gastrointestinal tract  staging and follow up  the number of imaging modalities available to stage and follow up patients with primary neoplasms of the gastrointestinal  gi  tract continues to increase  magnetic resonance imaging  mri   computed tomography  ct   and ultrasonography are useful techniques for both staging and follow up  for staging  ct is most frequently used for the detection of liver metastases and is increasingly used as a substitute for the chest radiograph in the detection of lung metastases  ct is still the imaging test of choice for the preoperative staging of esophageal carcinoma  ct is less helpful in staging the patient with gastric carcinoma or colorectal carcinoma  the current usefulness of mri in the staging of gi tract malignancies is limited by the lack of an adequate oral intraluminal contrast agent and degradation of images due to motion  sonography  especially the new technique of endoscopic ultrasound  is promising for the detection of local invasion from gi tract malignancies  ct is used in the follow up of patients with tumors of the gi tract to detect liver  adrenal  and nodal metastases as well as local recurrence because of the ability of ct to detect extraluminal masses  ct of the pelvis has been recommended as a routine follow up procedure in patients who have undergone abdominal peroneal resection  both ct and mri can be used to detect local recurrence  but suffer from the inability to differentiate scar from recurrent tumor  the initial hope that mri would be capable of differentiating postoperative scar tissue from recurrent tumor has not been realized  therefore  with positive ct or mri findings  occasionally a percutaneous biopsy will be required to confirm local recurrence  
class4	liver tumor imaging  liver tumor imaging is the paradigm of the dilemma of diagnostic decision making in the current era of abundant high technology  in part  this is a reflection of the multiplicity of imaging techniques now in wide use worldwide  these include ultrasound  us   radionuclide scintigraphy  rns   computed tomography  ct   magnetic resonance imaging  mri   and techniques especially designed for staging the extent of known liver cancer  such as computed tomography during arterial portography  ctap  and intraoperative ultrasound  ious   most authorities concede that ct scanning is the single test most closely fitting the designation  gold standard  for liver tumor imaging  although mri  a less mature technique  is already preferred by some  local factors profoundly influence the selection and sequence of imaging studies  including available equipment  radiologic skills  institutional interests  and especially the specific clinical circumstances of the patient  thus  diagnostic algorithms or decision trees for sequential imaging workup of liver tumor suspects tend to be somewhat institution specific  
class4	staging and follow up of breast cancer patients  staging systems for breast cancer  unlike those of neoplasms in distant or recessed sites  allowed for the early development of clinical staging evaluation  it was established that clinical assessment of the breast lesion was often wrong compared with the pathologic examination  benign vs  malignant   clinical measurement of the tumor in centimeters was often larger than histologic size  and clinical assessment of axillary nodes  clear or metastatic  was incorrect in about 30  of cases  although both clinical and pathologic staging provide effective discriminants for prognosis of treated patients  prognosis is more accurately determined by the pathologic stage  the single most important prognostic indicator is the axillary nodal status  and when positive  the number of positive nodes  the american joint committee on cancer and the union international contra cancer have agreed on a tnm staging for breast carcinoma  and this is the preferable staging system  follow up of treated patients is of most value in detecting local recurrence on the chest wall  after mastectomy  or in the irradiated breast  after lumpectomy   and also in early detection of contralateral breast cancer  physical examination and periodic mammography are most useful  there is a tendency to overinvestigate asymptomatic patients  with bone scans  blood tests  etc    but this has been correctly criticized in recent years  
class4	oncologic imaging  staging and follow up of renal and adrenal carcinoma  computed tomography  ct  has emerged from the 1980s to play a dominant role in the pretreatment staging of renal and adrenal carcinomas  for detection  definition  staging   and determination of resectability or recurrence  ct with intravenous contrast enhancement  and more recently  magnetic resonance imaging  mri  with gadolinium dtpa  may be the only cross sectional imaging studies required before institution of appropriate therapy  carcinoma of the kidney is frequently diagnosed by serendipity or detected on incidental ultrasound or ct examinations  real time ultrasound and color flow doppler offer unique information on tumor vascularity and major venous vascular involvement  positive predictive values of 96  can be achieved for the diagnosis of renal cell carcinoma using contrast enhanced ct scanning  for follow up ct and mri are the best imaging techniques for evaluation of the retroperitoneum  mri may distinguish tumor recurrence from fibrosis in selected cases  because primary neoplasms of the adrenal gland are rare and often exceed 10 cm at the time of initial diagnosis  the functional nature  endocrine  of adrenal carcinoma may be part of the clinical presentation  because initial stage is critical to survival and extent of surgical therapy  a knowledge of tumor classification is essential to the optimal diagnostic evaluation  newer imaging tests  ct and mri  have superseded conventional urography  ultrasound  and radionuclide studies for the diagnosis and staging of adrenal cancer  early diagnosis and low stage at presentation are critical to survival in patients with adrenal carcinoma  the current concepts for pretreatment imaging evaluation and the role of ct  mri  and ultrasound are outlined  an oncologic imaging approach based on tumor staging and classification for patients with real or suspected renal cell carcinoma and adrenal carcinoma is essential to optimal patient care  
class4	primary neoplasms of the central nervous system in children  modern diagnostic imaging techniques are able to detect primary neoplasms of the central nervous system  cns  in children safely and accurately but with less specificity as to cell type or degree of malignancy  these neoplasms  often peculiar in cell type and size  mediated by hydrocephalus in their clinical presentation  demand careful and often extensive imaging techniques best to evaluate their geography and character  added to these basic observations  determination of the neoplasm from surrounding edema  detection of possible spread  and evaluation of residual or recurrent neoplasm are prime responsibilities of the pediatric neuroradiologist toward the child  neurosurgeon  and oncologist  
class4	magnetic resonance imaging in the evaluation of spinal tumors  magnetic resonance imaging  mri   which has recently begun to replace myelography  postmyelography computed tomography  ct   and to some extent  bone scans  has become the procedure of choice in the evaluation of spinal tumors  the applications of mri in this role are reviewed  in the extradural space  mri is the most sensitive technique for the detection of tumors in the vertebral bodies  at the same time  it provides superb delineation of suspected thecal sac impingement  in the intradural extramedullary space  mri is generally as accurate as myelography and postmyelography ct while being noninvasive  finally  in the intramedullary space  mri is unquestionably the procedure of choice in the evaluation of suspected cord tumors  in general  mri has become the best initial procedure in the evaluation of suspected tumors of the spine  regardless of the space in which they may lie  frequently  it is the only required examination  
class4	radioimmunology  imaging and therapy  targeting of radioactivity to tumors using antitumor antibodies is evolving from a laboratory curiosity toward a practical diagnostic and therapeutic technique that promises widespread benefits for many common human cancers  the development of the hybridoma technique by kohler and milstein for producing monoclonal antibodies is probably the single most important contribution to the development of this field  a large array of monoclonal antibodies against many human tumors have been created and labeled with a variety of radioisotopes  110 clinical trials have been identified from the literature between the interval of 1978 to the present  these studies are beginning to form the basis for certain conclusions regarding likely benefits for certain combinations of antitumor antibodies and isotopes in specific instances of clinical management in patients with malignant neoplasms  for example  in melanoma  lymphoma  neuroblastoma  and colorectal malignancies  radiolabeled antibodies have demonstrated occult tumors  which could not be disclosed with conventional methodologies  radioimmunotherapy of malignant lymphoma is achieving durable remissions in patients who have failed conventional forms of therapy  for the most part  these advances have been achieved through intelligent application of known principles of immunochemistry  imaging physics  and tumor immunology  progress has been slow but steady  in a few instances  the term  magic bullet  is warranted in describing the targeting of a particular radiolabeled antibody to a human tumor  i 131  3 f8  an igg3 against the gd2 antigen of neuroblastoma  which was introduced by cheung  and in 111 t 101  against the cd5 antigen of t cells  which was developed by royston  stand out because of the consistency and high concentration of radioactive targeting to human tumors in clinical trials  if certain technical innovations fulfill their initial promise  the future will be bright for radioimmunologic methods of diagnosis and therapy  genetic engineering will permit the development of  humanized  antibodies with biologic properties that favor tumor localization  new chemical approaches will broaden the range of isotopes available as diagnostic and therapeutic radiolabels  application of modern imaging methodologies  such as positron emission tomography  pet   will detect more lesions of smaller size and permit quantitative imaging for dosimetry considerations  greater speed and ease of use of computerized work stations will lead to the broader application of fusion imaging in which radioantibody images will be viewed simultaneously with tct or mri for better anatomic correlation of abnormal sites of antigen reactive tumor deposits  
class4	single photon emission computed tomography and positron emission tomography in cancer imaging  single photon emission computed tomography  spect  and positron emission tomography  pet  are now being used to improve the information available from radioisotopic imaging of patients with cancer  these nuclear medicine techniques offer the potential for studying regional function and biochemistry by using radiolabeled substrates  the chemical changes of malignancy precede anatomic changes  and pet and or spect may detect these changes before anatomic changes have occurred  the superiority of spect compared with planar imaging has been demonstrated for cardiac and brain imaging  radiopharmaceuticals containing technetium 99 m  99mtc  are best suited for spect imaging because large amounts of radioactivity are administered and the collimator camera systems are optimized for the 140 kev photons of 99mtc  the current interest in imaging cancer with spect relates to the use of gallium 67 citrate and monoclonal antibodies labeled with iodine 123 or indium 111  spect can image these radioisotopes  but the advantages compared with planar imaging have not been clearly defined  furthermore  the ability to quantitate the distribution of single photon emitters other than 99mtc has not been demonstrated  new spect systems with three heads or rings of detectors offer promise for improved  quantitative imaging  pet has the capability of imaging tracers with the biologically important elements c 11  n 13  o 15  and f 18 used for positron labeling  these radioisotopes have short half lives and require a cyclotron close to the pet facility  the most prominently used radiopharmaceutical for pet is f 18 fluorodeoxyglucose  fdg   pet studies with fdg in patients with primary brain tumors have demonstrated the ability to determine the degree of malignancy  to differentiate necrosis from recurrent tumor after radiation therapy or chemotherapy  and to predict prognosis  other metabolic functions of cancer have been studied  including amino acid accumulation  thymidine uptake  oxygen utilization  intermediary metabolism  and receptor status  pet has the potential to make a major impact on the characterization of a malignancy and the effect of therapy  
class4	new directions in medical imaging of cancer  magnetic resonance methods and single photon emission computed tomography  magnetic resonance methods and single photon emission computed tomography  spect  are developing technologies that provide both functional and anatomic information  their role in the diagnosis and monitoring of cancer is the subject of current clinical research  magnetic resonance imaging  mri  delineates organs and tissue heterogeneities using differences in the relaxation parameters of water and fat protons  both protons and other nuclei can be imaged or studied by magnetic resonance spectroscopy  mrs  to provide information on the state of naturally occurring or infused molecules  spect quantifies the distribution of radiolabeled agents in tissues and organs  labeled monoclonal antibodies provide highly specific imaging of tumors  spatial resolution is the limiting technologic factor  proton mri provides the highest current resolution  better than 1 mm in vivo in deep tissues  whereas the resolution of mrs and spect is limited to several cubic centimeters  recent advances in these technologies have significantly increased their specificity and ability to detect small  deep lesions  
class4	imaging of adult central nervous system primary malignant gliomas  staging and follow up  a classification and staging system for primary adult gliomas was proposed  this system uses the high signal intensity found on proton density or t2 weighted magnetic resonance  mr  scans at the site of the tumor and surrounding edema  including infiltrating tumor   
class4	proliferation and dna ploidy in malignant breast tumors in relation to early oral contraceptive use and early abortions  in 175 premenopausal breast cancer patients  a history of oral contraceptive  oc  use before 20 years of age was significantly associated with higher tumor cell proliferative activity  as indicated by a higher s phase fraction  spf   and a higher fraction of dna aneuploid tumors  compared with later or never users  p   0 05 and p   0 01  respectively   the higher spf among early oc users was apparent in patients with aneuploid tumors but not in patients with euploid tumors  abortions  spontaneous or induced  before the first full term pregnancy also were associated with a higher spf compared with other young patients with breast cancer  p   0 03   adjusting for parity and abortions or oc use  respectively  an early oc use was associated with a 43  higher spf and early abortions were associated with 49  higher spf  younger patients had a higher spf and a higher frequency of aneuploid tumors  but this was found to be because the users of oc had a lower median age at diagnosis  among never users  no significant age relationship was seen for spf or the frequency of aneuploidy  for the dna analyses there is a selection of patients with breast cancer with larger tumors  and therefore the conclusions drawn in this article may not be generalizable to patients with smaller primary tumors  e g   cases diagnosed at breast cancer screening  the higher tumor proliferative activity and frequency of aneuploidy in early oc users are in line with previously reported findings of worse prognostic indicators and a worse survival in early users of oc compared with other young women with breast cancer  
class4	treatment of patients with advanced colorectal cancer with cisplatin  5 fluorouracil  and leucovorin  based on in vitro studies that have demonstrated synergy between 5 fluorouracil  5 fu   leucovorin  lv   and cisplatin  cddp  against human colon cancer cell lines  a clinical trial was initiated to determine the effects of this combination in patients with advanced unresectable colorectal carcinoma  fifty nine patients were enrolled in the study and 12 of them had received prior conventional 5 fu chemotherapy  treatment consisted of 4 weekly courses of high dose lv  200 mg m2  administered by intravenous  iv  bolus  followed by 5 fu  550 mg m2  and cddp  20 mg m2  each administered as a 2 hour infusion on 4 consecutive days  after a median of 5 5 treatment cycles  objective tumor response was seen in 20 of 59 patients  34    this included 3 complete remissions   the response rate in the 47 previously untreated patients was 38   95  confidence limits  26  to 53    stable disease occurred in 16  27   patients  whereas the tumor progressed in 23  39   patients  the median survival time was 11 5 months  with 15  of the patients alive at 2 years  the regimen was well tolerated and the primary side effects were mild and reversible gastrointestinal symptoms and myelosuppression  there was no episode of life threatening toxicity  eastern cooperative oncology group  ecog  grade iii adverse reactions that required 25  dose reductions occurred in only 14  of the patients  the results of this trial suggest that 5 fu  lv  and cddp is an active  safe  and well tolerated combination regimen in patients with advanced colorectal cancer  
class4	serum tumor markers and patient allocation to good risk and poor risk clinical trials in patients with germ cell tumors  the allocation of patients with advanced germ cell tumors  gct  to different treatment programs based on clinical characteristics is standard in the design of clinical trials today  studies have shown that substantial differences exist between entry criteria and that these differences could influence the outcome of clinical trials  the factors contributing to these differences are not clear due to patient selection biases  two hundred five unselected and consecutive patients allocated to and treated in good risk and poor risk treatment programs at memorial sloan kettering cancer center  mskcc  were reassigned risk status by the indiana university  iu  classification  the results were compared with those of the southeastern cancer study group  secsg   the results using both criteria indicated substantial agreement in total end results and the identification of good risk patients  the results in poor risk patients differed substantially  with 39 patients  19   classified as poor risk by mskcc criteria and 66  32   by indiana criteria  the major discrepancy occurred in iu stage 7  in which 26 of 32 patients  81   achieved a complete response  the major factor contributing to this difference in risk assignment was the use of serum tumor markers  serum tumor markers must be incorporated into risk assignment criteria for gct clinical trials to minimize the number of good risk gct patients in poor risk trials  
class4	salvage chemotherapy for patients with germ cell tumors  the memorial sloan kettering cancer center experience  1979 1989   twenty eight of 124  23   advanced germ cell tumor  gct  patients who were treated on four successive platin based induction regimens and who failed to achieve a durable complete response  cr  remain alive  median follow up  50 months   an analysis of prognostic factors for response and survival was conducted on the 94 patients who received salvage chemotherapy  survival and or response to salvage therapy were significantly enhanced for patients with a prior cr to induction chemotherapy  treatment with a cisplatin based salvage regimen  a testis primary site  a normal serum human chorionic gonadotropin level  a normal serum lactate dehydrogenase level  one site of metastasis  and an indiana class of 6 or less  patients with a prior incomplete response  ir  had a particularly poor prognosis  p   0 00007  with only 4 of 52  9   patients alive  median follow up  37 months  compared with 15 of 42  36   patients with a prior best response of a cr  median follow up  35 months   the poor survival of patients who fail to achieve a durable cr to induction chemotherapy warrants the continued investigation of new salvage therapy  the identification of prognostic features may direct salvage therapy and aid in the interpretation of clinical trials of salvage regimens  
class4	radiation therapy in metastatic spinal cord compression  a prospective analysis of 105 consecutive patients  one hundred thirty consecutive patients with metastatic spinal cord compression  mscc  were entered in a therapeutic protocol in which radiation therapy  rt  played the main role  when mscc is diagnosed by clinical radiologic methods such as myelography with or without computed tomography  ct  or magnetic resonance imaging  mri   steroids are given and rt treatment started within 24 hours  when diagnostic doubts exist or stabilization is necessary  surgery precedes rt  chemohormonal potentially responsive tumors are also treated with chemotherapy or hormonal therapy  twelve patients  9 2   underwent surgery plus rt  and 118  90 8   received rt alone  thirteen  11   early death patients were not evaluable  the 105 evaluable cases that received rt alone were analyzed  median follow up was 15 months  range  4 to 38 months   response among patients with back pain was 80   in cases with motor dysfunction  48 6  improved  and in 33 of 105 patients  31 4   without motor disability there was no deterioration  forty percent of patients with autonomic dysfunction responded to rt  median survival time was 7 months with a 36  probability of survival for 1 year  the median duration of improvement was 8 months  the most important prognostic factor was early diagnosis  radiosensitivity of tumor was only important in paraparetic patients in predicting response to rt  complete myelographic block significantly diminished response to rt  vertebral collapse did not influence response or survival  
class4	the prognostic value of image analysis in ovarian cancer  histologic grading is very important for treatment decisions in ovarian cancer  all grading systems contain a significant subjective component  which could be reduced by including objective measurements into the diagnostic decision  image analysis was used to determine nuclear area and ploidy distributions in 42 patients with epithelial ovarian cancer  and the results were related to tumor grade and clinical outcome  the mean nuclear area  mean optical density  number of hyperploid cells  and the standard deviation between measurements were significantly higher in grade 2 and 3 tumors compared with grade 1 tumors  in rapidly progressive tumors compared with less aggressive malignancies  and in recurrent tumors compared with primary lesions  the number of nuclei with very high dna content was found to be of prognostic importance  image analysis thus provides additional prognostic information in epithelial ovarian cancer  
class4	resection of the primary liver cancer of the hepatic hilus  primary liver cancer  plc  of the hepatic hilus was designated as a tumor situated at the main branch of the portal vein or pedicle of the hepatic veins in contact with the intrahepatic vena cava  that is  the main tumor located at segment i  iv  v  or viii and concentrating on the central part of the liver was called  the central type of plc   which differed from a tumor located at segment ii  iii  vi  or vii  the latter was called  the peripheral type of plc   surgical treatment of the plc has been significantly improved in the past two decades  but the resection of the central type of plc is difficult and hazardous  this institution admitted 903 plc from january 1970 to april 1988  of which 118 cases were the central type  65 cases were resected successfully  a resectability of 55 1   one patient died from sepsis within 1 month of operation  mortality 1 53    the modes of operation for the different segments are described  and suggestions for improvements are presented  the survival rates were compared with a similar number of patients with the peripheral type of tumor in the same period and treated by the same surgeons  the results show noticeable differences  the one year  three year  and five year survival rates after resection were 70 9   43 2   and 39 2  in the central type of plc  they were 98 3   85 0   and 76 4  in the peripheral type of plc  p less than 0 001   further discussion of improvements in surgical techniques and mental awareness are suggested  
class4	structural and functional integrity of ovarian tumor tissue obtained by ultrasonic aspiration  for patients with ovarian epithelial cancer  survival increases when residual disease approaches zero after surgical removal of the tumor  a previous study using the cavitron ultrasonic surgical aspirator  cusa   cavitron lasersonic corp   stamford  ct  showed the successful removal of ovarian tumors from areas often considered unresectable  the diaphragm  spleen  stomach  and small bowel  however  the cusa has not yet been approved by the food and drug administration for gynecologic surgery except on an experimental basis  this study was designed to test whether ultrasonic irradiation produced by the cusa caused alterations in cell structure or physiology of gynecologic tissue in adjacent areas  paired tumor samples  unirradiated and irradiated  were obtained from ten patients  and portions were sent for pathologic structural evaluation and physiologic tissue culture evaluation  histologic sections  stained with hematoxylin and eosin  showed that cusa irradiation produced only minor tissue distortion as observed under the light microscope  a correct diagnosis would have been made in all cases had only tissue fragments obtained from the cusa specimen trap been stained  for nine of ten patients  initial tumor cell viability was similar in the two specimen types  flow cytometric dna analysis confirmed that surgical methods produced matched samples  cells that survived high frequency ultrasound appeared functionally intact  for five of eight patients  the cells from the cusa specimen traps survived and or divided to a greater extent than those from the knife dissected tumors  cells from both surgical routes attained a similar number of passages in culture  it seems reasonable to extrapolate these in vitro observations with pelvic tumor tissues to normal surrounding tissue left in situ  thus pelvic tissue is believed to be uninjured by cusa ultrasonic irradiation  
class4	induction of cytotoxicity of the renal hilar lymph nodes by pedal subcutaneous administration of interleukin 2 in patients with renal cancer  the authors attempted to increase the cytotoxicity of the renal hilar lymph nodes in ten patients with renal cell carcinoma by administration of recombinant interleukin 2  il 2  into the subcutaneous tissue of the instep  a total of 5000 to 21 000 units was given over 3 to 12 preoperative days  mononuclear cells separated from the lymph nodes excised from the renal hilum at surgery served as the effector cells  fresh autologous tumor cells and three cultured cell lines  k562  raji  and achn  served as the target cells  cytotoxicity was measured by a chromium releasing assay  the results showed that the mononuclear cells from the lymph nodes of the patients given il 2 became cytotoxic to all target cells  surface markers of lymphocytes in the lymph nodes were unchanged  peripheral blood lymphocytes showed increased cytotoxicity only against raji cells  adverse effects were mild or moderate and included local redness  high fever  liver dysfunction  and toxic erythema  
class4	the lewis x antigen  a new paraffin section marker for reed sternberg cells  using a monoclonal antibody specific to the lewis x antigen  anti lex   the authors studied 103 cases of hodgkin s disease  hd  in comparison with 57 cases of non hodgkin s lymphoma  nhl   three cases of granulocytic sarcoma  gs   two cases of malignant histiocytosis  mh   one case of monoblastic leukemia  ml   one case of interdigitating reticulum cell sarcoma  ircs   six cases of histiocytosis x  hx   one case of reticulohistiocytoma  rh   44 various reactive conditions of the lymph node  ln   reed sternberg and related  r s  cells stained selectively in 80 of 92 cases of hd  87 0    excluding 11 cases of lymphocyte predominance type  the stain was better in b 5 fixed specimens than in formalin fixed specimens  showing a dense deposit of reaction products at a paranuclear site and on the cell surface  the staining results were compared with those of leu m1 and found to be superior both qualitatively and quantitatively  detection rate of r s cells  87 0  versus 68 5  of leu m1   granulocytes  rare epithelioid histiocytes  and some endothelial and or erythrocytes also stained with anti lex  the stain had positive results in three cases of gs showing a diffuse cytoplasmic staining pattern  of nhl  two of 29 peripheral t cell lymphomas stained to show rare paranuclear deposits without cell surface staining  the stain had negative results in mh  ml  ircs  hx  and rh  of 45 reactive ln  minute subcapsular collections of lewis x   altered appearing langerhans  like cells  were observed in all ten ln from human immunodeficiency virus  hiv  associated persistent generalized lymphadenopathy  pgl   the stain had negative results in all other various reactive conditions of ln  in conclusion  lewis x staining is useful as a marker for r s cells in paraffin sections with staining results superior to those of leu m1  lewis x staining also detects subcapsular clustering of altered appearing langerhans  like cells in pgl  which has not been described previously and warrants additional study  
class4	receptors for epidermal growth factor and steroid hormones in primary laryngeal tumors  the authors investigated the presence of epidermal growth factor  egf r   estrogen  er   progesterone  pr   and androgen  ar  receptors in 42 laryngeal squamous cell carcinomas and 20 normal laryngeal mucosa specimens  egf r were expressed in all tumor specimens analyzed  with significantly higher levels in tumor samples compared with normal mucosa  p less than 0 05   the immunohistochemical study demonstrated the presence of egf r in basal and parabasal cells of normal mucosa and in most of the cancer cells  there was no correlation between egf r and tumor localization or t classification  on the other hand  the authors did find an interesting correlation between egf r levels and grading  egf r levels being significantly higher in g3 than in g1 g2 tumors  moreover  the three patients whose tumors expressed the highest egf r levels had disease recur within 8 months  among tumor specimens  9 5   35 7   and 9 5  expressed very low but detectable er  pr  and ar levels  respectively  no statistically significant difference was found between the levels of steroid receptors in the tumor and normal mucosa specimens  and neither was there any correlation of er  pr  and ar with the pathologic findings  the authors  results suggest that the egf r system may play a role in regulating the growth of laryngeal cancer  additional studies should demonstrate whether  as in other tumor types  egf r expression may have prognostic significance in human laryngeal cancer  
class4	the expression of progesterone receptors coincides with an arrest of dna synthesis in human breast cancer  two main models to account for the heterogeneous expression of estrogen receptors  er  and progesterone receptors  pr  in human breast cancer have been proposed  the clonal model and the stem cell model  the authors previously provided evidence supporting the stem cell model since it was found that most of the proliferating cells in er positive  er   human breast cancer lack er and that the er negative  er   and er  subpopulations are interrelated  the authors have analyzed in eighteen er  pr  primary breast tumors the simultaneous expression of er or pr  by immunohistochemistry  and dna synthesis  by autoradiography  after 30 minutes of 3h thymidine incorporation  the authors demonstrated that   1  the average numbers of er  and pr  cells were similar  36 8     10 7  and 39 3     17 6   respectively    2  the thymidine labeling indexes of the er   er   pr   and pr  subpopulations were 0 53     0 69   0 74     0 49   0 21     0 21 and 0 94     0 54   respectively  and  3  75 2  of the dna synthesizing cells were er   and 88 8  of them were pr   the authors conclude that the cellular subpopulations expressing er and pr were not identical  and the expression of pr was associated with a lower rate of cellular proliferation than was er expression  
class4	lymphomas of the breast  a clinicopathologic and immunohistochemical study of primary and secondary cases  primary mammary lymphoma is rare  and little is known about the immunophenotype of such cases  the authors studied both primary and secondary breast lymphomas with a broad panel of t  and b cell markers using paraffin embedded tissue and the avidin biotin immunoperoxidase method  cases of primary b cell lymphoma were further tested to determine light and heavy chain type  thirty five cases were analyzed  including 16 primary lymphomas  diffuse large cell lymphoma was present in ten of 16 primary and 14 of 18 secondary cases  lymphoepithelial lesions in ducts and lobules and frequent vascular involvement were found in both primary and secondary cases  immunohistochemistry studies on 13 tumors revealed all of the primary tumors to be b cell in origin  except for one case of primary t cell lymphoma  to the authors  knowledge  this represents the first description of this entity  fifteen of 17 secondary tumors exhibited b cell markers and one of 17 exhibited t cell markers  in only one case could lineage not be determined  among primary b cell cases  igm was found to be the most frequent heavy chain type  iga reactivity was found in only one case  survival was related to stage and histologic characteristics  patients with stage ii disease and higher grade histologic lesions had a worse prognosis  half of the patients with primary lymphoma have had recurrent disease  although local recurrences were observed  the authors also saw a tendency for recurrence in other extranodal sites  the authors conclude that  although primary lymphoma of the breast is compatible with long term survival  a significant number of patients eventually die of their disease  as with other extranodal lymphomas  survival rate appears most related to stage of disease  also  the vast majority of primary tumors are b cell in origin  express igm heavy chain  and can be considered tumors of mucosa associated lymphoid tissue  
class4	prognostic implications of dna histogram  dna content  and histologic changes of regional lymph nodes in patients with lung cancer  forty six cases of resected lung cancer  including 20 cases at stages i and ii and 26 cases at stage iii  n2   were subdivided into two groups  a good prognosis group with a longer survival period and a poor prognosis group in which the patients died earlier of the cancer  from paraffin embedded lymph node tissues of these patients  the authors examined dna histogram pattern and dna content  using flow cytometry  and histologic hyperplasia of germinal center and paracortical area  they also evaluated their correlation with the prognosis  in the good prognosis group at stages i and ii  paracortical hyperplasia  ph  of the lymph nodes was observed significantly more frequently  in the good prognosis group at stage iii  the incidence of ph  g2m phase in the dna histograms  and dna content were all significantly higher  dna content was positively correlated with the grade of ph  
class4	association of expression between n myc gene and major histocompatibility complex class i gene in surgically resected human neuroblastoma  amplification of the n myc gene in neuroblastoma correlates with advanced stage and poor prognosis  association of the expression between n myc and major histocompatibility complex  mhc  class i genes in 33 neuroblastomas obtained from japanese children was investigated  amplification of the n myc gene was observed in two of five cases in stage iii  six of 11 cases in stage iv  and one of five cases in stage iv s  in each case  the expression of n myc gene was significantly increased  the expression was also increased in cases without amplification of the n myc gene  the origin being from the suprarenal region  expression of the mhc class i gene was significantly decreased in five of these nine with a high level of n myc expression with amplification  these results suggest that the down modulation of the mhc class i expression may be associated with the high level of expression and amplification of n myc gene in the advanced stage of neuroblastoma  
class4	clinical significance of hematologic parameters in non hodgkin s lymphoma at diagnosis  three hundred seventeen patients with non hodgkin s lymphoma  nhl   54 low grade  180 intermediate grade  76 high grade  and seven unclassified  treated with chemotherapy were evaluated for the presence of hematologic abnormalities at diagnostic staging  anemia was present in 42   leukopenia in 6   thrombocytopenia in 13   leukocytosis in 26   and thrombocytosis in 14  at presentation  the presence of bone marrow involvement by lymphoma was more likely to be associated with leukopenia and thrombocytopenia than the absence of bone marrow involvement  although anemia was slightly more common in patients with bone marrow lymphoma than in those without marrow lymphoma  the difference was not statistically significant  hematologic parameters were similar for patients with b cell or t cell lymphoma  evidence of bone marrow failure with multiple cytopenias was present in 26 patients  8    leukoerythroblastosis was present in 2   circulating lymphoma was present in 9 5   anemic patients had a shorter survival time than nonanemic patients  whether bone marrow was involved by lymphoma or not  survival was not affected by the presence of leukopenia or mild leukocytosis  but  in patients without marrow lymphoma  leukocytosis with a leukocyte count greater than 20 x 10 9  l was associated with short survival length  thrombocytopenia was associated with short survival time only in patients with bone marrow involvement by lymphoma  patients with multiple cytopenias or leukoerythroblastosis had short survival times  but the presence of circulating lymphoma did not alter survival when compared with other patients with bone marrow involvement by lymphoma  these data suggest that hematologic evaluation at the time of diagnostic staging of nhl provides useful prognostic information that may have therapeutic implications  
class4	amplification of oncogenes in mammary carcinoma shown by fine needle biopsy  a procedure that measures the amplification of oncogenes in human cancer cells is described  the cells were obtained by fine needle biopsy to allow repeated sampling from individual metastases  a drawback was the low number of cells obtained  but this could be overcome by using a slot blot hybridization technique to measure gene amplification  two patients with mammary cancer  primary tumors or metastases   analyzed for the levels of amplification of the oncogene erb b2  are described in detail  this technique is suitable for analyzing alterations occurring during cancer progression and for identifying subgroups of mammary cancer with different characteristics  
class4	flow cytometric determination of breast tumor heterogeneity  flow cytometric analysis was done on the dna content of nuclei obtained from different sites of small breast tumors  although specimens for analysis were obtained within a few millimeters of each other  dramatic differences were occasionally observed in the dna histograms  in a limited study involving 141 consecutive breast specimens submitted for flow cytometry  52   74  were found to have at least one dna aneuploid population  in 18  of dna aneuploid tumors  one or more specimens from areas grossly identified as tumor had no dna aneuploid population  because of the proposed correlation of aneuploidy with a poorer prognosis and possible responsiveness to chemotherapy  multiple sites should be assayed when flow cytometric dna analysis is done  
class4	predicting recurrence time of esophageal carcinoma through assessment of histologic factors and dna ploidy  cytophotometric analysis of nuclear dna content was done in 128 patients with squamous cell carcinoma of the esophagus  the relationship among histopathologic features  dna distribution pattern  and survival time was investigated from the standpoint of recurrence  of 128 patients  77  60 1   died of recurrence within 2 years after surgery  16  12 5   from 2 to 5 years and two  1 6   over 5 years  the rate of death of recurrence within 2 years was higher in patients with t4 or n1 than t1  t2  and t3 or n0  p less than 0 01   survivors over 5 years more frequently possessed type ii dna pattern than types iii and iv  p less than 0 05   the rate of death of recurrence within 2 years was 34 4  in type ii  which was lower than the 59 6  rate in type iii  p less than 0 05  and the 76 6  rate in type iv  p less than 0 01   survivors from 2 to 5 years were higher in type iii than in type iv  p less than 0 05   and recurrence over 5 years was found only in type ii  this inclination was more apparent in those with curative resection  in the patients with type ii  careful follow up may be needed over 5 years for late recurrence  however  in those with type iv  no recurrence over 2 years could be regarded as healed because most of their recurrences occur within 2 years  these findings suggest that the growth rate of esophageal carcinoma should reflect dna aneuploidy  and the dna analysis of esophageal carcinoma should be a valuable parameter for postoperative follow up planning  
class4	primary and metastatic pulmonary meningioma  patient 1 was a 53 year old man who had a very rare primary pulmonary meningioma that developed in the left lingular segment  when this report was written  7 years had passed since he underwent operation  and no recurrence of the meningioma had been detected  in patient 2  a 61 year old woman  multiple pulmonary metastases were confirmed 19 years after she had undergone operation for multiple cerebellar meningiomas  and the metastases were resected  after 2 years  multiple intraperitoneal metastases were found  and thus aggressive surgery was performed  currently  22 years after the operation for the primary cerebellar meningioma  the patient is alive without any subjective symptoms  although intraperitoneal metastases have recurred  to date  only four cases  all in women  of primary pulmonary meningioma have been reported  case 1 reported in this article is thus the first case in a male patient to be reported  and  in addition  this patient also has the first reported case to have been evaluated for more than 5 years  in case 2  however  each of the excised extracranial tumor lesions was histologically homogeneous and showed a hemangiopericytomatous pattern  the histologic picture of those tumor lesions was exactly the same as the picture of a small portion of the cerebellar meningiomas excised 19 years earlier  thus  all those extracranial tumor lesions were diagnosed to be metastatic meningiomas  however  it is difficult to explain why there had been no symptoms for as long as 19 years until the pulmonary metastases were discovered  
class4	transurethral resection zone prostate cancer detected at cystoprostatectomy  a detailed histologic analysis and clinical implications  the authors identified incidental adenocarcinoma of the prostate in serial cross sections of prostates from 61 of 100 patients having cystoprostatectomy for bladder cancer  in 20 patients  cancer foci were in the prostatic region accessible to transurethral resection  tur   eight of these 20 patients had stage a1 disease  less than or equal to 3 foci   in six of these patients all foci were located at or within the transition zone boundary only  twelve patients had stage a2 disease  greater than 3 foci   in none were more than three foci at or within the transition zone boundary  among the 20 patients  84 tumor foci were distributed as follows  62  in the peripheral zone  10  in the transition zone  3  in the central zone  and 25  in the transition zone boundary  the authors  data suggest that stage a prostate cancer  like larger clinically detectable cancers  is multifocal  multizonal  and similarly distributed with respect to the urethra  no case of stage a1 disease would have been reclassified as stage a2 by repeat tur of the entire transition zone and transition zone boundary  the authors  results confirm those of previous studies that report a high incidence of residual carcinoma in regions not accessible to tur in patients with presumptive stage a1 disease and suggest that ultrasonography and ultrasonographically guided biopsies  rather than repeat tur  may more accurately define the extent of stage a disease in some patients  
class4	serial immunocytologic analysis of blood for tumor cells in two patients with neuroblastoma  tumor surveillance tests are used to determine whether malignant cells are responsive or resistant to therapeutic regimens  for patients with neuroblastoma  conventional methods of surveillance are not sensitive enough  because tumor cells are shed into the circulation  immunocytologic analysis of blood may function as a sensitive monitoring system  in this study  five blood samples were obtained from two patients with disseminated neuroblastoma at diagnosis and during therapy  these samples were analyzed with monoclonal antibodies and immunoperoxidase staining to determine whether circulating neuroblasts were present  in both patients  the presence or absence of circulating neuroblasts yielded information that was more sensitive than that from conventional tests  the authors conclude that immunocytologic analysis of blood should be included with conventional monitoring methods for surveillance of patients with disseminated neuroblastoma  
class4	primary central nervous system lymphoma as a secondary malignancy  primary central nervous system lymphoma  pcnsl  is a rare neoplasm  but it is occurring with increased frequency even among apparently immunocompetent patients  although secondary malignancies frequently involve the lymphoreticular system  pcnsl has been reported as a second neoplasm only once previously  seven patients are discussed who developed pcnsl after successful treatment for a prior neoplasm  the original cancer was colon  one   breast  one   thyroid  one   hodgkin s disease  two   and non hodgkin s lymphoma  two   patients with systemic non hodgkin s lymphoma were thought to have a separate cerebral lymphoma on the basis of a prolonged disease free interval from their systemic lymphoma  and the absence of systemic disease  when pcnsl was diagnosed and through subsequent follow up  the pcnsl developed a median of 10 years after the diagnosis of the first tumor and 6 years after the last evidence of systemic disease  the diagnosis of pcnsl was often delayed because of confusion with brain metastases  and initial shrinkage or disappearance of the lesion after corticosteroids  formation of pcnsl may be a consequence of treatment for the first malignancy  reflect an unidentified inherent predisposition to neoplastic transformation  or result from the changing epidemiology of pcnsl in the general population  these mechanisms are not mutually exclusive  and a single hypothesis cannot account for all these cases  
class4	lung cancer in patients younger than 40 years of age  the records of 52 patients younger than 40 years of age who had bronchogenic carcinoma diagnosed between 1965 and 1985 were reviewed  the preponderance of adenocarcinoma  54    the lower male female ratio in this age group compared with patients age 40 or older  2 1   the importance of cigarette smoking as a causative factor  80  of patients   the long mean duration of symptoms  5 months   and the high incidence of advanced stage at diagnosis  77  stages iii and iv  in these patients are findings similar to those reported in other published series  there was no significant difference in resectability  23  versus 19    median survival length  5 3 months versus 6 9 months   median survival length of patients who had surgical resection  10 5 months versus 10 8 months   and 5 year survival rate  11 5  versus 6 3   in these patients compared with a randomly selected group of 260 patients with lung cancer who were age 40 or older  
class4	a recurrent pelvic desmoid tumor successfully treated with tamoxifen  a case of recurrent retroperitoneal desmoid tumor successfully treated with tamoxifen  nolvadex tablets  ici pharma  division of ici americas  wilmington  de  is reported  the patient presented late in her second pregnancy with a large retroperitoneal pelvic desmoid tumor that was treated with surgical excision and megestrol acetate  when the tumor recurred 12 months later  it was again treated with surgery  this time followed by radiation therapy  the desmoid tumor quickly recurred  the patient was then treated with tamoxifen  resulting in a complete tumor regression that has remained stable for 27 months  tamoxifen should be considered as first line therapy in recurrent desmoid tumors  
class4	the use of ketoconazole in ectopic adrenocorticotropic hormone syndrome  the authors report a patient with ectopic adrenocorticotropic hormone  acth  syndrome  eas  resulting from small cell lung cancer  treatment with ketoconazole  kcz  resulted in significant suppression of serum cortisol levels  the authors confirmed kcz to be a useful adjunct in the treatment of cushing s syndrome  
class4	serous papillary adenocarcinoma of the tunica vaginalis of the testis with metastasis  testicular or paratesticular neoplasms that resemble the common epithelial type of ovarian tumor are quite rare  the authors report the case of a 29 year old man with a metastatic serous papillary adenocarcinoma arising from the tunica vaginalis  to the authors  knowledge  this is the first reported case of a serous carcinoma of the tunica vaginalis behaving in a malignant fashion  the fact that clinically apparent metastatic disease occurred 4 years after initial presentation suggests that development of metastases is a late event  unfortunately  the tumor has been refractory to therapy with chemotherapeutic agents with activity against ovarian malignancies  
class4	rural urban differences in stage at diagnosis  possible relationship to cancer screening  stage at diagnosis was examined for various malignancies identifiable through screening to determine whether rural urban differences exist in georgia  data were obtained from a population based cancer registry which registers all incident cancers among residents of metropolitan atlanta and ten neighboring rural counties  black and white patients with a first primary invasive malignancy newly diagnosed between 1978 and 1985 were included in this study  residents of the rural area were twice as likely to have unstaged cancers  18 3   as were urban residents  9 6    among patients with known stage at diagnosis  rural patients tended to have more advanced disease than urban patients  the relative excess of nonlocalized malignancies in rural georgia was 21  for whites and 37  for blacks  the rural excess of nonlocalized prostate cancer among blacks was especially pronounced  differences in access to or utilization of early detection methods may contribute to the rural urban differential in the extent of disease at diagnosis  
class4	hereditary ovarian cancer  heterogeneity in age at diagnosis  an unknown fraction of the ovarian cancer burden occurs in women with a family history indicative of a putative autosomal dominantly inherited cancer susceptibility syndrome  the results from a five generation  extended  hereditary breast ovarian cancer kindred are described 10 years after it was initially ascertained  significantly more cancers were observed in high risk family members during this decade than were expected  p less than 0 001   the age of ovarian cancer diagnosis was studied in additional ovarian cancer prone families of three types  site specific ovarian cancer syndrome  the breast ovarian cancer syndrome  and lynch syndrome ii  the age of onset in each of the three sets was significantly  p less than 0 001  earlier than the general population mean of 59  and there were significant differences in the age of onset  p   0 050  among these three cohorts  ovarian cancer histology was similar to that of patients with negative family histories  there may be clinically significant heterogeneity in the age at diagnosis of ovarian cancer among these ovarian cancer prone syndromes  this has important implications for understanding its natural history and targeting surveillance management strategies  
class4	cancer in relatives of survivors of childhood sarcoma  relatives of 88 long term survivors of childhood sarcoma were examined for the familial cancer syndrome of sarcoma  breast cancer  and other neoplasms  li fraumeni syndrome   twenty six of 402 close relatives developed cancer  expected  23 8   including breast cancer in four mothers  expected  3 1   two sarcoma probands who developed second malignant tumors have multiple relatives with cancer and might have an inherited predisposition  an increased cancer risk and exceptional requirement for disease screening appear to be confined to first degree relatives of a small fraction of children with sarcoma  notably probands with second cancers  
class4	dna ploidy pattern in rectal carcinoid tumors  the nuclear dna pattern of 22 rectal carcinoids was determined by cytophotometry of paraffin embedded tissues  the results were compared with clinical as well as histopathologic features of the tumor  three of the carcinoids with synchronous or metachronous metastasis had aneuploid dna pattern  whereas 19 tumors with no metastasis showed diploid dna pattern  no other single clinical or pathologic feature of the tumor could predict more accurately the malignant potential and the subsequent course of the rectal carcinoid  it is concluded that dna aneuploidy in rectal carcinoid tumors is not so rare as indicated by earlier studies and that it is a factor of significant prognostic value  
class4	detection by ct during arterial portography of colorectal cancer metastases to liver  a prospective evaluation of the accuracy of real time ultrasonography  us   computed tomography  ct   infusion hepatic angiography  iha   and computed tomography during arterial portography  ct ap  was performed on 65 resected liver metastases of colorectal cancers  the total detection rate was 58 5 percent for us  56 3 percent for ct  55 4 percent for iha  and 86 2 percent for ct ap  the sensitivity of 29 lesions with diameters of smaller than 1 cm was 65 5 percent for ct ap  ct found only two  and both us and iha localized no more than three  the smallest lesions detectable by ct ap were as small as 0 4 cm in diameter  ct ap proved most useful in detecting the liver metastases  and the use of this technique is recommended for preoperative planning of hepatectomy on patients with liver metastases  
class4	intraepithelial bodies in colorectal adenomas  leuchtenberger bodies revisited  the presence of intraepithelial inclusion bodies  leuchtenberger bodies  was recorded in rectal or colonic specimens from 130 patients  large to moderate number of intraepithelial bodies were recorded in 81 8 percent of 55 colorectal adenomas from patients with familial adenomatous polyposis  fap   conversely  none of the 55 non fap adenomas or of the 20 specimens with ulcerative colitis  10 with dysplasia  had similar amounts of intraepithelial granules  feulgen studies demonstrated that the granules contain dna and are probably nuclear fragments of destroyed lymphocytes  although the pathogenesis of this phenomenon remains obscure  it appears that the presence of large to moderate number of intraepithelial bodies in colorectal adenomas should strongly raise the suspicion of fap  
class4	subsite distribution and incidence of colorectal cancer in new zealand  1974 1983  the purpose of this study was to examine changes in subsite distribution and incidence of colorectal cancer within different age groups  registration of colorectal cancer by the national cancer registry of new zealand approached 100 percent by 1974  the present study was based on 15 395 individuals aged 25 years and over and registered for colorectal cancer between 1974 and 1983  subsite distribution  right colon  left colon  rectum  for different age groups  25 49  50 69  70  years  was significantly skewed  with an excess of right colonic cancer in individuals aged 25 49 years and 70  years  this right colonic excess was accompanied by a relative reduction in left colonic cancer  age adjusted incidence rates for the periods 1974 78 and 1979 83 were compared and stratified by age group and subsite  incidence rates increased in all subsites in individuals aged 50  years  this was particularly evident for right sided cancer in the elderly of both sexes  there was a marked reduction in the incidence of left colonic cancer and rectal cancer in individuals under 50 years  in contrast  the incidence of right colonic cancer remained relatively stable in young individuals  time trend studies indicate that the skewed subsite distribution of large bowel cancer in different age groups may increase with time and is probably due to varying etiological factors acting on different cohorts  
class4	colorectal cancer  differences between community and geographically distant patients seen at an urban medical center  many studies in clinical oncology rely on hospital derived patients  hospitals vary in the proportions of patients from the local catchment area vs  those from more distant places  of whom a larger proportion are presumably referrals  to study the differences between these two types of patients  we analyzed 1 245 colorectal cancer patients seen at a large urban medical center over a seven year period  three hundred ninety eight patients were from the local community  32 percent   489 were from the extended community  39 3 percent   and 358 from more distant communities  28 8 percent   the patients from the local community tended to be older and from minority ethnic groups  in addition  the local community patients were more likely to have advanced disease at the time of presentation  the grade of the tumor and its site distribution within the large bowel were similar for the three groups  after adjusting for age  sex  race  and stage of disease  the survival was somewhat better for the distant community patients as compared with the local and extended communities  p less than 0 02   overall  in our patient population  the distant patients tended to have more favorable socioeconomic factors and less advanced disease  and these differences may account  in large part  for a better prognosis for these patients  particularly in large cooperative trials  studies may need to take into account the respective proportions of local community and geographically distant patients in analyzing and generalizing treatment outcomes  
class4	a case of cecocolic intussusception with complete invagination and intussusception of the appendix with villous adenoma  villous adenoma of the appendix is a rare neoplasm and intussusception of the appendix is a rare pathologic condition  a very rare case seen in a 35 year old male with pain in the right lateral abdomen is reported  in this patient  the appendix along with the villous adenoma intussuscepted and invaginated into the cecal lumen  and presented as cecocolic intussusception  a polypoid lesion was diagnosed in the cecum by fiberoptic colonoscopy  unlike polypoid lesions at other sites in the large intestine  polypoid lesions of the cecum may accompany intussusception and invagination of the appendix  consequently  caution is required in performing endoscopic polypectomy in cases of polypoid lesions of the cecum  
class4	intra abdominal desmoid tumors in familial polyposis coli  a case report of tumor regression by prednisolone therapy  a case of intra abdominal desmoid tumors in familial polyposis coli  fpc   which regressed and disappeared by prednisolone treatment  is reported  a 37 year old japanese man with abdominal lumps was admitted to our hospital  he had had proctocolectomy two years before because of fpc with rectal cancer  at laparotomy  tumors were present in the abdominal wall  mesentery  and retroperitoneum  only a small part of the tumors was resected and diagnosed microscopically to be desmoid tumors  with prednisolone administration  20 to 5 mg day  subjective symptoms were ameliorated and desmoid tumors slowly regressed  bilateral hydronephrosis continued and resulted in  retroperitoneal fibrosis   to our knowledge  this case is the first well documented case of retroperitoneal fibrosis in a patient with fpc  the characteristics of the desmoid tumor in familial polyposis coli or in gardner s syndrome and the methods for its management are discussed  
class4	polycystic ovary syndrome and bulimia  one hundred fifty three patients classified as suffering from polycystic ovarian syndrome  pcos  and 109 patients who were suffering from a clear organic disorder or endocrinopathy received the bulimia investigation test  edinburgh   bite  questionnaire for abnormal eating behaviors  patients with pcos showed a significant increase in their mean bite score for approximately a third had abnormal eating patterns  and 6  have scores suggestive of clinical bulimia compared with only 1  of women in the group with organic endocrinopathies  the work suggests that women with pcos should be screened for abnormal eating behaviors and raises the possibility that treatment by psychological means should be considered when abnormal eating behaviors are present  
class4	effect of baseline ovarian cysts on in vitro fertilization and gamete intrafallopian transfer cycles  the presence of ovarian cysts may compromise the success of in vitro fertilization  ivf  and gamete intrafallopian transfer  gift   we prospectively studied 212 consecutive ovulation induction cycles in 120 patients for ivf and or gift  a baseline cyst was defined as any intraovarian cystic structure greater than or equal to 12 mm noted on ultrasonography before superovulation  cycle outcomes were compared between patients with cysts  n   62  versus those with no cysts  n   150   there were no differences in follicular or luteal phase lengths or amount of human menopausal gonadotropins used  peak estradiol  e2  levels were significantly lower and cancellation rates significantly higher in the cyst group  for noncanceled cycles  there were no significant differences in peak e2 levels  the mean number of follicles greater than or equal to 12 mm  mature oocytes retrieved  or ova transferred for gift or embryos for ivf  the pregnancy rates overall and for noncanceled cycles were not significantly different  
class4	endoscopic ultrasonography in diagnosis of the extent of gallbladder carcinoma  endoscopic ultrasonography  eus  was performed preoperatively in 39 patients with gallbladder carcinoma  diagnosis of the anatomical extent of gallbladder carcinoma was compared with histologic analysis  and staging accuracy was evaluated according to the tnm classification  carcinoma considered to be at an early stage with no lymph node metastasis was correctly diagnosed in 87 5   differential diagnosis between early and advanced staged tumors was possible in 79 5   overall accuracy for depth of tumor invasion  t  was 76 9   limitations were due to many stones in the gallbladder and microinfiltration of carcinoma  assessment of regional lymph node metastasis  n  was at a sensitivity of 81 8  and specificity of 92 9   for an overall accuracy of 89 7   we believe endoscopic ultrasonography is useful in the clinical staging of gallbladder carcinoma  
class4	endoscopic biopsy has limited accuracy in diagnosis of ampullary tumors  endoscopic biopsy specimens and surgically resected specimens in a collective series of 78 japanese patients with ampullary tumor were retrospectively reviewed to investigate the clinical implications of endoscopic biopsy  endoscopic biopsy specimens were classified into five groups based on the degree of epithelial atypia  group 1  no atypia   group 2  mild atypia   group 3  moderate atypia or adenoma   group 4  severe atypia or carcinoma in situ   and group 5  invasive carcinoma   final diagnosis of the 78 resected ampullary tumors was adenoma in five cases  carcinoma in 27 cases  and both adenoma and carcinoma in 46 cases  biopsy accuracy of carcinoma  group 4 or 5  was 70   51 of 73  overall in 73 carcinoma cases  biopsy accuracy was 50   7 of 14  in the intramural protruding type  64   21 of 33  in the exposed protruding type  and 88   23 of 26  in the ulcerating type  the diagnostic accuracy of adenoma  group 3  was 80   4 of 5  in five cases of ampullary adenoma  in 18  25   of the 73 carcinoma cases  biopsy diagnosis was adenoma  group 3   whereas carcinoma was found in the deeper layers of surgically resected specimens  biopsy diagnosis of adenoma does not rule out the possibility of deeper carcinoma in ampullary tumors  
class4	evaluation of endosonography in tn staging of oesophageal cancer  strategies for the treatment of cancer of the oesophagus depend on the tumour stage at the time of diagnosis  resection  the only curative treatment  is confined to early tumour stages  tumours with local infiltration are usually unresectable and require palliative treatment  computed tomography has been widely used for preoperative staging but often fails to define this correctly  endoscopic ultrasound allows direct visualisation of the parietal wall and may be useful in staging gastrointestinal tumours  in a comparative prospective study  52 patients with tumours of the oesophagus were investigated preoperatively both by endoscopic ultrasound and computed tomography to determine the stage of tumour infiltration and local lymph node involvement  thirty seven of these patients underwent operation  resection  or dissection and entered the study  the intraoperative findings or the histopathological assessment  or both  were taken as a reference  for all tn stages of oesophageal tumours  correct preoperative staging was accomplished by endoscopic ultrasound in 89  for t stage and 69  for n stage compared with 51  and 51  respectively by computed tomography  highly significant using fisher s exact test   this study shows that endoscopic ultrasound is useful in preoperative tn staging of tumours of the oesophagus  
class4	alcohol consumption in patients with colorectal adenomatous polyps  the risk of developing colorectal adenomatous polyps is probably increased by a variety of dietary and environmental factors  we found an association with current alcohol and cigarette consumption  the risk of polyps was increased three times in drinkers who did not smoke and two times in smokers who did not drink  with those who both drank and smoked having 12 times the risk of total abstainers  since colonic adenomatous polyps are generally regarded as premalignant lesions  these results lend support to the view that alcohol consumption may be an important factor in the pathogenesis of colorectal neoplasia  thus reinforcing the proposed polyp carcinoma sequence in colorectal carcinogenesis  the role of smoking  however  is less clear particularly since the lack of association of colorectal carcinoma and smoking has been reported in many other studies  
class4	coeliac disease and malignancy of the duodenum  diagnosis by endoscopy  successful treatment of the malignancy  and response to a gluten free diet  a patient presented with subtotal villous atrophy and a malignant duodenal tumour of uncertain histogenesis  he was successfully treated by resection and chemotherapy and the small bowel mucosa recovered on a gluten free diet  the tumour was diagnosed at upper gastrointestinal endoscopy when barium studies and abdominal computed tomography were normal  thus making this one of the earliest coeliac malignancies diagnosed  
class4	spinal instability secondary to metastatic cancer  fifty five patients with severe pain from spinal instability secondary to metastatic cancer were referred to hope hospital  none being judged to be in a terminal condition  one patient had too extensive disease for surgery so 54 were treated by 55 spinal stabilisations  49 obtained complete relief of pain and two had partial relief  there were three failures  twenty eight of the patients had clinical evidence of spinal cord or cauda equina compression and were decompressed at the time of stabilisation  of these  20 had major recovery of neurological function  patients with pre operative evidence of extradural tumour had  prophylactic  decompression at the time of stabilisation  none of these patients later developed signs of cord or cauda equina compression  the results suggest that alleviation of pain and restoration of mobility are best achieved by segmental spinal stabilisation  a few patients require a combined anterior and posterior stabilisation  postoperative radiotherapy should be given whenever possible  and the causative tumour should be treated by endocrine or chemotherapy  as indicated  
class4	intraosseous lipomatosis  a case report  we report a case of systemic intraosseous lipomatosis involving the proximal femur  both ends of the tibia  and the tarsal and metatarsal bones  the lesions progressed during a five year follow up with a pathological fracture of the tibial plateau  ct scans were characteristic and helpful in diagnosis but mr imaging added little information  intraosseous lipomatosis is a hamartomatous malformation due to hyperplasia of adipose tissue  and is fundamentally different from solitary benign intraosseous lipoma  management involves reconstruction of any pathological fracture  large progressive lesions should be treated by curettage and grafting in an attempt to prevent such fractures  
class4	bone lesions secondary to benign phaeochromocytoma  four cases in childhood  metaphyseal sclerotic bone changes associated with benign phaeochromocytoma are very rare in childhood  we report four cases  in each of which the radiographic changes returned to normal after removal of the tumour  
class4	chondrosarcoma of the soft tissues  two different sub groups  chondrosarcomas arising from soft tissues are rare  two different varieties are described  myxoid and mesenchymal  we have collected nine cases of the tumour  five myxoid and four mesenchymal  from a review of 513 cases of chondrosarcoma seen between 1904 and 1988  we report the principal clinical  radiographical and histological differences between the two varieties and discuss their surgical treatment and prognosis  
class4	determination of plasma calcitonin gene related peptide concentrations by a new immunochemiluminometric assay in normal persons and patients with medullary thyroid carcinoma and other neuroendocrine tumors  there is doubt about concentrations of circulating calcitonin gene related peptide  cgrp  and the value of plasma cgrp measurements in the detection and follow up of medullary thyroid carcinoma  mtc   thus  we developed an immunochemiluminometric sandwich assay for cgrp using antibodies purified from a polyclonal antiserum against human cgrp  the assay was sensitive  limit of detection  0 4 pmol l  multiply by 3 7892 to derive nanograms per l  and highly specific  no cross reaction with human calcitonin  ct    normal plasma cgrp values ranged from less than 0 4 to 4 5 pmol l  median  0 8  n   31   with 61  having detectable levels  values in samples from patients with mtc were elevated  unoperated patients  n   10   4 7 137 pmol l  median  7 1   and operated patients with gross persistent or recurrent tumor  n   14   4 7 171 pmol l  median  23 2   in contrast  cgrp values were normal in 78  of nine postoperative patients with elevated ct  but no detectable tumor  range  less than 0 4 to 6 3 pmol l  median  1 6   cgrp levels increased after pentagastrin injection in mtc patients  but less than did ct values  cultured mtc cells in vitro secreted large amounts of cgrp  and rat nerve root ganglia  human osteoblasts  and microvessel endothelial cells secreted lesser amounts  we conclude that cgrp circulates in normal plasma  but at very low levels  plasma cgrp concentrations are frequently high in patients with mtc  but primarily in those with gross tumor or metastases  plasma ct assay is the preferable test for mtc  but cgrp assay deserves prospective study for a possible role in predicting gross metastasis  
class4	use of m  131i iodobenzylguanidine in the treatment of malignant pheochromocytoma  the efficacy and safety of m  131i iodobenzylguanidine   131i mibg  were assessed in 15 patients with malignant pheochromocytomas in a nonrandomized  single arm trial  in which patients were treated with  131i mibg  sa  740 megabequerel mg  every 3 months  seven of these patients had bone and soft tissue metastases  4 had only soft metastases  and 4 had only bone metastases  the follow up period ranged from 6 54 months  the number of doses ranged from 2 11  with 2 9  78 4 mci  to 9 25 gigabequerel  gbq   250 mci  administration and a cumulative activity from 11 1 85 90 gbq  300 2322 mci   the absorbed cumulative dose in tumors ranged from 12 155 gy  a beneficial effect of the treatment was observed in 9 patients  60    no complete remission of the disease was observed  seven patients died during the study  among whom 4 never responded to the treatment  seven had hormonal responses  4 complete and 3 partial   with a duration ranging from 5 48 months  among these patients  4 relapsed  and 3 died within 3 months  five patients had partial tumoral responses mainly located in soft tissues and for a duration ranging from 29 54 months  all patients with a hormonal response had objective improvement in clinical status and blood pressure  there was no clear cut relationship between the cumulative dose and the responses  the main side effect observed in 1 patient with widespread bone metastases after three doses  12 9 gbq  was a pancytopenia  which resolved after treatment was discontinued  this study suggests that repeated  131i mibg treatment could be effective in patients with advanced malignant pheochromocytoma  
class4	quantitation of g0 and g1 phase cells in primary carcinomas  antibody to m1 subunit of ribonucleotide reductase shows g1 phase restriction point block  human cancers have an apparent low growth fraction  the bulk of cells presumed to being out of cycle in a g0 quiescent state due to the inability in the past to distinguish g0 from g1 cells  the allosteric m1 subunit of ribonucleotide reductase  m1 rr  is constitutively expressed by cycling cells  i e   g1  s  g2 m   it is acquired during transition from g0 to g1  lost during exit to g0 and thus distinguishes g0 from g1 cells  to estimate the proportion of g0 and g1 cells in primary human breast  n   5  and colorectal  n   12  adenocarcinomas  we used both analytical dna flow cytometry  adfc  and immunoperoxidase staining of sections with the monoclonal antibody to m1 rr  mab m1 rr   adfc of fresh tumors revealed a low percentage of cells in the s phase  4 0     3 4   but immunoperoxidase staining for m1 rr revealed an unexpectedly high proportion of positive cells  52 4     12 7   in the g1  s  g2 m phases indicating a high g1 content of primary human tumors  thus  human cancers are blocked in transition in g1 and are not predominantly in a g0 or quiescent differentiated state  this block was interpreted to mean that human cancers are responding to putative regulatory events at a restriction point in the g1 phase  such as relative growth factor deficiency  density inhibition  antiproliferative cytokines  or gene products  using flow cytometry for both dna and m1 rr content we found that human colon cancer cell lines arrest in the g1 but not g0 phase upon serum deprivation or density inhibition  similarly  human breast cancer cell lines are arrested in g1 but not g0 phase by medroxyprogesterone acetate  mpa  or tamoxifen exposure  these findings match our in situ observations  and support the concept of a restriction point block in primary human tumors  
class4	mutations in the k ras oncogene induced by 1 2 dimethylhydrazine in preneoplastic and neoplastic rat colonic mucosa  these experiments were conducted to determine whether point mutations activating k ras or h ras oncogenes  induced by the procarcinogen 1 2 dimethylhydrazine  dmh   were detectable in preneoplastic or neoplastic rat colonic mucosa  rats were injected weekly with diluent or dmh at 20 mg kg body wt for 5  10  15  or 25 wk  killed  and their colons dissected  dna was extracted from diluent injected control animals  histologically normal colonic mucosa from carcinogen treated animals  and from carcinomas  ras mutations were characterized by differential hybridization using allele specific oligonucleotide probes to polymerase chain reaction  amplified dna  and confirmed by dna sequencing  while no h ras mutations were detectable in any group  k ras  g to a  mutations were found in 66  of dmh induced colon carcinomas  these mutations were at the second nucleotide of codons 12 or 13 or the first nucleotide of codon 59 of the k ras gene  the same type of k ras mutations were observed in premalignant colonic mucosa from 2 out of 11 rats as early as 15 wk after beginning carcinogen injections when no dysplasia  adenomas  or carcinomas were histologically evident  suggesting that ras mutation may be an early event in colon carcinogenesis  
class4	insulin like growth factor ii mediated proliferation of human neuroblastoma  neuroblastoma is an embryonal tumor that typically arises in cells of the developing adrenal medulla  igf ii mrna is expressed at high levels in the adrenal cortex before birth but it is not detectable until after birth in the adrenal medulla  neuroblastoma cell lines corresponding to early adrenal medullary precursors did not express igf ii  although all three cell lines we tested were growth stimulated by igf ii  cell lines corresponding to more mature adrenal medullary cells expressed igf ii  and one  sk n as  grows by an igf ii autocrine mechanism  j  clin  invest  84 829 839  el badry  romanus  helman  cooper  rechler  and israel  1989  an examination of human neuroblastoma tumor tissues for igf ii gene expression using in situ hybridization histochemistry revealed that igf ii is expressed by tumor cells in only 5 of 21 neuroblastomas  but is detectable in cells of nonmalignant tissues including adrenal cortical cells  stromal fibroblasts  and eosinophils in all 21 tumors  these findings indicate that igf ii may function as an autocrine growth factor for some neuroblastomas and as a paracrine growth factor for others  they suggest that the growth regulatory pathways utilized by neuroblastoma mimic those used in the precursor cell type from which individual tumors arise  
class4	recombinative events of the t cell antigen receptor delta gene in peripheral t cell lymphomas  recombinative events of the t cell antigen receptor  tcr  delta chain gene were studied in 37 cases of peripheral t cell lymphoma  ptcl  and related to their clinical presentation and the expression of the alpha beta or gamma delta heterodimers as determined by immunostaining of frozen tissue samples  there were 22 cases of alpha beta  5 cases of gamma delta  and 10 cases of silent tcr expressing neither the alpha beta nor gamma delta tcr  5 different probes were used to examine the delta locus  the 22 cases of alpha beta ptcl displayed biallelic and monoallelic deletions  a monoallelic v delta 1 j delta 1 rearrangement was observed in 1 case and a monoallelic germ line configuration in 7 cases  the 5 cases of gamma delta ptcl displayed biallelic rearrangements  the productive rearrangements could be ascribed to v delta 1j delta 1 joining in 3 cases and vj delta 1 joining in 2 cases according to the combined pattern of dna hybridization with the appropriate probes and of cell reactivity with the tcr delta 1  delta tcs 1  and anti v delta 2 monoclonal antibodies  in the vj delta 1 joining  the rearranged v segments were located between v delta 1 and v delta 2  interestingly  in the third group of 10 cases of silent ptcl  5 cases were found to have a tcr gene configuration identical to that in the tcr alpha beta ptcl  as demonstrated by biallelic delta gene deletion  these 5 cases were cd3 positive  the 5 remaining cases showed a monoallelic delta gene rearrangement with a monoallelic germ line configuration in 4 and a monoallelic deletion in 1  four of these cases were cd3 negative  which was consistent with an immature genotype the tcr commitent of which could not be ascertained  finally  tcr gamma delta ptcl consisted of a distinct clinical morphological and molecular entity whereas tcr alpha beta and silent ptcl had a similar presentation  
class4	patterns of epidermal growth factor receptors in basal and squamous cell carcinoma  the presence of immunoreactive epidermal growth factor receptors in human skin tumors was investigated using the indirect immunoperoxidase technique  sixteen basal cell carcinomas and 11 squamous cell carcinomas were evaluated  all of the specimens studied were receptor positive  in 70  of the specimens there was prominent staining of the cell membranes  in 54  of the nodular basal cell carcinoma specimens there was increased staining at the periphery of the tumor cell masses  
class4	basal cell carcinoma recurring after radiotherapy  a unique  difficult treatment subclass of recurrent basal cell carcinoma  twenty seven basal cell carcinomas  bccs  recurring following radiation therapy alone or in addition to other treatment modalities were treated with mohs micrographic surgery  mms  from 1983 to 1989  mean tumor size was 2 1 cm  of the tumors  70 4  arose in the mid face region  55 6  had undergone multiple previous treatment modalities  the present recurrence rate is 7 4   mean follow up  25 months   basal cell carcinoma recurring following radiotherapy deserves special subclassification among recurrent bcc  it is very difficult to eradicate  with high recurrence rates following standard surgical excision or further radiotherapy  tumors are usually large  aggressive  and invasive  most arise in the cosmetically crucial mid face region  where extension into subcutaneous tissue planes is common  mohs surgery  with its inherent abilities to examine all margins  map tumor extension  and conserve tissue  is uniquely suited to treatment of these difficult tumors  
class4	skin ultrasound in dermatologic surgical planning  high resolution ultrasonography was performed on 55 patients with palpable skin lesions  all submitted to surgical excision and to histologic diagnosis  in all the cases  the ultrasound picture was confirmed by the surgical appearance of the lesions  the sonographic structure was characteristic in the case of cysts and angiomas  lymphangiomas in particular  ultrasonography is considered a simple and reliable technique for the pre operative evaluation of skin nodules  as it gives a clear picture of their size  depth  and outline  however  sonography cannot substitute for the clinical dermatologic approach and the need for an histologic diagnosis  
class4	prospective follow up for malignant melanoma in patients with atypical mole  dysplastic nevus  syndrome  a total of 357 white patients who had melanocytic nevi that fulfilled the clinical criteria for the  classic  atypical mole  dysplastic nevus  syndrome  100 or more melanocytic nevi  one or more melanocytic nevi 8 mm or larger in diameter  and  one or more melanocytic nevi with atypical features  were followed for the development of cutaneous malignant melanomas  seventeen patients  4 8   developed malignant melanomas during an average follow up period of 49 months  one patient developed two malignant melanomas  eight of the malignant melanomas detected were in situ and ten were invasive melanomas  less than 0 86 mm in breslow thickness   implying an excellent prognosis  the number of malignant melanomas detected in these patients exceeded significantly the number expected to occur in age  and sex matched white controls  all groups were shown to have an increased risk for the development of malignant melanomas  total body photographs were helpful in detecting changes in size  shape  and color that led to the diagnosis of malignant melanoma  these data support the concept that patients with this readily regionalized clinical presentation of classic atypical mole syndrome are at an increased risk for malignant melanomas and  therefore  should be examined regularly  
class4	the medical necessity of evaluation and treatment of port wine stains  new lasers and improved laser delivery systems have allowed for the safe and effective treatment of port wine stains in patients of all ages  the satisfactory results obtained by laser treatment have increased the number of patients seeking consultation regarding their birthmarks  it is imperative that physicians recognize the various medical syndromes and problems associated with port wine stains  a review of 415 patients with facial port wine stains has revealed hypertrophy and or nodularity in 65  of patients by the fifth decade of life  which increases significantly the morbidity of these lesions  it is believed that laser treatment will minimize the medical and psychologic complications that result from the natural evolution of port wine stains  
class4	retroviral transduction of protein kinase c gamma into cytotoxic t lymphocyte clones leads to immortalization with retention of specific function  the molecular pathways that are responsible for delivering the proliferative signals from the cell surface to the nucleus in t lymphocytes are still unresolved  but recent data implicates protein kinase c  pkc  involvement in the tcr signaling pathway  to further address the role of pkc in t cell activation  the effects of high level expression of the pkc gamma isoenzyme in murine ctl clones were examined  unlike the parental cells that required periodic ag stimulation for cell activation and growth  cells expressing a retrovirally transduced pkc gamma gene propagated in culture independent of the need for ag stimulation  although maintaining identical functional specificity to the parental ctl  constitutive pkc gamma expression may therefore mimic physiologic pkc activation  thereby abrogating the requirement for tcr ag interaction in t cell activation  
class4	dexamethasone inhibits the induction of monocyte chemotactic activating factor production by il 1 or tumor necrosis factor  recently purified and molecularly cloned monocyte chemotactic and activating factor  mcaf  may play a major role in recruiting and activating monocytes in the inflammatory process  we examined the effects of a potent anti inflammatory agent  dexamethasone  dxs   on the production of this factor  over a wide range of concentrations  10  5  to 10  8  m   dxs inhibited the production of mcaf at the mrna and protein level in a human fibrosarcoma cell line  which was stimulated with either il 1 or tnf alpha  we examined the turn over of synthesized mcaf mrna that showed dxs decreased the stability of mcaf mrna  furthermore  the addition of actinomycin d and cycloheximide abolished this effect of dxs  indicating that de novo mrna and protein synthesis were required for this process  in addition  a nuclear run off analysis revealed that dxs also inhibited the transcription of il 1  or tnf activated mcaf genes  therefore  both the destabilization of mcaf mrna and the inhibition of transcription of the gene contribute to the decrease in the mcaf mrna steady state level by dxs  
class4	dna sequences 3  of the ig h chain cluster rearrange in mouse b cell lines  a mouse myeloma cell line mpc11  igg2b  kappa  and variants derived from it have been used to study dna rearrangements that occur at the ig h chain locus  one variant  f5 5  has acquired both vh gene and c epsilon gene rearrangements  through genomic southern blot analysis initially directed to mapping the c epsilon gene rearrangement  we observed that the vh region rearrangement was linked  through an inversion event  to sequences that originate 3  of the ch cluster  i e   3  of the c alpha gene  subsequent studies have shown that dna rearrangements within the region 3  of the c alpha gene are detected in several other mouse myeloma and hybridoma cell lines and are not associated with the expression of specific isotypes  
class4	examination of htlv i integration in the skin lesions of various types of adult t cell leukemia  atl   independence of cutaneous type atl confirmed by southern blot analysis  the various clinical features of adult t cell leukemia lymphoma  atl  are frequently accompanied by skin eruptions  recently  a cutaneous type of atl has been proposed by clinical studies  we analyzed the viral integration of human t cell leukemia virus i  htlv i  and monoclonal rearrangement of t cell receptor  tcr  gene in blood lymphocytes and the cutaneous infiltrated cells of nine atl patients with various clinical features and skin eruptions  we classified them by the results of southern blot analysis and propose a cutaneous type atl accordingly  in two of them  we could detect the monoclonal integration of htlv i and t cell monoclonality only in the skin but not in the peripheral lymphocytes  we also demonstrated the time course study in one patient  clinicians should be aware of the htlv i positive cutaneous t cell lymphoma that can be named cutaneous type atl  examination of viral integration and t cell monoclonality in skin lesions is required to make an exact diagnosis of cutaneous atl  
class4	immunolocation of tnf alpha cachectin in human melanoma cells  studies on co cultivated malignant melanoma  we have investigated the ability of metastatic cells to produce the macrophage cytokine  tnf alpha cachectin  as these cells have macrophage like properties such as infiltration and migration  we looked for tnf alpha cachectin in three tumor cell lines derived from human malignant melanomas and six co cultivated malignant melanomas derived  in vitro  from these three cell lines plus angioma fibroblasts  immunohistochemistry with an anti tnf alpha cachectin monoclonal antibody showed that tnf alpha cachectin was produced by two of the three parent melanoma cell lines  all the tumor cells in both the co cultivated malignant melanomas and their in vitro tumorous nodules produced tnf alpha cachectin  even those derived from the melanoma cell line  which originally did not  the results clearly show that tnf alpha cachectin can be produced by non hematopoietic tumor cells  a co cultivated tumor model prepared from other types of human tumor cell lines promises to provide a useful tool for exploring the relationship between tnf alpha cachectin and oncogenesis  
class4	immunohistochemical alterations in basement membrane components of squamous cell carcinoma  to investigate alterations in the basement membrane  bm  in squamous cell carcinoma  scc   we investigated 20 tumors  four had the cytologic characteristics of bowen s disease  scc bd  and 16 did not have them  scc nb   tumors were studied immunohistochemically by double immunofluorescent staining by using mouse monoclonal antibodies to the core protein of heparan sulfate proteoglycan  hspg  and chondroitin 6 sulfate glycosaminoglycan  ch6s  as well as rabbit antiserum to laminin  ln  and type iv collagen  c 4   in well differentiated and highly keratinized scc nb  ln  c 4  and hspg could be detected in the tumor nest bm and showed no loss of continuity  but they were largely lost in poorly differentiated and poorly keratinized scc nb  this suggests that poorly differentiated scc nb cause greater enzymatic degradation of bm components than well differentiated scc nb  ch6s was detected in parts of the bm of scc bd  but it was absent in all scc nb examined  it appears that scc nb have lost the ability to synthesize ch6s  and that scc bd degrade ch6s although they continue to produce it  thus  it appears that in scc the bm is qualitatively different from that of normal epidermis  and that scc bd can be distinguished from scc nb by the ch6s content of the bm  
class4	identification of a melanoma progression antigen as integrin vla 2  the expression of the integrin receptors vla 1   2   3  and  6 was studied in normal cultured melanocytes and in five melanoma cell lines  normal melanocytes synthesized vla 3  but did not reveal detectable levels of vla 1   2  and  6  all melanoma cell lines  however  expressed vla 2   3  and  6  vla 1 was synthesized by two of five melanoma lines  in parallel  we had analyzed the expression of four previously characterized melanoma cell surface antigens  one of them  antigen a 1 43   which is associated with tumor progression of human melanoma  revealed a striking similarity to vla 2  in sequential immunoprecipitation experiments  we show that a 1 43 is identical with the integrin vla 2  a cell surface receptor for collagen  laminin  and fibronectin  
class4	mandibular involvement in oral cancer  it is difficult to predict the tumour invasion into the mandible by oral cancer pre operatively  and consequently the decision to preserve or sacrifice the mandible is largely individualistic  the present study of 44 cases analyses the reliability of pre operative parameters to assess mandibular involvement  clinical  radiological and scintigraphic features have been compared with the detailed histology of the bone  this study confirms the usefulness of superior marginal resections in lesions which are close to but not involving the mandible  as well as for superficial lesions which are actually seen to involve the mandible but their ct and bone scans are negative for tumour invasion  
class4	non hodgkins lymphoma of the head and neck  experience in the grampian area  the records of 44 cases of non hodgkins lymphoma  nhl  presenting to the ear  nose and throat department in the grampian area from 1980 1988 were examined in relation to site of occurrence  histology  age at presentation  clinical stage  treatment and survival  the median age was 67 years and there was a preponderance of high grade histology  especially in disease affecting the tonsil  most deaths occurred in the first year  patients with high grade disease and those in stages three and four had a significantly poorer survival during the first year  the site of disease had no influence on survival  
class4	haemangiopericytoma of the temporal bone  haemangiopericytoma is an uncommon vascular tumour with a widespread distribution  although meningeal involvement is well recognized  only a few sporadic cases of temporal bone lesions have been documented  all with doubtful sites of origin  late presentation together with the restrictive anatomy of this region often precludes its effective removal and even minimal residual disease may progress rapidly  a series of three such patients are presented in order to discuss the natural history  histological features and treatment of this disease  
class4	forty years of neuroglycopenia  neuropsychiatry for the internist  the case of a 65 year old patient with an insulin secreting pancreatic tumour and a 40 year history of neuropsychiatric disease is reported  the physiopathology and clinical features of acute  subacute  and chronic neuroglycopenia in patients with endogenous insulin hypersecretion are discussed  
class4	reproducibility of image interpretation in immunoscintigraphy performed with indium 111  and iodine 131 labeled oc125 f ab  2 antibody injected into the same patients  an important criterion for the clinical use of a new imaging technique is the correct reproducibility of interpretation  forty six paired immunoscintigraphic examinations were performed on 43 patients with suspected ovarian carcinoma recurrence using f ab  2 fragments of oc125 antibody labeled first with indium 111 and then with iodine 131  planar scintigraphy  ps  and emission computed tomography  ect  images were interpreted blindly and separately by three observers  and reproducibility was evaluated by a kappa concordance index  intra  and interobserver reproducibility were generally satisfactory  kappa values of 0 6 and 0 7  respectively   binomial analysis of kappa values for ect showed the superiority of indium 111 for intraobserver  p   0 035  and interobserver  p   0 0039  study  however  for ps there was no significant difference in reproducibility with the two radionuclides  
class4	relationship of uptake of technetium 99m sn  n pyridoxyl 5 methyltryptophan by hepatocellular carcinoma to prognosis the relationship of technetium 99m sn  n pyridoxyl 5 methyltryptophan  99mtc pmt  uptake by hepatic tumors to survival was studied in 162 cases of hepatocellular carcinoma  hcc   the median survival of 82 patients in whom hepatic tumors showed increased uptake in delayed 99mtc pmt imaging was 1013 days  which was significantly longer than the survival time of 398 5 days of 80 patients in whom hepatic tumors did not show increased uptake of radioactivity  p less than 0 002   the relationship between the ability of hepatic tumors to take up 99mtc pmt and survival was also analyzed in patients with hcc showing filling defects in 99mtc colloid liver images and  in relation to the therapy  serum values of bilirubin and alpha fetoprotein  results indicated that the degree of 99mtc pmt uptake by hepatic tumors is closely correlated with the prognosis of patients with hcc  
class4	comparison of 1073 mbq and 3700 mbq iodine 131 in postoperative ablation of residual thyroid tissue in patients with differentiated thyroid cancer  in a randomized prospective study  we compared the efficacy of low dose  1073 mbq  and high dose  3700 mbq  iodine 131 administration in postoperative ablation of residual functioning thyroid tissue in 63 patients with differentiated thyroid cancer  we were unable to demonstrate any difference between the low  and the high dose of radioactive iodine in scintigraphic ablation of remnant tissue  in 81   21 26  of the patients  1073 mbq ablated after the first dose  77   21 26   3 5   24 31  after the first plus second dose  and 69   24 31   0 4   24 35  after the first  second  and third dose  radioiodine  3700 mbq  ablated in 84   73   and 69  of the patients after respectively 1   1  plus 2   and 1  plus 2  plus 3  dose  forty percent of the patients ablated with the low dose and 44  ablated with the high dose had elevated thyroglobulin levels at the time of complete scintigraphic ablation  in conclusion  we did not find any difference between 3700 mbq and 1073 mbq iodine 131 as regard to number of doses needed for complete scintigraphic ablation of residual functioning thyroid tissue  
class4	variables influencing tumor uptake of anti melanoma monoclonal antibodies radioiodinated using para iodobenzoyl  pib  conjugate tumor uptake was examined with respect to antigen expression  time dependent biodistribution  dose of mab injected  tumor size  and tumor site  i e   subcutaneous versus lung or liver metastases   nr ml 05  96 5  and p94 showed significantly greater uptake in subcutaneous tumors than cl207 and 5 1  p less than 0 05   nr ml 05 had a significantly higher tumor uptake at 24 hr  11 9     0 51  than at 72 hr  4 0     0 37  or 144 hr  2 7     0 84  after injection  p less than 0 001   the other four mabs had similar tumor distribution at all three time points  the tumor uptake of four mabs  96 5  p94  cl207  5 1  differed with respect to in vitro versus in vivo binding to tumor  tumor type  dose of mab  and tumor site  subcutaneous versus metastases   in contrast  nr ml 05 demonstrated consistent uptake in tumors independent of the above parameters  these data suggest that certain host parameters can influence in vivo tumor targeting depending on characteristics of each mab studied  
class4	extracranial metastatic glioblastoma  appearance on thallium 201 chloride technetium 99m hmpao spect images  sequential thallium 201 chloride and technetium 99m hexamethylpropyleneamine oxime single photon emission computed tomography  spect  images were obtained in a patient with extracranial metastatic glioblastoma multiforme  thallium 201 uptake was high  three times the scalp background  in all pathologically confirmed extracranial metastases and moderate  1 6 times scalp background  intracranially  where most biopsy specimens showed gliosis with scattered atypical astrocytes  technetium 99m hmpao uptake was decreased intracranially in the right frontal and parietal lobes which had been irradiated  it was also decreased in one well encapsulated scalp lesion and high in another scalp mass with less defined borders  possible mechanisms of tumor uptake of these agents are reviewed  
class4	technetium 99m methylene diphosphonate  mdp  uptake in a sympathetic effusion  an index of malignancy and a review of the literature  we report a patient with a sympathetic pleural effusion secondary to t cell lymphoma that accumulated the bone imaging agent  technetium 99m methylene diphosphonate  99mtc mdp   this case is significant in that malignant cells were not present on three cytologic examinations of the pleural fluid or multiple pleural biopsies  we also present a review of the published literature on pleural effusions that accumulate bone tracers  we conclude that pleural effusions that accumulate 99mtc mdp should be considered malignant or secondary to a malignancy and further work up is essential even if the cytologic exam of the pleural fluid is unremarkable  
class4	htlv i associated leukemia lymphoma in south florida  we report here 10 cases of adult t cell leukemia lymphoma  atl  seen in south florida between february 1988 and july 1989  all were seropositive for human t lymphotropic virus type i  htlv i  and seronegative for human immunodeficiency virus type 1  hiv 1   dna extracted from tumor biopsies peripheral blood lymphocytes of nine patients was shown by the polymerase chain reaction  pcr  to contain htlv i proviral dna  blot hybridization of dna extracted from seven patients with an htlv i cdna probe revealed a monoclonal pattern of proviral integration consistent with a diagnosis of atl  eight of the 10 patients were women  six patients were from haiti  three from jamaica  and one from the bahamas  all patients had very aggressive non hodgkin s lymphoma  two patients presented with sinus and retro orbital involvement  another had gastric lymphoma that perforated  nine patients developed hypercalcemia  eight patients died within 1 year of diagnosis  two were lost to follow up  during the course of this study  66 new cases of non hodgkin s lymphoma were diagnosed at this hospital  ten of these cases were atl  the prevalence of htlv i related lymphoma in this sample was 15   since tissue from all patients was not available for htlv i screening  however  it is possible that other cases of atl went undetected  we conclude from this initial survey that a retroviral etiology should be considered in patients from populations known to be at risk for htlv i infection who present with non hodgkin s lymphoma  
class4	treatable abdominal pathologic conditions and unsuspected malignant neoplasms at autopsy in veterans who received mechanical ventilation  study objective  to determine  in medical patients who received mechanical ventilation  the frequency and types of major unexpected diagnoses at autopsy that  if known before death  would probably have led to improved survival  class i errors  or substantively changed management but not survival  class iib errors   design  retrospective cohort study  setting  six medical intensive care units in a department of veterans affairs cooperative study  patients  one hundred seventy two autopsied patients of the 401 veterans who received mechanical ventilation and died in the hospital  results  the class i error rate was 12   abdominal pathologic conditions  abscesses  bowel perforations  or infarction  were as frequent as pulmonary emboli as a cause of class i errors  while patients with abdominal pathologic conditions generally complained of abdominal pain  results of examination of the abdomen were considered unremarkable in most patients  and the symptom was not pursued  six percent of patients had extensive malignant neoplasms  class iib errors   conclusions  atypical presentation of potentially treatable abdominal pathologic conditions is a common cause of class i errors in veterans who receive mechanical ventilation  conversely  several patients with unrecognized terminal conditions underwent intensive intervention  if the information gained at autopsy had been known before death  management would have probably changed substantively in 18  of patients  
class4	mucoepidermoid carcinoma of the salivary glands  a reappraisal of the influence of tumor differentiation on prognosis  thirty nine cases of mucoepidermoid carcinoma of the salivary glands were reviewed for a reappraisal of the influence of the grade of differentiation on the outcome of the disease  the age of the patients ranged between 7 and 84 years  fifteen patients were females and 24 males  the tumors were located at the parotid gland  n   30   the submaxillary gland  n   1   the soft palate  n   5  and the oral mucosa nos  n   3   at presentation 4 tumors were intraglandular and 35 extraglandular  three patients had lymph node metastases and one patient lung metastases  the grade of differentiation was assessed using the criteria of healey et al  twelve tumors were classified as grade i  17 as grade ii  and 10 as grade iii  follow up information was obtained with a duration of 5 144 months  mean 44 7 months   six cases recurred locally and 5 developed metastases  five years cumulative survival was 100  for grade i  70 1  for grade ii  and 47 2  for grade iii  the results point to the usefulness of the assessment of the grade of differentiation as a guide to anticipate the outcome of the disease  
class4	comparison of characteristics of esophageal squamous cell carcinoma associated with head and neck cancer and those with gastric cancer  in ongoing reviews of 339 patients with surgically treated primary squamous cell carcinoma  there were 19  5 6   with concurrent gastric cancer and 11  3 2   with head and neck cancer  the incidences of intra esophageal multiple occurrence of esophageal cancer are 27 3  and 26 3  in those with associated head and neck cancer and gastric cancer  respectively  and higher than 7 1  in those without such a concurrent cancer  there was no difference in the clinicopathological characteristics of those with concurrent head and neck and gastric cancers  except for the higher incidence of metachronous occurrence in the former  these findings suggest that  in cases of esophageal cancer associated with concurrent head and neck cancer and gastric cancer  intraesophageal multiplicity of the esophageal carcinoma is frequent and that preoperative serial evaluations is most important to design treatment and estimate the prognosis  
class4	immune competent cells of regional lymph nodes in colorectal cancer patients  i  flow cytometric analysis of lymphocyte subpopulation  lymphocyte subpopulations of the regional lymph nodes in 20 colorectal cancer patients were measured by flow cytometry to analyze nodal lymphocytes phenotypically  eleven patients with cholelithiasis were used as controls  comparison of lymphocyte subpopulations between colorectal cancer and control groups revealed a significantly increased rate of leu 12  cells in the cancer patients  furthermore  a significant increase of leu 3a  leu 8  cells and a significant decrease of leu 3a  leu 8  cells were also found in the paracolic nodes of the cancer patients  however  leu 2a  leu 15  cells were not different between the both groups  meanwhile  in the cancer patients  the rates of leu 4   leu 3a   and leu 3a  leu 8  cells were higher in the paracolic nodes compared with the intermediate nodes  additional investigation of the correlation between clinicopathological features of the tumors and lymphocyte subpopulations  showed that leu 12  cells were related to the tumor size and leu 2a  15  cells related to the histopathological type  the foregoing results indicate that the rates of both b and helper t cells  which may specifically participate in the antibody production  increase in the regional lymph nodes of colorectal cancer patients  
class4	activation and in vitro expansion of tumor reactive t lymphocytes from lymph nodes draining human primary breast cancers  the feasibility of in vitro activation of lymphocytes from the draining lymph nodes  dln  of breast cancer patients was examined  lymphocytes isolated from 48 dln from 12 patients were examined for their proliferative responses to ril 2  autologous tumor cells  or ril 2 plus tumor cells  three general patterns of cellular responses were observed  cells from some dln  17   were unresponsive to any stimuli  lymphocytes from 52  of the dln responded moderately to ril 2 alone  the combination of ril 2 and tumor antigen had a synergistic effect on the proliferation of cells from 31  of the dln assayed  phorbol dibutyrate and ionomycin plus ril 2 stimulated expansion of dln lymphocytes by up to 850 fold after 35 days  these expanded cell populations  as well as those stimulated with antigen plus ril 2  were predominantly cd3  and cd16  cells  varying in proportions of cd4  and cd8  subsets  both populations were cytotoxic against autologous tumor  mcf 7  and k562 target cells  
class4	neuroendocrine carcinoid tumours of the breast  a variant of carcinoma with neuroendocrine differentiation  carcinoid tumours most frequently develop in the gastrointestinal tract but have been described in many organs of the body  in 1977 the first cases were reported in the mamma  followed by descriptions of argyrophilic carcinoid like  neuroendocrine mammary tumours by many investigators who performed immunohistochemical and ultrastructural examinations  the existence of true carcinoids in the mamma is still a controversial issue  eight mammary neoplasms with monomorphous cytonuclear features  five of the small cell carcinoid like variety and three composed of larger cells  were examined by immunohistochemical and ultrastructural examination  we believe this kind of tumours are ductal or lobular carcinomas with focal or more extensive neuroendocrine features and are the result of a dual differentiation of neoplastic precursor stem cells along epithelial and endocrine lines  consequently  we consider that treatment of such cases should not be different from that of the ordinary type of mammary carcinomas  
class4	characterization and histopathological correlation of cytosol proteins of benign and malignant breast tumors  significant differences in cytosol protein level exist between normal benign and cancerous breast tissues  there is a positive correlation between the cytosol protein level and histological grade of carcinoma  well differentiated carcinoma have a lower value of cytosol protein than poorly differentiated carcinoma  in slab gel electrophoregrams  the total numbers of bands are almost identical in normal  benign  and malignant conditions  in addition  37 kd protein band is consistently present in malignant cases and always absent in normal or benign cases  more extensive biophysical examination of this band may provide further insight into the protein alterations in cancer cells at the molecular level  
class4	surgical resection of a solitary liver metastasis in a 46 year old patient with a malignant thymoma  clinical history  surgical treatment  and pathologic findings of a solitary liver metastasis of a malignant thymoma in a 46 year old female are reported  an extensive literature review has revealed no record of surgical resection of liver metastasis in a patient with invasive thymoma  
class4	lactation following conservation surgery and radiotherapy for breast cancer  a 38 year old woman with early stage invasive breast cancer was treated with wide excision of the tumor  axillary lymph node dissection  and breast irradiation  three years later  she gave birth to a normal baby  she attempted breast feeding and had full lactation from the untreated breast  the irradiated breast underwent only minor changes during pregnancy and postpartum but produced small amounts of colostrum and milk for 2 weeks postpartum  there are only a few reports of lactation after breast irradiation  these cases are reviewed  and possible factors affecting breast function after radiotherapy are discussed  because of scant information available regarding its safety for the infant  nursing from the irradiated breast is not recommended  
class4	subrenal capsule assay as a chemosensitivity test for primary esophageal squamous cell carcinoma  the efficiency of the subrenal capsule assay  srca  was studied with fresh tissue of esophageal squamous cell carcinoma  the day to day changes in 10 carcinoma cases were evaluated for 9 days  the cancer cells continued to proliferate from the 3rd to the 7th day after the implantation and then decreased  the host reaction was recognized histologically from the 3rd or 4th day to the 9th day  however  the immune reaction did not significantly influence the evaluation of srca until the 7th day  the immunohistochemical staining with anti bromodeoxyuridine monoclonal antibody revealed the existence of cancer cells at the dna synthesizing stage  s stage  in the graft until the 7th day  in chemosensitivity test by srca  21 patients were studied  and all were evaluable  5 fu administration produced a response in 8 21 cases  38 1    vds in 8 21  38 1    and cddp in 3 21  14 3    used in combination  cddp   vds was effective in 7 18 cases  38 9   and cddp   blm in 6 18 cases  33 3    
class4	expression of hla dr and secretory component antigens and lymphocyte infiltration in human gastric nonmalignant and malignant tissues  an immunohistochemical study  the relation between hla dr and secretory component  sc  expression and the degree of lymphocyte infiltration was immunohistochemically examined in human gastric mucosa with or without intestinal metaplasia and gastric carcinoma tissues  gastric mucosa without obvious inflammation showed neither expression of hla dr or sc nor remarkable lymphoid infiltration  in contrast  gastric mucosa with chronic inflammation  tissues with incomplete type of intestinal metaplasia  and carcinoma demonstrated both hla dr and sc in almost the same area and also prominent lymphoid infiltration in the surrounding stroma  this simultaneous expression of hla dr and sc was not observed in complete type of intestinal metaplasia  the results indicate a close relationship between expression of hla dr and sc and the presence of lymphocyte infiltration in gastric mucosa  areas of incomplete type of intestinal metaplasia and in gastric carcinomas  
class4	clinical management of gastric cancer and concomitant esophagogastric varices  we report the late results of treatment of 13 consecutive patients with gastric cancer and concomitant esophagogastric varices  of seven good risk patients classified as child s class a or b  gastrectomy together with selective shunt operation was performed in two  total gastrectomy with splenectomy in three  and distal partial gastrectomy with paraesophageal devascularization without splenectomy in one  the remaining patient with early gastric cancer underwent distal partial gastrectomy following repeated endoscopic injection sclerotherapy  eis  for treatment of the esophageal varices  although the majority of patients who underwent surgical repair of varices  i e   shunt  splenectomy  or devascularization  died  total gastrectomy with splenectomy was the only procedure that led to control of the esophageal varices  since partial gastrectomy combined with eis limits the morbidity and mortality of an extensive resection and at the same time controls esophageal variceal bleeding  it is probably the procedure of choice for patients with a carcinoma in the lower two thirds of the stomach  concerning non surgical cases  two patients were effectively treated using laser endoscopy and eis  without the occurrence of variceal bleeding  the remaining four patients  given chemotherapy or irradiation for treatment of gastric carcinoma  died within 4 months with variceal bleeding or liver failure  for the poor risk patients with evidence of severe liver dysfunction  laser treatment and eis would be the treatment of choice  
class4	squamous carcinoma of the distal esophagus  a survival study  a survival study for squamous carcinomas of the distal esophagus treated by the southern california permanente medical group in the interval of 1954 to 1988 was undertaken  we found radiation therapy and surgery equally efficacious in terms of cure for patients without distant disease and performance status sufficient to tolerate treatment  we did not find survival benefit for patients treated with palliative surgery  and plan less invasive endoscopic means along with chemotherapy and radiation for palliation  reserving surgery for special circumstances  
class4	lymphoscintigraphy with 123i labelled epidermal growth factor we have used 123i labelled epidermal growth factor  egf  scans to study 14 patients with advanced cervical cancer  abnormal lymph node imaging was seen most clearly 6 8 h after the injection and revealed abnormal uptake by pelvic lymph nodes in 11 patients  4 of these 11 had abnormal computerised tomographic and ultrasound scans  in the other 7 conventional radiology did not confirm the presence of disease  
class4	comparison of continuous subcutaneous and intravenous hydromorphone infusions for management of cancer pain  to compare the safety and efficacy of subcutaneous and intravenous infusion of opioid analgesics  a randomised  double blind  crossover trial was carried out in inpatients  15 patients with severe cancer pain received two 48 h infusions of hydromorphone  one subcutaneously and one intravenously in randomly allocated order  the study was made double blind by the use of two infusion pumps throughout  during the active subcutaneous infusion the intravenous pump delivered saline and vice versa  serial measurements of pain intensity  pain relief  mood  and sedation by means of visual analogue scales showed no clinically or statistically significant difference between the two infusion routes  side effects were slight  and the mean number of morphine injections for breakthrough pain did not differ significantly between the routes  4 8  sd 4 5  for intravenous vs 5 3  5 6  for subcutaneous   plasma hydromorphone concentrations measured at 24 h and 48 h of infusion showed stable steady state pharmacokinetics  the mean bioavailability from subcutaneous infusion was 78  of that with intravenous infusion  because of the simplicity  technical advantages  and cost effectiveness of continuous subcutaneous opioid infusion into the chest wall or trunk  intravenous opioid infusion for the management of severe cancer pain should be abandoned  
class4	imaging modalities in recurrent head and neck tumors  patients with recurrent neoplasms of the head and neck present perplexing management problems  and accurate preoperative assessment of their disease is crucial  thirty eight patients with suspected recurrent neoplasms comprise this study  30 had computed tomography scans  4 had magnetic resonance images  and 4 patients underwent both computed tomography and magnetic resonance imaging to assess the anatomical extent of pathology in 34 malignant and 4 benign tumors  contrast enhancement was essential for detecting disease on computed tomography scan  differentiation of recurrent tumor was more difficult when the patient had undergone radiation  magnetic resonance imaging demonstrated superior visibility in recurrent parotid and paranasal sinus neoplasm  but was less helpful in laryngeal and pharyngeal recurrences  computed tomography demonstration of a mass with infiltration of normal fat or tissue planes or lymphadenopathy correlated highly with recurrent disease  imaging techniques and fine points for determining recurrent neoplasms are presented  
class4	management decisions in laryngeal carcinoma in situ  twenty one patients with laryngeal carcinoma in situ  n   12  or carcinoma in situ with microinvasion  n   9  were treated with laser mucosal dissection of the vocal cords and or superficial laser cordectomy  the normal architecture of the vocal cords was preserved because the depth of vaporization was usually superficial in these early cases  five patients had recurrence  new tumor  or persistence of abnormal tissue that required additional laser surgical treatments  with a follow up range of 6 months to 4 years  all patients currently are free of laryngeal abnormality  and no patient has needed open laryngeal surgery or radiation therapy  transoral endoscopic laser resection of laryngeal carcinoma in situ with or without microinvasion should be the treatment of choice for these early lesions  
class4	the use of bromodeoxyuridine cytokinetic studies as a prognostic indicator of cancer of the head and neck  traditional measures of head and neck tumors often fail to predict patient outcome or clinical course  particularly in nonadvanced disease  this problem of unpredictable tumor behavior has been one focus of cell proliferation studies  such studies  however  have been limited by difficult methodology  a newer method of quantifying tumor cell proliferation using bromodeoxyuridine is applicable for head and neck squamous cell carcinomas  as shown in the present study  the relative ease with which cell proliferation can be evaluated using this technique will allow large numbers of head and neck tumors to be studied  enabling correlations with tumor behavior to be made  
class4	epidermal nevus syndrome  a neurologic variant with hemimegalencephaly  gyral malformation  mental retardation  seizures  and facial hemihypertrophy  the epidermal nevus syndrome  ens  is a sporadic neurocutaneous disorder that consists of epidermal nevi and congenital anomalies involving the brain and other systems  from among over 60 patients with ens presenting with neurologic manifestations  we identified 17 who had hemimegalencephaly based on pathologic or radiologic studies  associated brain and neurologic abnormalities included gyral malformations in 12 of 12  mental retardation in 13 of 14  seizures in 16 of 17  including 9 with infantile spasms   and contralateral hemiparesis in 7 of 12  all had ipsilateral epidermal nevi of the head  and several had ipsilateral facial hemihypertrophy  we concluded that these abnormalities comprise a recognizable neurologic variant of ens that we believe represents the full expression of primary brain involvement  several patients also had evidence of acquired brain lesions such as infarcts  atrophy  porencephaly  and calcifications  which are best explained by prior ischemia or hemorrhage  given repeated observations of blood vessel anomalies in ens patients  we hypothesize that underlying vascular dysplasia predisposes to these acquired lesions  the same cause may be invoked to explain the wide variety of neurologic symptoms reported in ens patients without hemimegalencephaly  while the cause of ens remains unknown  several observations suggest a somatic mutation  
class4	vascular abnormalities in epidermal nevus syndrome  we report a patient with epidermal nevus syndrome and right hemispheric infarct and review 3 others with neurologic manifestations best explained by ischemia or hemorrhage  each had a significant vascular abnormality such as occlusion or blood vessel dysplasia  none had hemimegalencephaly  we hypothesize that underlying vascular dysplasia is the cause of the neurologic lesions in these patients  
class4	percutaneous aspiration of brain tumor cysts via the ommaya reservoir system  we performed percutaneous aspiration of 21 brain tumor cysts in 20 patients using the ommaya reservoir system  ages ranged from 3 to 70 years  median 48  sixteen were primary tumors  12 anaplastic glioma  2 craniopharyngioma  1 oligodendroglioma  1 brainstem glioma  and 4 were metastatic  fourteen had the ct appearance of a true cyst and 7 a pseudocyst  we placed 18 catheters through twist drill holes via ct stereotactic guidance and 3 through burr holes via ct guidance and effectively aspirated 3 to 50 ml cyst fluid from 1 to 18 times in each patient  postaspiration ct showed complete or significant reduction in cyst size in all patients in whom it was performed  18 after initial aspiration and 9 after subsequent aspirations   asymptomatic intracyst hemorrhage occurred in 2 patients after cyst wall biopsy and catheter placement  there have been no other complications at follow up of 4 to 114 weeks  in our experience  tumor cyst aspiration by the ommaya reservoir system is as effective as percutaneous needle aspiration  but after catheter placement aspiration can be performed with minimal technical skill  avoiding repeated ct guidance required for needle aspiration of recurrent deep seated cysts  
class4	the  numb cheek limp lower lid  syndrome  a patient developed isolated numbness  1st confined to the lateral nose and upper lip  but later involving the cheek  lower lip  upper gingiva  and the palate  this numbness was later associated with paresis of the muscles of the upper lip and angle of the mouth and with ipsilateral lower lid droop  the  numb cheek limp lower lid  syndrome   squamous cell carcinoma was discovered infiltrating the infraorbital nerve and distal branches of the facial nerve  cheek numbness associated with lower eyelid or upper lip weakness may herald a neoplasm affecting the infraorbital nerve and distal facial nerve branches  
class4	repetitive conservative surgery for recurrence of endometriosis  we evaluated the recovery of fertility and the relief of pain symptoms in a long term follow up of 42 women undergoing repetitive conservative surgery for recurrent endometriosis  the mean age of the patients was 31 1     4 3 years  at the time of their second operation the disease was stage iv in 14 women  stage iii in 25  and stage i in three  after reoperation  the patients were followed for a mean period of 41 8     30 3 months  pain symptoms returned in eight women  dysmenorrhea and deep dyspareunia in eight  and pelvic pain in seven  eight of the 28 women  28 6   who attempted to conceive achieved a total of 13 pregnancies  the corrected pregnancy rate was 35   and the cumulative rate at 27 months was 30 7   a third operation was necessary in six women after a mean period of 35 months  conservative surgery is an effective therapeutic option for infertile patients with recurrent endometriosis  
class4	endometrial carcinoma  the relevance of cervical cytology  in patients with endometrial carcinoma  preoperative identification of poor prognostic factors is helpful in planning therapy  extended surgical staging  including pelvic and periaortic node dissection  is indicated in patients with deep myometrial invasion or high grade tumor  or when other risk factors for extrauterine spread are present  in this study  cervical cytology was reviewed in 86 patients with endometrial carcinoma  all of whom underwent surgical staging  to correlate the cytologic results with surgical and pathologic findings  cervical cytology was normal in 20 patients  23    whereas suspicious or malignant endometrial cells were present in 23 and 43 cases  27 and 50    respectively  suspicious or malignant cervical cytology was associated with deeper myometrial invasion  p    011   higher postoperative tumor grade  p    006   positive peritoneal washings  p    012   and more advanced stage by international federation of gynecology and obstetrics criteria  p    024   when compared with patients with normal cervical cytology  those who had malignant endometrial cells had over twice the risk of deep myometrial invasion  67 versus 30    twice the risk of grade 2 or 3 tumor  60 versus 30    and three times the risk of positive peritoneal washings  33 versus 10    seventy four percent of patients with malignant cervical cytology were stage ic or more  in contrast  70  of patients with normal cervical cytology were stage ia or ib  patients with endometrial carcinoma who have malignant endometrial cells detected by cervical cytology are at increased risk of having a deeply invasive  high grade  advanced stage tumor  and therefore are more likely to require extended surgical staging  
class4	introduction to limb salvage surgery for sarcomas  this article provides a history of limb salvage surgery and definitions of terms used to describe aspects of the procedure  staging is also discussed  
class4	mobile knee reconstructions after resection of malignant tumors of the distal femur  limb salvage surgery involving mobile knee reconstructions for malignant tumors about the distal femur is a desirable and achievable goal  with limb salvage  the survival rate does not decrease significantly  and the resulting function is superior to when an amputation plus a prosthesis are used  immediate and delayed morbidity is greater after limb salvage surgery than after amputation  however  with thorough preoperative planning  use of neoadjuvant chemotherapy as indicated  and an experienced team of surgeons  limb salvage surgery can provide a mobile knee with excellent function in the vast majority of cases for patients with malignant tumors of the distal femur  
class4	limb salvage in pediatric surgery  the use of the expandable prosthesis  limb sparing in growing children has proved to be very effective from an oncologic perspective  with good  long term acceptance by the patients  as in the adult  when performed by experienced surgeons  limb sparing neither compromises the survival rate nor significantly increases the local recurrence rate  compared with cross bone amputation  discussions include patient evaluation  surgical options  materials and methods  and results  
class4	resection and reconstruction for bone tumors in the proximal tibia  the proximal tibia is a common site for both benign and malignant tumors  this article reviews pertinent anatomy  clinical presentation  and staging methods for tumors of this area  discussion is given to various methods of resection and reconstruction with useful guidelines for procedure selection  the use of allografts for reconstruction is discussed in depth  
class4	endoprosthetic reconstruction after bone tumor resections of the proximal tibia  the advent of successful adjuvant chemotherapy and radiation therapy protocols for primary malignant tumors and the development of custom designed metallic endoprostheses has now made possible a successful limb salvage procedure for malignancies of the proximal tibia  use of the transposed medial gastrocnemius flap  as proposed by dr  jean duboussett of paris  has been critical to the soft tissue reconstruction that routinely permits an excellent active and passive range of motion for these patients  this article describes the operative techniques and technical considerations necessary for a successful proximal tibial endoprosthesis reconstruction  
class4	resection and reconstruction for soft tissue sarcomas of the extremity  soft tissue sarcomas are uncommon malignant tumors  and when a diagnosis is made early  the patient has up to an 80  chance of surviving  in treating soft tissue sarcomas  the goal of the surgeon is the prolongation of patient survival  the total eradication of local disease  and the minimization of functional deficits  in addition to treatment  this article discusses evaluation  histology  and staging  
class4	allograft reconstructions of the shoulder after bone tumor resections  large skeletal defects resulting from tumor resections about the shoulder create reconstructive challenges for the orthopedic surgeon  bone allografts offer several advantages compared with other reconstructive techniques  and functional outcomes are generally satisfactory  they may be used either as osteoarticular grafts  intercalated segments to create an arthrodesis  or in combination with standard proximal humerus metallic implants  patient expectations and specific oncologic factors must be considered when selecting the optimal method of reconstruction  
class4	resections and reconstructions for tumors of the distal radius  the primary objective in surgical management of the patient with a distal radius tumor is control of the disease  accurate staging and diagnostic methods applied preoperatively will predict not only the amount of resection necessary to obtain adequate tumor margins  but also the amount of remaining bone and soft tissues to assist reconstruction  with this information  a method of reconstruction can be chosen that provides the patient optimal long term function and stability with predictable results and the fewest potential complications  
class4	pelvic resections  the rizzoli institute experience  materials  methods  and techniques of pelvic resections are discussed  results  including the complications of nerve damage  infection  and vascular  visceral  and reconstructive complications are tabulated  
class4	tumors of the shoulder girdle  technique of resection and description of a surgical classification  limb sparing surgery is safe and reliable for most bone and soft tissue tumors of the shoulder girdle  eighty to ninety percent of patients with high grade sarcomas of the shoulder can be safely treated by the various surgical techniques described  attention must be paid to appropriate patient selection  preoperative staging  and planning  in addition  careful skeletal and muscular reconstruction of the surgical defect is necessary for a successful outcome  a new  universal  classification schemata  types i vi  of shoulder girdle resections has been developed  this classification system is based on the bones resected  the status of the abductor mechanism  and the relationship to the glenohumeral joint  this system permits easy description and comparison of the various limb sparing procedures performed  
class4	reconstructions after resections of tumors involving the proximal femur  advances in prosthesis design  the use of allografts  and a systematic approach to the staging and surgical treatment of musculoskeletal tumors have made limb salvage possible in the proximal femoral region  with the use of effective adjuvant therapy  limb salvage is now an option for the majority of patients presenting with locally invasive neoplasms in this area  the increase in functional outcome is sufficient to warrant serious consideration of limb salvage over the corresponding amputation  preoperative planning is discussed along with surgical techniques  
class4	inhibition of growth of experimental prostate cancer with sustained delivery systems  microcapsules and microgranules  of the luteinizing hormone releasing hormone antagonist sb 75  inhibitory effects of the sustained delivery systems  microcapsules and microgranules  of a potent antagonist of luteinizing hormone releasing hormone n ac  3  2 naphthyl  d alanine1  4 chloro d phenylalanine2  3  3 pyridyl  d alanine3  d citrulline6  d alanine10 lh rh  sb 75  on the growth of experimental prostate cancers were investigated  in the first experiment  three doses of a microcapsule preparation releasing 23 8  47 6  and 71 4 micrograms of antagonist sb 75 per day were compared with microcapsules of agonist  d trp6 lh rh liberating 25 micrograms day in rats bearing dunning r3327h transplantable prostate carcinoma  during 8 weeks of treatment  tumor growth was decreased by  d trp6 lh rh and all three doses of sb 75 as compared to untreated controls  the highest dose of sb 75  71 4 micrograms day  caused a greater inhibition of prostate cancer growth than  d trp6 lh rh as based on measurement of tumor volume and percentage change in tumor volume  doses of 23 8 and 47 6 micrograms of sb 75 per day induced a partial and submaximal decrease  respectively  in tumor weight and volume  tumor doubling time was the longest  50 days  with the high dose of sb 75 vs  15 days for controls  the body weights were unchanged  the weights of testes  seminal vesicles  and ventral prostate were greatly reduced in all three groups that received sb 75  and testosterone levels were decreased to nondetectable values in the case of the two higher doses of sb 75  lh levels were also diminished  similar results were obtained in the second experiment  in which the animals were treated for a period of 8 weeks with microgranules of sb 75  therapy with microgranules of sb 75 significantly decreased tumor growth as measured by the final tumor volume  the percentage change from the initial tumor volume  and the reduction in tumor weight  the results indicate that antagonist sb 75  released from sustained delivery systems  can produce a state of chemical castration and effectively inhibit the growth of experimental prostate cancers  the efficacy of the antagonist sb 75 in inhibiting androgen dependent dunning prostatic carcinoma and the absence of side effects suggest its possible usefulness for the treatment of hormone sensitive tumors  
class4	molecular localization of the t 11 22  q24 q12  translocation of ewing sarcoma by chromosomal in situ suppression hybridization  chromosome translocations are associated with a variety of human leukemias  lymphomas  and solid tumors  to localize molecular markers flanking the t 11 22   q24 q12  breakpoint that occurs in virtually all cases of ewing sarcoma and peripheral neuroepithelioma  high resolution chromosomal in situ suppression hybridization was carried out using a panel of cosmid clones localized and ordered on chromosome 11q  the location of the ewing sarcoma translocation breakpoint was determined relative to the nearest two cosmid markers on 11q  clones 23 2 and 5 8  through the analysis of metaphase chromosome hybridization  by in situ hybridization to interphase nuclei  the approximate physical separation of these two markers was determined  in both ewing sarcoma and peripheral neuroepithelioma  cosmid clone 5 8 is translocated from chromosome 11q24 to the derivative chromosome 22 and a portion of chromosome 22q12 carrying the leukemia inhibitory factor gene is translocated to the derivative chromosome 11  the physical distance between the flanking cosmid markers on chromosome 11 was determined to be in the range of 1000 kilobases  and genomic analysis using pulsed field gel electrophoresis showed no abnormalities over a region of 650 kilobases in the vicinity of the leukemia inhibitory factor gene on chromosome 22  this approach localizes the ewing sarcoma breakpoint to a small region on chromosome 11q24 and provides a rapid and precise technique for the molecular characterization of chromosomal aberrations  
class4	mutational activation of the c ha ras gene in liver tumors of different rodent strains  correlation with susceptibility to hepatocarcinogenesis  the frequency and pattern of mutations at codon 61 of the c ha ras gene have been analyzed in 195 liver tumors and 132 precancerous liver lesions from various rodent strains with differing susceptibility to hepatocarcinogenesis  by using the polymerase chain reaction and allele specific oligonucleotide hybridization  c    a transversions at the first base and a    t transversions or a    g transitions at the second base of c ha ras codon 61 were detected in 20 60  of spontaneous or carcinogen induced liver tumors of the c3h he  cba  cf1  and b6c3f1 mouse strains  which are highly susceptible to hepatocarcinogenesis  no such mutations  however  could be found in any of the 31 liver tumors of the insensitive c57bl 6j and balb c mouse strains or in any of the 35 liver tumors of the comparatively resistant wistar rat  further analyses of c ha ras codon 12 mutations in liver tumors from the three insensitive rodent strains also failed to give any positive results  in early precancerous liver lesions  c ha ras codon 61 mutations were found in 13 14  of lesions of the sensitive c3h he and b6c3f1 mouse strains but not in any of the 34 lesions of the insensitive c57bl 6j mouse  taken together  our results indicate a close correlation between the mutational activation of the c ha ras gene in liver tumors of the different rodent strains and their susceptibility to hepatocarcinogenesis  whereby the mutations appear to provide a selective growth advantage  leading to a clonal expansion of the mutated liver cell population  only in livers of sensitive but not of insensitive strains  
class4	cdna cloning and sequencing of human fibrillarin  a conserved nucleolar protein recognized by autoimmune antisera  we have isolated a 1 1 kilobase cdna clone that encodes human fibrillarin by screening a hepatoma library in parallel with dna probes derived from the fibrillarin genes of saccharomyces cerevisiae  nop1  and xenopus laevis  rna blot analysis indicates that the corresponding mrna is approximately 1300 nucleotides in length  human fibrillarin expressed in vitro migrates on sds gels as a 36 kda protein that is specifically immunoprecipitated by antisera from humans with scleroderma autoimmune disease  human fibrillarin contains an amino terminal repetitive domain approximately 75 80 amino acids in length that is rich in glycine and arginine residues and is similar to amino terminal domains in the yeast and xenopus fibrillarins  the occurrence of a putative rna binding domain and an rnp consensus sequence within the protein is consistent with the association of fibrillarin with small nucleolar rnas  protein sequence alignments show that 67  of amino acids from human fibrillarin are identical to those in yeast fibrillarin and that 81  are identical to those in xenopus fibrillarin  this identity suggests the evolutionary conservation of an important function early in the pathway for ribosome biosynthesis  
class4	free radical derived quinone methide mediates skin tumor promotion by butylated hydroxytoluene hydroperoxide  expanded role for electrophiles in multistage carcinogenesis  free radical derivatives of peroxides  hydroperoxides  and anthrones are thought to mediate tumor promotion by these compounds  further  the promoting activity of phorbol esters is attributed  in part  to their ability to stimulate the cellular generation of oxygen radicals  a hydroperoxide metabolite of butylated hydroxytoluene  2 6 di tert butyl 4 hydroperoxyl 4 methyl 2 5 cyclohexadienone  bhtooh   has previously been shown to be a tumor promoter in mouse skin  bhtooh is extensively metabolized by murine keratinocytes to several radical species  the primary radical generated from bhtooh is a phenoxyl radical that can disproportionate to form butylated hydroxytoluene quinone methide  a reactive electrophile  since electrophilic species have not been previously postulated to mediate tumor promotion  the present study was undertaken to examine the role of this electrophile in the promoting activity of bhtooh  the biological activities of two chemical analogs of bhtooh  4 trideuteromethyl bhtooh and 4 tert butyl bhtooh  were compared with that of the parent compound  4 trideuteromethyl bhtooh and 4 tert butyl bhtooh have a reduced ability or inability  respectively  to form a quinone methide  however  like the parent compound  they both generate a phenoxyl radical when incubated with keratinocyte cytosol  the potency of bhtooh  4 trideuteromethyl bhtooh  and 4 tert butyl bhtooh as inducers of ornithine decarboxylase  a marker of tumor promotion  was commensurate with their capacity for generating butylated hydroxytoluene quinone methide  these initial results were confirmed in a two stage tumor promotion protocol in female sencar mice  together  these data indicate that a quinone methide is mediating tumor promotion by bhtooh  providing direct evidence that an electrophilic intermediate can elicit this stage of carcinogenesis  
class4	osteoblastoma of the spine  a review of 75 cases  clinical and radiologic features of 75 cases of osteoblastoma of the spine were reviewed  in addition to pain  which was the most frequent complaint  18 patients demonstrated objective neurologic deficit  while scoliosis was observed in 17 patients  aspirin yielded pain relief in 13 patients  pathologic fracture was not encountered  the radiologic and histologic characteristics of osteoblastoma of the spine are indistinguishable from those arising in other sites  the typical lesion exhibited a well defined  geographic margin with a sclerotic  frequently lobulated border  approximately one half of the cases were predominantly lucent  the remainder displaying varying degrees of matrix mineralization  distribution of the osteoblastomas through the spinal axis was as follows  cervical 29  thoracic 16  lumbar 17  sacral 13  other significant findings included posterior element involvement in 73 of 75 cases  and a striking male to female ratio of 2 5 to 1  
class4	survival after groin dissection for malignant melanoma  groin dissection was performed in 158 patients with malignant melanoma  superficial dissection  76 patients  radical dissection  82 patients   of 63 patients with palpable nodes  57 patients  90   had histologic involvement  of 93 patients with nonpalpable nodes  31 patients  33   had histologically positive nodes  the 5 year survival rate for patients with histologically negative nodes  n   69  was 77   the 5 year survival rate for patients with histologically positive nodes  n   89  was 43   the respective 5 year disease free survival rates were 72  and 34   of 57 patients with palpable  positive inguinal nodes  21 patients  37   had involvement of the deep nodes  of 31 patients with nonpalpable  histologic involvement of the inguinal nodes  six patients  19   had or developed involvement of the deep nodes  one of two patients with uncertain clinical status of the nodes preoperatively had positive deep nodes  in prophylactic node dissection  frozen section of the inguinal group of the nodes does not provide a reliable method  because of sampling errors  in determining microscopic involvement of the nodes and in deciding whether a superficial or radical groin dissection is to be done  for patients with positive nodes the 5 year survival rate was 48  when only the inguinal group was involved and was 28  when both inguinal and deep nodes were involved  the respective 5 year disease free survival rates were 39  and 20   survival after therapeutic groin dissection may partly depend on the thoroughness of the procedure  patients who have positive  deep nodes and who are undergoing an incontinuity dissection of the inguinal  iliac  and obturator nodes have an appreciable 5 year survival rate  
class4	the role of resection in the management of melanoma metastatic to the adrenal gland  melanoma metastatic to the adrenal gland diagnosed before death was exceedingly rare before the development of computed tomographic  ct  scanning  the records of 28 patients with melanoma metastatic to the adrenal gland seen since 1975 were reviewed  eighteen patients were men and 10 were women  twenty three patients had unilateral disease  four patients were diagnosed only at autopsy  leaving 24 for analysis of treatment and survival  twenty one patients had received specific active immunotherapy  four had received chemotherapy  dacarbazine  lomustin  bleomycin  and vincristine   and three had received both before the diagnosis of their adrenal disease  adrenal metastases were diagnosed by ct scanning in 14 patients with symptoms  10  91   of whom had pain  ten patients were diagnosed by ct before entry into a chemotherapy protocol  of eight patients who underwent resection of all known disease  five underwent unilateral adrenalectomy  two underwent unilateral adrenalectomy and bowel resection  and one underwent bilateral adrenalectomy  two patients underwent partial resection of large unilateral tumors  fourteen patients with adrenal metastases and disease elsewhere were initiated or continued with chemotherapy or were treated symptomatically  mean survival in the group that underwent resection for cure was 59 months  3 to 112 months   whereas survival in the group with unresectable tumors was 15 months  1 5 to 132 months   four of eight patients who underwent resection for cure lived more than 5 years after detection of adrenal metastasis  whereas in only one of 14 patients with unresectable tumors was the same true  patients with metastatic melanoma localized to one or both adrenal glands may benefit from early detection and surgical intervention  
class4	evaluation of preoperative computed tomography in gastric malignancy  ninety patients with gastric malignancy underwent computed tomography  ct  before surgery  the ct findings regarding neoplastic invasion of adjacent organs and metastasis or enlarged lymph nodes were compared with the findings at laparotomy  85 cases  or autopsy  5 cases   thus permitting evaluation of the diagnostic accuracy of ct and its usefulness for predicting resectability  when present  neoplastic invasion of adjacent organs was overestimated or underestimated by ct in 21 cases  invasion of adjacent organs according to ct was false positive in 17 cases and false negative in 11 cases  when liver metastasis or enlarged regional or distant lymph nodes were present  ct overestimated or underestimated their extent in 17 cases  and the diagnosis was false positive in one case and false negative in 33 cases  the positive and negative predictive values of ct concerning resectability of the tumor were 81  and 64   respectively  routine preoperative ct in gastric malignancy is concluded to be of limited value and surgical exploration  when feasible  remains the method of choice  
class4	total gastrectomy for gastric cancer in the elderly  of 1070 patients with gastric cancers  292 patients underwent total gastrectomy during 13 years  sixty patients were more than 70 years of age and 232 were under 69 years  the incidence of well differentiated carcinomas and poorly differentiated carcinomas was the same in the elderly patients  whereas the latter was dominant in the young patients  however  there was no significant difference between the two groups regarding location  size  macroscopic patterns  extent of lymph metastases  or stage classification  the rates of preoperative surgical risk factors were significantly different between the two groups  p less than 0 01   90 0  for the elderly and 34 9  for the young patients  however  the rates of postoperative morbidity and mortality were 31 7  and 3 3  for the elderly and 24 1  and 1 3  for the young patients  respectively  with no significant difference  the 5  and 10 year survival rates after curative total gastrectomy were 48 6  and 23 2  for the elderly compared with 49 4  and 33 6  for the young patients  respectively  with no significant difference  a 5 year survival rate after noncurative operation was 0  for the elderly and 6 4  for the young patients  these results indicate that  when performed for cure  total gastrectomy with systematic lymphadenectomy can provide good long term results for elderly  as well as young  patients  
class4	a hepatoblastoma originating in the caudate lobe radically resected with the inferior vena cava  complete resection of a rare hepatoblastoma in the caudate lobe  involving the inferior vena cava  ivc   is reported  after systemic chemotherapy  a 5 year old child underwent exploratory laparotomy at another hospital  but resection was not attempted because the tumor in the caudate lobe had extensively invaded the retrohepatic ivc  however  because not only the lack of distant metastases but also the establishment of extrahepatic collaterals were confirmed by imaging  we thought it was possible to radically resect the tumor  we successfully performed an extended left hepatic lobectomy including total excision of the caudate lobe and the involved portion of the ivc  although we did not reconstruct the ivc  no clinical manifestations arising from caval congestion were seen  the serum alpha fetoprotein value declined below the normal limit  our experience with this case has introduced a radical resectability for hepatic malignancy in the caudate lobe  even if it has extended into the ivc  
class4	hepatocellular carcinoma with tumor thrombus extending into the right atrium  report of a successful resection with the use of cardiopulmonary bypass  hepatocellular carcinoma with a tumor thrombus extending into the right atrium has been considered beyond the reach of resection  these patients usually die within a short period because of pulmonary embolism  heart failure  or cancer progression  the only treatment is hepatic resection with removal of the tumor thrombus  a 38 year old woman underwent left lobectomy with removal of the tumor thrombus with the use of cardiopulmonary bypass  the patient had an uneventful course and is doing well 15 months after surgery  without signs of recurrence  we have proved that hepatic resection with removal of a tumor thrombus extending into the right atrium can be carried out successfully  the next problem is whether the lives of these patients can be prolonged by this operation  
class4	a new method for mapping hepatic subsegment  counterstaining identification technique  hepatic subsegmentectomy requires identification of the borders of tumor bearing subsegment  usually achieved by injecting dye into the portal veins feeding the domain  we describe an alternative technique for performing systematic subsegmentectomy in patients with cirrhosis and hepatocellular carcinoma  in whom hepatic arterial and portal venous embolizations were already performed as a preoperative adjuvant  under ultrasonic guidance  each of the neighboring portal units is sequentially stained  thus defining the avascular subsegment to be resected as the nonstaining area  this allows the subsegment to be totally resected  this counterstaining identification technique can be used for all subsegments undergoing complete embolization and for other situations in which the usual staining method is impossible because of the presence of arterioportal shunting or portal tumor thrombus  
class4	effects of hypothyroidism on bronchial reactivity in non asthmatic subjects  the effect of hypothyroidism on non specific bronchial reactivity was studied in 11 patients without pulmonary disease  mean age 40  sd 13  years  who had had a total thyroidectomy and radioiodine treatment for thyroid cancer 41  36  months before the study  all patients when mildly hyperthyroid while having long term thyroxine replacement treatment and once when hypothyroid two weeks after stopping triiodothyronine for the purpose of screening for metastases  bronchial reactivity was assessed by measuring specific airways conductance  sgaw  after increasing doses of inhaled carbachol  45 1260 micrograms   the dose producing a 35  decrease in sgaw  pd35  was determined from the cumulative log dose response curve by linear regression analysis  mean baseline sgaw values were similar when the patients were hypothyroid and when they were hyperthyroid  1 35  0 36  and 1 41  0 56  s 1 kpa 1   the interstudy coefficients of variation of baseline sgaw were higher in the thyroid patients than in a euthyroid control group  14  versus 8    geometric mean pd35 was lower when the patients were hypothyroid  97 micrograms  than when they were mildly hyperthyroid  192 micrograms   it is concluded that acute hypothyroidism increases non specific bronchial reactivity in nonasthmatic subjects  
class4	performance and prognosis in patients with lung cancer  the edinburgh lung cancer group  the edinburgh lung cancer group prospectively registered 651 new patients presenting with lung cancer during 1981  only 47 survived five years  7    the survival rate was highest in patients selected for surgery  35 116  30   and in this group was related to cell type  stage of disease  and possibly to karnofsky performance score  not statistically significant   by comparison with non surgical patients these 116 patients undergoing surgery were highly selected in terms of age  favourable histological type  stage of disease  and performance score  forty two of the 535 non surgical patients were given radical radiotherapy alone and seven  17   survived five years  the remaining 493 received palliative radiotherapy  chemotherapy  alone or combined with radiotherapy   or symptomatic treatment alone  only five  1   survived five years  median survival was related to cell type  adenocarcinoma 2 6 months  squamous cell carcinoma 6 2 months   stage  stage i 8 5 months  stage iii 4 months   and karnofsky performance index  greater than or equal to 90 9 3 months  less than or equal to 50 1 2 months   age and sex had no independent prognostic value in any group  performance score was highly correlated with stage  and age  and in this study represented the  best prognostic factor  in clinical practice  
class4	hemibody irradiation in advanced prostatic carcinoma  in summary  hemibody irradiation has developed as a safe  efficient technique for palliating multiple sites of symptomatic osseous metastases  which occur so often in advanced prostatic carcinoma  the rapidity  frequency  and duration of pain relief  as well as the convenience to the patient of a solitary treatment to multiple symptomatic areas simultaneously  make this type of treatment especially appealing  by following premedication and radiation dose guidelines  both acute and delayed side effects can be kept tolerable or at a minimal incidence  although sequential hemibody radiation has also been explored as  systemic  therapy  the results in prostatic carcinoma have not proved dramatic  and complications have been considerable  hormonal therapy would certainly seem to be less life threatening and equally beneficial according to present data  as a palliative treatment  however  hemibody irradiation is a pragmatic option for relieving prostatic cancer pain  
class4	management of spinal cord compression secondary to metastatic prostatic carcinoma  spinal cord or cauda equina compression from prostatic cancer is an oncologic emergency necessitating prompt evaluation and treatment  the strong correlation between pretreatment motor status and treatment outcome underscores the importance of immediate treatment before further neurologic deterioration and before the damage to the spinal cord becomes permanent  patients with known osseous metastases should be alerted by their clinicians to seek medical help within hours should they develop weakness in an extremity  prompt mri of the entire spine should be done prior to treatment  myelography should be reserved for those patients who cannot undergo a technically adequate or expeditious mri study  the convenience of mri relative to myelography allows clinicians to diagnose actual or impending spinal cord compression earlier  high dose steroids  dexamethasone  should be instituted immediately  and endocrine therapy should be started if not already in use  ambulatory and moderately paraparetic patients seem best treated initially with radiation alone  immediate surgical decompression should be used in patients with an expected lifespan of at least 6 months who deteriorate during radiation  who have had previous radiation to the involved site  or who have a potentially correctable unstable spine  in addition  paraplegic patients or severely paraparetic patients with recent neurologic deterioration should be treated with immediate surgical decompression if they are judged reasonably able to tolerate the surgery  these patients should then receive postoperative radiation treatment  
class4	treatment of metastatic prostate cancer of the spine  there is a wide spectrum of presentations for prostate cancer metastatic to the spine  important factors are the patient s age and general health  the extent and location of spinal involvement  the patient s neurologic status and degree of pain  the relative contribution of a blastic or lytic response  and the experience and training of the spinal surgeon  medical oncologist  and radiation oncologist  the spine is both a weight bearing structure and a housing for the spinal cord  and failure to consider both functions may lead to unsatisfactory treatment results  treatment options include hormonal therapy  inhibitors of bone metabolism  glucocorticoid therapy  radiotherapy  halo vest  surgical debridement  decompression and stabilization  and appropriate pain management and support  one must not lose sight of the fact that the goals are palliation and that ultimate demise is unavoidable in patients with metastatic prostate cancer  
class4	partial and total penectomy for cancer  squamous carcinoma of the penis remains an uncommon tumor in the united states  in the properly selected patient  partial or total penectomy performed with an understanding of the salient surgical anatomy results in adequate local control of these cancers with excellent functional and cosmetic results  
class4	imaging of patients with stage d prostatic carcinoma  in conclusion  it would appear from present evidence that several statements can be made  first  mri is the most accurate method of staging the periprostatic spread of carcinoma  both the prostate and the regional nodes can be evaluated  the role of ultrasound is  at present  unclear  second  the utility of ct has diminished with the emergence of high quality mri  but in situations in which mri scans are inconclusive  e g   in the assessment of paraaortic node disease  in which images are degraded by peristaltic movement   ct may be useful  third  the choice of method for the assessment of nodal disease is a more difficult question  although mri and ct have replaced lymphography in most centers  the latter study  especially when combined with fine needle aspiration biopsy  still is useful  fourth  bone metastases are best assessed with scintigraphy  which can point to areas requiring supplemental plain radiography  an mri study of the spine  although highly sensitive  is not practical  fifth  mri is superior to ct myelography in assessing spinal disease  finally  the chest radiograph is the mainstay of assessing chest involvement  
class4	initial results with slightly modified kock pouch  my initial experience with 20 patients undergoing kock pouch continent urinary diversion is reviewed  the procedure has been slightly modified from that described by kock and skinner  all patients have been followed for at least four months  median  33 months   there have been no early complications related to the pouch  the most significant problem  incontinence  has occurred in 2 patients  10   at three and four months  respectively  after surgery  only 1 of these patients required temporary use of an external appliance  leakage was due  in both cases  to a patulous efferent nipple valve  both were repaired by plication of the nipple  and no new efferent limbs were constructed  in 1 patient  5   prolapse of the afferent limb associated with reflux and pyelonephritis developed one year post surgery  stones have developed in 3 patients  15    all patients are currently continent and stone free  and all are pleased with the result  
class4	carcinoma of female urethra  manitoba experience  1958 1987  fourteen female patients with primary urethral carcinoma were treated at the manitoba cancer foundation in the last twenty nine years  the relationship of natural history to the stage  location  and therapeutic modality has been reviewed  a higher stage and length of urethral involvement affected prognosis negatively  whereas lower stage had a positive prognostic effect and location of tumor had no prognostic influence  two patients with stage c  who failed to received inguinal node radiotherapy  died of disease recurring in the inguinal area  patients who received inguinal radiation  3 patients stages b  c  and d1  had no regional recurrence  it is suggested that  for all female urethral carcinoma  bilateral ilioinguinal nodes be included in the radiation field  for radical treatment  iridium 192 insertion in combination with external beam treatment is recommended  
class4	association of germ cell tumors and hodgkin s disease  two patients presented with synchronous hodgkin s disease and testicular germ cell neoplasms  both patients are in complete remission following treatment with multidrug chemotherapy and radiation therapy  despite epidemiologic similarities between hodgkin s disease and testicular cancer  only 13 cases of their association in the same patient have been reported in the literature  and in all those instances the tumors occurred metachronously  however  the very rare occurrence of synchronous presentation suggests a possible common pathogenetic factor in our 2 patients  
class4	coexistence of testicular carcinoma and hairy cell leukemia  the coexistence of two relatively rare disorders in 1 patient often induces speculation about possible cause and effect of these disorders  the suitable therapeutic regimen for both diseases and roentgenologic manifestations are described  
class4	bilateral renal cell carcinoma with metastasis to thyroid  a case of bilateral synchronous renal cell carcinomas with metastases to the regional lymph nodes and later to the thyroid gland was treated with aggressive surgical extirpation and adjuvant gamma interferon  the patient continues to have an excellent performance status sixteen months after initial diagnosis despite a large tumor burden at presentation  
class4	intravesical bacillus calmette guerin for patients with high risk superficial bladder cancer  intravesical bacillus calmette guerin  bcg  was employed in the treatment of 55 patients with aggressive superficial transitional cell carcinoma of the bladder  cta  ct1  ctis   all of the patients had a previous history of recurrent superficial disease  and 41  75   were treatment failures following other intravesical therapy  thirty six  66   patients responded to treatment  and 19  34   were treatment failures  twenty seven  66   of 41 patients with cta ct1 tumors and 9  64   of 14 patients with ctis responded  with a mean follow up period of 30 5 months  disease progression was noted in 8  15   of the patients and muscle invasive disease in 6  patients with a history of three or more previous events of tumor recurrence  positive urinary cytology  and multicentric disease  all fared worse than patients without these characteristics  p less than 0 05   bcg is an effective agent in controlling superficial transitional cell carcinoma of the bladder  even in a high risk group of patients who failed previous intravesical therapy  bcg should be employed in this group of patients prior to radical surgery  
class4	percutaneous urinary diversion in patients with hormone refractory prostate cancer  twenty two patients with hormone refractory prostate cancer underwent percutaneous urinary diversion  at the time  all but one had metastatic disease  eleven patients received postnephrostomy therapy  the median survival time for all the patients was one hundred nineteen days  overall  41 percent of the patients  remaining lifetime was spent in the hospital  six never left the hospital and 10 required rehospitalization  the remaining 6 patients were never rehospitalized  the median survival time for this group of patients was shorter than the expected survival of similar patients without ureteral obstruction  it appears that percutaneous urinary diversion does not improve the quality of life of these patients  
class4	prognostic factors and value of adjunctive nephrectomy in patients with stage iv renal cell carcinoma  we reviewed 57 cases of stage iv renal cell carcinoma to clarify the factors influencing prognosis and to evaluate the value of nephrectomy  cumulative survival from the initial diagnosis was analyzed with respect to the patients  age  sex  side of primary tumor  initial performance status  ps   site of metastasis  and nephrectomy  overall survival for the patients was 51 percent at one year  22 percent at three years  and 11 percent at five years  age  sex  and side of primary tumor had no influence on survival  improved survival was correlated with good ps  metastases limited to single organ  and removal of the primary tumor  with regard to histopathologic features in nephrectomized patients  low grade and stage were correlated with longer survival  these factors should be considered in the analysis of results of future clinical trials of metastatic renal cell carcinoma  
class4	cytologic criteria to distinguish hepatocellular carcinoma from nonneoplastic liver  the authors reviewed a series of fine needle aspiration biopsy  fnab  specimens of the liver to identify useful cytologic criteria to distinguish hepatocellular carcinoma  hcc  from nonneoplastic liver  ten cytologic features were examined in this study  high cellularity  acinar pattern  trabecular pattern  hyperchromasia  pleomorphism  irregularly granular chromatin  uniformly prominent nucleoli  multiple nucleoli  increased nuclear cytoplasmic ratio  and atypical naked hepatocytic nuclei  these features were examined in a series of 82 fnab specimens from 52 patients with hcc and 30 patients with nonneoplastic lesions  with the use of a step wise logistic regression analysis  three features were identified as predictive of hcc  increased nuclear cytoplasmic ratio  p   0 001   trabecular pattern  p   0 002   and atypical naked hepatocytic nuclei  p   0 03   when these three criteria were used  the sensitivity of diagnosing hcc by fnab was 100   and the specificity was 87   
class4	cytologic identification of clinically occult proliferative breast disease in women with a family history of breast cancer  a cytologic method for sampling the normal breast by fine needle aspiration  fna  was used to determine the frequency of clinically inapparent proliferative breast disease  pbd  in women with family histories of breast cancer  the authors attempted to obtain specimens from each quadrant of both breasts in 51 female first degree relatives of breast cancer patients  the study group had no detectable masses by physical examination or mammography  samples were prepared on membrane filters  papanicolaou stained  and evaluated cytomorphologically  three hundred seventy eight of 408  92 6   possible quadrants were sampled  cellular material was obtained from 290  76 7   quadrants  pbd was identified in 20 of the 51 women  39 2    when epithelium was obtained  nuclear area  perimeter  and diameter were measured with the use of computerized image analysis  nuclei in samples containing atypical hyperplasia showed significant differences in these parameters when compared with cells from samples containing normal epithelium or benign hyperplasia  the authors  findings indicate that fna sampling and computerized image analysis are useful in the detection and characterization of clinically inapparent pbd  
class4	metastatic small cell tumor of bone with  true  rosettes and glial fibrillary acidic protein positivity  a 15 year old black girl was admitted to st  jude children s research hospital with a lytic lesion involving the right fourth metacarpal bone with a solitary metastasis to the ipsilateral axillary lymph node  histologic examination of both the primary lesion and metastasis revealed a primitive small round cell lesion  abundant rosettes with central lumina were present in the metastasis  immunohistochemical stains performed on sections of the metastasis were strongly positive for glial fibrillary acidic protein  gfap  and negative for neuron specific enolase  nse   s 100 protein  and leu 7  electron microscopic examination of the metastasis revealed lumen formation with apical microvilli and juxtaluminal junctional complexes  this tumor exhibits features that are suggestive  but not definitive  of primitive ependymal differentiation and further expands the morphologic and immunophenotypic range of small round cell tumors of bone  
class4	primary hepatic carcinoid tumor  an electron microscopic and immunohistochemical study  a case of primary carcinoid tumor of the liver with striking morphologic and electron microscopic features is reported  conventional histologic examination showed a prominent paranuclear clear zone in numerous tumor cells  by electron microscopic examination  this clear zone corresponded to a paranuclear mass of intermediate filaments admixed with neurosecretory granules and other cytoplasmic organelles  
class4	papillary carcinoma of the thyroid with mucoepidermoid features  the significance and differential diagnoses of signet ring cells found in the fine needle aspirate of metastatic mucoepidermoid carcinoma from the thyroid are reported and discussed  the primary tumor occurred in a 35 year old man  who had a history of neck irradiation during his childhood  despite postoperative treatment with 60 gy external radiation and 1 200 mci 131i  the patient has at present  12 years after the initial operation  progressive disease with local recurrence in the neck as well as lung metastases  
class4	surface and cytoplasmic expression of cd45 antigen isoforms in normal and malignant myeloid cell differentiation  the cd45 family contains protein tyrosine phosphatase  ptpase  activity and is expressed in one or more of its isoforms on all lymphohematopoietic cells  considerable work has focused on cd45 expression by lymphoid cells  but minimal work has involved granulocytes  granulocytic  or myeloid  cell differentiation is accompanied by a number of morphologic and immunophenotypic changes  this study used flow cytometric and immunocytochemical methods in conjunction with morphologic assessment to investigate the expression of cd45 isoforms during differentiation of normal and malignant granulocytic cells  on normal bone marrow cells  the quantity of surface cd45 did not change during earlier stages but did increase significantly at the terminal stages  bands and polymorphonuclear leukocytes  pmns    cd45ro  the low relative molecular mass  mr  isoform  was very dimly expressed on immature cells but became increasingly brighter beginning at approximately the myelocyte stage  the high mr isoform  cd45ra  was virtually absent from the cell surface at all stages  only a small percentage  3 15   of pmns expressed surface cd45ra  however  there was a cytoplasmic pool of each isoform associated with membrane bound granules found throughout differentiation  with remarkable increases in expression at the terminal stages  in the case of acute myeloid leukemias  amls   most cases expressed surface cd45ra with  or without  cd45ro  regardless of their french american british  fab  classification  this appeared to be a stable process at diagnosis and relapse in individual patients and may therefore serve as a diagnostic aid  the biologic significance of this aberrant expression of cd45ra by malignant cells is unknown but raises important questions regarding the cellular processes of phosphorylation dephosphorylation in normal and malignant cells  
class4	a6  a new 45ro monoclonal antibody for immunostaining of paraffin embedded tissues  the authors report on the extensive characterization  on normal and pathologic tissues  of the t cell specific monoclonal antibody  moab  a6  which the authors previously found to identify a fixation  and paraffin embedding resistant epitope  a6 reacted with most t lymphocytes  macrophages  and langerhans  cells of normal tissues and with peripheral t cell lymphomas  31 of 34   ki 1  lymphomas  12 of 18   and t cell leukemias  1 of 5   all cases of x and non x histiocytosis examined and monocytic leukemias with mature phenotype only were a6 positive  three of 47 cases of b cell lymphoma and leukemia were labeled  hairy cell leukemias  multiple myelomas  and hodgkin s and reed sternberg cells were negative  the a6 reactivity was preserved with different fixatives  formalin  bouin s fluid  carnoy s fixative  and b5  and decalcification procedures and was slightly enhanced by trypsin digestion  the pattern of reactivity of a6 was similar to that obtained with moab uchl 1  recognizing the cd45ro determinant of leukocyte common antigen  however  in pathologic tissues  a6 labeled a higher percentage of cells than uchl 1  cross blocking and enzyme digestion studies  pronase e  sigma chemical  st  louis  mo  and neuraminidase  sigma chemical   indicated that the two moabs may identify close epitopes on the same molecule  in conclusion  the authors  study indicates that a6 is an excellent reagent for detection of the cd45ro molecule on paraffin embedded normal and pathologic tissues  
class4	use of a probe to repeat sequence of the y chromosome for detection of host cells in peripheral blood of bone marrow transplant recipients  in situ hybridization for the y chromosome  y ish  was used to identify residual host cells in the peripheral blood of 51 recipients of sex mismatched allogeneic marrow not depleted of t cells following conditioning with high dose cyclophosphamide and total body irradiation  tbi   one patient who rejected the graft showed rapid reappearance of host cells after transient donor marrow engraftment  host cells were detected at low levels in 49 of the remaining 50 patients  host peripheral blood mononuclear cells  pbmc  decreased with time and reached a plateau at 1 0     0 2  within four weeks after transplantation  while the percentage of host granulocytes  gran  reached a plateau at background level  the mean absolute numbers of host pbmc or gran were less than 0 015 x 10 9  l and did not vary significantly over the period studied  neither the percentages nor the absolute numbers of host pbmc or gran were significantly affected by hla matching  tbi dose intensity  pretransplant remission status  subsequent development of acute or chronic graft versus host disease or relapse after transplantation  the authors conclude that it is common to find a few residual host cells in the peripheral blood of allogeneic marrow transplant recipients  and the presence of these cells has no clinical significance  
class4	granulocytic sarcoma presenting as an epidural mass with acute paraparesis in an aleukemic patient  granulocytic sarcomas are rare tumors composed of granulocytic precursor cells  they are most commonly encountered in patients with acute myelogenous leukemias and myeloproliferative disorders in blast crisis  rarely  patients presenting with granulocytic sarcoma show no evidence of acute leukemia  the authors report an aleukemic patient with acute paraparesis from an epidural granulocytic sarcoma  only five such cases have been reported previously  immunoperoxidase stain for lysozyme and chloroacetate esterase stain were used to prove the myeloid origin of the tumor cells  
class4	secretin provocation test in the diagnosis of zollinger ellison syndrome  the secretin stimulation test has become the preferred provocative test in suspected cases of zollinger ellison syndrome  a pure secretin preparation  a gastrin specific radioimmunoassay  and an appropriate sampling sequence are important for the proper interpretation of this test  gastric acid analysis is necessary in the assessment of hypergastrinemia to confirm acid hypersecretion and exclude achlorhydria  when properly performed and interpreted  the secretin provocation test offers a safe  expeditious  and reliable means of evaluating patients with hypergastrinemia  
class4	dna flow cytometry of colorectal carcinoma  correlation of dna stemlines with other prognostic indices  dna flow cytometry  fcm  was performed on paraffin embedded tissue blocks of 38 surgically resected colorectal carcinomas  crc   forty seven percent of tumors exhibited aneuploidy and 53  were diploid  seventy two percent of patients in the aneuploid but only 35  in the diploid group were alive after a mean follow up of 30 7 and 28 8 months  p   0 01   and 5 yr survival of 56 7  and 11 7   respectively  p less than 0 05   the site of tumor location  dukes  stage  and serum cea level did not predict a certain dna stemline  however  irrespective of the ploidy pattern  a serum cea level greater than 5 0 was associated with a higher mortality and poor 5 yr survival  p less than 0 005   similarly  advanced dukes  stage was associated with higher mortality  p less than 0 05   forty six percent of the patients with lesions that were dukes  b2 or advanced stage received adjuvant therapy  eighty five percent of this subgroup of patients died  18  of these patients had aneuploid tumors  the role of fcm in the assessment of prognosis of crc deserves further clinical evaluation in a randomized control trial  
class4	magnetic resonance imaging of small hepatocellular carcinoma  thirty eight patients with small hepatocellular carcinomas  hccs   size less than 20 mm  initially detected by ultrasound  us  and histologically confirmed  were examined by magnetic resonance  mr  imaging  computed tomographic  ct  scan  and angiography  mr imaging demonstrated hcc nodules in nine  75 0   of 12 patients with tumors less than 10 mm in diameter and in 22  84 6   of 26 patients with tumors 10 20 mm in diameter  in total  hcc nodules were detected in 31 of 38 patients  81 6   by mr imaging  on the other hand  hcc lesions were found on ct scan in 14 of 26 patients  53 8   and in 27 of 35 patients  77 1   by angiography  with mr imaging  hcc nodules were demonstrated in 21 of 31 patients on both t1 and t2 weighted images  and 13 of 21 patients  61 9   were shown to have low intensity areas or iso intensity areas on t1 weighted image  whereas the other eight patients  38 1   were shown to have high intensity areas  all 21 patients were shown to have high intensity areas on t2 weighted image  among 15 resected cases  four patients had a high intensity area on t1 weighted image  and a significant fatty change was noted in hcc nodules by histological study of the resected specimen  we suggest that mr imaging is a useful diagnostic imaging modality  even in small hcc of less than 20 mm  
class4	intrahepatic lymphatics opacified during hepatic arteriography in a patient with hepatocellular carcinoma  extrahepatic lymph node metastases are not uncommon in advanced cases of hepatocellular carcinoma  hcc   this is the account of a hcc case in which intrahepatic lymphatics running toward the hepatic hilus were clearly opacified during hepatic arteriography  the patient was treated by hepatic artery embolization followed by selective embolization of the portal branches  but lymph node metastases at the hepatic hilus were later found during follow up  the clinical course of this case suggests that the communication between the tumor and the lymphatics was responsible for the lymph node metastasis  
class4	inflammatory pseudotumor of the liver associated with acute myelomonocytic leukemia  a patient with inflammatory pseudotumor of the liver associated with acute myelomonocytic leukemia  m4  is reported  he had spiking fever  epigastralgia  and elevated levels of serum c reactive protein  crp  and alkaline phosphatase  alp   ultrasonography showed a hypoechoic mass in the liver  and ultrasonically guided fine needle aspiration biopsy of the mass revealed that it was composed of fibrous connective tissue infiltrated with plasma cells  eosinophils  and neutrophils  accordingly  a diagnosis of inflammatory pseudotumor of the liver was made  marked reduction in the size of the lesion and a decrease of the levels of the crp and alp occurred without specific treatment  we emphasize the importance of ultrasonically guided aspiration biopsy in diagnosis of inflammatory pseudotumor of the liver without the need for surgery  
class4	endosalpingosis as a cause of chronic pelvic pain  endosalpingosis  a condition characterized by ectopic oviduct epithelium  is diagnosed histologically by the appearance of benign ciliated and nonciliated columnar cells in an abnormal location  endosalpingosis is typically without symptoms  our unusual case report shows symptomatic endosalpingosis first seen with chronic pelvic pain  various aspects of this disease will also be discussed  
class4	endodermal sinus tumor of the ovary during pregnancy  a case report  serum alpha fetoprotein screening led to the detection of an endodermal sinus tumor of the ovary in a 24 year old female in week 17 of pregnancy  after surgery  chemotherapy was postponed  in week 28 levels of serum alpha fetoprotein increased  but delivery was delayed until 33 weeks  gestation  after delivery  the patient received four chemotherapy courses  cisplatin  etoposide  and bleomycin   mother  24 months after last chemotherapy  and child are doing well  
class4	analysis of antigen expression at multiple tumor sites in epithelial ovarian cancer  the question of whether the antigenic phenotype of human epithelial ovarian cancer varies in a given patient between the primary tumor and metastatic sites or among metastatic sites themselves is an important issue in planning potential therapeutic strategies for ovarian cancer  we have obtained tumor specimens from at least two separate sites during operations on 12 patients with epithelial ovarian cancer  and we have typed these specimens with a group of 18 monoclonal antibodies that react with cell surface glycoprotein and carbohydrate antigens  including blood group antigens  antibodies with relative specificity for malignant cells as well as those that detect more widely distributed epithelial antigens were used  a total of 31 specimens from 12 patients with advanced adenocarcinoma  8 serous  3 undifferentiated  1 endometrioid  of the ovary were studied  including fresh ascites cells in two patients  frozen sections of tumor specimens were stained with the antibodies by the indirect immunoperoxidase technique and graded semiquantitatively  little difference was seen in antigenic expression of tumors that were obtained from various sites in the same patient for either the epithelial cell markers or blood group markers  intratumoral antigenic heterogeneity was seen  but this was generally quite consistent within a given patient s specimens  as anticipated  variations in antigen expression were seen among specimens from different patients  the antigenic phenotype of the tumor specimens in a given patient  as determined immunohistochemically by our group of antibodies  showed only minor variation among primary and metastatic sites  
class4	ovarian neoplasms and the risk of adnexal torsion  previous reports examining adnexal torsion suggested that benign ovarian neoplasms are more likely to undergo torsion than malignant ovarian neoplasms  to our knowledge  this clinical observation has not been quantified  to examine this hypothesis  we reviewed our experience with ovarian neoplasms found at the time of surgery over a 10 year period  benign ovarian neoplasms had a 12 9 fold increased risk of undergoing adnexal torsion when compared with malignant ovarian neoplasms  95  confidence interval  10 2 to 15 9   the histologic type of ovarian neoplasm does not appear to affect the rate of adnexal torsion  adnexal torsion rarely involves cancer  
class4	laparoscopic pelvic lymphadenectomy in the staging of early carcinoma of the cervix  laparoscopic pelvic lymphadenectomy was performed in 39 patients  an incision of the peritoneum between the round and infundibulo pelvic ligament on each side gave access to the retroperitoneal space  subsequently  laparoscopic surgery allowed precise dissection of external and internal iliac vessels  umbilical artery  and obturator nerve  the peritoneum was left open  and the lymph was drained into the peritoneal cavity  no lymphocele was observed  three to 22  mean  8 7  nodes were removed  and there was no significant morbidity  sensitivity and specificity were 100  in this preliminary experience  it is thus possible to remove the first line regional lymph nodes of the cervix for pathologic examination  because  skip  metastases are quite rare in early cervical carcinoma  the risk of missing a positive node is low  brachytherapy alone  vaginal surgery  or  in microinvasive carcinoma  conization alone can be applied safely without the need of a staging laparotomy in cases with negative nodes  
class4	the increased frequency of cervical dysplasia neoplasia in women infected with the human immunodeficiency virus is related to the degree of immunosuppression  cytologic and histologic investigations of the uterine cervix and studies of the lymphocyte functions were performed in human immunodeficiency virus infected and human immunodeficiency virus antibody negative women to study possible linkages between human papillomavirus induced dysplasia and degree of human immunodeficiency virus induced immunosuppression  cytologic smears of the uterine cervix of 111 human immunodeficiency virus infected women were compared with findings in 76 female intravenous drug users negative for human immunodeficiency virus antibodies and in a group of 526 women of the outpatient population of the hospital  cervical dysplasia neoplasia  including five cases of invasive carcinoma  was seen in 41  of the human immunodeficiency virus infected patients  in human immunodeficiency virus negative intravenous drug users dysplasia neoplasia was seen in 9   and in the sample from outpatients in 4   including two cases of invasive carcinoma  p less than 0 01   cytologic features that were attributable to infection with human papillomavirus were observed in human immunodeficiency virus infected women four times more often than in the sample from the outpatient population  p less than 0 01   frequency and severity of dysplasia appear to increase with diminishing numbers of cd4  helper inducer t lymphocytes and correlated significantly  p less than 0 01  with a loss of blastogenic response to phytohemagglutinin  pokeweed mitogen  and tetanus toxoid  these results suggest an increased risk for the development of dysplasia of the uterine cervix in women with human immunodeficiency virus infection  which is related to the degree of immunosuppression  
class4	the value of squamous cell carcinoma antigen in patients with locally advanced cervical cancer undergoing neoadjuvant chemotherapy  serum levels of squamous cell carcinoma antigen were measured in 688 samples from 119 patients with cervical cancer  ninety seven patients had primary tumors and 22 had recurrent disease  serum samples were obtained before each cycle of chemotherapy  before surgery  at least 4 weeks after surgery  and at 2  to 3 month intervals during follow up from 78 of the patients with locally advanced cervical cancer who were receiving neoadjuvant chemotherapy  squamous cell carcinoma antigen serum levels were elevated  greater than 2 5 ng ml  in 71  of the patients with primary tumors and in 77  of the patients with recurrent carcinomas  the percentage of positivity increased significantly with stage  p   0 03  and was higher in squamous cell tumors than in adenocarcinomas  p less than 0 001   pretreatment squamous cell carcinoma antigen levels were not predictive of neoadjuvant chemotherapy response  however  the serial measurement during chemotherapy showed a good correlation with clinical response  in the patients who had surgery  squamous cell carcinoma antigen positivity did not correlate to pathologic findings  lymph node status  cervical and parametrial infiltration   disease free survival was significantly longer in patients with squamous cell carcinoma antigen pretreatment values that were lower than 5 ng ml  compared with patients with marker higher than 5 ng ml  p less than 0 01   abnormal squamous cell carcinoma antigen serum levels preceded the clinical detection of recurrence in eight of 11 patients with a median lead time of 5 months  
class4	clinical implications of screening for cervical cancer under medicare  the natural history of cervical cancer in the elderly  what do we know  what do we need to know  despite the recent passage of coverage for papanicolaou test screening under medicare  several aspects of the natural history of cervical cancer in the elderly remain uncertain  this article reviews what we know about cervical cancer in elderly women to provide clinicians with the background necessary for assessments of screening recommendations  integration of new data into practice  and development of consensus approaches to screening in the elderly  two central questions that affect a screening program for the elderly are how long the neoplastic process takes from preinvasive disease to the development of invasive cancer  and how likely is it that a given neoplastic state observed in an elderly woman will  in fact  progress to a more severe state  the ultimate success of the new medicare benefit will also be affected by the use of papanicolaou testing  the technique of obtaining the smear  and the adequacy of reporting and follow up  the expansion of medicare benefits to include early cervical cancer detection has the potential to improve the quality and the duration of older women s lives  
class4	epidermal growth factor receptor expression in normal ovarian epithelium and ovarian cancer  i  correlation of receptor expression with prognostic factors in patients with ovarian cancer  previous studies in breast and bladder cancer have suggested that epidermal growth factor receptor is expressed by only a proportion of cancers and is associated with poor clinical outcome  we used a monoclonal antibody specifically reactive with the extracellular domain of the epidermal growth factor receptor to localize this receptor immunohistochemically in frozen sections of normal ovary and epithelial ovarian cancer  normal ovarian epithelium was found to express epidermal growth factor receptor in all cases  among 87 ovarian cancers  however  23  did not express immunohistochemically detectable receptor  epidermal growth factor receptor expression was not related to histologic grade or stage  but was associated with poor survival  p less than 0 05   the median length of survival of patients with tumors that did not express epidermal growth factor receptor was 40 months compared with 26 months in patients with tumors that did express epidermal growth factor receptor  as in breast and bladder cancer  expression of epidermal growth factor receptor in ovarian cancer appears to be a poor prognostic factor  
class4	mucogenic secondary open angle glaucoma in diffuse epithelial ingrowth treated by block excision  we treated a 40 year old man with an acute  unilateral  open angle glaucoma caused by a gelatinous translucent material in the anterior chamber  a clinical diagnosis of mucogenic secondary open angle glaucoma caused by diffuse epithelial ingrowth after ocular trauma one year earlier was suspected  but a primary or secondary ciliary body or iris neoplasm could not be ruled out  a curative 9 mm block excision was performed  six years later  intraocular pressure was normal  and the visual function was unchanged  light and electron microscopy disclosed an island of diffuse columnar epithelium with numerous goblet cells on the iris surface and copious mucinous material extending into the trabecular mesh work  
class4	detection of loss of heterozygosity in formalin fixed paraffin embedded tumor specimens by the polymerase chain reaction  a polymerase chain reaction based procedure was used for the detection of dna length polymorphisms generated by naturally occurring genetic deletions or insertions of known sequence  this method consists of a simple one step assay that does not require any restriction enzyme analysis or southern blot hybridization  allowing identification in ethidium bromide stained gels  the procedure described here was used to detect loss of heterozygosity at various loci  including the hbb beta globin gene cluster  in chemically induced mouse skin tumors  using a variety of tissue preparations  including microdissection of formalin fixed  paraffin embedded specimens  short term cultures  and fluorescence activated cell sorting of epithelial populations  this approach may be useful in detecting tumor specific reduction to homozygosity at polymorphic chromosomal loci  allowing the mapping of putative tumor suppressor loci involved in carcinogenesis  
class4	characterization of preneoplastic and neoplastic lesions in the rat pancreas  nodules of acinar cells with increased proliferative potential develop in the pancreas of carcinogen treated rats and in untreated aged rats  large nodules are classed as adenomas  phenotypic and genotypic characteristics of nodule cells were compared with normal pancreas and transplantable acinar cell carcinomas by several methods  nuclei of acinar cells from normal pancreas  adenomas  and three carcinomas in situ had normal diploid dna content as determined by flow cytometry  one of two primary carcinomas had a hypodiploid dna content  two of three transplantable carcinomas were aneuploid with a dna content in the tetraploid range  explants from nodules and adenomas failed to grow in soft agar  whereas several carcinomas were positive in this assay  a primary carcinoma was serially transplanted  but transplantation of nodules or adenomas failed  transfection of dna from carcinomas in situ yielded a higher frequency of nih 3t3 transformants than dna from adenomas  dnas from the transformants did not contain ras sequences  these studies indicate that cells from nodules and adenomas have low growth potential and lack critical phenotypic and genotypic characteristics of transformed malignant cells that were present in some primary and transplanted carcinomas  
class4	induction of different morphologic features of malignant melanoma and pigmented lesions after transformation of murine melanocytes with bfgf cdna and h ras  myc  neu  and e1a oncogenes  malignant melanomas show a remarkable degree of heterogeneity because of different morphologic features  biologic behavior  and prognosis  in this communication  the authors attempted to correlate morphologic heterogeneity of melanomas with transformation by different activated oncogenes  they studied the histologic features of melanocytic lesions induced by murine melanocytes transformed by basic fibroblast growth factor  b fgf cdna  or h ras  neu  myc  and e1a oncogenes  and the lesions were compared with those observed in human pathology  tumors formed after grafting onto syngenic mice or subcutaneous injections in nude mice were studied  in syngenic mice  benign melanocytic lesions reminiscent of intradermal nevus were observed with melanocytes transformed with b fgf cdna  and myc and e1a oncogenes  benign lesions were also formed by neu transformed melanocytes when they were grafted concomitantly with keratinocytes  whereas malignant tumors were formed by the same cells when grafted alone or together with fibroblasts  in contrast  h ras melanocytes always formed malignant tumors  in nude mice  b fgf transformed melanocytes induced benign lesions  whereas transformed melanocytes by the other oncogenes formed malignant tumors with distinctive and homogeneous morphologic features that depended on the transforming oncogene  melanomas with either epithelioid cell  spindle cell  small round cell  and anaplastic cell growth patterns could be distinguished after transformation with h ras  neu  e1a  and myc oncogenes  respectively  these various histologic types are analogous to those that may be observed in human melanomas  even within the same tumor  these studies suggest a possible molecular mechanism for tumor heterogeneity in which distinct oncogenes or oncogenelike activities can be activated in different tumors or discrete parts of the same tumor  
class4	marker profile of different phases in the transition of normal human ovarian epithelium to ovarian carcinomas  to investigate whether early changes in the transformation of normal ovarian epithelial cells into tumor cells can be detected with monoclonal antibodies  a comparative immunohistochemical study was performed on normal human ovarian mesothelial cells  cystomas  cystadenomas  ovarian carcinomas  as well as granulosa cell tumor  using monoclonal antibodies against different keratin subtypes  it was shown that mesothelial cells  ovarian cysts  cystadenomas  and carcinomas all reacted positively with broad spectrum anti keratin monoclonal antibodies  mabs   as well as with mabs to keratins 7  8  18  and 19  keratins 4 and 13 were not found in mesothelial cells  but positive groups of cells were identified in several cystomas  adenomas  and carcinomas  while mesothelial cells did not react with the pan epithelial marker bw495 36  invaginating metaplastic mesothelial cells  inclusion cysts  cystomas  adenomas  and carcinomas showed an increasing reactivity with bw495 36  with an increasing degree of malignancy  the reactivity of mabs against ovarian carcinoma associated antigens  ov tl 3  oc 125  mov 18  and ov tl 10  was limited to weak staining reaction in some mesothelial cells but were found to be positive on more than 50  of the ovarian cystadenomas and more than 90  of the ovarian carcinomas  thecal and granulosa cells of primordial  primary  and secondary follicles all reacted positively with antibodies to the broad spectrum keratins ov tl 12 5 and rck 102  and to keratins 8 and 18  but not with keratins 4  7  13  and 19  these keratins decreased or disappeared in granulosa cells of mature follicles  graafian follicles   whereas granulosa cell tumors did not react with anti keratin antibodies  the reactivity of bw 495 36 was negative or limited to traces in some granulosa cells  ovarian carcinoma associated antigens were not expressed in granulosa cells or granulosa cell tumors  the data indicate that mesothelial cells undergoing metaplastic changes finally resulting in ovarian cystadenomas  and carcinomas  initiate the synthesis of a 200 kd glycoprotein recognized by mab  bw 495 36   the production of ovarian carcinoma associated antigens  in addition to focal production of keratin 4 and or 13  as seen in several samples  the granulosa cell tumors decrease or switch off their keratin production and remain negative for the 200 kd glycoprotein and the ovarian carcinoma associated antigens  
class4	keratin subsets in spindle cell sarcomas  keratins are widespread but synovial sarcoma contains a distinctive keratin polypeptide pattern and desmoplakins  the presence of individual keratin polypeptides and desmoplakins was immunohistochemically studied in 25 spindle cell sarcomas of different types using acetone fixed frozen sections  results revealed that keratins 8 and 18 were present in a high number of tumors  9 of 9 synovial sarcomas  5 of 7 leiomyosarcomas  5 of 5 malignant schwannomas  and 1 of 4 undifferentiated spindle cell sarcomas  in addition to keratins 8 and 18  the glandular component of synovial sarcoma showed prominent reactivity with antibodies to keratins 7 and 19  also the glandular epithelial cells in synovial sarcoma showed desmoplakin immunoreactivity preferentially in a luminal distribution  but desmoplakin was absent in other spindle cell sarcomas  furthermore keratin 13 was seen focally in 4 of 9 synovial sarcomas  in contrast  keratins 7  13  and 19 were practically absent in leiomyosarcomas  malignant schwannomas  and undifferentiated spindle cell sarcomas  the widespread presence of keratins 8 and 18 in various spindle cell sarcomas may reflect aberrant keratin expression in mesenchymal cells  previously described in cultured transformed fibroblasts  the presence of keratins 7 and 19 and desmoplakin is highly associated with morphologically observable epithelial differentiation restricted to synovial sarcoma among spindle cell sarcomas  
class4	treatment of angiomas with sclerosing injection of hydroxypolyethoxydodecan  the authors discuss the indications for hydroxypolyethoxydodecan in the sclerosing treatment of angiomas  with particular reference to cavernous  venous  and evolutive angiomas  ie  immature angiomas that fail to involute by eight to ten months   moreover  the sclerosing agent may be employed  in connection with embolization and subsequent surgery  in arteriovenous angiomas with a relevant cutaneous subcutaneous development  the authors have successfully used the  interstitial  sclerosing technique  according to andrews  method  this technique involves interstitial injections to obtain the sclerosis of the thin threads of fibrous tissue stroma between the blood vessels  the sclerosing therapy may cause the complete regression of  low flow  angiomas or  at least  a partial reduction that simplifies the ensuing surgical excision  in the case of partial regression of the angioma obtained with the sclerosing therapy  the surgery of the remaining angioma causes a lesser degree of bleeding  especially in areas that do not particularly lend themselves to surgical exploration  ie  the oral cavity   an increased reliability in the radicality of the intervention  due also to the reduced size of the lesion   and better results from an aesthetic functional point of view  
class4	intraoperative pancreatic fine needle aspiration biopsy  results in 166 patients  intraoperative fine needle aspiration biopsy  nab  of undiagnosed pancreatic masses was studied in 166 patients over a 17 year period  the cytologic diagnoses were correlated with histologic specimens  autopsy results  or clinical follow up  benign disease was documented if the patient was alive without malignancy at least 2 years after laparotomy   aspirates were interpreted as benign  suspicious  malignant  or unsatisfactory  malignant disease was the final diagnosis in 109 patients  the cytology was concordant in 101 and was interpreted as suspicious in four  four patients with benign cytology later proved to have malignant disease  a false negative rate of 2 5 per cent  a total of 57 patients had benign disease  51 of these had benign cytology  the remaining patients had  unsatisfactory  cytology reports  a 93 per cent sensitivity  100 per cent specificity  and 0 per cent complication rate are reported  there were no false positive cytology reports  complications are rare and represent case reports  thus  additional sampling is at minimal risk  intraoperative pancreatic nab is a safe  easy  more accurate biopsy technique than historical wedge or core needle biopsies  it is the biopsy method of choice for pancreatic masses found at laparotomy  
class4	skull base malignancy following long term sinus mucocele and osteomyelitis  a case of skull base malignancy following long term sinus mucocele is presented  while the similarity in clinical signs between sinus mucocele and malignancy has recently been emphasized in the literature  no previous case of skull base malignancy following frontoethmoid mucocele has been reported  the literature is reviewed and the association between inflammatory conditions and sinus malignancy is outlined  
class4	surgical voice restoration with the blom singer prosthesis following laryngopharyngoesophagectomy and pharyngogastric anastomosis  surgical voice restoration using the blom singer technique is a well established procedure in patients who have undergone simple laryngectomy  operations for hypopharyngeal carcinoma are more extensive and require reconstruction using regional skin or myocutaneous flaps  or reanastomosis with colon  jejunum  or stomach  we report the use of the blom singer prosthesis in four patients who had undergone pharyngogastric repair following laryngopharyngoesophagectomy and who had failed to achieve a satisfactory voice  all patients initially developed good speech using the prosthesis  two patients subsequently had their prostheses removed  one because of recurrent malignant disease and one because the procedure had not significantly altered the quality of the voice  the remaining two patients have continued to use the device at 2 and 5 years after insertion with good voice production  
class4	management of subglottic stenosis in the adult  twenty one adult patients were surgically treated for severe subglottic stenosis refractory to endoscopic treatment  patients were treated by anterior or anterior and posterior cricoid division with costal cartilage grafting  seventy six percent of the patients were successfully decannulated  success of treatment was not dependent on cause of the stenosis or age or sex of the patient  there was a significantly better outcome  p less than  05  in patients with isolated subglottic stenosis versus those with combined glottic and subglottic stenosis  
class4	selenium in forage crops and cancer mortality in u s  counties  the potential protective effect of selenium status on the risk of developing cancer has been examined in animal and epidemiologic studies  this ecological study investigated the association between u s  county forage selenium status and site  and sex specific county cancer mortality rates  1950 1969  using weighted least squares regression  consistent  significant  p less than  01  inverse associations were observed for cancers of the lung  rectum  bladder  esophagus  and cervix in a model limited to rural counties and for cancers of the lung  breast  rectum  bladder  esophagus  and corpus uteri in a model of all counties  no consistent significant positive associations were observed in the rural county models  this remarkable degree of consistency for the inverse associations strengthens the likelihood of a causal relationship between low selenium status and an increased risk of cancer mortality  
class4	rapid analysis of carcinoembryonic antigen levels in gallbladder bile  identification of patients at high risk of colorectal liver metastasis recently it was found that immunoanalysis of carcinoembryonic antigen  cea  levels in gallbladder bile may be a sensitive method to detect colorectal liver metastases in humans  methods used in the past for the detection of cea in various body fluids were cumbersome and time consuming  requiring acid extraction  extensive dialysis  and column purification  single step  solid phase radioimmunoassays  designed specifically for serum cea analysis  were developed commercially to replace these methods  parameters and methodology necessary to adapt these kits for parameters and methodology necessary to adapt these kits for use with gallbladder bile are presented here  a combination of pretreatment procedures for bile  before radioimmunoassay  permit rapid  reproducible  and accurate measurement of cea levels in gallbladder bile  
class4	liver transplantation for hepatoblastoma  the american experience  the current role of liver transplantation in treating malignant tumors of the liver is uncertain  except for select histologic types  pooled data on the results of liver transplantation in 12 children with hepatoblastoma is presented here  one half of the children are alive 24 to 70  44     19  months after transplantation with no evidence of recurrence  three patients  25   died of tumor recurrence and three  25   died of other causes  unifocal and intrahepatic tumors were associated with better prognosis compared to the multifocal tumors and tumors with extrahepatic spread  p   0 04 and 0 13   microscopically vascular invasion and the predominance of embryonal and or anaplastic epithelium were associated with a poor prognosis compared to the tumors with no vascular invasion and with predominantly fetal epithelium  p   0 08 and 0 1   it is concluded that continued efforts to treat unresectable hepatoblastomas by liver transplantation is justified and the role of adjuvant chemotherapy in improving the results needs to be better defined  
class4	adenocarcinoma in barrett s esophagus  a clinicopathologic study of 65 cases  the natural history of barrett s esophagus  particularly the prevalence and incidence of malignant changes in it  remains controversial  furthermore the prognosis of surgically treated patients with carcinoma in barrett s esophagus has not been elucidated fully  to examine these and other issues  the records of 65 patients with carcinoma in barrett s esophagus presenting at the lahey clinic medical center from january 1973 to january 1989 were reviewed  during this period  241 patients with documented barrett s esophagus were seen  for a prevalence of carcinoma of 27   adenocarcinoma in barrett s esophagus accounted for 30  of the surgically treated carcinomas of the thoracic esophagus during this period  all but four of these patients were men  symptoms of chronic reflux were present in less than one half of the patients and dysphagia was often the presenting symptom  in eight patients the carcinoma was discovered on routine surveillance endoscopy  and in four patients progression of disease from benign columnar epithelium to dysplasia to carcinoma was documented  tumors developed in six patients who had undergone previous antireflux surgery  and in four other patients a second carcinoma developed in residual barrett s epithelium after a previous resection  of the 65 patients  61  94   were considered to have operable disease  all of whom underwent resection  two patients  3 3   died within 30 days of operation  the resected specimens were staged as follows  stage 0  4  stage i  10  stage ii  17  stage iii  25  stage iv  4  of the resected specimens  73  showed areas of dysplasia adjacent to the tumor  the overall adjusted actuarial 5 year survival rate was 23 7   the 3 year survival rate was 100  for patients with stage 0 carcinoma  85 7  for patients with stage i carcinoma  53 6  for patients with stage iia carcinoma  45  for patients with stage iib carcinoma  25 2  for patients with stage iii carcinoma  and 0  for patients with stage iv carcinoma  the premalignant nature of barrett s esophagus requires endoscopic surveillance to detect early carcinoma because symptoms often occur late or are absent  antireflux surgery does not protect against the development of carcinoma  all of the barrett s epithelium must be resected because a second carcinoma may develop in residual columnar epithelium  severe dysplasia should be considered an indication for resection  although operability and resectability rates are high  long term survival is not  early detection is mandatory if long term survival is to be achieved  
class4	mastectomy following preoperative chemotherapy  strict operative criteria control operative morbidity  the surgical morbidity associated with aggressive preoperative chemotherapy in 106 patients with advanced primary breast cancer who had chemotherapy followed by mastectomy was examined  these patients were compared with a group of 91 consecutive patients who had mastectomy without preoperative chemotherapy  strict operative criteria were used to determine the timing of mastectomy following chemotherapy  wound infection rates were no different in the preoperative chemotherapy group compared to the mastectomy alone groups  7  versus 4   p   0 62   the incidence of wound necrosis was similar  11  versus 6   p   0 29   seroma formation was decreased significantly in the preoperative chemotherapy group compared to the mastectomy alone group  15  versus 28   p   0 04   intensive preoperative chemotherapy did not delay the reinstitution of postoperative treatment  30  versus 20   p   0 27   however  when delay in instituting postoperative chemotherapy was more than 30 days  there was a significant decrease in overall survival rate  p   0 04   this study provides evidence that intensive preoperative chemotherapy and mastectomy can be performed without increased morbidity  furthermore it is important to institute systemic chemotherapy within 30 days of mastectomy to achieve maximum survival  
class4	a population based study of functional status and social support networks of elderly patients newly diagnosed with cancer  we assessed the functional status and social support networks of 799 men and women aged 65 years or older newly diagnosed with cancer and living in six new mexico counties  functional limitations included depending on others for transportation  33   and mental incompetence or poor recent memory  42    the percentage of patients with functional limitation increased sharply with increasing age  in a substantial number of patients there was also evidence for poor social support networks  26 5  of subjects lived alone and 38 9  had no children living in the vicinity  in a multiple logistic regression analysis  the predictors of having a poor social support network included non hispanic white ethnicity  advanced age  low income  and being a recent migrant to the area  subjects with functional limitations were more likely to have poor social support networks than subjects without such limitations  the deleterious combination of impaired functional status and a limited social support network may explain why elderly cancer patients are at increased risk for not receiving appropriate therapy  given the potential complexities involving the evaluation and appropriate treatment of cancer  care must be taken to adequately assess functional status and support mechanisms of older patients  and to provide adequate support to ensure compliance with treatment  
class4	the origin of epidermal melanocytes  implications for the histogenesis of nevi and melanomas  among the most venerable concepts in dermatopathology is unna s 19th century notion of abtropfung  ie  that melanocytes drop off from the epidermis to the dermis during the histogenesis of melanocytic tumors  paradoxically  however  unna s basic premise of an epidermal origin for melanocytes has been seriously questioned for over 40 years  based on experimental evidence favoring a neural crest origin for melanocytes  recent work has strengthened the evidence for a neural crest origin of epidermal melanocytes  and it has been suggested that the concept of abtropfung be replaced by the concept of hochsteigerung  the concept of hochsteigerung holds that melanocytes migrate up from the dermis into the epidermis not only in normal development  but also during normal tissue maintenance  it now seems likely that the precursor of melanocytes  in both normal and abnormal differentiation  may not be a melanoblast  a primitive cell committed to melanocytic differentiation  but rather a pluripotential cell  although axon investing schwann cells have been the traditional focus as the closest relative of the epidermal melanocyte  recent studies suggest that another nerve sheath cell  the perineural cell  might be a better candidate  these concepts have profound implications for the histogenesis of melanocytic nevi and melanomas  
class4	recurrent pigmented melanocytic nevus  a benign lesion  not to be mistaken for malignant melanoma  melanocytic nevi that recur after incomplete removal are pigmented lesions that may clinically and pathologically simulate malignant melanoma in situ  five examples of recurrent pigmented melanocytic nevus  with emphasis on light microscopic and immunohistochemical findings  are reported herein  prominent hmb 45 staining in these nevi may cause further confusion in differentiating them from malignant melanoma  the differential diagnosis of recurrent pigmented melanocytic nevi is discussed  with particular emphasis on distinguishing these lesions from malignant melanoma  our immunohistochemical observations indicate that the recurrences most likely develop as a result of proliferation of melanocytes remaining in the epidermis and or adnexae following incomplete removal  the approach and management of recurrent nevi are also discussed  
class4	pulmonary tumor embolism to alveolar septal capillaries  a prospective study of 12 cases  pulmonary tumor embolism leading to subacute cor pulmonale has been extensively studied  however  to our knowledge  the involvement of pulmonary alveolar capillaries has not previously been studied in detail  a prospective study was conducted on 112 autopsied patients with cancer to determine the presence of microembolism in the alveolar septal capillaries  fifteen sections of predetermined lung areas were obtained and examined  tumor embolism to alveolar septal capillaries was detected in 12 cases  10 7    with simultaneous involvement of other vascular territories in 11  seven patients had dyspnea  four  right ventricular failure  four  hypertrophy of the right ventricle  and three  arterial vascular sclerosis  the present data have led us to conclude that pulmonary tumor embolism to alveolar septal capillaries occurs in association with the involvement of arterial or lymphatic vessels and should be analyzed within the context of the study of subacute cor pulmonale  
class4	mucocelelike tumor of the breast associated with atypical ductal hyperplasia or mucinous carcinoma  a clinicopathologic study of seven cases  we studied seven patients with mucocelelike tumors of the breast  known to be benign lesions that may be confused with mucinous carcinomas of the breast  all patients had a palpable mass  microscopically  the most striking feature was the cystic character of the lesion  the epithelial lining of the cysts was usually flat or cuboidal to low columnar  and mucin pools frequently appeared near the ruptured cysts  three mucocelelike tumors contained a microscopic focus of mucinous carcinoma  the other tumors had areas of atypical ductal hyperplasia containing abundant intraluminal mucinous materials  the mucin was composed predominantly of neutral and nonsulfated acid mucins whose character was identical to that of those in mucinous carcinoma  because all mucocelelike tumors in our series were associated with either atypical ductal hyperplasia or carcinoma and because some mucocelelike tumors may indeed be early mucinous carcinomas of the breast  we recommend examination of the entire specimen and careful clinical follow up  
class4	secretory carcinoma of the breast  most studies of secretory carcinoma of the breast have been single case reports or separate analyses of the problem in either children or adults  we studied 10 female patients  aged 5 to 87 years  most patients presented with a palpable mass  often near the areola  five of six tumors were estrogen receptor negative  three analyzed for progesterone receptor were positive  histologic patterns present in varying proportions were  classic  secretory carcinoma with microacini  abundant secretion with papillary features  and with prominent solid and papillary apocrine features  the tumors had strong reactivity for alpha lactalbumin  s100  and carcinoembryonic antigen  polyclonal  and were negative for gross cystic disease fluid protein and anti carcinoembryonic antigen  monoclonal   six patients had mastectomy  four had local excision  none had axillary nodal metastases initially  with follow up of 3 to 72 months  mean  47 months  median  48 months   two patients treated by local excision had local recurrences  one patient had axillary nodal metastases  all patients are alive  comparison of patients under and over 30 years of age revealed one important difference  younger patients had a longer interval between detection and biopsy 30 vs 2 months  treatment recommendations are initial wide excision or quadrantectomy with low axillary dissection in most cases and  in premenarchal patients  strong effort to preserve the breast bud without jeopardizing local control  
class4	intraluminal crystalloids in struma ovarii  immunohistochemical  dna flow cytometric  and ultrastructural study  we recently encountered a unique case of follicular variant of papillary carcinoma arising in struma ovarii that contained numerous intrafollicular crystalloids  there was no evidence of capsular or vascular invasion or metastases  though the dna content of the papillary carcinoma was aneuploid  in contrast  diploid dna was manifested in the histologically benign thyroid tissue  the nature of the crystalloids and the significance of aneuploid dna content are discussed  
class4	steroid cell tumor of the ovary in a child  an 8 year old girl exhibited severe  progressive virilization of 2 years  duration associated with markedly elevated circulating testosterone concentrations  based on her initial clinical presentation and results of a chemical evaluation  she was originally thought to have non classic 21 hydroxylase deficiency  but her condition did not respond to corticosteroid therapy  further evaluation confirmed the presence of an ovarian neoplasm  the excised ovary contained an attached gray brown mass  light microscopic and ultrastructural examination revealed the mass to be a steroid cell tumor  because reinke s crystals were not present  it was designated to be a steroid cell tumor not otherwise specified  this case represents one of 22 reported cases of steroid cell tumor occurring in children described in the literature  most of which have been associated with heterosexual precocity  to our knowledge  steroid cell tumors are benign when they occur in prepubertal children  although they are rare  steroid cell tumors of the ovary should be considered in cases of childhood virilization  
class4	gross cystic disease fluid protein 15 in salivary gland tumors  gross cystic disease fluid protein 15  gcdfp 15  is a 15 kd glycoprotein that is expressed by normal apocrine epithelia and in a majority of breast carcinomas  however  recent studies have demonstrated that this substance is also present in tumors of the salivary glands  sweat glands  and prostate gland  to determine whether the expression of cgdfp 15 might aid in the differential diagnosis of salivary gland lesions  the anti gcdfp 15 monoclonal antibody d6 was applied to paraffin sections of 133 such neoplasms  benign tumors  76  reactive  were more often labeled than malignant lesions  28  reactive  by this antibody  overall  53  41   of 133 cases were positive for gcdfp 15  notably  the tubuloglandular components in 17  81   of 21 pleomorphic adenomas were reactive  but no example of either adenoid cystic carcinoma or polymorphous low grade adenocarcinoma were labeled  in contrast  24  of adenocarcinomas stained with this antibody  the apparent expression of gcdfp 15 by a spectrum of salivary gland tumors supports their biologic relationship to lesions of the cutaneous apocrine glands and breast  furthermore  the demonstration of this determinant may be of use in suggesting the salivary gland nature of poorly differentiated carcinomas of the head and neck  and it may facilitate the separation of pleomorphic adenoma from histologically similar malignant neoplasms in the salivary glands themselves  
class4	the tall cell variant of papillary carcinoma of the thyroid gland  comparison with the common form of papillary carcinoma by dna and morphometric analysis  the tall cell variant of papillary carcinoma of the thyroid manifests a more aggressive behavior than the usual form of papillary carcinoma of the thyroid  morphometric analysis of nuclear features and dna analysis may yield information predictive of aggressive behavior  accordingly  the dna content and morphometric features of the neoplastic cells of the tall cell variant were measured and compared with measurements obtained from neoplastic cells of the usual form of papillary carcinoma  six of the 11 tall cell neoplasms were aneuploid  as were four of the eight usual papillary neoplasms  although benign cells were separated from malignant cells in each case  differences between tall and usual papillary carcinoma cells were not observed regarding dna content  chromatin texture  or nuclear size and shape  differences in the clinical behavior of these neoplasms will likely need to be explained on the basis of other characteristics  
class4	squamous cell carcinoma in situ arising in an ovarian mature cystic teratoma  report of one case with histopathologic  cytogenetic  and flow cytometric dna content analysis  a squamous cell carcinoma in situ arose in an ovarian mature teratoma  ie  dermoid cyst  in a 62 year old woman  flow cytometric dna content analysis of paraffin embedded in situ carcinoma showed a normal dna content with moderate to high proliferative activity  s phase fraction estimate  16  to 18    cytogenetic analysis of the in situ cancer and the benign cystic portion of the tumor revealed a 46 xx karyotype  in addition  the benign cystic portion of the tumor revealed homozygous chromosomal heteromorphisms  compared with heterozygous markers found in peripheral blood lymphocytes  these results show that this squamous cell carcinoma in situ was euploid and suggest that the mature cystic teratoma was derived from a single germ cell after meiosis i  
class4	ring neutrophils in plasma cell dyscrasia  sporadic reports in the medical literature concern the significant incidence of neutrophils with ring shaped nuclei in myeloproliferative disorders  we report our first encounter with ring neutrophils in patients with lymphoproliferative disorders  a significant incidence of ring neutrophils was observed in all of 20 patients with multiple myeloma and in nine of 10 patients with monoclonal gammopathy of undetermined significance  the mean percent of ring neutrophils was 9 5   range  1 0  to 28 0   in patients with multiple myeloma  which was significantly greater than in those with monoclonal gammopathy of undetermined significance or in healthy controls  in multiple myeloma  the incidence of ring neutrophils in the pretreatment phase was greater than that in the remission phase  a great deal of overlap was noted between multiple myeloma in the remission phase and monoclonal gammopathy of undetermined significance  the incidence of ring neutrophils seemed to vary according to disease stage  ring neutrophils may reflect abnormal granulopoiesis in plasma cell dyscrasias  
class4	extramammary paget s disease of the bronchial epithelium  we report the first case  to our knowledge  of extramammary paget s disease of the bronchial epithelium  the tumor displayed paget s cells scattered within the bronchial epithelium in most of the lesion  but infiltrating into the bronchial submucosa and pulmonary parenchyma with microglandular and papillary patterns in some area  in addition to the histologic findings of coexistence with adenocarcinomatous components  in situ involvement into bronchial glands and ducts by paget s cells was observed  suggesting that extramammary paget s disease of the bronchial epithelium may be a variant of pulmonary adenocarcinoma  which is associated with bronchial glands  
class4	lipomatous hamartoma of the orbit  proliferations of mature adipose tissue  while common in retroperitoneal and subcutaneous sites  rarely occur in the orbit  we describe the clinical  radiographic  and histopathologic findings of a nonencapsulated lipomatous tissue overgrowth of the right orbit in a 35 year old man  the mass had caused proptosis since childhood and was apparently present since birth  due to the age at onset  the histologic similarity to normal orbital fat  and the lack of encapsulation or choristomatous elements  we propose the term lipomatous hamartoma for this entity  
class4	lipomatous hypertrophy of the interatrial septum  an unusual intraoperative finding  lipomatous hypertrophy of the interatrial septum was an incidental finding in a man of 45 undergoing coronary artery bypass grafting for unstable angina  he was not overweight and did not have any rhythm disturbances  the diagnosis was made on frozen section  
class4	tenascin expression in hyperproliferative skin diseases  the expression of tenascin  a recently discovered extracellular matrix glycoprotein  was studied by immunohistochemistry in normal human skin and in a number of skin diseases with epidermal hyperproliferation such as psoriasis  basal cell carcinoma  bowen s disease and solar keratosis  tenascin expression in the upper dermis of normal skin was found to vary from almost absent to patchy along the basal membrane  staining was continuous and intense around blood vessels  hair follicles and eccrine sweat ducts  in basal cell carcinoma a marked expression of tenascin was found in the tumour stroma  especially adjacent to the basal membrane surrounding the tumour cell nests  in bowen s disease and solar keratosis  tenascin expression was found in the dermis next to the keratinocytes  in psoriasis the dermal papillae of clinically involved skin were intensely stained and a continuous band of tenascin was present in the upper dermis along the basal membrane  the distribution of tenascin differed from other known extracellular matrix components  
class4	 high single dose  european puva regimen also causes an excess of non melanoma skin cancer  we report the results of a long term  12 8 years  follow up study of the detection of malignant and benign skin tumours in patients with psoriasis  who were treated with puva according to the european   high single dose  regimen  a total of 13 squamous cell carcinomas  scc  and 24 basal cell carcinomas  bcc  were diagnosed in 11 of 260 patients  the incidence of both scc and bcc was increased in comparison with the general dutch population  the ratio of scc to bcc in the general population was 1 8 but was 1 2 5 in our study group  a positive correlation was observed between the development of scc and the total uva dosage  the age of the patient at the start of the puva treatment and a history of arsenic use  this dose related increase in the incidence of scc  reported in studies from the u s a   has not been found in earlier european studies  the average time period between the start of puva therapy and the diagnosis of the first malignant skin tumour was 6 0 years for scc and 4 7 years for bcc  among the 49 benign skin tumours were actinic keratoses  a keratoacanthoma and  puva keratoses   a newly described hyperkeratotic lesion  especially found in puva treated patients  
class4	epidermodysplasia verruciformis associated papillomavirus infection complicating human immunodeficiency virus disease  three males infected with the human immunodeficiency virus  hiv  were noted to have extensive flat warts of the face and or body  in two there were also pityriasis versicolor like lesions  biopsies showed foamy  basophilic  distended cytoplasm in granular layer keratinocytes  characteristic of the human papillomavirus types seen in epidermodysplasia verruciformis  dna hybridization techniques demonstrated the presence of hpv type 8 in one patient and hpv 5 and 8 in another  patients with immune suppression due to hiv infection may demonstrate the clinical features of epidermodysplasia verruciformis with the same potentially oncogenic hpv types  
class4	an adult with common acute lymphoblastic leukaemia  c all  presenting with skin infiltration  a 22 year old man presented with multiple raised erythematous skin lesions  pyrexia and epistaxis  a diagnosis of common acute lymphoblastic leukaemia  c all  was made by morphological  cytochemical  immunological and cytogenetic examination of peripheral blood and bone marrow  biopsy of the skin revealed leukaemic infiltration by similar cells  
class4	the t 1 19  q23 p13  results in consistent fusion of e2a and pbx1 coding sequences in acute lymphoblastic leukemias  the t 1 19  q23 p13  chromosomal translocation is observed cytogenetically in 25  of children with pre b cell acute lymphoblastic leukemia  all  and is associated with an adverse treatment outcome  the t 1 19  juxtaposes the e2a gene from chromosome 19 with the pbx1 gene on chromosome 1  leading to the production of fusion transcripts and resultant chimeric proteins that contain the transcriptional activating motif of e2a and the dna binding homeodomain of pbx1  to investigate the molecular nature of e2a pbx1 fusion in patients with t 1 19  all we used an rna based polymerase chain reaction  pcr  procedure to amplify a portion of the chimeric transcript  we detected e2a pbx1 fusion transcripts in cells from 97   37 of 38  of cases in which the t 1 19  had been observed cytogenetically  molecular evidence of e2a pbx1 fusion transcripts was also observed in a patient in whom a t 1 19  was not detected cytogenetically and in one patient with subclinical levels of minimal residual disease before overt clinical relapse  in all pcr positive cases the junction of e2a and pbx1 coding sequences occurred at precisely the same location as demonstrated by hybridization of pcr products with a fusion site specific detection oligonucleotide  these findings demonstrate the consistent fusion of e2a and pbx1 coding sequences resulting from t 1 19  and suggest that site specific fusion of e2a and pbx1 is an important pathogenic event in t 1 19  all  
class4	monoclonal antibody purged autologous bone marrow transplantation therapy for multiple myeloma  eleven patients with plasma cell dyscrasias underwent high dose chemoradiotherapy and anti b cell monoclonal antibody  moab  treated autologous bone marrow transplantation  abmt   the majority of patients had advanced durie salmon stage myeloma at diagnosis  all were pretreated with chemotherapy  and six had received prior radiotherapy  at the time of abmt  all patients demonstrated good performance status with karnofsky score of 80  or greater and had less than 10  marrow tumor cells  eight patients had residual monoclonal marrow plasma cells and 10 patients had paraprotein  following high dose melphalan and total body irradiation  tbi  there were seven complete responses  three partial responses  and one toxic death  granulocytes greater than 500 mm3 were noted at a median of 21  range 12 to 46  days posttransplant  pt  and untransfused platelets greater than 20 000 mm3 were noted at a median of 23  12 to 53  days pt in 10 of the 11 patients  natural killer cells and cytotoxic suppressor t cells predominated early pt  with return of b cells at 3 months pt and normalization of t4 t8 ratio at 1 year pt  less than 5  polyclonal marrow plasma cells were noted in all patients after transplant  three of the seven complete responders have had return of paraprotein  two with myeloma  and have subsequently responded to alpha 2 interferon therapy  eight patients are alive at 18 9  8 9 to 43 1  months pt and four remain disease free at 12 3  17 5  18 9  and 29 months pt  this preliminary study confirms that high dose melphalan and tbi can achieve high response rates without unexpected toxicity in patients who have sensitive disease  and that moab based purging techniques do not inhibit engraftment  although the follow up is short  and long term outcome to be determined  relapses post abmt in these heavily pretreated patients suggest that abmt or alternative treatment strategies should be evaluated earlier in the disease course  
class4	adoptive immunotherapy with high dose interleukin 2  kinetics of circulating progenitors correlate with interleukin 6  granulocyte colony stimulating factor level  immunotherapy with interleukin 2  il 2  and lymphokine activated killer  lak  cells results in significant tumor regression in patients with advanced cancer  we have investigated the kinetics of circulating erythroid  bfu e  and granulocytic macrophage  cfu gm  progenitors after il 2 therapy in 11 cancer patients  mainly affected by metastatic melanoma and renal cell carcinoma  administration of il 2 from day 1 through day 5 constantly induced a dramatic decrease of the number of circulating bfu e and cfu gm  which then showed a striking rebound  up to values fourfold and sevenfold higher  respectively  than the pretherapy levels  on discontinuation of il 2  ie  from day 5 through day 10  a similar kinetic pattern was observed during and after the second cycle of il 2 administration  3 h  thymidine killing experiments showed that the cycling activity of the progenitors was virtually unmodified in the rebound phases  to explore the mechanism s  underlying this kinetic pattern  we have analyzed the plasma concentration of several hematopoietic growth factors  including il 1 beta  il 3  il 4  il 6  granulocyte macrophage colony stimulating factor  gm csf   g csf  and erythropoietin  ep   no modifications in the levels of il 3  gm csf  or il 1 beta were observed  whereas a pronounced increase of il 6 and g csf concentration was monitored  starting at day 3 and peaking at day 5 of treatment  a parallel  but modest  increase of ep level was also observed   the elevation of il 6 and g csf concentration is directly correlated with and may  at least in part  underlie the subsequent rebound of circulating hematopoietic progenitors  furthermore  the increase in il 4 level observed at day 10 of therapy may mediate the eosinophilia gradually starting at this stage of treatment  
class4	ki b5  a monoclonal antibody unrelated to cd45 recognizes normal and neoplastic human b cells in routine paraffin sections  in the search for immunoreagents appropriate for the histopathologic diagnosis of malignant b cell lymphomas in routinely processed paraffin sections  a new monoclonal antibody  ki b5  was generated using a high grade b cell lymphoma as the immunogene  ki b5 is a mouse igg1 kappa that recognizes five protein fractions of about 84  82  55  48  and 27 kd after biosynthetic radiolabeling and immunoprecipitation  protein fractions with the molecular weights of approximately 84 and 82 kd were expressed on the cell surface and show that ki b5 is probably unrelated to cd45  it was possible through electron microscopy to visualize the membrane bound portion of ki b5  extensive immunohistologic studies on normal human tissue and various neoplasias demonstrated the high specificity of ki b5 to normal human b cells and a minor subgroup of plasma cells  except for ml 2  which is a myelomonocytic human cell line  ki b5 exclusively recognized the b cell lineage  including eb 3  ball 1  and nalm 1  all carcinomas  sarcomas  and malignant melanomas tested with ki b5 were negative  although normal granulocytes and monocytes were constantly negative  three of eight myelomonocytic leukemias coreacted with this antibody  eight of the 57 t cell lymphomas studied were positive to ki b5  five were classified as lymphoblastic  two represented t8 cll  and one was classified as immunoblastic t cell lymphoma  only 3 of 126 cases of b cell lymphoma  including rare types not considered in the current classifications  were negative to ki b5  plasmacytomas were also negative  except for one case  irrespective of the cases of lymphoblastic lymphoma and plasmacytoma  ki b5 represents a new monoclonal antibody appropriate for the diagnosis and immunophenotyping of malignant lymphomas in routinely processed paraffin sections  
class4	an epitope on the transferrin receptor preferentially exposed during tumor progression in human lymphoma is close to the ligand binding site  we have previously reported an anti transferrin receptor antibody  trump  which was originally selected for its ability to discriminate low  and high grade lymphomas  this feature was distinct from the other anti transferrin receptor antibodies such as okt9  in the present study  further immunochemical analysis was performed to define the nature of the antigenic site recognized by the trump antibody  trump was found to block the binding of transferrin both to solubilized and to surface transferrin receptors  conversely  transferrin could block the binding of trump only to surface transferrin receptors  therefore  the epitope recognized by trump is near but not identical to the transferrin binding site  stimulation of peripheral blood lymphocytes with phytohemagglutinin induced both the okt9 epitope and the trump epitope  but 12 phorbol 13 myristate acetate induced only the okt9 epitope  growth of some cell lines was inhibited by trump but not by okt9  no structural difference was found between transferrin receptor molecules reactive with trump and those reactive with okt9  in support of these results  trump was able to immunoprecipitate transferrin receptor molecules solubilized from low grade follicular lymphoma cells even though it did not bind to the receptors exposed on the surface of these cells  these findings imply that low grade lymphoma cells differ from high grade lymphoma cells not in the structures of their transferrin receptors but in their exposure of the molecule on the cell surface  
class4	inactivation of the retinoblastoma gene in human lymphoid neoplasms  the absence of wild type retinoblastoma  rb  gene expression in a wide variety of human solid tumors suggests an etiologic role for this tumor suppressor gene in human cancer  we have evaluated the involvement of rb gene inactivation in the pathogenesis and progression of human lymphoma and leukemia  we examined the genomic configuration and transcription of the rb gene in cultured cell lines and primary cases of t  and b cell lymphomas and leukemias  by southern analysis  abnormalities of the rb locus were identified in 1 of 5 t cell acute lymphoblastic lymphoma  t all  cell lines  1 of 26 primary cases of t all  1 of 40 primary cases of chronic lymphocytic lymphoma well differentiated lymphoma  cll wdl   and 1 of 15 primary cases of intermediately differentiated lymphoma  idl   by northern analysis  markedly reduced or abnormal expression of the rb gene was identified in 2 of 5 t all cell lines  1 of 7 primary cases of t all  1 of 5 primary cases of cll wdl  and 1 of 6 primary cases of idl  these findings show that rb gene inactivation can be associated with a broad range of lymphoid neoplasms and that loss of the tumor suppressor function of rb may influence the pathogenesis and progression of lymphoma leukemia  
class4	the beta globin 3  enhancer element confers regulated expression on the human gamma globin gene in the human embryonic fetal erythroleukemia cell line k562  we have constructed fusion genes comprised of gamma and beta globin elements and globin sequences linked to neomycin resistance  neor  genes to define the cis acting sequences responsible for developmental stage specific expression and induction of fetal globin genes in embryonic fetal erythroleukemia k562 cells  the results indicate that the gamma promoter is required for proper initiation of transcription  however  the accumulation of gamma globin transcripts in response to hemin induction requires the additional presence of either gamma intervening sequence 2 or the 3  enhancer element of the beta globin gene  thus  the gamma promoter may provide the elements for developmental stage specific gene expression during fetal life  by contrast  the beta 3  enhancer is erythroid specific but not developmental stage  or gene specific  
class4	detection of residual leukemia after bone marrow transplant for chronic myeloid leukemia  role of polymerase chain reaction in predicting relapse  we used the polymerase chain reaction  pcr  to detect residual leukemia specific mrna in blood and marrow from 37 patients in complete hematologic and cytogenetic remission after allogeneic bone marrow transplant  bmt  for chronic myeloid leukemia  cml   our two step pcr method involved the use of  nested primers  in the second step and could detect one k562 cell diluted into 10 5  normal cells  elaborate measures were taken to exclude false positive and false negative results  in nine patients whose blood and marrow were studied simultaneously the results were concordant  two positive and seven negative   twenty three patients transplanted in chronic phase  cp  with unmanipulated donor marrow were studied  blood cells from nine of these patients were studied 3 to 6 months post bmt and six were pcr positive  three were negative on subsequent studies  blood cells from 18 patients studied between 8 months and 8 years post bmt were all pcr negative  nine patients transplanted in cp with t cell depleted marrow cells were studied  blood from five was positive 3 to 24 months post bmt  blood from five was negative 3 to 6 years post bmt  four patients no longer in first cp were studied after bmt with unmanipulated donor marrow  blood from all four was positive 5 to 19 months post bmt  based on the known clinical results of transplant in these three cohorts we conclude that pcr may be positive within 6 months of bmt in patients who can expect long lasting remission  whereas pcr positivity later after bmt may indicate that the probability of cure is reduced  thus  the technique may prove useful for early assessment of new transplant protocols that might inadvertently increase the risk of relapse  
class4	terminal cancer care and patients  preference for place of death  a prospective study  objective  to assess the preference of terminally ill patients with cancer for their place of final care  design  prospective study of randomly selected patients with cancer from hospital and the community who were expected to die within a year  patients expected to live less than two months were interviewed at two week intervals  otherwise patients were interviewed monthly  their main carer was interviewed three months after the patient s death  setting  district general hospital  hospices  and patients  homes  main outcome measure  stated preferred place of final care  actual place of death  reason for final hospital admission for those in hospital  community care provision required for home care  results  of 98 patients approached  84  86   agreed to be interviewed  of whom 70  83   died during the study and 59  84   stated a preferred place of final care  34  58   wished to die at home given existing circumstances  12  20   in hospital  12  20   in a hospice  and one  2   elsewhere  their own home was the preferred place of care for 17  94   of the patients who died there  whereas of the 32 patients who died in hospital 22  69   had stated a preference to die elsewhere  had circumstances been more favourable 67   41  of patients would have preferred to die at home  16   10  in hospital  and 15   9  in hospice  conclusion  with a limited increase in community care 50  more patients with cancer could be supported to die at home  as they and their carers would prefer  
class4	upper tract tumours following cystectomy for bladder cancer  is routine intravenous urography worthwhile  the incidence and presentation of upper tract tumours were studied in 180 patients who had previously undergone cystectomy for transitional cell carcinoma of the bladder  intravenous urography was performed routinely 3 months after cystectomy  1 year later and at 3 yearly intervals thereafter  ten patients developed upper tract tumours  1 presented with loin pain and the remainder with haematuria  six patients underwent nephroureterectomy and 5 of them lived for at least 4 years  4 were inoperable and only 1 survived longer than 6 months  in this series  all patients with upper tract tumours presented with symptoms and routine intravenous urography failed to detect any asymptomatic lesions  routine radiological assessment of the upper tracts to detect tumours is not justified following cystectomy  
class4	transitional cell carcinoma of the upper urinary tract  prognostic variables and post operative recurrences  in a retrospective study of 198 patients with transitional cell carcinoma of the upper urinary tract  post operative recurrences developed as contralateral tumours in 2 5   in the ureteric stump after conservative resection in 19  and in the bladder in 36 4   upper tract recurrences resembled the primary tumours in terms of grade and stage  of the bladder tumours  89  were similar in grade and 72  similar in stage to the primary tumours  age  sex  grade and stage had no effect on the number of bladder recurrences  but ureteric tumours had significantly more recurrences than renal pelvicaliceal tumours  sex  bladder recurrences and site of primary tumours did not influence survival  thus grade and stage of the primary tumour were the only predictive variables of the final outcome  
class4	pattern of urological malignancy in zambia  a hospital based histopathological study  the pattern of urological malignancy among the indigenous population of zambia  determined on the basis of histopathological reports from a major national hospital during an 8 year period  is presented  a total of 6514 malignancies were observed  of which 784  12   were of urological origin  bladder carcinoma  predominantly squamous type  was the commonest urological tumour  51    followed by carcinoma of the prostate  26    carcinoma of the penis  18    renal tumours  4 3   and testicular malignancy  0 7    in nearly 32  of the bladder tumours  bilharzial ova were demonstrated histopathologically  nephroblastoma accounted for 70  of the renal tumours and from a total of 7 cases of testicular tumours 5 were embryonal carcinoma and 2 seminoma  a brief reference is made to the pattern and aetiology of urological malignancies in some neighbouring countries  
class4	clinical significance of the  palpable mass  in patients with muscle infiltrating bladder cancer undergoing cystectomy after pre operative radiotherapy  between 1976 and 1985  132 patients with t2 t3 t4a bladder cancer underwent cystectomy after pre operative radiotherapy  46 gy  67 patients  20 gy  65 patients   after a median time of 41 months  62 patients were alive  51 had died from recurrent bladder cancer and 19 from intercurrent disease without recurrence of their malignancy  distant metastases developed in 40 patients  accompanied in 5 cases by local recurrence  local recurrence was the first sign of relapse in 11 patients  in 3 patients the localisation of the relapse remained unknown  the corrected 5 year survival rate was 60   t category and a palpable bladder tumour were independent pre treatment prognostic factors in a cox regression analysis  together with the interval between initial diagnosis and cystectomy  the presence of a palpable tumour before the start of treatment was associated with a particularly poor prognosis in t3 t4a tumours  whereas the survival of patients with non palpable t3 t4a tumours was similar to that of patients with t2 bladder cancer  another important prognostic factor was post irradiation stage reduction  no residual muscle infiltration in the cystectomy specimen   significantly more patients with non palpable bladder tumours experienced post radiation stage reduction than did those with a palpable tumour  however  the prognostic value of stage reduction was statistically significant only in patients with palpable bladder tumours  
class4	adjuvant topical chemotherapy versus immunotherapy in primary superficial transitional cell carcinoma of the bladder  in a prospective randomised controlled study  the efficacy of ethoglucid was compared with that of keyhole limpet haemocyanin  klh  in preventing recurrent tumours following transurethral resection of primary superficial transitional cell carcinoma of the bladder  patients treated with ethoglucid  n   39  received 0 565 g  1  solution  ethoglucid weekly for 6 weeks and then monthly for 1 year  patients treated with klh  n   38  were immunised subcutaneously with 1 mg klh  bladder instillations of 30 mg were then given weekly for 6 weeks and thereafter monthly for 1 year  the recurrence rates  disease free intervals and tumour progression rates were evaluated  the end point of the study was either progression in stage or grade or more than 1 recurrence during the observation period  the minimum length of follow up was 1 year  the recurrence rates  mean disease free intervals and progression rates in the 2 groups showed no statistically significant differences  
class4	short term radiotherapy as palliative treatment in patients with transitional cell bladder cancer  we report the results and complications of treatment with palliative  short term radiotherapy in 162 elderly or disabled patients  improvement in tumour associated symptoms was noted in 75 of these patients and 72 survived for more than a year  those who responded to radiotherapy had a 5 year cancer free survival rate of 58  compared with 4  in patients who did not respond to treatment  survival was also affected by stage and indications for radiotherapy  in 85 patients without severe symptoms  where the tumour was judged curable but the patient was unsuitable for a full course of radiotherapy  the 5 year cancer free survival rate was 21   which is in accordance with what can be achieved with full course radiotherapy  42  had various minor acute side effects  the 5 year late complication rate was 7   
class4	indications for the surgical treatment of osteomas of the frontal and ethmoid sinuses  sixty one patients with an osteoma of the frontal or ethmoid sinuses have been studied  the following indications for surgical removal of these osteomas are suggested  osteomas extending beyond the boundaries of the frontal sinus  if enlarging  if localized in the region adjacent to the nasofrontal duct  if signs of chronic sinusitis are present  osteomas of the ethmoid sinuses  irrespective of their size and if patients with osteomas complain of headache and other causes of headache have been excluded  the operation of choice is the osteoplastic flap operation  
class4	the reliability of palpation in the assessment of tumours  there is now a joint uicc ajc classification for cervical lymph nodes based mainly on the size of the nodes  there is a recognized error in palpation  not only for detecting the presence of tumour but also its size  this study used an animal tumour model system to compare the ability of 6 independent observers of varying experience to detect and stage superficially transplanted growths  a preclinical medical student was as good as a consultant ent surgeon in predicting the presence of tumour but the ability to stage tumours accurately was related to experience  whilst the most experienced observers accurately estimated the size of tumours less than 2 cm  they were less accurate for larger  greater than 2 cm  tumours which were constantly understaged  this phenomenon may have important clinical implications particularly related to current nodal staging criteria  
class4	cyclic amp binding proteins in the head and neck  results are presented of a preliminary study in which camp binding activity was measured in 34 specimens from a variety of head and neck sites  a wide range of camp binding protein levels was detected in all tissues assessed  there appeared to be a subgroup of parotid adenomas with increased camp binding activity  the biological significance of these proteins remains to be determined and their relationship to tumour growth in the head and neck is likely to be complex  
class4	occupational exposure and head and neck carcinoma  an epidemiological case control study was conducted to investigate occupational risk factors in cancers of the upper respiratory and digestive tract  cases were men with squamous cell carcinoma of the oropharynx  667   hypopharynx  348   glottis  246   supraglottis  219   epilarynx  204   and 4 subsites of the oral cavity  787   controls were healthy patients or patients with cancer of another site or another histological type  147 men   past occupational exposures of cases and controls were compared  the analysis was performed independently for each site of cancer  controlling for age  amount and type of alcohol and tobacco consumption  and state of dentition  results showed that cancer of the supraglottis was associated with exposure to oil and grease  odds ratio   2 4  95  confidence interval 1 0 5 8   and with exposure to cement  odds ratio   4 2  95  confidence interval   1 1 16 4   cancer of the glottis was also associated with exposure to dye  odds ratio   6 4  95  confidence interval   0 7 56 6   exposure to flour occurred more frequently among controls than among patients with pharyngeal or oral cancer  this might reflect an association between this occupational exposure and some particular types of cancer included in the control group  
class4	nuclear medicine in otolaryngology  nuclear medicine has a distinct role to play in otolaryngological practice  accurate diagnosis of endocrine conditions is now possible using precise in vitro hormone measurement  specific clinical questions can be answered using in vivo investigations  99mtco 4 123i scintigraphy is used to evaluate thyrotoxicosis and solitary thyroid nodules  99mtc 201t1 subtraction scanning is of value in the preoperative localization of parathyroid adenomas and 99mtco 4 is particularly useful in assessing salivary and lachrymal gland function and drainage  99mtc mdp bone scanning is useful in the evaluation of osteomyelitis  temporomandibular joint dysfunction  bone graft viability and some facial fractures  the role of radioisotopes in the management of differentiated and medullary carcinoma of the thyroid is now well established  although there are many other agents available to image head and neck cancer  few can actually achieve the required diagnostic sensitivity and specificity  the introduction of monoclonal antibodies into routine imaging has been hampered by distinct practical problems and the search is now on for more sensitive non specific diagnostic agents  it is now possible to evaluate new 99mtc labelled tumour imaging agents using animal tumour model systems and the use of radioactivity in all aspects of otolaryngological research adds an extra quantitive dimension  together with spect  and the introduction of positron emission tomography  pet  to image the physiology of normal tissues and tumours  the use of radionuclide investigations can lead only to an increase in ent diagnostic sensitivity and specificity and  subsequently  to an overall improvement in the way we diagnose  stage and treat head and neck cancer  
class4	epidemiology of primary osteogenic sarcoma in the san francisco bay area of california  this epidemiologic study represents an analysis of all registered new cases of osteogenic sarcoma  ogs  during the 14 year period from january 1973 to december 1986 in five san francisco bay counties  inclusion into the study was limited to patients who were diagnosed in the first three decades of life and who were residents within the bay area at the time of diagnosis  to determine epidemiologic characteristics of ogs  records on 96 patients from the bay area resources for cancer control with histologically proven ogs were reviewed  the incidence of ogs was influenced by age  gender  and race  but none of the effects were statistically significant  a geographic variation in the incidence of ogs was discovered  although it was not statistically significant  the results are presented in support of a continued search for environmental variables that may someday reveal the etiologic factors of ogs  
class4	spontaneous necrosis in osteosarcoma  the percentage of necrosis in a primary osteosarcoma after the patient has received preoperative chemotherapy is prognostic and is usually used to select subsequent chemotherapy  however  the percentage of necrosis that occurs spontaneously  without preoperative chemotherapy  has not been adequately studied  the examination of histologic macrosections of 76 osteosarcomas from patients who had not received preoperative treatment and of 20 patients who had received preoperative chemotherapy revealed a significant difference in the percentage of necrosis  there was minimal spontaneous necrosis  but necrosis after preoperative chemotherapy was usually extensive  the larger the tumor  the greater the percentage of spontaneous necrosis  however  size did not correlate with the percentage of necrosis with preoperative chemotherapy  survival among those patients who did not receive preoperative treatment correlated with the size and percentage of necrosis  necrosis in an osteosarcoma in a patient who has received preoperative chemotherapy can be considered the result of chemotherapy and not a spontaneous event  
class4	solitary fibromatosis of bone  a rare variant of congenital generalized fibromatosis  congenital generalized fibromatosis is part of the spectrum of the fibromatoses of infancy and childhood  the lesions are usually multiple and fibrous in nature  they may appear in virtually every organ outside the central nervous system  congenital generalized fibromatosis can be limited to the skeleton and rarely manifests itself as a solitary bone lesion  solitary osseous lesions often behave differently than multiple osseous lesions  solitary lesions often do not regress without treatment and can have a high incidence of recurrence with less than marginal excision  multiple osseous lesions often regress without treatment  
class4	assessment of  squamous cell carcinoma antigen   scc  as a marker of epidermoid carcinoma of the anal canal  we measured squamous cell carcinoma antigen  scc  in epidermoid carcinoma of the anal canal in 66 patients  samples were taken at diagnosis  before treatment  and during follow up  353 samples were analyzed  the positive threshold was taken as 2 ng ml  at diagnosis  the sensitivity of the marker was 44 percent and its specificity 92 percent  in our series  the pretherapeutic level of scc does not correlate with t as in papillons  clinical staging system  but it does correlate with nodal invasion  p less than 0 05   it is of no prognostic value at the time of diagnosis  during follow up  at relapse the level of scc is 20 3     43 ng ml  this increase is significant  p less than 0 01   the sensitivity of the marker is 77 percent  in patients who have relapsed  development of the illness correlates with the level of scc  which is of prognostic value  p less than 0 01   in conclusion  the level of scc should be associated with the clinical follow up of patients with epidermoid carcinoma of the anal canal  
class4	anti tumor x anti lymphocyte heteroconjugates augment colon tumor cell lysis in vitro and prevent tumor growth in vivo  cross linking an anti tumor antibody  specific for tumor cell surface antigens  and an anti lymphocyte antibody  specific for the t lymphocyte receptor complex  tcr cd3   produces a heteroconjugate that can direct t cells to lyse tumor cells  we tested the ability of anti tumor x anti lymphocyte  cd3  heteroconjugates to redirect human peripheral blood lymphocytes  pbls  to lyse human colon cancer cells in cytotoxicity assays and in a murine colon tumor model  we demonstrated in vitro  that cultured human pbls alone produced low levels of tumor lysis  but pbls treated with anti tumor x anti cd3 heteroconjugates produced significantly greater tumor cell lysis  p less than 0 0025   similarly  nude mice injected with ls174t human colon cancer cells and treated with cultured human pbls and anti tumor x anti cd3 heteroconjugates survived significantly longer than saline control mice  p less than 0 01   or mice treated with pbls alone  p less than 0 01   or heteroconjugates alone  p less than 0 05   f ab  2 heteroconjugates were equally as effective in prolonging animal survival  but irrelevant heteroconjugates and monoclonal anti tumor antibodies showed no therapeutic benefit  anti tumor x anti cd3 heteroconjugates may represent an effective approach to tumor specific cellular immunotherapy  
class4	polyamine levels in healthy and tumor tissues of patients with colon adenocarcinoma  tissue polyamine levels were determined in patients with colon adenocarcinoma to try to identify biochemical indicators able to characterize the growth and the metabolism of human solid tumors  polyamine content was determined in the tumor and in the  healthy  mucosa sampled at different distances within the resection edges  for each patient the polyamine content in the tumor was compared with that in the mucosa  the results demonstrated that the spermidine concentration was higher in the tumor than in the healthy mucosa  the differences were statistically significant  however  spermine in the tumor increased to a lesser degree  no statistically significant differences were observed among these mucosae at different localizations  but the spermine concentration in the mucosa after the tumor showed values very close to those of the neoplasia  
class4	crohn s disease and adenocarcinoma of the intestinal tract  report of four cases  four patients with intestinal adenocarcinoma complicating crohn s disease are reported  the youngest of the four patients was a 21 year old female with a 9 year history of crohn s disease of the terminal ileum as well as of the entire colon  she developed mucus producing moderately differentiated adenocarcinoma in the cecum  of the remaining three patients with crohn s disease  one presented an adenocarcinoma in the ascending colon  one in the rectum and the remaining one in the duodenum  all three colorectal adenocarcinomas originated in areas of high grade dysplasia and all four in areas with chronic transmural inflammation  the review of the literature indicates that a total of 174 small and large bowel cancers occurring in crohn s disease have been recorded  including the four reported herein   the vast majority of the reported cases have been found in the north american subcontinent  only in a few instances were bowel adenocarcinoma and crohn s disease observed in the european continent  it is therefore remarkable that three of our four cases were seen within a period of 12 months  interestingly  six patients having colorectal adenocarcinoma in association with crohn s disease were recently reported from a single hospital in england  the question therefore arises whether our cases and those reported recently from england are unrelated and merely coincidental or whether carcinomas are now also affecting european cd patients  if the latter is the case  the surveillance policy for patients with cd should be reconsidered at this hospital  
class4	isolation and characterization of normal and neoplastic colonic epithelial cell populations  the aim of the present study was to characterize rat mucosal colonic cells harvested from the crypt continuum during differentiation and dimethylhydrazine induced neoplasia  the collection of colonocytes was performed using a modified nonenzymatic isolation procedure based on ca2  chelation and gentle mechanical dissociation  light and electron microscopy histomorphological examinations   3h thymidine incorporation studies  and activity gradients of alkaline phosphatase  thymidine kinase  and cytoskeleton associated protein tyrosine kinase indicated that distinct cell populations were harvested from the various crypt regions in a temporal sequence mirroring their zonal and functional distribution in situ  after dimethylhydrazine administration  marked protein tyrosine kinase activity was noted in colonic cells harvested from upper crypt zones  the misplaced and sustained kinase activity preceded the actual polyp or tumor formation  this observation is consistent with the expansion of colonic proliferative compartments beyond allowable boundaries during the preneoplastic period  companion studies in human colonic epithelial specimens corroborate the findings observed in normal and transformed murine colonocytes  it is believed that the characterization and manipulation of colonocytes using our in vitro model will provide important clues to the molecular events underlying the differentiation program and carcinogenic process in the colonic cell  
class4	ampullary hamartoma  endoscopic diagnosis and treatment  this study shows a patient who presented with intermittent biliary tract obstruction caused by ampullary hamartoma  endoscopic retrograde cholangiopancreatography showed a large ulcerated papilla and dilated biliary ducts  tissue diagnosis was established by a large particle biopsy obtained with a snare  the patient underwent a successful endoscopic sphincterotomy and has remained symptom free for 4 years  
class4	prosthetic arthroplasty of the knee after resection of a sarcoma in the proximal end of the tibia  a report of sixteen cases  the results of a specific type of prosthetic reconstruction of the knee  total replacement arthroplasty  after resection of a sarcoma of the proximal part of the tibia in sixteen patients were retrospectively reviewed  the diagnosis was stage iib osteogenic sarcoma in nine patients  stage iib malignant fibrous histiocytoma in three patients  and stage ib sarcoma of various types in four patients  the length of tibial resection ranged from 100 to 257 millimeters  of the eleven patients who were available for functional examination  mean duration of follow up  sixty three months   three patients had an excellent result  seven had a good result  and one had a fair result  of the five patients who were not available for functional testing  one who was doing well was lost to follow up at eighty months  one had died of metastases at sixteen months  and three had had a secondary amputation for infection or for loosening of the prosthesis  
class4	a human cd5  b cell clone that secretes an idiotype specific high affinity igm monoclonal antibody  we previously demonstrated the occurrence of a naturally arisen human anti idiotypic b cell clone  that we transformed with ebv  ebv383   we show evidence that ebv383 not only expresses the cd5 surface ag  but also contains the 2 7 kb mrna transcript encoding this protein  in addition  we show the presence of the 3 6 kb mrna precursor  most ig produced by cd5  b cells are polyreactive natural igm antibodies encoded by unmutated copies of germline vh genes  however  in this study we present data demonstrating the monoreactive high affinity character of the anti idiotypic antibody  mab383  produced by ebv383  these data are in agreement with our previous observations  showing that the vh chain of mab383 is encoded by an extensive somatically mutated vhv gene in a way that is consistent with an ag driven immune response  a possible role for this remarkable anti idiotypic antibody in the maintenance of b cell memory is discussed  
class4	mhc restricted recognition of autologous melanoma by tumor specific cytotoxic t cells  evidence for restriction by a dominant hla a allele  autologous melanoma specific ctl recognize a common tumor associated ag  taa  in the context of hla class i antigens  we have demonstrated that hla a2 can be a restricting ag and  in t cell lines homozygous for hla a2  that ctl can be generated by stimulation with hla a2 allogeneic melanomas  in the current study  we have investigated t cell lines from patients who are heterozygous at hla a region locus  to determine the relative importance of each a region allele in this mhc restricted recognition of tumor  we have shown that hla a1 can be a restricting ag  and that allogeneic melanomas expressing hla a1 can substitute for the autologous tumor in the generation of hla a1 restricted ctl  however  when t cell lines express both hla a1 and hla a2  the hla a2 allele governed restriction of the melanoma taa  three autologous stimulated hla a1  a2 ctl lines all demonstrated restriction by the hla a2 allele  when examined in cytotoxicity assays  cold competition assays  and proliferation assays  there was no evidence of restriction by the second hla allele  hla a1  although the autologous stimulated ctl use a single a region allele for tumor recognition  the autologous hla a1  a2 tumors are lysed by both hla a1 restricted and hla a2 restricted ctl  the dominance of restricting alleles was further demonstrated when hla matched allogeneic melanomas were used as the stimulating tumor to generate tumor specific ctl  stimulation of the heterozygous  hla a1  a2  lymphocytes with hla a2 matched allogeneic melanomas resulted in ctl specific for the autologous tumor  and restricted by the hla a2 ag  however  stimulation with an hla a1 matched allogeneic melanoma failed to induce tumor specific ctl restricted by the hla a1 ag  the data suggest there is a dominance of hla a region ag at the level of the t cell  such that only one is restricting in the recognition of the autologous melanoma  at the level of the tumor  however  the taa is expressed in the context of both hla a region alleles  we can generate specific ctl from lymph node cells or pbl and hla a region matched allogeneic melanomas  however  because most patients are heterozygous at the hla a region locus  an understanding of the dominant restricting alleles must be obtained so that an appropriately matched allogeneic melanoma can be selected  
class4	cytotoxic t cell clones isolated from ovarian tumor infiltrating lymphocytes recognize multiple antigenic epitopes on autologous tumor cells  ctl clones were developed from tumor infiltrating lymphocytes  til  from the ascites of a patient with ovarian carcinoma by coculture of til with autologous tumor cells and subsequent cloning in the presence of autologous tumor cells  these ctl clones expressed preferential cytolytic activity against autologous tumor cells but not against allogeneic ovarian tumor cells and the nk sensitive cell line k562  the cytolytic activity of these ctl against autologous tumors was inhibited by anti tcr  wt31 mab   anti hla class i  and anti cd3 mab but not by the nk function antibody leu 11b  cloning of the autologous tumor cells in vitro revealed that the ctl clones of the ovarian til expressed differential abilities to lyse autologous tumor cell clones  the specificity analysis of these autologous tumor specific ctl suggested that they recognize several antigenic determinants present on the ovarian tumor cells  our results indicate the presence of at least three antigenic epitopes on the tumor cells  designated ova 1a  ova 1b  and ova 1c   one of which  ova 1c  is unstable  these determinants are present either simultaneously or separately  and six types of ovarian clones can be distinguished on the basis of their expression  these results indicate that ctl of the til detect intratumor antigenic heterogeneity  the novel heterogeneity identified within the ovarian tumor cells in this report may be of significance for understanding cellular immunity in ovarian cancer and developing adoptive specific immunotherapeutic approaches in ovarian cancer  
class4	evidence for the functional binding in vivo of tumor rejection antigens to antigen presenting cells in tumor bearing hosts  spleen cells of balb c mice bearing a syngeneic csa1m fibrosarcoma were treated with anti thy 1 2 antibody plus c  yielding a t cell depleted  apc containing fraction  the apc containing fraction was first tested for its capacity to present exogenous modified self or another tumor  meth a  ag after in vitro pulsing  the results showed comparable ag presenting capacities to those obtained by apc containing fraction from normal spleen cells  indicating that apc function is not affected in tumor bearing mice  we next examined whether apc from csa1m bearing mice bind endogenously generated csa1m tumor ag onto its surfaces to stimulate tumor specific t cells  five rounds of inoculation of apc containing fraction from csa1m bearing mice without further in vitro pulsing resulted in the induction of potent anti csa1m immune resistance  the involvement of anti csa1m t cells in the induction of anti csa1m immunity was excluded by the fact that the in vivo immunity was excluded by the fact that the in vivo immunity was delivered by thy 1  cell depleted  but not by thy 1  cell enriched fractions of spleen cells from csa1m bearing mice  moreover  the failure of sephadex g10 passed spleen cells to deliver anti csa1m resistance demonstrated the absolute requirement of apc for inducing the in vivo immunity  finally  this in vivo resistance was found to be tumor specific  because apc fractions from csa1m bearing and meth a bearing balb c mice induced immune resistance selective against the corresponding tumor cell challenge  these results indicate that apc from tumor bearing hosts can not only exert unaffected apc function against exogenous ag  but also function to present tumor ag generated endogenously in the tumor bearing state and to produce tumor specific immunity in vivo  
class4	multiple spinal epidural metastases  an unexpectedly frequent finding  in a prospective study  patients with known malignant disease who were suspected of having a spinal epidural metastasis  had myelography which was not confined to the clinically suspected site  but included at least the whole lumbar and thoracic spinal canal  fifty four of the 106 myelograms revealed at least one epidural metastasis  twelve of these 54 myelograms showed two separate lesions  and four myelograms showed three separate lesions  in all 16 cases with multiple lesions at least one of the lesions was asymptomatic at the time of the diagnosis  it is concluded that multiple spinal epidural metastases are of common occurrence and occur in about one third of the cases  this finding may have important clinical implications  examination of the spinal canal for epidural metastases should not be confined to the clinically suspected site  but should include as extensive an area as possible of the spinal canal  whatever technique is to be used  
class4	touch and surgical division of the anterior quadrant of the spinal cord  an investigation was carried out to determine whether tactile sensibility was affected by anterolateral cordotomy  there were 65 patients who had cordotomies for painful forms of cancer  thirty eight had necropsy examination with histological investigation of the spinal cord  no form of mechanoreception was removed in any of the 65 patients and in the majority no forms of tactile sensibility were altered by division of the pathways in the anterolateral and anterior columns  in no case was graphaesthesia affected  knowledge of joint position and movement and awareness of vibration was normal in 62 of the 65 patients  but information carried by these anterolateral pathways does reach neural levels of consciousness  for with total lesions of the posterior columns  previously reported  touch and pressure are still felt  itch was removed by division of the anterolateral pathways  although the posterior columns are essential for discrimination in mechanoreception  discrimination may be disturbed by lesions of the anterolateral pathways  notably two point discrimination  the evidence on the pathways essential for conveying impulses giving rise to tickle was inconclusive  
class4	diagnostic value of anti neuronal antibodies for paraneoplastic disorders of the nervous system  the diagnostic value of the presence of anti neuronal antibodies in serum was examined in 21 patients suspected of paraneoplastic disorders of the nervous system  ns   group 1  and was compared to three control groups  group 2  25 patients with a neurological disease  without cancer and no sign of paraneoplastic disorder  group 3  27 patients with neurological disease and cancer and no signs of a paraneoplastic disorder  group 4  94 patients with cancer and without neurological disease  in group 1  anti neuronal nuclear antibodies were detected in eight patients  38    in titres from 1 1000 to 1 32 000  a small cell lung cancer was present in six patients  ovarian cancer in one patient and in one patient no tumour could be detected  the neurological symptoms preceded a diagnosis of cancer in five out of eight patients  anti neuronal antibodies were found in the serum of two out of 94 patients  2   from control group 3 but not in serum from any of the other control groups  these data indicate a moderate sensitivity of 38   but a high specificity of 98 6   95  confidence interval 95 5 99 8   for the presence of anti neuronal nuclear antibodies if a paraneoplastic ns disorder is suspected  
class4	gemistocytic astrocytomas  a reappraisal  although gemistocytic astrocytomas are considered slow growing astrocytomas  they often behave aggressively  to clarify the biological and clinical behavior of these rare tumors  the authors retrospectively identified 59 patients with gemistocytic astrocytoma whose tumors were diagnosed and treated between june  1976  and july  1989  three patients who were lost to follow up review were excluded  as were two whose original slides could not be obtained and three whose tumors were diagnosed at recurrence or at autopsy  the pathological material of the remaining 51 patients was reviewed using two sets of histological criteria  thirteen patients  group a  had  pure  gemistocytic astrocytoma  defined as a glial tumor with more than 60  gemistocytes high power field and a background of fibrillary astrocytes  fifteen patients  group b  had  mixed  gemistocytic astrocytoma  defined as a glial tumor with 20  to 60  gemistocytes high power field and a background of anaplastic astrocytes  twenty three tumors did not meet these criteria and were excluded from analysis  the median age of the patients was 48 5 years in group a and 38 3 years in group b  p less than 0 05   in both groups  the median karnofsky performance scale score was greater than 90   all patients underwent surgical procedures  four total and 19 partial resections  and five biopsies  and postoperative radiation therapy  the majority also had interstitial brachytherapy  chemotherapy  or both  ten patients had one reoperation for tumor recurrence and one had two reoperations  other treatments for recurrence included brachytherapy  chemotherapy  and repeat irradiation  all four patients who originally underwent gross total resection are still alive  all five who had a biopsy have died  there was no significant difference in median survival times between groups  136 5 weeks in group a  range 10 to 310  weeks  and 135 6 weeks in group b  range 31 to 460  weeks   analysis of all 28 patients showed a better prognosis for patients less than 50 years of age  185 vs  36 weeks survival time  p less than 0 001   patients with preoperative symptoms lasting for more than 6 months  228 1 vs  110 2 weeks survival time  p less than 0 05   and patients with seizures as the first symptom  185 7 vs  80 weeks survival time  p less than 0 01   survival time did not correlate with the presence of perivascular lymphocytic infiltration  the authors conclude that the presence of at least 20  gemistocytes in a glial neoplasm is a poor prognostic sign  irrespective of the pathological background  it is proposed that gemistocytic astrocytomas be classified with anaplastic astrocytomas and treated accordingly  
class4	improved survival with the use of adjuvant chemotherapy in the treatment of medulloblastoma  between 1975 and 1989  108 children with newly diagnosed medulloblastoma primitive neuroectodermal tumor  mb pnet  of the posterior fossa were treated at the authors  institution  the patients were managed uniformly  and treatment included aggressive surgical resections  postoperative staging evaluations for extent of disease  and craniospinal radiation therapy with a local boost  beginning in 1983  children with mb pnet were prospectively assigned to risk groups  those with  standard risk  mb pnet were treated with radiation therapy alone  while those in the  poor risk  group received similar radiation therapy plus adjuvant chemotherapy with 1  2 chloroethyl  3 cyclohexyl 1 nitrosourea  ccnu   vincristine  and cisplatin  the 5 year actuarial disease free survival rate for all patients treated between 1975 and 1982 was 68   and 73  when patients who died within 2 weeks after operation were excluded  this survival rate was statistically better for patients treated after 1982  82   compared to those treated between 1975 and 1982  49    p less than 0 004   there was no difference in disease free survival rates over time for children with standard risk factors  however  there was a significant difference in the 5 year survival rate for poor risk patients treated prior to 1982  35   compared to those treated later  87    p less than 0 001   for the group as a whole  a younger age at diagnosis correlated with a poorer survival rate  however  this relationship between age and outcome was significant only for children treated before 1983  p less than 0 001   these results demonstrated an encouraging survival rate for children with mb pnet  especially those treated with aggressive surgical resection followed by both radiation therapy and chemotherapy  the results strongly suggest that chemotherapy has a role for some  and possibly all  children with mb pnet  
class4	interstitial chemotherapy with drug polymer implants for the treatment of recurrent gliomas  malignant gliomas have been difficult to treat with chemotherapy  the most effective agent  bcnu  carmustine   has considerable systemic toxicity and a short half life in serum  to obviate these problems  a method has been developed for the local sustained release of chemotherapeutic agents by their incorporation into biodegradable polymers  implantation of the drug impregnated polymer at the tumor site allows prolonged local exposure with minimal systemic exposure  in this phase i ii study  21 patients with recurrent malignant glioma were treated with bcnu released interstitially by means of a polyanhydride biodegradable polymer implant  up to eight polymer wafers were placed in the resection cavity intraoperatively  upon completion of tumor debulking  the polymer releases the therapeutic drug for approximately 3 weeks  three increasing concentrations of bcnu were studied  the treatment was well tolerated at all three levels  there were no adverse reactions to the bcnu wafer treatment itself  the average survival period after reoperation was 65 weeks for the first dose group  64 weeks for the second dose group  and 32 weeks for the highest dose group  the overall mean survival time was 48 weeks from reoperation and 94 weeks from the original operation  the overall median survival times were 46 weeks postimplant and 87 weeks from initial surgery  eighteen  86   of 21 patients lived more than 1 year from the time of their initial diagnosis and eight  38   of 21 patients lived more than 1 year after intracranial implantation of the polymer  frequent hematology  blood chemistry  and urinalysis tests did not reveal any systemic effect from this interstitial chemotherapy  since the therapy is well tolerated and safe  a placebo controlled clinical trial has been started  the trial will measure the effect of the second treatment dose on survival of patients with recurrent malignant glioma  
class4	characterization of astrocytomas  meningiomas  and pituitary adenomas by phosphorus magnetic resonance spectroscopy  phosphorus magnetic resonance  mr  spectroscopy allows noninvasive measurement of phosphate containing compounds and ph within brain cells  the authors obtained localized phosphorus mr spectra from 10 normal brains  four low grade astrocytomas  six glioblastomas  four meningiomas  and three pituitary adenomas and found differences in the spectra of each tumor type  compared to normal brain  the spectra from low grade astrocytomas showed a significant reduction of the phosphodiester  pde  peak  glioblastomas were characterized by a significant reduction of the pde peak  elevation of the phosphomonoester  pme  peak  and a relatively alkaline intracellular ph  the spectra from meningiomas and pituitary adenomas were markedly different from the glial tumors  meningiomas showed significant reductions in phosphocreatine  pde  and inorganic phosphate  as well as a relatively alkaline ph  pituitary adenomas resembled meningiomas  but had a much higher pme peak  although the number of tumors studied was small  there appears to be a characteristic spectrum associated with these different tumor types  the present findings can be useful in the preoperative identification of these tumors and in furthering understanding of their growth and metabolism in vivo  
class4	tethered cord syndrome from a choristoma of mullerian origin  case report  the authors report a case of tethered cord syndrome due to a choristoma of mullerian origin located in the spinal cord at the lumbosacral junction  two similar cases were found upon review of the literature  the embryology of this lesion is discussed  
class4	intradural chordoma of the tentorium cerebelli  case report  a rare case of intradural chordoma is described  the literature contains seven examples of intradural extraosseous chordoma  all reported in a ventral location  this is the first reported case of a primary intradural chordoma distant from the clivus and involving both the supra  and infratentorial compartments  
class4	hemangiopericytoma of the sciatic nerve  case report  the authors report the case of a hemangiopericytoma arising in a sciatic nerve  it was found to be invasive within the epineurium but sparing surrounding tissues  adequate resection required sacrifice of the nerve  hemangiopericytomas can be added to the short list of mesodermal peripheral nerve tumors  
class4	a vascular malformation mimicking an intracanalicular acoustic neurilemoma  case report  a patient with an enhancing  completely intracanalicular mass on magnetic resonance imaging was operated on for a presumed acoustic neurilemoma  but was found at surgery to have an intracanalicular vascular malformation  this rare lesion should be distinguished from angiomatous change within an acoustic neurilemoma and in the past has been termed  vascular tumor    hemangioma   or  fibro angioma   the clinical distinctions between intracanalicular acoustic neurilemomas and intracanalicular vascular malformations and the ability of magnetic resonance imaging to distinguish between the two are discussed  
class4	dose dependency of time of onset of radiation induced growth hormone deficiency  growth hormone  gh  secretion during insulin induced hypoglycemia was assessed on 133 occasions in 82 survivors of childhood malignant disease  all had received cranial irradiation with a dose range to the hypothalamic pituitary axis of 27 to 47 5 gy  estimated by a schedule of 16 fractions over 3 weeks  and had been tested on one or more occasions between 0 2 and 18 9 years after treatment  results of one third of the gh tests were defined as normal  gh peak response  greater than 15 mu l  within the first 5 years  in comparison with 16  after 5 years  stepwise multiple linear regression analysis showed that dose  p   0 007  and time from irradiation  p   0 03   but not age at therapy  had a significant influence on peak gh responses  the late incidence of gh deficiency was similar over the whole dose range  4 of 26 gh test results normal for less than 30 gy and 4 of 25 normal for greater than or equal to 30 gy after 5 years   but the speed of onset over the first years was dependent on dose  we conclude that the requirement for gh replacement therapy and the timing of its introduction will be influenced by the dose of irradiation received by the hypothalamic pituitary axis  
class4	biphasic reduction and concanavalin a binding properties of serum alpha fetoprotein in preterm and term infants  reference values for postnatal serum alpha fetoprotein  afp  and concanavalin a  cona  binding subfractions of afp in preterm and term infants are presented  preterm infants had 10 fold higher serum concentrations of afp than did term infants at birth  the reduction of serum values of afp was biphasic in both groups and differed significantly between the two groups  the first declining phase continued for approximately 4 months in preterm and for 2 months in term infants  and was related to the degree of prematurity  the afp values reached adult levels by 12 months in preterm and by 9 months in term infants  the developmental pattern of the carbohydrate moiety of afp was determined by cona fractioning  the proportion of the cona nonreactive subfraction of afp in preterm and term infants at birth was 6  and 13   respectively  it increased more rapidly in term than in preterm infants but reached 85  to 95  by the age of 6 months in both infant groups  our results indicate that the postnatal maturation of afp synthesis is dependent on gestational age  malignant recurrences of neonatal sacrococcygeal teratomas were associated with an increase in serum concentration of afp and a decrease in the proportion of the cona nonreactive subfraction of afp  
class4	carcinoma of the vulva  clinicopathologic factors involved in inguinal and pelvic lymph node metastasis  eighty five women with vulvar squamous cell carcinoma were subjected to radical vulvectomy with bilateral inguinal and femoral node dissection or to radical vulvectomy with bilateral inguinofemoral and deep pelvic node dissection  the association between lymph node status  metastatic or not  and several parameters was analyzed  tumor location  size and clinical stage  tumor thickness  histologic grade and mitotic index  blood vessel  lymphatic and perineural infiltration  and lymphocytic and plasma cell infiltrates  there were no metastases to the pelvic lymph nodes without previous inguinal lymph node involvement  unilateral vulvar carcinomas did not have contralateral metastatic nodes when there was no ipsilateral nodal involvement  lymphatic vessel infiltration showed a statistically significant correlation with inguinal node metastases  p less than  05   no correlation was found between lymph node metastasis and tumor size  clitoral invasion  tumor thickness  histologic grade  blood vessel and perineural infiltration  lymphocytic and plasma cell infiltrates  and mitotic index  
class4	human papillomavirus in women with vulvar intraepithelial neoplasia iii  untreated cases of vulvar intraepithelial neoplasia  vin  iii may progress to invasive vulvar carcinoma  tissues from 29 new zealand women with vin iii were examined for the presence of human papillomavirus  hpv  types 6  11  16 and 18 by in situ hybridization and polymerase chain reaction  hpv 16  the only hpv type detected in the lesions  was identified in about half the cases  hpv positive women were younger than hpv negative women  and their lesions displayed koilocytosis more often  in four of five cases in which there was a progression to invasive cancer  hpv 16 was detected in both the vin iii and invasive cancer tissue  
class4	deep femoral lymphadenectomy with preservation of the fascia lata  preliminary report on 42 invasive vulvar carcinomas  forty two patients with primary invasive vulvar carcinoma were treated with radical vulvectomy and deep femoral lymphadenectomy with preservation of the fascia lata and cribriform fascia  the rationale for using this technique was based on anatomic knowledge of the topographic distribution of groin lymph nodes  which was confirmed by the study of 50 cadavers  the preliminary data show that the number of superficial and deep femoral lymph nodes removed from the 42 patients  mean number of nodes  20  range  8 32  was similar to the number reported in anatomy books  in addition  the five year actuarial survival rate  70   was comparable to that in the literature  these preliminary results suggest that the surgical technique used in this study is as radical an oncologic procedure as way s classic groin lymphadenectomy  which consists of removing the fascia lata and cribriform fascia  
class4	performing cytogenetic studies on ascitic  amniotic and hygroma fluid  the importance of obtaining cytogenetic studies on antenatally diagnosed structural malformations is well recognized  in two cases  three fetal compartments were sampled  each resulting in successful cytogenetic studies  fluid was obtained under ultrasound guidance from amniotic fluid  fetal ascites and cystic hygroma fluid  fluid from the hygroma itself may be the easiest compartment to analyze  
class4	breast self examination in relation to the occurrence of advanced breast cancer  two hundred nine female enrollees of the group health cooperative of puget sound who developed advanced stage breast cancer during the period 1982 1988 were interviewed about their practice of breast self examination  bse   use of other breast cancer screening modalities  and medical and reproductive histories  each subject s description of how she performed the examination was scored according to her mention of up to 10 recommended bse techniques  a random sample of 433 women without advanced stage breast cancer from the same population was interviewed for comparison  relative to women not practicing bse  the risk of advanced stage breast cancer among bse users was 1 15  95  confidence interval  0 73 1 81   frequency of bse did not differ between women with advanced stage breast cancer and control subjects  whether in all subjects or in subgroups defined by age  use of mammography  or frequency of clinical breast examinations  while self described proficiency in bse was generally low in both case and control subjects  the small percentage of women reporting more thorough self examinations  regardless of frequency  had about a 35  decrease in the occurrence of advanced stage breast cancer compared to women who did not perform bse  these results suggest that  while carefully performed bse may avoid the development of some advanced stage breast cancers  bse as practiced by most seattle area women is of little or no benefit  
class4	preoperative chemotherapy  cisplatin and fluorouracil  and radiation therapy in stage iii non small cell lung cancer  a phase ii study of the lung cancer study group  the lung cancer study group conducted a phase ii pilot study of concurrent chemotherapy and radiation therapy  chemoradiotherapy  before surgery in 85 eligible patients with non small cell cancer limited to the chest but in whom attempted resection would have been likely to leave residual disease  advanced stage iiia and minimal stage iiib disease   cisplatin  75 mg m2  was given on days 1 and 29  fluorouracil  1 g m2 per 24 hours  was administered as a continuous infusion on days 1 through 4 and on days 29 through 32  and thoracic radiation  30 gy in 15 fractions  was administered on days 1 through 19  two patients achieved a complete response and 46 patients had a partial response for an overall response rate of 56   toxicity from chemoradiotherapy was moderate but acceptable  eight weeks after therapy was initiated  54 patients underwent thoracotomy and tumor resection was attempted  29  34   had complete resection and 15  18   had incomplete resection  although surgical dissection was generally more difficult than in patients not pretreated with chemoradiotherapy  there was no apparent increase in postoperative complications  in 8 patients  9    no viable tumor was detected pathologically in the resection specimen  of the 18 patients whose tumors were completely resected and had disease recurrence  none had recurrence only in the chest  12  67   had recurrence only in distant sites  and 3 developed second primary tumors  median survival of all patients was 13 months  the overall results do not indicate a major benefit from this preoperative chemoradiotherapy regimen in patients with advanced but potentially resectable non small cell lung cancer  these results suggest a need to define better the relative roles of preoperative radiotherapy and chemotherapy  
class4	expression of the antimetastatic gene nm23 in human breast cancer  an association with good prognosis  the nm23 gene was identified in murine melanoma cells  in which its expression is associated with the cells  metastatic potential  expression of nm23 has been detected in human breast tumors by means of hybridization and immunocytochemistry  we measured nm23 mrna in 71 patients with primary breast cancer and found variable levels of nm23 expression  the nm23 gene was expressed at higher levels in well differentiated tumors  p less than  02   there was a significant inverse relationship between nm23 expression and nodal status  p less than  02   expression of nm23 was positively associated with longer disease free survival and overall survival  and the relationships were significant  p less than  002 and p less than  003  respectively   this study showed that nm23 expression in human breast cancer was associated with good prognosis and a lack of lymph node metastasis and suggests that the nm23 gene product may play an important role in suppressing the metastatic phenotype  
class4	pathologic fracture through a solitary enchondroma of the radial diaphysis  case report  solitary enchondromata are rare but well recognised benign bone tumours  they are extremely rare in the radius  we report the case of a pathologic fracture through a solitary enchondroma in the radial diaphysis and its successful treatment  
class4	microscopic pulmonary tumor embolism causing subacute cor pulmonale  a difficult antemortem diagnosis  published erratum appears in mayo clin proc 1991 apr 66 4  439  microscopic pulmonary tumor embolism is difficult to diagnose  the most common initial clinical symptom is subacute progressive dyspnea  and the initial laboratory evaluation typically shows hypoxemia in a patient with clear lung fields on a chest roentgenogram  another distinguishing feature may be hepatic abnormalities  in general  pulmonary angiography discloses no evidence of emboli  but multiple subsegmental peripheral perfusion defects are noted on ventilation perfusion lung scans  the diagnosis of microscopic pulmonary tumor embolism can be confirmed by open lung or transbronchial lung biopsy or by microvascular pulmonary cytology  a less invasive procedure that could be performed at the time of pulmonary angiography  herein we describe two patients with unsuspected microscopic pulmonary tumor embolism that eventuated in subacute cor pulmonale and death  these cases illustrate the characteristic findings of this entity and emphasize the need for early diagnosis  
class4	oxygen exacerbated bleomycin pulmonary toxicity bleomycin is an antineoplastic agent with potential for producing pulmonary toxicity  attributed in part to its free radical promoting ability  clinical and research experiences have suggested that the risk of bleomycin induced pulmonary injury is increased with the administration of oxygen  we report a case in which the intraoperative administration of oxygen in the setting of previous bleomycin therapy contributed to postoperative ventilatory failure  our patient recovered with corticosteroid therapy  physician awareness of a potential interaction between oxygen and bleomycin may help reduce the morbidity and mortality related to bleomycin therapy  
class4	progressive coma after the transsphenoidal decompression of a pituitary adenoma with marked suprasellar extension  report of two cases  two cases of neurological deterioration and coma after the transsphenoidal decompression of a pituitary adenoma with marked suprasellar extension and invasion of the 3rd ventricle are presented  emergency ventricular shunting led to prompt neurological improvement  which  supplemented by radiation therapy  allowed long term amelioration of symptoms  three possible explanations for this complication are offered  1  traction of the attached 3rd ventricle into the decompression site  causing increased obstructive hydrocephalus  2  vasopressin release by surgical manipulation of the pituitary stalk and circumventricular organs causing cerebral edema  and 3  edema in the residual tumor secondary to surgical manipulation causing further hydrocephalus  subsequent patients with similar clinical and imaging criteria will have a planned perioperative ventricular shunting procedure performed  
class4	ectopic retinoblastoma within the 3rd ventricle  case report  ectopic intracranial retinoblastomas are rare  these tumors usually occur in the pineal  parasellar  or suprasellar regions several years after the successful treatment of ocular retinoblastomas with no evidence of direct extension or distant metastasis  we report here a case of ectopic retinoblastoma occurring within the third ventricle  the tumor was surgically excised by the transventricular approach  ectopic retinoblastomas exhibit greater differentiation than one would expect to observe in a metastatic lesion of this tumor  the distinction of ectopic retinoblastomas and metastasis from ocular retinoblastomas is important  since ectopic retinoblastomas  unlike metastasis  can be successfully managed by intensive therapy including radical excision  
class4	long term follow up of patients with recurrent malignant gliomas treated with adjuvant adoptive immunotherapy  between august 1986 and october 1987  the denver brain tumor research group conducted a clinical trial using autologous human recombinant interleukin 2  ril 2  activated lymphocytes to treat 20 patients with recurrent high grade gliomas  the trial involved surgical resection and or decompression followed by intracavitary implantation of lymphokine activated killer  lak  cells and autologous stimulated lymphocytes  asl  along with ril 2 in a plasma clot  one month later  stimulated lymphocytes and ril 2 were infused through a rickham reservoir attached to a catheter directed into the tumor bed  the lak cells were ril 2 activated peripheral blood lymphocytes cultured for 4 days  the asl were lectin  and ril 2 activated peripheral blood lymphocytes cultured for 10 days  of the 20 patients treated  11 were evaluated as a group  mean age  44 years  range  15 61 years  mean karnofsky rating  69  range  50 100  mean decadron dose at entry  14 mg d  range  0 32   the average number of lymphocytes implanted was 7 6 x 10 9   range  1 9 27 5 x 10 9   together with 1 to 4 x 10 6  u of ril 2  to date  10 of the 11 patients died  all from recurrent tumor growth  the median overall survival time was 63 weeks  range  36 201  mean  86   the median survival time after immunotherapy was 18 weeks  range  11 151  mean  39   no significant difference in survival after immunotherapy was found between those patients who had received previous chemotherapy and those who had not  the use of steroids or prior chemotherapy did not influence the in vitro generation of asl or lak cells  
class4	immunohistochemical study of erythropoietin in cerebellar hemangioblastomas associated with secondary polycythemia  although cerebellar hemangioblastomas are known to be associated with secondary polycythemia  the cellular derivation of erythropoietin  epo  in hemangioblastomas still remains obscure  specimens from 18 patients with cerebellar hemangioblastomas were immunohistochemically studied using anti epo monoclonal antibody  eight cases of brain tumors  including 2 meningiomas  2 medulloblastomas  2 glioblastomas  and 2 metastatic brain tumors were studied as controls  in 9 of 18 cases  epo positive cells were scattered around the capillaries and were ultrastructurally shown to be mast cells  these cases were not  however  associated with secondary polycythemia  in contrast  the stromal cells were positive for epo in 3 cases  among them  one was associated with secondary polycythemia  furthermore  one half of the control cases of brain tumor contained epo positive mast cells  accordingly  it was suggested that mast cells  or small granulocytes  have little relationship to the release of epo  however  some stromal cells might release epo with a resultant polycythemia  
class4	disposition of cerebral metastases from malignant melanoma  implications for radiosurgery radiosurgery is becoming more generally available and indications for its use continue to be defined  cerebral metastases from malignant melanoma are often treated with whole brain irradiation  but with limited benefit  innovative treatments  such as radiosurgery  make possible the delivery of doses of radiation that are higher than usual  to determine how many patients might be candidates for radiosurgery  a retrospective analysis of computed tomographic brain scans performed on 41 patients with cerebral metastases from malignant melanoma was undertaken  one third of these patients were found to have cerebral metastases amenable to a radiosurgical approach  as illustrated radiation dose volume histograms  patient and tumor characteristics suggest that this series is represent with cerebral metastases from malignant melanoma  the implications of radiosurgery for normal tissue radiation tolerance and its effects on melanoma are discussed  
class4	the transoral approach for the management of intradural lesions at the craniovertebral junction  review of 7 cases  the main difficulty in dealing with intradural lesions located ventrally in the region of the craniovertebral junction  cvj  is related to their relative inaccessibility  posterolateral approaches involve some manipulation of the brain stem and provide limited access because of the necessity of working between the cranial nerves  even then  the view of the ventral midline and across is limited  the transoral approach  which has been widely used for the management of extradural lesions in this area  is also useful for the treatment of intradural lesions  it provides an unimpeded although somewhat restricted  view of the ventral aspect of the cvj without the need for brain retraction  the cranial nerves and vertebral arteries are not interposed between the surgeon and the lesion  the risks of cerebrospinal fluid leakage and infection are greatly diminished by the use of fibrin adhesive and prolonged diversion of the cerebrospinal fluid  the use of this approach  together with its technical difficulties and results  in the management of seven purely intradural lesions located ventrally at the cvj  is discussed  
class4	improved access to lesions of the central skull base by mobilization of the zygoma  experience with 54 cases  improved access to lesions at the medial end of the sphenoid wing or in the interpeduncular cistern after mobilization of the zygoma has been a subject of growing interest in recent years  this study describes the operative technique we have adopted and records our experience with 55 operations in 54 patients who underwent the procedure in the past 3 years  seven patients had vascular lesions  44 had tumors  and 3 had miscellaneous lesions  the majority of the tumors were medial meningiomas  and particular note is made of those arising from the cavernous sinus with respect to their resectability  sixteen of these tumors were encountered  and total excision was possible in 11 cases  access to the infratemporal fossa is facilitated  and in 2 cases we were able to excise completely trigeminal neuromas that had extended there  the extra maneuver adds little to the overall operating time  and complications relating to it are uncommon  mild in degree  and usually self limiting  we conclude that the operation is extremely valuable in appropriate circumstances  
class4	submandibular cystic hygroma resembling a plunging ranula in a neonate  review and report of a case  cystic hygromas are large lymphangiomas that are most often found in the posterior triangle of the neck and the axilla in children  they are most frequently found before age 2 and may be massive  after upper respiratory infection  they may become infected and enlarged  causing dysphagia and toxemia  the diagnosis can usually be made by history and physical examination and confirmed by biopsy  treatment is by surgical excision of small lesions and staged debulking excisions in more severe cases  a patient with a cystic hygroma having many clinical characteristics of a plunging ranula is presented  the cyst fluid was aspirated and analyzed for its amylase  sodium  potassium  chloride  urea nitrogen  glucose  and total protein content  the characteristics of the fluid were also compared with those of lymph and saliva  this report demonstrates the difficulty in determining the diagnosis of a tumor that has the clinical features of a cystic hygroma  as well as a plunging ranula  the necessity of a proper presurgical diagnosis is essential since the form of therapy for each is different and conflicting  a method that distinguishes between the cervical cystic hygroma and a plunging ranula by means of aspirated fluid is discussed  
class4	hiv infection  clinical features and treatment of thirty three homosexual men with kaposi s sarcoma  the clinical findings of patients with oral kaposi s sarcoma are reviewed  these oral findings commonly included candidiasis  hairy leukoplakia  gingivitis associated with human immunodeficiency virus  hiv   periodontitis  and other symptoms  including xerostomia  the other common symptoms of hiv disease that may be of importance in leading to a diagnosis are reviewed in this patient group  treatment by local radiotherapy or by intralesional vinblastine of these oral kaposi s sarcomas resulted in successful palliation  with more than 50  regression of the lesions in 80  of the patients treated  
class4	effect of antileukemia chemotherapy on marrow  blood  and oral granulocyte counts  this study was designed to elicit the effects of antileukemia chemotherapy on marrow production  blood carriage  and oral extravasation of granulocytes  and on the phagocytic activity of those harvested from the mouth  fifteen adult patients with various morphologic forms of acute leukemia were followed through one to four courses of chemotherapy  oral saline rinse samples were obtained thrice weekly and prepared for enumeration in a hemocytometer  the oral granulocyte counts were compared with concurrent counts in the bone marrow and peripheral blood  phagocytic activity of the oral granulocytes was measured by the method of smith and rommel  the 15 patients were followed through 30 courses of chemotherapy and recovery  during each  there was a drug induced decrease in marrow  blood  and oral granulocytes that was reversed when therapy was discontinued and bone marrow activity was restored  phagocytic activity of the oral granulocytes was not perceptibly affected by the antileukemic drugs  oral granulocyte counts provide a noninvasive method for monitoring the onset and recovery of chemotherapy induced myelosuppression and granulocytopenia in patients with leukemia  
class4	melanocytic hyperplasia of the oral mucosa  lesions that exhibit melanocytic hyperplasia are uncommon in the oral mucosa  they are even more rare than the various morphologic types of nevomelanocytic lesions  this article reports the clinicopathologic features of oral lesions diagnosed as lentigo simplex  junctional lentigo   jentigo    atypical melanocytic hyperplasia  melanoma in situ   and melanocanthoma  the proper terminology for these lesions is also discussed  
class4	ectopic thyroid tissue in the submandibular region  this report describes an unusual location of ectopic thyroid gland tissue  a growth in the left submandibular area was surgically excised  and the microscopic examination of the specimen revealed thyroid tissue with colloid goiter  because this entity cannot be clinically distinguished from a salivary gland tumor  ectopic thyroid tissue should be considered in the differential diagnosis of swellings involving the submandibular area  
class4	orofacial metastasis of pulmonary giant cell carcinoma  a patient was admitted to the hospital with multiple skin nodules of recent origin and signs and symptoms suggestive of acute pulmonary infection  because one of the skin masses was located overlying the left mandibular body region  the patient was referred to the hospital dentistry clinic for evaluation  historical  clinical  and radiographic assessments were consistent with reactive lymphadenopathy  and an intraoral excisional biopsy was performed  the biopsy results were indicative of giant cell carcinoma  which was confirmed by biopsy results from a similar skin lesion on the shoulder and by malignant cells recovered in the sputum and pleural fluids  although this carcinoma has been shown to rarely metastasize to the skin and lymphatics of the neck  this is the first case report of metastasis to facial lymphatics  
class4	blue rubber bleb nevus syndrome with oral hemangiomas  a case of blue rubber bleb nevus syndrome with oral hemangiomas is reported  attention is directed to this syndrome because  although rare  it is usually associated with oral lesions  the blue rubber bleb nevus syndrome should always be considered a possibility in patients with oral hemangiomas and bluish skin nodules  
class4	early diagnosis of breast cancer  universal screening is essential  breast cancer strikes 1 in 10 women in the united states  early diagnosis of breast cancer improves chances of survival  with universal screening and expert evaluation of early clinical signs and symptoms of breast cancer  mortality rates can be reduced by 30  to 40   physicians can help achieve this goal by taking an active role in patient education and promoting the availability of affordable screening mammography  
class4	nipple discharge in women  is it cause for concern  nipple discharge is one of the most common breast complaints in women  galactorrhea  milky discharge  may occur during pregnancy or breast feeding or as a result of drug therapy  hypothyroidism  or hyperthyroidism  nonbloody discharge is most common and is usually benign  bloody discharge should be considered a sign of cancer until proved otherwise  persistent galactorrhea and nonbloody discharge can be treated by transecting the mammary ducts  simple mastectomy may be appropriate in patients with persistent bloody discharge who have a strong family history of breast cancer  
class4	ct and mr imaging in staging non small cell bronchogenic carcinoma  report of the radiologic diagnostic oncology group  the accuracies of magnetic resonance  mr  imaging and computed tomography  ct  in determining tumor classification and assessing mediastinal node metastases were compared in a prospective cooperative study of 170 patients with non small cell bronchogenic carcinoma  the sensitivity of ct in distinguishing t3 t4 tumors from t0 t2 tumors was 63   specificity was 84   these values for mr imaging were not significantly different  56  and 80    with receiver operating characteristic  roc  analysis  no difference existed between the accuracies of ct and mr imaging in diagnosis of bronchial involvement or chest wall invasion  but mr imaging was significantly more accurate than ct  p    047  in diagnosis of mediastinal invasion  lymph node sampling was performed in 155 patients  642 node stations   cancerous nodes were found in 14  of stations in 21  of patients  there was no significant difference between the accuracies of ct and mr imaging in detecting mediastinal node metastases  n2 or n3   the sensitivities were 52  and 48   respectively  and specificities were 69  and 64   roc analysis also showed no difference between ct and mr imaging  
class4	primary ct diagnosis of abdominal masses in a pacs environment whether the display medium  film versus cathode ray tube  crt   affects observer performance during interpretation of computed tomographic  ct  images is an important research issue in these times of implementation and growth of picture archiving and communications systems in radiology  the authors performed a multiobserver receiver operating characteristic  roc  study to determine the performance of radiologists who read abdominal ct studies displayed on film  as well as on a high resolution workstation  video monitor  that made use of three different display modes  a total of 166 examinations were evaluated by eight radiologists  who recorded their ordinal confidence ratings of the demonstration of presence or absence of abdominal masses  roc analysis showed small differences in the confidence ratings assigned by individual readers for the detection and interpretation tasks  results for the group as a whole showed no significant reduction or improvement in observer performance when ratings for any one of the workstation display modes were analyzed  the results of this study demonstrate that current crt display technology is adequate for enabling the primary detection of abdominal masses with ct examinations  
class4	zollinger ellison syndrome  prospective assessment of abdominal us in the localization of gastrinomas  the ability of abdominal ultrasound  us  to help localize gastrinomas was prospectively studied in 79 patients with zollinger ellison syndrome  the results were assessed by means of laparotomy  autopsy  or percutaneous liver biopsy  for hepatic gastrinoma  us had a sensitivity of 63  and a specificity of 100   with a positive predictive value of 100  and a negative predictive value of 89   us was slightly less sensitive for detecting gastrinoma in the liver than were computed tomography  ct   66   and selective angiography  78    for detection of extrahepatic gastrinoma  us had a sensitivity of 30   a specificity of 94   a positive predictive value of 100   and a negative predictive value of 25   us enabled detection of tumor in eight cases not detected with ct and in four not detected with angiography  specificity for extrahepatic gastrinoma was similar for all three modalities  89  95    ct and us were equally effective for the detection of extrahepatic gastrinoma  and angiography was significantly more effective than both us and ct  p less than  01   the authors conclude that us  although of low sensitivity  remains useful as the initial imaging modality in patients with zollinger ellison syndrome  
class4	oral magnetic particles in mr imaging of the abdomen and pelvis  two phase 2 clinical trials of an oral superparamagnetic contrast agent for enhancement on magnetic resonance images of the intestine were performed  in trial 1  31 male patients with cancer of the testis underwent follow up examinations of the abdomen at 0 5 and 1 5 t after oral administration of magnetic particles  in trial 2  31 female patients with pelvic and lower abdominal disease were examined at 1 5 t after administration of the contrast material  the patients each ingested 800 ml of contrast material over approximately 2 hours  concentrations of 0 25 and 0 5 g l did not induce blurring or metallic artifacts  distribution was homogeneous through the gastrointestinal tract  in all patients  a loss of signal intensity was observed on proton density   t1   and t2 weighted images  the diagnostic information from postcontrast images in trial 2 was greater in 16 patients  52    contrast enhancement was independent of field strength  no major side effects were observed  artifacts from moving bowels were less troublesome  and delineation of intraabdominal and pelvic organs was better with the use of oral magnetic particles  
class4	capsular transgression of prostatic carcinoma  evaluation with transrectal us with pathologic correlation  one hundred twenty five patients with biopsy proved clinical stage a or b prostatic carcinoma were evaluated with biplane transrectal ultrasonography  us  prior to radical prostatectomy  sonograms were evaluated for capsular transgression of the tumor into the posterior and posterolateral aspects of the glands as manifested by local contour deformity and irregularity or interruption of the periprostatic fat echoes  correlation of the findings at us with the findings at pathologic examination of the step sections was obtained  and the presence and depth of capsular penetration were assessed  of the 250 halves or hemispheres of the prostate gland that were evaluated  capsular penetration was seen at pathologic examination in 86  us enabled correct identification of pericapsular tumor spread in 59 of the 86 hemispheres but did not depict pericapsular tumor spread in 27 hemispheres  absence of pericapsular tumor spread was verified at pathologic examination in 149 of the 164 hemispheres that either did not have tumor or did not show pericapsular tumor spread  pericapsular tumor spread was incorrectly diagnosed in 15 hemispheres  a positive us diagnosis of pericapsular tumor spread correlated moderately well with the depth of penetration demonstrated at pathologic examination  transrectal us is an effective noninvasive procedure that demonstrates the presence of prostatic cancer  
class4	prostate cancer  local staging with endorectal surface coil mr imaging  endorectal surface coil magnetic resonance  mr  imaging was used to stage the local extent of prostate cancer in 22 patients  the endorectal coil images were acquired with a 10 12 cm field of view and a 4 mm section thickness  all pathologic specimens were reviewed by one pathologist  endorectal surface coil mr imaging was 82  accurate in the differentiation of stage b from stage c cancer  one case was overestimated  and three cases were underestimated  the three underestimated cases consisted of two cases of microscopic capsular invasion and one case of minimal seminal vesicle invasion  in a comparison of retrospective  blinded readings of endorectal coil and body coil images  there was an average improvement in accuracy of 16  in staging prostate cancer with endorectal coil images  
class4	combined gadolinium enhanced and fat saturation mr imaging of renal masses  combined gadopentetate dimeglumine enhancement and fat saturation  fs  spin echo  se  magnetic resonance  mr  imaging for the detection and characterization of renal masses was evaluated in 43 patients with a total of 71 lesions  28 solid masses and 43 cysts   se mr sequences compared were the following  short repetition time  tr  echo time  te   conventional se  short tr te fs se  long tr te conventional se  gadolinium enhanced short tr te conventional se  and gadolinium enhanced short tr te fs se techniques  mr findings were compared with findings of contrast enhanced computed tomography  ct  and with pathologic findings in all patients  the sensitivities for detection of renal masses with gadolinium enhanced fs  71 of 71 lesions  and with gadolinium enhanced short tr te conventional  65 of 71 lesions  se sequences were significantly  p less than  01  greater than with any unenhanced  short tr te conventional  40 of 71 lesions   or long tr te  39 of 71 lesions   se sequence  lesion characterization was also best with the gadolinium enhanced fs se sequence  65 of 71 lesions correctly classified   when combined pre  and postcontrast short tr te fs se images were analyzed with both qualitative  visual  and quantitative  region of interest measurements  assessment  lesion characterization improved even further  70 of 71 lesions were correctly characterized   all lesions detected with ct were visualized with the gadolinium enhanced fs se mr sequence  which in addition depicted seven cysts and two small renal cell carcinomas  in summary  the use of gadopentetate dimeglumine  especially when combined with the fs technique  was superior to unenhanced mr imaging for detection and characterization of renal lesions  
class4	epithelial tumors of the ovary  ct findings and correlation with us  one hundred thirty patients with 170 epithelial ovarian tumors were prospectively studied with computed tomography  ct  before surgery  ultrasound  us  was performed in 108 patients with 138 tumors  at pathologic examination  78 tumors  46   were benign  14  8   borderline  and 78  46   malignant  ct results were compared with surgical and pathologic findings in all patients  ct enabled detection of 148 of 170 tumors  87    and us enabled detection of 118 of 138 tumors  86    benign serous cystadenomas  n   42  were correctly characterized with a sensitivity of 69  at ct and 70  at us  benign mucinous cystadenomas  n   21  were correctly characterized with a sensitivity of 62  at ct and 50  at us  malignancy was suggested in nine of 14 patients  64   with borderline tumors at ct and in five of 14  36   at us  the overall accuracy of characterization of benign versus malignant tumors  including borderline tumors  was 94  with ct and 80  with us  in the 108 patients studied with both ct and us  the sensitivity of ct was significantly superior to that of us  p less than  03   whereas there was no significant difference in specificity  p    125   
class4	lesions that manifest as medial cheek and nasolabial fold masses  seventeen cases were collected in which the patient presented with a medial cheek or nasolabial fold mass  most of these lesions were uncommon  and some were rare  the most reliable differentiating finding was the type of associated bone involvement  the malignancies had bone erosion and as a group could be distinguished from the other masses  computed tomographic attenuation and magnetic resonance imaging signal intensities were nonspecific and did not allow a definitive diagnosis to be made  the types of pathologic conditions and their sectional imaging findings are reviewed  
class4	intraoperative i 125 seed implantation for extensive recurrent head and neck carcinomas  from 1978 to 1988  41 patients with extensive recurrent carcinomas of the head and neck were treated with surgical resection plus intraoperative iodine 125 seed implantation  surgery was performed to resect the tumors and to expose the tumor beds for implantation  i 125 seeds were implanted intraoperatively  with a spacing of 0 75 1 cm between adjacent seeds  either into the soft tissue in the tumor bed or onto small patches of gelatin sponges to cover the bone  nerve  or blood vessel involved with disease  reconstructive flaps were used in 18 patients  the average i 125 dose delivered by the implanted seeds was 8 263 cgy  the determinate 5 year actuarial survival rate for the entire group was 40   the 5 year local disease control rate was 44   major complications were transient wound infection  32    flap necrosis  24    fistula formation  10    and carotid blowout  5    these results indicate that surgical resection plus i 125 seed implantation provides a potentially curative treatment for patients with extensive recurrent head and neck carcinomas that would be considered traditionally unresectable and that would be treated only with palliative therapy  
class4	carcinoma of the head of the pancreas  optimal treatment for unresectable carcinoma of the pancreas remains controversial  this study was done to examine the relationship between perioperative jaundice and postoperative morbidity  and type of palliative biliary bypass and postoperative morbidity and jaundice clearance  seventy six patients with obstructive jaundice secondary to carcinoma of the head of the pancreas were studied  forty nine patients underwent one of four different types of palliative bypass  1  cholecystojejunostomy  n   22   2  choledochojejunostomy  n   11   3  choledochoduodenostomy  n   9   and 4  cholecystoduodenostomy  n   7   age  sex and preoperative health status were similar for all operative groups  as well as for those with and without postoperative morbidity  the postoperative complication rate was 33 per cent and there was one postoperative death  length of preoperative jaundice and peak preoperative bilirubin levels were independent of morbidity  postoperative morbidity was similar for each type of bypass used and no significant difference was found when cholecystoenteric  1 and 4  and choledochoenteric  2 and 3  bypass were compared  the results of this study support the view that postoperative morbidity is not directly related to the presence of jaundice preoperatively  furthermore  the rate of jaundice clearance and the occurrence of postoperative complications are not dependent on the type of bypass used  
class4	the value of symptom directed evaluation in the surveillance for recurrence of carcinoma of the breast  specific postoperative tests used to diagnose recurrent carcinoma of the breast were evaluated for their ability to have an impact on the over all course of the disease  sixty four patients with recurrent or new contralateral primary disease were divided into two groups based on the method of diagnosis  those patients with a new complaint at an interval between scheduled follow up visits and who went on to have tests to document a recurrence were categorized as interval follow up  those who were seen at a prearranged regular follow up period and received tests as recommended by the attending physician or surgeon and had a documented recurrence were classified as routine follow up  thirteen patients presented with new contralateral primary disease and 51 with metastatic disease  16  bone  13  lung  11  local  three  liver  and eight  multiple   the median time to discovery of recurrence from the primary treatment was 29 and 28 months for the interval and routine groups  respectively  ninety per cent of the failures occurred by 53 months  the survival time after recurrence was significantly greater in those patients diagnosed routinely  p   0 003   however  the over all survival time  from primary therapy to death  was only significantly improved for the routine group when the contralateral new primary diseases were included  p   0 009   the method of diagnosis of a contralateral primary carcinoma was physical examination and mammogram  strong recommendations for follow up testing can be limited to mammogram and physical examination  
class4	trends in thirty years of vaginal hysterectomy  vaginal hysterectomy  as currently performed at the university of vienna  was first described by halban in 1932  from 1955 to 1985  a total of 9 967 hysterectomies were performed  the vaginal route was used for 6 078  60 9 per cent  of these procedures  sixty four per cent of the women operated upon were multiparous  27 per cent were uniparous and 8 per cent were nulliparous  a comparison of the periods 1955 to 1975 and 1976 to 1985 revealed the following trends  the incidence of uterine myomas  30 6 to 27 1 per cent   in situ carcinoma of the cervix  6 5 to 7 9 per cent  and endometrial carcinoma  1 4 to 0 6 per cent  remained largely constant  in the past decade  indications for positional abnormalities  uterine descent and prolapse  were encountered more often  27 6 to 41 6 per cent  than in the first observation period  while the incidence of recurrent metrorrhagia was found to decline  33 9 to 22 8 per cent   the most common complications included hemorrhage during the operation  lesions of the bladder  hemorrhage until 48 hours after surgical treatment and hemorrhage from days 2 to 14 postoperatively  around 0 5 per cent  respectively   during the second observation period  no postoperative fistulas developed  two instances of tubal prolapse were seen  laparotomy was done in four of 6 078 instances  two patients died of septic complications  whenever possible  we prefer vaginal hysterectomy because of its low complication rate  low mortality rate and low postoperative morbidity  
class4	axillary lymphadenectomy for intraductal carcinoma of the breast  during a ten year period  175 axillary lymph node dissections were done as part of the treatment for intraductal carcinoma of the breast  98 patients were treated with modified radical mastectomy and 77 were treated by mammary preservation  consisting of excision of the lesion  axillary dissection and radiation therapy  one of 175 axillary node dissections yielded positive nodes  axillary dissection for intraductal carcinoma of the breast is unlikely to yield involved nodes and is not indicated for use in most instances  it should be reserved for lesions demonstrating microinvasion  
class4	an analysis of the results of mammographically guided biopsies of the breast  three hundred and fifty three women underwent 358 biopsies of the breast for nonpalpable mammographic lesions during a five year period  cancer was identified in 95  27 per cent   mammographic findings in the patients with cancer were calcifications only  54 per cent   a mass  27 per cent   a mass with calcifications  15 per cent   an asymmetric distortion  1 per cent  and an asymmetric distortion with calcifications  3 per cent   cancer was identified in 29 per cent of the biopsies done for calcifications  20 per cent of those done for a mass with calcifications  6 per cent of those done for an asymmetric distortion and 38 per cent of those done for an asymmetric distortion with calcifications  forty nine per cent of the mammographically suspicious calcifications were cancer  while 100 per cent of the indeterminate calcifications were benign  forty five per cent of the spiculated masses were cancerous  while only 3 per cent of the circumscribed masses were malignant  for those patients with carcinoma undergoing axillary lymph node dissection  13 per cent had one or more positive nodes  a strategy for increasing the effectiveness of mammographically guided biopsies of the breast is presented  
class4	modified technique of pringle s maneuver in resection of the liver  crushing of the hepatic parenchyma with hepatic clamps to minimize blood loss during resection of the liver leads to mechanical damage of hepatocytes  pringle s maneuver may precipitate liver failure by hepatic warm ischemia as well  therefore  we controlled bleeding from the surface of the resection by using light compression on the hepatic parenchyma with a band while applying a hepatic arterial clamp at the hepatic hilus  this vascular control method can be done because the portal pressure is about one tenth of the hepatic artery pressure and provides an efficient and harmless transection of the liver  
class4	iron and the liver  iron is essential for life  but iron overload is toxic and potentially fatal  the liver is a major site of iron storage and is particularly susceptible to injury from iron overload  especially when  as in primary hemochromatosis  the iron accumulates in hepatocytes  iron can be taken up by the liver in several forms and by several pathways including   1  receptor mediated endocytosis of diferric or monoferric transferrin or ferritin   2  reduction and carrier facilitated internalization of iron from transferrin without internalization of the protein moiety of transferrin   3  electrogenic uptake of low molecular weight  non protein bound forms of iron  and  4  uptake of heme from heme albumin  heme hemopexin  or hemoglobin haptoglobin complexes  normally  pathway 2 is probably the major one for uptake of iron by hepatocytes  iron is stored in the liver in the cores of ferritin shells and as hemosiderin  an insoluble product derived from iron rich ferritin  iron in hepatocytes stimulates translation of ferritin mrna and represses transcription of dna for transferrin and transferrin receptors  the major pathologic effects of chronic hepatic iron overload are   1  fibrosis and cirrhosis   2  porphyria cutanea tarda  and  3  hepatocellular carcinoma  although precise pathogenetic mechanisms remain unknown  iron probably produces these and other toxic effects by increasing oxidative stress and lysosomal lability  vigorous efforts at diagnosis and treatment of iron overload are essential since the pathologic effects of iron are totally preventable by early vigorous iron removal and prevention of iron re accumulation  
class4	expression of beta 1 integrins in normal human keratinocytes  the majority of cell adhesive events to the extracellular matrix are mediated by cell surface receptors  beta 1 integrins  keratinocytes express at least six different polypeptides of beta 1 integrin class  namely beta 1  alpha 2  alpha 3  alpha 5  and alpha 6  alpha 6 is mainly associated with beta 4 polypeptide   these epithelial cells use alpha 2 beta 1 as a collagen receptor and alpha 3 beta 1 as a fibronectin receptor  while alpha 6 beta 4 is the major basement membrane receptor  expression of alpha 5 beta 1 complex is low  processing of beta 1 integrins is fast in keratinocytes  half maximal maturation takes only 3 hours  in addition to their function in cell matrix interactions  beta 1 integrins  alpha 2 beta 1 and alpha 3 beta 1  have also a role in maintaining keratinocyte cell cell interactions  it is possible that resting basal keratinocytes use beta 1 integrins as cell cell adhesion receptors  and during activation  like in wound healing  these receptors relocalize to mediate events involving cell matrix interactions  
class4	using a state cancer registry to increase screening behaviors of sisters and daughters of breast cancer patients  the pennsylvania cancer registry was used to contact breast cancer patients and  through them  their adult sisters and daughters  the sisters and daughters were counseled concerning their higher than average risks for breast cancer and their need for mammography and breast self examination  results showed a 9 percent increase in mammography and a 10 percent increase in breast self examination rates for the counseled over control group  costs were  49 per counseled sister or daughter indicating a need to increase cost effectiveness before implementation is practical  
class4	subscapular elastofibroma in a young pitcher  a case report  subscapular elastofibromas and scapulothoracic bursitis can cause symptomatic masses in baseball pitchers  both processes appear to represent reactive soft tissue responses to repetitive stress at the inferior border of the scapula  it is assumed that most masses in the subscapular area represent scapulothoracic bursitis rather than an elastofibroma  however  it is possible that some of the masses treated conservatively as scapulothoracic bursitis may be elastofibromas  a study is currently under way to evaluate the incidence of subscapular masses in college and professional pitchers in the united states  a follow up report is anticipated when the study has been completed  the author requests information concerning any confirmed cases of elastofibroma in baseball pitchers  
class4	the glucose transporter and blood brain barrier of human brain tumors  the glucose transporter of the human brain has been localized to endothelial cells expressing the blood brain barrier  but little is known regarding its mechanism of induction or whether its expression is exclusively linked with restricted vascular permeability  we investigated glucose transporter expression by vessels in human astrocytic tumors and pulmonary metastases to the brain using immunohistochemical techniques  vessels in 9 of 10 low grade astrocytomas and 8 of 10 anaplastic astrocytomas were positive for glucose transporter  glioblastoma vessels were transporter positive in only 2 of 10 specimens  vessels in all three metastatic tumors were negative for the glucose transporter  the decrease in transporter expression observed in higher grade tumors occurred independently of increases in vascular permeability  in low grade astrocytomas and glioblastomas transporter expression and contrast enhancement were inversely related  but vessels in 6 of 9 anaplastic astrocytomas were transporter positive despite contrast enhancement  these findings suggest that separate mechanisms induce the glucose transporter and the permeability restrictions of the human blood brain barrier  they also have potential implications for the therapy and prognosis of astroglial neoplasms  
class4	effects of treatment on long term survivors with malignant astrocytomas  we reviewed the records of 160 consecutive patients with glioblastoma and anaplastic astrocytoma to evaluate the long term consequences of radiation therapy and chemotherapy  we defined long term survivors as those patients with glioblastoma or anaplastic astrocytoma who lived at least 100  longer than median survival of historical controls  for example  2 years for patients with glioblastoma and 4 years for patients with anaplastic astrocytoma  there were 9  5 6   long term survivors  three  30   became demented and died without evidence of tumor recurrence  one  after survival of 10 years  died of tumor recurrence  of the remaining survivors  2  22   have significantly impaired short term memory function and other neurological deficits such as gait apraxia  three  30   can function independently  it is likely but cannot be proved that it is radiotherapy and not chemotherapy that is the causal factor of this dismal therapeutic outcome  our study suggests restraint in the use of radiotherapy for patients with brain tumors that have more favorable prognoses than glioblastomas and anaplastic astrocytomas  such as low grade astrocytomas and oligodendrogliomas  
class4	chemotherapy for medulloblastoma primitive neuroectodermal tumors of the posterior fossa  chemotherapy has only marginal efficacy in adult malignant brain tumors  in contrast  drug therapy is considerably more effective in medulloblastoma primitive neuroectodermal tumors  mb pnet  of the posterior fossa  the most common childhood primary central nervous system tumor  at the time of disease recurrence  a variety of different single agents and drug combinations result in tumor shrinkage and increased survival  the addition of chemotherapy to standard radiotherapy improves the rate and length of disease free survival for those children with mb pnet who have the most extensive tumors at diagnosis  it remains to be determined which drug or drug combinations are the most effective in mb pnet  and which patients are most likely to benefit from chemotherapy  chemotherapy may be useful to reduce or  in selected cases  obviate the need for radiotherapy and reduce treatment related sequelae  
class4	general assay for phosphoproteins in cerebrospinal fluid  a candidate marker for paraneoplastic cerebellar degeneration  the components of protein phosphorylation systems  protein kinases  protein phosphatases  and their phosphoprotein substrates  are highly enriched in neuronal cells compared with other cell types  we exploited this relative neuronal enrichment of protein phosphorylation system components to develop a general assay technique for putative protein kinase substrates  phosphoproteins  in human cerebrospinal fluid  using this cerebrospinal fluid phosphoprotein assay  we have detected a putative protein kinase c substrate protein of apparent mr 60 kd in 6 of 14 patients with paraneoplastic cerebellar degeneration but not in any of 55 patients with a variety of other neurological diseases  phosphoproteins in cerebrospinal fluid may provide novel and unique markers for the diagnosis or staging of neuronal diseases as well as offer potential insights into the biochemical characterization of affected neuronal populations  
class4	comparative in vitro activities of newer quinolones against pseudomonas species and xanthomonas maltophilia isolated from patients with cancer  the in vitro susceptibilities of three pseudomonas species  pseudomonas aeruginosa  pseudomonas putida  and pseudomonas fluorescens  and xanthomonas maltophilia to quinolone antimicrobial agents were determined  several newer agents  particularly pd117558  pd117596  pd127391  sparfloxacin  at 4140   a 56620  and temafloxacin  were active against pseudomonas species  x  maltophilia isolates were generally less susceptible than were pseudomonas isolates but were inhibited by some of the newer quinolones  
class4	therapeutic outcome of patients suffering from malignant melanomas of the conjunctiva  eighty one cases of conjunctival melanoma treated between 1960 and 1988 were studied to determine factors that might affect outcome in patients with such lesions  the therapeutic procedures performed were local excision  16   local excision followed by brachytherapy with sr 90 y 90  32   local excision followed by cryotherapy with liquid nitrogen  16   brachytherapy with sr 90 y 90  12   local excision followed by external beam irradiation  3   and local excision followed by brachytherapy and cryotherapy  2   the median follow up period was 5 5 years  longest 26  shortest 1 year   sixty two patients  76 5   showed a complete regression of the melanoma  19  23 5   developed recurrences  and 15  18 5   died from metastases  the melanomas had developed with almost equal frequency from a pre existing naevus  25 9    from primary acquired melanosis  25 9    and  de novo   30 9    small tumours had a higher chance of regressing  80 6   than larger ones  68 6    the cumulative survival rate was 76  after five years and 60  after 10 years from any causes of death and 87 6  after five years and 76 3  after 10 years from deaths caused by metastases  most deaths from metastases occurred within 5 years  at 88 5   the cumulative survival rate of patients with small tumours  less than one quadrant of the bulbar conjunctiva and less than 2 mm thickness  was significantly higher than that of patients with larger tumours  more than one quadrant of the bulbar conjunctiva and or more than 2 mm thickness  with 65  after eight years  local excision followed by beta ray irradiation  sr 90 y 90  or cryotherapy can be recommended as the treatment of choice  nevertheless the behaviour of conjunctival melanomas remains unpredictable in individual cases  
class4	malignant fibrous histiocytoma of the conjunctiva  malignant fibrous histiocytoma  mfh  of the conjunctiva is an extremely rare tumour  and only three previous cases have been reported  we describe two patients with mfh of the conjunctiva  a 58 year old white male with epibulbar tumour who had exenteration and is alive after five years  follow up  and a 3 1 2 year old african girl with xeroderma pigmentosum and an mfh of her right eye conjunctiva  the first reported case of this association  the characteristics and the methods of diagnosis of mfh are discussed  
class4	increased lysis of patient cd10 positive leukemic cells by t cells coated with anti cd3 fab  antibody cross linked to anti cd10 fab  antibody  an anti cd3 fab  x anti cd10 fab  bispecific hybrid f ab  2 antibody  ab  was generated  this bispecific ab had a molecular mass of 100 to 110 kd  and the capacity to react with both cd3  t cells and cd10  acute lymphoblastic leukemia  all  cells  we studied whether cytotoxic t lymphocytes  ctls  could lyse patient cd10  all cells after addition of the bispecific ab  as effector ctls  interleukin 2  il 2  stimulated peripheral blood mononuclear cells  pbmcs  and ctl clones were used  when il 2 stimulated pbmcs were assayed for cytotoxicity to 61cr labeled cd10  all cells  their activity was shown to be markedly enhanced by the addition of the bispecific ab  most of the ctl clones established lacked cytotoxicity for cd10  all cells  but addition of the bispecific ab induced a significant level of cytotoxicity  ctls derived from all patients also showed significant cytotoxicity for autologous cd10  all cells after addition of the bispecific ab  however  this ab did not affect the cytotoxicity of ctls when cd10  leukemic cells were used as the targets  these findings suggest that the bispecific ab can be used for immunotherapy in patients with cd10  all  
class4	philadelphia chromosome and monosomy 7 in childhood acute lymphoblastic leukemia  a pediatric oncology group study  during an 8 year period  3 638 children from institutions of the pediatric oncology group  pog  were diagnosed with acute lymphoblastic leukemia  all   fifty seven patients had philadelphia chromosome positive  ph1  all  blast cells obtained at diagnosis from 13 of these 57 cases  23   were also found to have partial or complete monosomy 7   7   this subgroup of children with ph1  7 all was comprised primarily of older males with early b lineage all  bone marrow specimens from six ph1  7 patients were studied further using the polymerase chain reaction and primers that flank the all  and chronic myelogenous leukemia breakpoints to determine the molecular characteristic of the 9 22 translocation  rearrangements were detected in rna from bone marrow and or peripheral blood cells of six patients  although four were in hematologic remission at the time of the analysis  five cases showed the all breakpoint  while one child with ph1  7 showed the chronic myelogenous leukemia breakpoint  the induction failure rate was much higher in this subgroup  31   as compared with ph1 negative cases  and the projected duration of event free survival reflected the aggressive nature of this subgroup because no children are projected to remain in remission at 2 years  all with both the 9 22 translocation and  7 appears to represent a unique and previously undescribed subgroup of childhood all associated with a particularly adverse outcome  leukemic transformation in such patients may involve the interaction of a dominant oncogene  ph1  and a tumor suppressor gene   7   
class4	preliminary studies for an immunotherapeutic approach to the treatment of human myeloma using chimeric anti cd38 antibody  multiple myeloma is a disease in which conventional chemotherapy has only limited value  but which may be ideal for treatment with passive antibody against a suitable cell surface antigen on the neoplastic plasma cell  the cd38 antigen is known to be present on the majority of neoplastic plasma cells  and this was confirmed by detailed examination of bone marrow aspirates from three patients  strong expression of cd38 was confined to cells which  by the criteria of light scattering profiles and possession of cytoplasmic ig  were plasma cells  the vast majority of neoplastic plasma cells appeared to be involved  using a cell line as a model  it was found that the cd38 antigen acts as a target for a chimeric antibody prepared from the antibody okt10  the chimeric antibody consists of the fab portion of the mouse monoclonal antibody linked by a stable thioether bond to an fc molecule derived from human igg1  thereby forming mouse fab human fc  in contrast to the parent antibody  the chimeric molecule mediates antibody dependent cellular cytotoxicity  adcc  very efficiently with human blood mononuclear effector cells  and is effective at low concentration  also  even though the cd38 antigen is present on natural killer cells  there appears to be little deleterious action of the antibody on effector cell function  the antibody also failed to affect the growth of progenitor cells of the granulocyte macrophage or erythroid lineages present in normal bone marrows  despite the suspicion that these cells express the antigen  other advantages of the cd38 molecule are that it is not found in the serum of patients with myeloma  and it does not appear to modulate in vitro  fourteen patients with florid myeloma and on various chemotherapeutic regimes had an undiminished capacity to mediate adcc with the chimeric antibody  when compared with normal individuals  the maintenance of adcc activity  coupled with the known suppression of the antibody response in these patients  augers well for treatment with chimeric antibody  
class4	nb4  a maturation inducible cell line with t 15 17  marker isolated from a human acute promyelocytic leukemia  m3   acute promyelocytic leukemia  apl  is a well defined entity among acute leukemia  cytogenetically characterized by a t 15 17   q22 q11 12  translocation  in vitro and in vivo studies suggest that all trans retinoic acid  ra  treatment restores cell maturation  we have isolated the first permanent cell line with t 15 17   derived from the marrow of a patient with apl in relapse  the establishment of the cell line  its morphologic  karyotypic  and immunohistochemical features are reported  ra induced cell line maturation  cells strongly expressed myeloid markers  but also some t cell markers  additional karyotypic abnormalities  a 12p rearrangement and the possible presence of a homogeneous staining region  hsr  on 19q  are discussed both in relation to t cell  cd2  cd4  and monocyte  cd9  markers  and to the acquired cell growth autonomy  the cell line represents a remarkable tool for biomolecular studies  
class4	interphase cytogenetic analysis detects minimal residual disease in a case of acute lymphoblastic leukemia and resolves the question of origin of relapse after allogeneic bone marrow transplantation  we used in situ hybridization with a probe for the x chromosome to study interphase cells of bone marrow and peripheral blood specimens from a male patient with acute lymphoblastic leukemia characterized by hyperdiploidy  including trisomy x  in a posttreatment bone marrow specimen  which was interpreted as a regenerating bone marrow morphologically and which demonstrated a normal karyotype cytogenetically  trisomy x was found in 16 of 1 000 interphase cells  this finding indicated the presence of leukemic cells that were undetected by conventional morphologic and cytogenetic techniques  ie  minimal residual disease   cytogenetic studies of a relapse specimen obtained after a sex mismatched bone marrow transplant showed only a normal female karyotype in each of 40 metaphase cells  suggesting that the relapse occurred in donor cells  however  interphase analysis demonstrated trisomy x in more than 80  of interphase cells and indicated that the relapse was of the original clone and was not a transformation of donor cells  this case illustrates that interphase analysis can be useful as an adjunct to conventional cytogenetic analysis in the detection of minimal residual disease and in the analysis of interphase cells that are not accessible to routine cytogenetic methods  it also illustrates that previously reported instances of relapse of leukemia in donor cells could have been incorrect if supported by cytogenetic data alone  
class4	selective hypersensitivity to granulocyte macrophage colony stimulating factor by juvenile chronic myeloid leukemia hematopoietic progenitors  juvenile chronic myelogenous leukemia  jcml  is a good model for the study of myeloproliferation because jcml hematopoietic progenitor cells grow in vitro at very low cell densities without the addition of exogenous stimulus  previous studies have demonstrated that this proliferation is dependent on granulocyte macrophage colony stimulating factor  gm csf   and that removal of monocytes from the cell population before culture eliminates this  spontaneous  myeloproliferation  suggesting a paracrine role of monocyte stimulation  however  subsequent studies have shown that increased gm csf production from the jcml monocytes is not a consistent finding and therefore not a plausible sole mechanism  in examining hematopoietic growth factor dose response curves  both jcml gm and erythroid nonadherent progenitor cell populations displayed a marked and selective hypersensitivity to gm csf  responses to interleukin 3 and g csf were identical to control dose response curves  this is the first demonstration of a myeloid leukemia in which hypersensitivity to a specific growth factor appears to be involved in the pathogenesis of the disease  
class4	expression of intercellular adhesion molecule 1  cd54  on hematopoietic progenitors  the distribution of intercellular adhesion molecule 1  icam 1   a ligand for lymphocyte function antigen 1  on hematopoietic tissue was determined using the anti icam 1 monoclonal antibody cl203 4 with flow cytometry and short term semi solid hematopoietic progenitor cultures  after timed incubation in media with fetal bovine serum  29  of erythroid burst forming units  bfu e   24  of erythroid colony forming units  cfu e   and 52  of granulocyte macrophage colony forming units  cfu gm  bone marrow progenitors expressed icam 1  this finding  which is consistent with the detection of icam 1 on acute non lymphoblastic leukemic blasts  is at variance with recent reports  icam 1 was also detected on bone marrow blasts  proerythroblasts  promyelocytes  and cells of monocyte macrophage lineage  but was not detected on erythroblasts  normoblasts  neutrophilic myelocytes  metamyelocytes  bands  or on most lymphocytes  these results indicate that maturation of cells of the erythroid and myeloid lineage is associated with loss of icam 1  the distribution of icam 1 on bone marrow progenitors  early precursor cells  and accessory cells in conjunction with the function of this molecule in cell cell interactions suggests that icam 1 may play a role in the cell cell and cell stromal interactions that regulate hematopoiesis  
class4	synergistic effects of nerve growth factor and granulocyte macrophage colony stimulating factor on human basophilic cell differentiation  we have recently shown that nerve growth factor  ngf  promotes human granulopoiesis  specifically augmenting basophilic cell differentiation observed in methylcellulose hematopoietic colony assays of human peripheral blood  because the ngf effect was seen in the presence of conditioned medium derived from a human t cell line  mo cm  containing granulocyte macrophage colony stimulating factor  gm csf   we examined interactions of purified ngf and recombinant human gm csf  rhgm csf  on granulocyte growth and differentiation  rhgm csf stimulated a dose dependent increase in methylcellulose colony growth at concentrations between 0 1 u ml and 10 u ml  and in the presence of ngf at 500 ng ml this effect was enhanced  the number of basophilic cell colony forming units  cfu baso  and histamine positive colonies increased synergistically when ngf was added to rhgm csf  furthermore  because mo cm acts with sodium butyrate to promote basophilic differentiation of alkaline passaged myeloid leukemia cells  hl 60  we also examined the interaction of ngf and mo cm or rhgm csf using this assay  in the presence of ngf  mo cm at concentrations of 0 5  to 20  vol vol  and rhgm csf at concentrations of 0 1 u ml to 100 u ml synergistically increased histamine production by butyrate induced  alkaline passaged hl 60 cells  this was associated with the appearance of metachromatic  tryptase negative  ige receptor positive cells  the effects of rhgm csf or mo cm were completely abrogated by a specific anti rhgm csf neutralizing antibody in methylcellulose  with or without ngf  the ngf synergy with rhgm csf in the hl 60 assay was also inhibited by either anti rhgm csf or anti ngf antibody  these studies support the notion that differentiation in the basophilic lineage may be enhanced by ngf acting to increase the number of gm csf responsive basophilic cell progenitors  
class4	tumor necrosis factor regulates the expression of granulocyte macrophage colony stimulating factor and interleukin 3 receptors on human acute myeloid leukemia cells  tumor necrosis factor  tnf  acts as a potent enhancer of granulocyte macrophage colony stimulating factor  gm csf   and interleukin 3  il 3  induced human acute myeloid leukemia  aml  growth in vitro  we have analyzed the effects of tnf alpha on the expression of gm csf and il 3 receptors on aml cells  incubation of blasts from seven patients with aml in serum free medium with tnf  10 3  u ml  and subsequent binding studies using 125i gm csf and 125i il 3 show that tnf increases the specific binding of gm csf  30  to 280   and il 3  40  to 600   in all cases  from scatchard plot analysis it appears that tnf upregulates  1  low affinity gm csf binding sites   2  common high affinity il 3 gm csf binding sites  and  3  unique  non gm csf binding  il 3 binding sites  the effect of tnf is dose dependent and is half maximal at a concentration of 100 u ml  and becomes evident at 18 hours of incubation with tnf at 37 degrees c  but not at 0 degree c  the gm csf dose response curve of aml colony forming units plateaus at a higher level in the presence of tnf  which indicates that additional numbers of cells become responsive to gm csf  incubation of aml blasts with the phorbol ester 12 0 tetradecanoylphorbol 13 acetate or formyl met leu phe  protein kinase c activators  does not influence gm csf receptor expression  suggesting that receptor upregulation by tnf is not mediated through activation of protein kinase c  on the other hand  the protein synthesis inhibitor cycloheximide abrogates receptor upregulation induced by tnf  in contrast to these findings in aml  tnf does not upregulate gm csf receptor numbers on blood granulocytes or monocytes  we conclude that tnf exerts positive effects on growth factor receptor expression of hematopoietic cells  
class4	genetics of common diseases of adulthood  implications for prenatal counseling and diagnosis  genetic factors play an important role in the development of many common diseases of adulthood that result in early morbidity and mortality  prevention of these disorders and their sequelae is best established through early detection and early intervention  although it may be feasible to screen the entire population for some disorders  e g   hypertension   this approach would be expensive and impractical for others  e g   colon cancer   the family history provides an inexpensive and convenient method of identifying families at risk for premature diseases of adulthood  family screening for a disorder should be recommended if there is increased risk for the disorder among family members  if screening methods are available to detect the condition at an early age or preclinical stage  and if early intervention will alter the course of the disease  for many disorders screening and intervention can prevent the occurrence of clinical disease  the prenatal counseling session affords an ideal setting for identifying families at risk for diseases of adulthood with major genetic components  by reviewing the family history  key family members can be identified and investigated  in order to establish a specific genetic diagnosis  at risk relatives can then be counseled and screened for the disorder preclinically and premorbidly  the screening and intervention available for a disease depends on the nature of the disorder  our understanding of its physiology and etiology  and our current technology  the disorders discussed earlier are typical of conditions of adulthood that are influenced strongly by genetic factors  especially when they appear in younger adults  atherosclerosis  colon cancer  and diabetes are complex phenotypes  each can be caused by single gene defects  but commonly the genetics are more complex  empiric data help to establish the risk to an individual in the latter cases  in all three examples  early detection should lead to treatment  which can prevent more serious sequelae  by treating the dyslipidemia  coronary artery disease can be prevented  by removing the benign polyp  malignant cancer can be avoided  and when impaired glucose tolerance is detected  diet and exercise can prevent or delay frank diabetes and its complications  the complete evaluation of individuals at risk for disorders such as those in table 1 and their families can be a complicated task  referral to a center experienced in the genetics of common diseases often may be necessary  abstract truncated at 400 words   
class4	pneumocystis carinii pneumonia complicating multiple myeloma  pneumocystis carinii pneumonia complicated the course of two patients with multiple myeloma  the diagnosis was established in both cases by bronchoalveolar lavage  which demonstrated the typical pneumocysts  clinical and roentgenographic improvement in both patients was observed following a course of trimethoprim sulfamethoxazole  one patient had lymphocyte subsets performed with a cd4 cd8 ratio of 0 8  both patients were hiv antibody negative by elisa  both patients tolerated prophylactic tmp smx given concurrently with the subsequent chemotherapy for myeloma  we suggest that the immune defect seen in multiple myeloma may have placed these patients at risk for opportunistic infections such as p carinii pneumonia  however  as opposed to patients with aids  our patients tolerated therapy with tmp smz quite well  
class4	left atrial bacterial mural endocarditis  an unusual case of staphylococcus aureus endocarditis confined to the mural left atrium is presented  echocardiographic studies revealed a 1 5 x 2 0 cm vegetation mimicking a myxoma situated in the path of a mitral regurgitant jet on a color doppler test  emboli to upper and lower extremities and brain complicated the patient s preoperative course  surgical excision and pathologic examination confirmed this rare occurrence  
class4	central neurogenic hyperventilation in invasive laryngeal carcinoma  we describe a patient with central neurogenic hyperventilation secondary to extension of a laryngeal tumor into the base of the brain  resulting in extrinsic compression of the medulla  such an association has not been previously described  unique features which distinguish this patient from previously reported cases are emphasized  possible mechanisms involved in pathogenesis  as well as types of therapy  are outlined  
class4	ampullary tumor caused by metastatic renal cell carcinoma  in this paper we report the case of a renal cell carcinoma  rcc  metastatic to the ampullary region  the patient presented with severe anemia due to blood loss from the ampullary tumor 11 years after nephrectomy for the primary renal cancer  the diagnosis was established by means of endoscopy and biopsy  
class4	expression of laminin and its receptor lbp 32 in human and rat hepatoma cells  dramatic cellular changes that occur during hepatocarcinogenesis are associated with major alterations in extracellular matrix formation and in the relationships between cells and their microenvironment  we have studied the expression of laminin  the major noncollagenous glycoprotein of basement membrane  and the laminin receptor 32 kd laminin binding protein in two rat  faza 967 and htc  and two human  hepg2 and hbgc2  hepatoma cell lines that express a variety of liver specific functions  laminin was found in the rough endoplasmic reticulum of these cells when the indirect immunoperoxidase method and electron microscopic examination were used  radiolabeled laminin  immunoprecipitated from both media and cell extracts  was resolved by electrophoresis on sodium dodecyl sulfate gel in two major polypeptides that comigrated with the a and b subunits from engelbreth holm swarm tumor laminin  immunoblot analysis showed that the mr   400 000 polypeptide did not correspond to the a subunit of laminin  northern blot analyses demonstrated large amounts of b1 and b2 mrnas but no a chain mrna  we conclude that the tumor cells produce the laminin b chains only  in contrast  normal adult hepatocytes from either man or rat lacked laminin mrnas  whereas in 1 day primary culture  b chain mrnas became detectable  the steady state level of 32 kd laminin binding protein mrna was 10 fold and threefold higher in rat hepatoma cells than in freshly isolated and 1 day cultured normal rat hepatocytes  respectively  in human hepatocytes  the steady state levels of 32 kd laminin binding protein mrnas varied depending on the donor and never reached the level of the human hepatoma cells  
class4	differences in glycolytic capacity and hypoxia tolerance between hepatoma cells and hepatocytes  viability  glycolytic capacity and energy metabolism under anaerobic conditions were studied in the hepatoma cell lines htc  fu5 and hepg2 and in rat and human hepatocytes using glucose and fructose as glycolytic precursors  during 6 hr of anaerobic incubation without additional substrate  viability decreased rapidly in fu5 and htc cells  whereas viability of hepg2 cells was not significantly affected  in all tumor cells  10 mmol l glucose prevented hypoxic cell injury almost completely  lactate formation from glucose was about five times higher than in hepatocytes under these circumstances  atp content of the tumor cells remained almost constant under anaerobic conditions in the presence of glucose  ten millimoles per liter of fructose diminished glycolysis in the hepatoma cells compared with glucose  ranging from 87  reduction in htc cells to 43  reduction in hepg2 cells  accordingly  atp content decreased rapidly in the fu5 and slowly in the hepg2 cells  viability was strongly diminished in the htc and fu5 cells in the presence of fructose  whereas in the hepg2 cells no effect of fructose on viability was detectable  in contrast to the hepatoma cells  rat and human hepatocytes exhibited higher rates of anaerobic glycolysis in the presence of fructose and thus were able to maintain their viability under these conditions  these differences in glycolytic capacity  energy metabolism and hypoxia tolerance of hepatoma cells compared with hepatocytes may be used for the treatment of liver cancer by isolated liver perfusion and ex situ revision of the organ  
class4	cyclosporine enhances the growth of carcinogen induced enzyme altered foci in rat liver  cyclosporine  a powerful immunosuppressant  has been used successfully for organ transplantation  its efficacy on liver transplants of patients with primary hepatic tumors remains controversial because of a high rate of recurrence of the original tumors in the transplanted livers  in this study  we experimentally tested whether cyclosporine exerts any effects on the growth of carcinogen initiated liver cells using the short term assays of rat liver carcinogenesis  dietary cyclosporine  which maintained sufficient levels of blood cyclosporine and suppressed host immune functions  enhanced the development of the glutathione s transferase  placental form positive hepatocyte foci in the liver of male f 344 rats treated with a single weekly dose of diethylnitrosamine  75 mg kg  for 3 wk  dietary cyclosporine also accelerated the growth of preformed glutathione s transferase  placental form positive foci induced by a single dose of diethylnitrosamine  250 mg kg  followed by the promoting regimen of a choline deficient diet  it is possible that the enhancement of the size of hepatocyte foci by cyclosporine could be due to stimulation of growth or inhibition of regression  the mechanisms by which cyclosporine modifies the growth of preneoplastic lesions in the liver are not yet fully understood  possible involvement of immunologically relevant cells in the liver  kupffer cells and pit cells in the process is suggested  
class4	regulation of insulin like growth factor ii gene expression by hepatitis b virus in hepatocellular carcinoma  in this study we investigated the regulation of insulin like growth factor ii gene expression to explain a role for this growth factor in concert with hepatitis b virus involvement in the development of hepatocellular carcinoma from cirrhosis  sections of normal liver and tumor and non tumor bearing liver disease tissue were hybridized in situ with  35s  labeled insulin like growth factor ii oligonucleotide probe  parallel sections were tested for presence of insulin like growth factor ii polypeptide using immunohistochemistry  to investigate a possible role for hepatitis b virus in insulin like growth factor ii gene expression in hepatocellular carcinoma  results were analyzed against patient seropositivity for hepatitis b virus  levels of insulin like growth factor ii transcripts in normal liver  n   4  sections and in those from non tumor bearing individuals  n   10  were so low that specific signal was not detectable above homogeneous tissue background  in contrast  4 of 8  50   of the sections of hepatocellular carcinoma arising from cirrhosis or noncirrhotic chronic liver disease with hepatitis b virus involvement showed increased expression of insulin like growth factor ii messenger rna transcripts  up regulation was observed in cell foci in the hepatocellular regions of the surrounding cirrhotic lobular cells and the fibrous septa  numerous cell foci were observed in patch distribution in the tumor areas  the level of insulin like growth factor ii messenger rna transcripts in sections of hepatocellular carcinoma arising from cirrhotic and noncirrhotic tissues obtained from patients seronegative for hepatitis b virus was similar to that of normal liver  
class4	hepatitis b virus integration in hepatitis b virus related hepatocellular carcinoma in childhood  in taiwan  hepatocellular carcinoma is one of the major malignancies in children between 5 and 14 yr of age  we studied the status of hepatitis b virus dna in the hepatocellular carcinoma and nontumorous liver tissues of eight children with positive serum hbsag and maternal hbsag  the hepatocellular carcinoma tissues from five of the eight children showed integration of hepatitis b virus dna into host cellular dna sequences  a pattern of single site integration in four children and a multiple site integration pattern in one child were demonstrated  in the remaining three children  hepatitis b virus dna could not be demonstrated in the tumor tissues  using subgenomic fragments of the hepatitis b virus genome as probes  we found that the x gene fragment and the surface antigen gene fragment were the most conserved sequences  the single site integration of hepatitis b virus dna in childhood hepatocellular carcinoma may have hit the critical region  resulting in insertional mutagenesis and early development of hepatocellular carcinoma  with a short incubation period and less exposure to environmental carcinogens during early life  childhood hepatocellular carcinoma may provide a good model to study the carcinogenic potential of hepatitis b virus  
class4	incidence of hairy cell leukemia  mycosis fungoides  and chronic lymphocytic leukemia in first known htlv ii endemic population  unlike human t cell leukemia lymphoma virus type i  htlv i   htlv ii has not been convincingly linked to a malignancy  in the first 10 months of serologic screening for htlv i ii among blood donors in new mexico in 1988 1989  htlv i ii infection was found in 27 donors  htlv i ii infection was present in 1 0  1 6  of american indian and 0 16  0 27  of hispanic donors compared with 0 009  0 06  of non hispanic white donors  htlv ii was identified by dna amplification in 12 of 13 samples from indian and hispanic seropositive donors  despite apparent endemic htlv ii infection in these populations  new mexico tumor registry data showed that the incidences of hairy cell leukemia  mycosis fungoides  and chronic lymphocytic leukemia were comparable among the three ethnic groups  a population with endemic htlv ii infection has been identified  and there is no evidence of increased risk for these three malignancies in the endemic groups  
class4	changes in plasma high density lipoprotein cholesterol and phospholipid in acute viral hepatitis and cholestatic jaundice  forty four male and female subjects aged 22 57 years were studied  thirteen patients had acute viral hepatitis  and eleven patients had cholestatic jaundice due to carcinoma of the head of the pancreas  twenty healthy volunteers who served as controls were also included  in hepatitis patients  the mean plasma levels of total cholesterol  tc  and the high density lipoprotein  hdl  phospholipid phospholipid  hdlpl pl  ratio were reduced  and hdl cholesterol  hdlc   hdl phospholipid  hdlpl  and the phospholipid total cholesterol  pl tc  ratio were normal  while total phospholipid  pl  levels and the hdlc tc ratio were significantly increased compared to the control values  in patients with cholestatic jaundice the mean plasma total cholesterol  phospholipid and hdlc levels were elevated  and hdlpl pl  hdlpl  hdlc tc and pl tc remained normal compared to the control values  a comparison within the patient groups showed that plasma tc  pl and hdlc levels were significantly increased in cholestatic jaundice when compared with the corresponding levels in hepatitis patients  the mean plasma levels of hdlpl  hdlc tc and pl tc did not show any significant variation within the patient groups  alkaline phosphatase  alp  correlated positively with tc  and total protein correlated negatively with tc and hdlpl  while albumin correlated negatively with tc  hdlc and hdlpl in cholestatic jaundice  alanine amino transferase  alat  also correlated positively with pl in cholestatic jaundice  while albumin correlated positively with tc in hepatitis  the results suggest that lipoproteins might be metabolized differently in these two forms of cholestasis  
class4	serum erythropoietin levels in the anaemia of chronic disorders  serum erythropoietin  s epo  levels were measured in 50 patients with anaemia of chronic disorders  acd   classified into three groups according to their aetiology  inflammatory  n   20   infectious  n   15  and neoplastic  n   15   the inflammatory group showed a higher mean s epo level  mean value     sem  69     11 mu ml 1  than the neoplastic  43     5 mu ml 1  p less than 0 05  and infectious groups  27     4 mu ml 1  p less than 0 01   the s epo level in the inflammatory group also differed from that of 32 healthy controls  36     3 mu ml 1  p less than 0 05   fourteen patients with added iron deficiency  12 subjects from the inflammatory group  showed the highest s epo concentration  72     17 mu ml 1   conversely  s epo levels were lower in febrile subjects  12 patients with infection and five with malignancy  than in non febrile patients  28     4 mu ml 1 vs  55     7 mu ml 1  p less than 0 01   in the infectious group  the logarithm of s epo correlated directly with the haemoglobin and haematocrit values  we conclude that differences in s epo concentration in acd may be further related to the patient s iron stores and temperature  a decrease in epo production may contribute to the pathogenesis of acd secondary to infection  
class4	high cardiac output as a paraneoplastic syndrome  a high cardiac output  17 1 min 1  was recorded in a young man suffering from lymphoplasmatocytotic lymphoma  the evolution of the blood disease was characterized by two relapses  during which clinical signs of heart failure were prominent but resolved with efficient blood chemotherapy  the known aetiologies of high cardiac output were excluded  the complete normalization of the cardiac parameters with blood remission suggests that the high cardiac output represented an unusual paraneoplastic syndrome  the pathogenesis of which still remains unknown  although several hypotheses were tested  
class4	the vascularized fibula graft in mandibular reconstruction  the use of a vascularized graft from the fibula for mandibular reconstruction is presented  the great strength  pliability  and long vascular pedicle that characterize such grafts make them particularly suitable for this type of repair  the results in six cases were highly satisfactory  masticatory function was well restored  without alteration of the facial contour  and with minimal sequelae at the donor site  
class4	fine needle aspiration biopsy of head and neck lesions  the case records of 213 fine needle aspiration biopsies  fnab  of head and neck masses performed on 209 patients over a 3 year period were reviewed to assess the diagnostic accuracy and safety of this technique in comparison with surgical histologic examination  cytologic diagnoses based on fnab were compared with histologic diagnoses in 110 patients who underwent surgery  based on cytology alone  40 3  of the lesions were reported as malignant  45 1  as benign  and 14 6  as indeterminant  a specific cytologic diagnosis was made in 85 5  of the cases  cytologic diagnoses concurred with surgical histologic diagnoses 90  of the time  fine needle aspiration biopsy was found to have a false positive rate of 0 5  and a false negative rate of 2 3   the sensitivity and specificity of fnab in determining a malignant diagnosis were 81 1  and 99   respectively  positive and negative predictive values were calculated at 98 9  and 82 8   respectively  diagnostic rate  sensitivity  and negative predictive value increased consistently throughout the study period  indicating that the diagnostic accuracy of fnab improved with experience  
class4	nasopalatine duct cyst  an analysis of 334 cases  the nasopalatine duct cyst  npdc  is the most common cyst of nonodontogenic origin in the maxilla  however  the information reported about this lesion consists primarily of small surveys and isolated case reports  the purpose of this retrospective investigation was to gather demographic  clinical  and histologic data on a large series of npdcs  and to compare the findings with those of previous studies  in this study  the overall mean age at diagnosis was 42 5 years  and there was a slight male predilection  the mean radiographic diameter was 17 1 mm  but 75  of the lesions were 20 mm or less in diameter  symptoms were present in at least 70  of the cases  only 28  of the specimens contained respiratory epithelium  there was no correlation between radiographic size  patient s age  presenting symptoms  or type of epithelium  recurrence was noted in only 2  of the cases  
class4	synergism of herpes simplex virus and tobacco specific n  nitrosamines in cell transformation  previous studies indicate that herpes simplex virus  hsv  enhances the carcinogenic activity of smokeless tobacco and tobacco related chemical carcinogens in animals  since tobacco specific n  nitrosamines  tsnas  such as n  nitrosonornicotine  nnn  and 4  n methyl n  nitrosamino  1  3 pyridyl  1 butanone  nnk  are major chemical carcinogens of smokeless tobacco and are known to be responsible for the development of oral cancers in smokeless tobacco users  the combined effects of tsnas and hsv in cell transformation were investigated  exposure of cells to nnn or nnk followed by virus infection resulted in a significant enhancement of transformation frequency when compared with that observed with chemical carcinogens or virus alone  this study suggests that tsnas and hsv can interact together and show synergism in cell transformation  
class4	immunohistochemical demonstration of keratin in ameloblastoma as an indication of tumor differentiation  keratin expression was studied immunohistochemically in 27 ameloblastomas using polyclonal antibody against wide spectrum keratins  ttl  and monoclonal antibodies against lower  and higher molecular weight keratins  pkk1 and kl1   respectively  to clarify the tumor differentiation  reactions with ttl and kl1 antibodies were generally positive in the stellate cells of the follicular or acanthomatous ameloblastomas  cell nests of the basal cell type were positive for pkk1  on the other hand  the reactions with ttl or kl1 in the plexiform type were generally weak or absent  from these facts  it was concluded that the follicular  as well as acanthomatous  ameloblastoma is liable to undergo squamous differentiation  whereas the plexiform ameloblastoma remains in primitive stage of tumor differentiation  
class4	liposarcoma arising in the cheek  report of a case and review of the literature  the following points can be made about liposarcoma of the oral cavity  1  it is rare and slow growing  2  it is often mistaken for a benign lesion  3  there is a direct correlation of microscopic appearance with biological behavior and prognosis  4  treatment is primarily surgical  with radiation used for selected cases  and 5  the better differentiated tumors seem to respond more favorably to radiation  
class4	a cohort study of fat intake and risk of breast cancer  between 1982 and 1987  519 newly incident  histologically confirmed cases of breast cancer were identified in a cohort of 56 837 women enrolled in the canadian national breast screening study  these women had completed a dietary questionnaire before the occurrence of their breast cancer  and this has been used to estimate their intake of dietary fat and several other nutrients  there is evidence of a positive association between breast cancer and total fat intake  with a relative risk of 1 35  95  confidence interval  1 00 1 82  per 77 g per day  and some evidence of a dose response relationship  p    052   
class4	genetic analysis as an aid in diagnosis for patients with midline carcinomas of uncertain histologies the tumors of nine patients with carcinomas of uncertain histogenesis  eight with poorly differentiated carcinomas involving primarily midline structures and one with a diagnosis of seminoma and atypical clinical features  were studied by cytogenetic and southern blot analyses  four of the eight patients with poorly differentiated carcinomas had abnormalities of chromosome 12 consistent with a diagnosis of germ cell tumor  these abnormalities comprised an i 12p  in two patients and a del 12q  in a third patient detected by cytogenetic analysis and multiple copies of 12p detected by southern blot analysis in a fourth patient  three of these four patients with a diagnosis of germ cell tumor established by genetic analysis achieved a complete response to cisplatin based chemotherapy  the tumor biopsy of one patient showed a t 11 22   q24 q12   and this patient had chemotherapy directed to neuroepithelioma  cytogenetic analysis was unsuccessful for the tumors of three patients  these tumors did not have multiple copies of 12p detected by southern blot analysis  these patients did not respond to cisplatin based chemotherapy  one patient with a diagnosis of extragonadal seminoma failed to respond to cisplatin based chemotherapy and had a second tumor biopsy performed that demonstrated a t 8 14   q24 q32   this patient s diagnosis was changed to a non hodgkin s lymphoma  thus  genetic analysis provided a diagnosis in six of nine patients  cytogenetic and molecular analyses are useful clinical tools for the determination of histogenesis in some patients with poorly differentiated carcinomas of uncertain histology  
class4	disseminated human malignant melanoma in congenitally immune deficient  bg nu xid  mice  congenitally immune deficient bg nu xid  bnx  mice are severely compromised in their ability to mount t cell  b cell  and lymphokine activated killer  lak  cell responses  successful engraftment of bnx mice with human hematopoietic stem cells has been demonstrated recently  we have investigated the potential use of bnx mice for studies relating to the biology and immunotherapy of human malignant melanoma  the intravenous injection of fresh single cell suspensions of human malignant melanomas into mice resulted in widely disseminated disease  metastatic spread of human melanoma in bnx mice mimicked that observed in patients  eg  there were numerous tumor nodules identified in the subcutaneous tissues as well as in a variety of visceral organs  including spleen  kidneys  thyroid  adrenals  lungs  heart  and brain  bnx mouse lymph nodes were replaced consistently by human malignant melanoma cells  the presence of human tumor cells in these mice was confirmed by histologic analysis and microcytofluorometry analyses using human melanoma specific monoclonal antibodies  mabs   moreover  human melanoma cells passaged in bnx mice remained lysable in vitro by specifically cytolytic  autologous human tumor infiltrating lymphocytes  tils   the capacity of fresh human malignant melanoma to disseminate widely in bnx mice may prove valuable not only for study of the biology of metastatic spread but also for studies of the immunotherapy of human melanoma using melanoma specific mabs and chemotherapeutic agents  as well as human tils and lak cells with or without retrovirus mediated gene transfer modification  
class4	a hypothesis  nonsteroidal anti inflammatory drugs reduce the incidence of large bowel cancer  nonsteroidal anti inflammatory drugs  nsaids  inhibit prostaglandin synthesis and tumor growth in the rodent colon  we assessed nsaid use in relation to risk of human large bowel cancer in a hospital based  case control study of 1326 patients with colorectal cancer and 4891 control patients  for regular nsaid use that continued into the year before interview  the multivariate relative risk estimate was 0 5  95  confidence interval  0 4 to 0 8   the estimate decreased as the duration of use increased  but the trend was not statistically significant  similar results were obtained whether cancer or non cancer controls were used  and the inverse association was apparent for both colon cancer and rectal cancer in men and women and in subjects younger and older than 60 years  regular nsaid use that had been discontinued at least 1 year previously and non regular use were not associated with risk  almost all regular nsaid use was of aspirin containing drugs  the present data suggest that the sustained use of nsaids reduces the incidence of human large bowel cancer  
class4	obesity and colorectal adenomatous polyps  obesity has been investigated as a risk factor for various malignancies  including colon cancer  a case control study was conducted on patients in three colonoscopy practices in new york city to determine possible risk factors for colorectal adenomatous polyps  a known precursor lesion for most cases of colorectal cancer  among 301 case subjects with incidence adenomatous polyps  174 men and 127 women  and 506 control subjects  223 men and 283 women   an increased risk was observed with increasing body mass index in women  odds ratio 2 1  95  confidence interval 1 1 4 0  for highest versus lowest quartile  linear trend p    02   a nonsignificant trend was observed for men  the increased risk seen in women is consistent with prior observations regarding reproductive hormonal and dietary risk factors for colorectal cancer  
class4	rising incidence of adenocarcinoma of the esophagus and gastric cardia analyses of cancer incidence data from nine areas of the united states revealed steadily rising rates from 1976 to 1987 of adenocarcinomas of the esophagus and gastric cardia  the increases among men in this period ranged from 4  to 10  per year  and thus exceeded those of any other type of cancer  in contrast  there were relatively stable trends for squamous cell carcinoma of the esophagus and slight declines for adenocarcinoma of more distal portions of the stomach  adenocarcinomas of the esophagus and gastric cardia disproportionately affected white men and rarely occurred among women  by the mid 1980s  among white men  adenocarcinomas accounted for about one third of all esophageal cancers  while cardia cancers accounted for about one half of all stomach cancers with specified subsites  the rising incidence rates and similar demographic patterns point to the need for investigation into the causes of these poorly understood cancers  
class4	activated protooncogenes in human lung tumors from smokers  fourteen primary human lung tumor dnas from smokers were analyzed for transforming activity by two dna transfection assays  activated protooncogenes were detected in 3 of 11 tumor dnas by the nih 3t3 focus assay  whereas activated protooncogenes were detected in 11 of 13 tumor dnas by the nih 3t3 cotransfection nude mouse tumorigenicity assay  k  or nras genes activated by point mutation at codons 12 or 61 were detected in a large cell carcinoma  a squamous cell carcinoma  and 5 adenocarcinomas  an hras oncogene activated by a different mechanism was detected in an epidermoid carcinoma  one adenocarcinoma was found to contain an activated raf gene  two unidentified transforming genes were detected in a squamous cell carcinoma dna and two adenocarcinoma dnas  eight of 10 lung adenocarcinomas that had formed metastases at the time of surgery were found to contain ras oncogenes  no significant increase in metastasis was observed in the lung adenocarcinomas that contained one or more 6 kilobase ecori alleles of the lmyc gene  overall  12 of 14  86   of the lung tumor dnas from smokers were found to contain activated protooncogenes  ras oncogenes appear to play a role in the development of metastases in lung adenocarcinomas  
class4	influence of chromosomal integration on glucocorticoid regulated transcription of growth stimulating papillomavirus genes e6 and e7 in cervical carcinoma cells  in most cervical carcinoma cells the e6 and e7 genes of specific human papillomaviruses are transcribed from viral sequences integrated into host cell chromosomes  glucocorticoids activate the promoter elements of various human papillomaviruses in transient expression assays  we have analyzed the effect of dexamethasone on the transcription rate of human papillomavirus 18 e6 and e7 genes integrated at different chromosomal sites in four cervical cancer cell lines  dexamethasone led to an increase in the transcription rate of the integrated e6 e7 sequences in c4 1 and c4 2 cells but led to a decrease in sw 756 cells and did not affect the transcription rate in hela cells  however  when the viral promoter elements derived from hela or sw 756 cells  in which dexamethasone does not activate transcription of the integrated e6 e7 sequences  were tested in transient expression assays within the same cell lines  dexamethasone consistently activated the viral promoter  it thus appears that dominant regulatory mechanisms presumably depending on the chromosomal integration site are able to override the response of the viral promoter to steroid hormones  the growth rate of all dexamethasone treated cell lines correlated consistently with the expression of the papillomavirus e6 and e7 genes  supporting their role in the maintenance of the proliferative phenotype of cervical carcinoma cells  since human papillomaviruses are integrated into the host cell genome at variable  presumably randomly selected chromosomal loci  regulatory mechanisms that influence viral gene expression  and hence cell growth  may differ among cancers of independent clonal origin  
class4	human catechol o methyltransferase  cloning and expression of the membrane associated form  a cdna clone for human catechol o methyltransferase  hcomt  s adenosyl l methionine catechol o methyltransferase  ec 2 1 1 6  was isolated from a human hepatoma cell line  hep g2  cdna library by hybridization screening with a porcine cdna probe  the cdna clone was sequenced and found to have an insert of 1226 nucleotides  the deduced primary structure of hcomt is composed of 271 amino acid residues with the predicted molecular mass of 30 kda  at its n terminus it has a hydrophobic segment of 21 amino acid residues that may be responsible for insertion of hcomt into the endoplasmic reticulum membrane  the primary structure of hcomt exhibits high homology to the porcine partial cdna sequence  93    the deduced amino acid sequence contains two tryptic peptide sequences  t 22  t 33  found in porcine liver catechol o methyltransferase  comt   the coding region of hcomt cdna was placed under the control of the cytomegalovirus promoter to transfect human kidney 293 cells  the endogenous comt activity  which was approximately 9 98 units per mg of protein in the untransfected cells  increased to 206 units per mg of protein upon transfection with a plasmid containing the comt cdna  the comt activity of recombinant protein was inhibited competitively  ic50   700 nm  by the selective comt inhibitor ro 40 7592  an anti comt monoclonal antibody recognized  on immunoblots  a major polypeptide with apparent molecular mass of 29 kda  in reasonable agreement with the predicted molecular mass  the recombinant hcomt was shown by immunoblot analysis to be mainly associated with the membrane fraction  rna blot analysis revealed one comt mrna transcript of 1 4 kilobases in hep g2 poly a   rna  
class4	stimulation of camp and phosphomonoester production by melanotropin in melanoma cells  31p nmr studies  a major part of the present understanding of the molecular basis of signal transduction has been gained from in vitro studies using classical biochemical methods  in this study  we used 31p nmr spectroscopy to investigate the response of live m2r mouse melanoma cells to stimulation by melanocyte stimulating hormone  msh  melanotropin   in the presence of 3 isobutyl 1 methylxanthine and a synergistic dose of forskolin  1 67 microm   msh induced a transient  approximately 60 min  rise in the cellular concentration of 3  5  cyclic adenosine monophosphate  camp   which coincided in time with an equivalent decrease  approximately 40   in atp  however  no detectable change in phosphocreatine concentration was observed  concomitantly  msh induced a striking and unexpected increase in the concentration of three phosphomonoester  pme  metabolites  approximately 2 fold increase in total pme signal area   one signal has been assigned to phosphoethanolamine  the levels of the pmes remained high for 2 4 hr and declined slowly  approximately 10 hr  to basal level  following perfusion with fresh culture medium  the increase in pme was also observed after stimulation with msh alone  in contrast  stimulation with a high dose of forskolin  50 microm  and isobutylmethylxanthine  0 2 mm   although effective in stimulating the production of camp  did not induce the pme response  evaluation of the cells  energetics indicated that the enhanced production of phosphoethanolamine is probably not due to ethanolamine phosphorylation  therefore  it is likely to result from hydrolysis of phosphatidylethanolamine by a specific phospholipase c  the response of the pmes appears to be regulated by a camp independent process  suggesting the existence of an alternative transduction pathway controlled by msh  
class4	mononuclear phagocytes  a major population of effector cells responsible for rejection of allografted tumor cells in mice  to understand the in situ mechanism of immunological response of recipient animals to allografted tumor cells  the types of cells that infiltrated into the rejection site were examined  when meth a cells  h 2d  were given i p  to an allogeneic  c57bl 6  h 2b   strain of mouse  the tumor cells ceased to grow on the 6th day  accompanied by an i p  infiltration of leukocytes  the tumor cells were totally eliminated from the peritoneal cavity around the 12th day  the highest cytotoxic activity against meth a cells was obtained with the peritoneal exudate cells harvested on day 8  on this day  the exudate cells consisted of three populations when examined by flow cytometry  and each was isolated by sorting  each of them appeared to be homogeneous  and they were morphologically identified as lymphocytes  granulocytes  and medium sized  mononuclear  less granular cells  the cytotoxic activity was confined exclusively to the last population  the effector cells  h 2b  were cytotoxic against not only meth a cells  h 2d  but also concanavalin a stimulated allogeneic spleen cells  c3h he  h 2k   cba n  h 2k   a j  h 2a   balb c  h 2d   and dba 2  h 2d  strains of mouse   the effector cells were totally inert against concanavalin a activated syngeneic spleen cells  c57bl 6  h 2b  and c57bl 10  h 2b  strains of mouse   the effector cells were phenotypically  thy 1 2  cd3  lyt 1  lyt 2  l3t4  immunoglobulin  asialo gm1    morphologically  and functionally distinct from cytotoxic t cells  natural killer cells  and lymphokine activated killer cells but were adherent mononuclear phagocytes  
class4	recombinant epstein barr virus with small rna  eber  genes deleted transforms lymphocytes and replicates in vitro  strains of epstein barr virus  ebv  with deletions of the small rna  eber  genes were made by homologous recombination using the ebv p3hr 1 strain  which has undergone deletion of the essential transforming gene that encodes the ebv nuclear antigen  ebna 2  and a dna fragment that was wild type at the ebna 2 locus but from which the eber genes had been deleted  even though the eber and ebna 2 genes are separated by 40 kilobases  selection for transforming p3hr 1 recombinants that required a restored ebna 2 gene resulted in 20  cotransfer of the eber deletion  eber deleted recombinants transformed primary b lymphocytes into lymphoblastoid cell lines  lcls   which were indistinguishable form lcls transformed by wild type ebv in their proliferation  in latency associated ebv gene expression  and in their permissiveness for ebv replication cycle gene expression  eber deleted virus from infected lcl clones could infect and growth transform primary b lymphocytes  these procedures should be applicable to the construction of other ebv recombinants within 40 kilobases of the ebna 2 gene  the eber deleted ebv recombinants should be useful in further evaluating the role of ebers in ebv infection  
class4	leukemia initiated by hemopoietic stem cells expressing the v abl oncogene  we report a mouse model with which to study leukemogenesis initiated by a specific genetic change introduced into a primary lymphoid myeloid pluripotent stem cell  fetal liver hemopoietic cells were infected with a high titer of helper free abelson murine leukemia virus  a mulv  and were used to reconstitute lethally irradiated mice  two weeks later  progenies of a single primitive hemopoietic stem cell carrying a specifically integrated a mulv proviral dna could be detected in both colony forming units in spleen and myeloid colony forming cells in the bone marrow  beginning at 3 weeks after transplantation  the recipients developed elevated leukocyte counts  splenomegaly  and increase of blast cells in the peripheral blood  multiple clones of a mulv infected cells were infused into each recipient  however  in the same animal  dna extracted from various affected organs and from factor independent lymphoid and myeloid immortalized cells all contained an identical  specifically integrated proviral genome  the a mulv infected stem cells differentiated into various lineages of hemopoietic cells  our data show that the expression of the v abl oncogene in a primary lymphoid myeloid hemopoietic stem cell directly initiates leukemogenesis by stimulating factor independent growth  the monoclonal type disease development seen in these animals may require the occurrence of an additional genetic event  
class4	tumoral thrombosis of cerebral venous sinuses  preoperative diagnosis using magnetic resonance phase imaging  intracranial  dural based neoplasms will not infrequently invade adjacent venous sinuses  therefore  the preoperative diagnosis of venous invasion is important  as it will alter the surgical approach to the lesion  magnetic resonance imaging is a noninvasive means of visualizing the cerebral venous sinuses  the preoperative diagnosis of venous thrombosis can  however  be difficult and confusing with conventional spin echo magnetic resonance imaging because of variable appearances produced by blood clot degradation products as well as flowing blood  phase magnetic resonance imaging is a simple method that can be acquired simultaneously with conventional spin echo sequences  and is based primarily on whether protons are stationary or moving  in the context of venous sinus occlusion  phase imaging can demonstrate the presence or absence of blood flow more easily than spin echo imaging  three cases of dural based neoplasms are presented that demonstrate the utility of phase imaging in diagnosing tumoral occlusion of the venous sinuses  
class4	angiotropic intravascular large cell lymphoma  malignant angioendotheliomatosis   report of a case and review of the literature  we present a case of angiotropic large cell lymphoma and review the literature in order to define the neurologic features of this rare disorder  this is the first report of gadolinium dtpa imaging in angiotropic large cell lymphoma that demonstrates infarcts of multiple ages  as well as striking meningeal enhancement  angiotropic large cell lymphoma should be suspected in patients with clinical evidence of small and large cerebral vessel disease and diagnosis requires skin  liver  renal  meningeal  or brain biopsy  single modality treatment  using either radiation therapy or steroids  has been ineffective  and new findings of a lymphomatous origin of this neoplasm suggest that combination chemotherapy may be indicated  
class4	intracranial chordoma in a preadolescent  case report  chordomas are rare tumors derived from notochord remnants occurring primarily in the sacrum  clivus  and cervical regions  exceptionally  these tumors occur in children  though usually in the sacrum  eight cases of clivus chordoma have been described in preteenagers  in this report  a clival chordoma with unusual radiologic features is described in an 11 year old boy  the literature regarding this entity is reviewed  
class4	solitary  isolated metastasis from ewing s sarcoma to the brain  case report  we report a case of a 30 year old woman who developed an intraparenchymal cerebral metastasis from a ewing s sarcoma of the chest wall diagnosed and treated 3 years earlier and in apparent remission at the time of the neurological presentation  seizures   the case was complicated by a spontaneous preoperative intratumoral hemorrhage that occurred the morning of the scheduled surgical resection and caused a left dense hemiparesis  the tumor and the hematoma were removed  the patient improved after surgical intervention and a postoperative course of cranial irradiation followed by systemic chemotherapy was given  nineteen months after treatment the patient remains disease free from the clinical and radiological standpoint  
class4	treatment of leptomeningeal carcinomatosis with continuous intraventricular infusion of recombinant interleukin 2  a 42 year old man developed leptomeningeal carcinomatosis 6 years after treatment of a malignant melanoma  he was treated with two courses of recombinant interleukin 2  administered as a continuous intraventricular infusion  6 x 10e5 u 24 h  during 5 days  during the first day of the first course he also received 5 x 10e9 lymphokine activated killer cells intraventricularly  this gave rise to a severe elevation of intracranial pressure  with headaches and meningismus  during the second course no lak cells were administered  this course was tolerated much better  the neurological status did not change during the treatment  recombinant interleukin 2 levels were maintained at about 300 u ml during both courses  
class4	relationship of transfusion and infectious complications after gastric carcinoma operations  to determine the effect of transfusion on the incidence of postoperative infection  a retrospective cohort study of 196 patients who underwent surgery for gastric carcinoma in the period from 1985 through 1989 was carried out  seventy one patients  36 2   developed postoperative septic complications  they had received an average of 4 2 blood units  as compared with 2 7 units received by patients not affected  p less than 0 0053   the hypothesis of dose response relationship is supported by the mantel haenszel test  as applied to the overall results  p less than 0 01  and the results grouped by duration of operation  p less than 0 02   furthermore  logistic regression analysis shows transfusion to be an independent risk factor in the incidence of infection  p less than 0 01   as are antibiotic prophylaxis  p less than 0 015   urinary tract catheterization  p less than 0 002   and the duration of surgery  p less than 0 027   this significance is attained after adjustment for age  gender  period of evolution of symptoms  preoperative infection s   number of white cells  hemoglobin level and total proteins on diagnosis  location of tumor  tumor  nodes  and metastasis staging  operative technique  drainage of the area of operation  enteral nutrition  and the histologic studies and macroscopic appearance of the tumor  this study is further evidence that transfusion may cause an increased incidence of postoperative infection  
class4	immunochemical studies on the differential binding properties of two monoclonal antibodies reacting with tn red cells  two monoclonal antibodies  moabs   bric 66  igm  and bric 111  igg1   were produced by immunizing mice with ovarian cyst blood group a1 glycoprotein and tn red cells  rbcs   respectively  their specificities were determined by inhibitions using tn sialoglycoproteins  sgps   mucins  armadillo  asg  and ovine  osg  submaxillary glycoproteins   and monosaccharides  bric 66 agglutinated both tn and group a rbcs and reacted immunohistochemically with both the vascular endothelium and tumor cells from a group a adenocarcinoma  bric 66 was inhibited by n acetylgalactosamine  galnac   tn sgps  and mucins on both hemagglutination inhibition tests and radioimmunoassay  bric 111 agglutinated tn rbcs only  and it specifically stained tumor cells from a group o patient s breast carcinoma and a group a patient s adenocarcinoma  in hemagglutination inhibition tests  bric 111 was readily inhibited by tn sgps  only partially inhibited by galnac  and not inhibited by mucins  in a sensitive radioimmunoassay  bric 111 was inhibitable by galnac  tn sgp was 2000 fold more effective as an inhibitor than the mucins  asg and desialized osg   which contain a high content of terminal alpha galnac o serine  threonine  residues  it is postulated that bric 66 is specific for terminal alpha galnac units in carbohydrate chains  the exclusive reaction of bric 111 with tn sgp indicates a combining site larger than galnac alpha 1  which probably includes amino acid residues in juxtaposition to galnac in tn sgp  in view of its specific agglutination of tn rbcs  bric 111 is a useful reagent for the examination of polyagglutinable rbcs  
class4	medullary thyroid cancer  an immunohistochemical and humoral study using six separate antigens the authors investigated the humoral and tissue expression of six antigens associated with medullary thyroid cancer  mtc   calcitonin  ct   calcitonin gene related peptide  cgrp   carcinoembryonic antigen  cea   neuron specific enolase  nse   somatostatin  srif   and thyroglobulin  tg   the antigens were studied in the neoplastic c cells using immunohistochemistry with specific antisera and in the plasma using specific radioimmunoassay  eighteen patients  8 male and 10 female patients  aged 12 72 years  were studied  mean follow up was 70 7 months  range  2 179 months   nine patients  50   died of their disease after a mean follow up of 47 2 months  range  2 116 months   by immunostaining  primary tumors expressed ct and cea in all cases and nse was positive in 90   cgrp in 66   srif in 63   and tg in 58   metastatic tissues were positive in all cases of ct staining  92 8  of cea  71 4  of nse  73 3  of cgrp  38 5  of srif  and only 13 3  of tg staining  in positive cases the percentage of positive cells and the degree of staining were variable among the different antigens  the expression of an antigen in the neoplastic cells was associated with the hypersecretion of the corresponding antigen in the circulation in the case of ct and cea  the levels of these antigens were elevated in all patients with metastases and could accurately predict the appearance of new metastases or indicate the effective treatment of previous metastases by surgery  in the case of nse  cgrp  and srif  few patients had increased plasma concentrations of the antigens and these usually occurred during very advanced phases of the disease  detectable levels of serum tg were never observed  when the outcome of the disease was compared with the expression of ct  cea  nse  cgrp  and tg  no correlation could be found  on the contrary  srif expression in the primary tumor could differentiate two groups of patients with different survival rates  srif positive patients had survival rates of 100  and 50  at five and seven years  respectively  whereas srif negative patients had survival rates of 40  at five years and 25  at seven years  
class4	papillary carcinoma of thyroid with exuberant nodular fasciitis like stroma  report of three cases  three examples of an unusual morphologic variant of papillary thyroid carcinoma  ptc  are reported  the presence of a prominent stromal component resulted in low power microscopic appearances resembling fibroadenoma  phyllodes tumor  or fibrocystic disease of the breast in two cases  the carcinomatous component grew in the form of anastomosing narrow tubules  clustered glands  solid sheets with or without squamous differentiation  and or papillae  and exhibited the typical nuclear features of ptc  the abundant stroma had a nodular fasciitis like quality and was composed of short fascicles of spindle cells separated by varying amounts of mucoid matrix  collagen  and extravasated red blood cells  this was interpreted as an exuberant mesenchymal reaction to the carcinoma  the importance of recognizing this variant of ptc is that  when one encounters a fibroproliferative lesion of the thyroid  a diligent search should be made for papillary carcinoma  this variant also must be distinguished from the vastly more aggressive papillary carcinomas with anaplastic transformation and the so called carcinosarcomas  
class4	small cell carcinomas of the large intestine  the authors studied the clinical and pathologic features of 38 small cell carcinomas of the large intestine  most were located in the right colon  overlying adenomas were present in 45  and squamous differentiation in 21  of tumors  endocrine differentiation was present in all tumors by at least one method  neuron specific enolase  dense core granules  and synaptophysin were present in most cases  seventy one percent of tumors metastasized to the liver  64  of patients were dead at five months follow up  twenty one poorly differentiated adenocarcinomas and undifferentiated carcinomas of the large intestine accessioned during the same period showed less endocrine  7 of 21  and squamous differentiation  1 of 15  and fewer liver metastases  4 of 15  than did small cell carcinomas  among all 59 tumors studied  small cell histologic characteristics correlated better with liver involvement than did endocrine markers or other histologic features  small cell carcinomas of the large intestine are aggressive tumors with a propensity for early liver involvement  although there is a spectrum of squamous  endocrine  and glandular features in large bowel tumors of low degrees of differentiation  the identification of a small cell component appears to be most clinically relevant  
class4	the use of monoclonal antibody 44 3a6 in cell blocks in the diagnosis of lung carcinoma  carcinomas metastatic to lung and pleura  and pleural malignant mesothelioma  monoclonal antibody  moab  44 3a6 recognizes a glandular differentiation associated antigen and has been used to identify exocrine differentiation in pulmonary carcinomas  the authors assessed its value in the diagnosis of lung carcinomas metastatic to lung pleura and pleural malignant mesothelioma  mm   using cell blocks derived from cytologic specimens  sixty three primary lung carcinomas  31 metastatic adenocarcinomas  acs   from breast  gastrointestinal tract  or genitourinary tract   and 36 mms were immunostained with 44 3a6  leu m1  and anti carcinoembryonic antigen  cea   the results confirm the value of 44 3a6 in identifying acs but do not allow distinction between those of pulmonary  breast  git  or ovarian mucinous derivation  endometrial  ovarian serous  and renal acs are essentially nonreactive  as are almost all mms  the occurrence of one positive mm predicates caution in interpreting 44 3a6 positivity in isolation  but  judiciously used with other discriminating antibodies such as leu m1 and anti cea  44 3a6 is of value in the differential diagnosis of acs and mms  further  its applicability to cytologic specimens may obviate the need for more invasive diagnostic procedures and lead to rapid  accurate diagnosis  
class4	granulomatous prostatitis and poorly differentiated prostate carcinoma  their distinction with the use of immunohistochemical methods  granulomatous prostatitis and poorly differentiated prostate carcinoma can mimic each other both clinically and histologically  to develop criteria useful in resolving problem cases  the authors compared the reactivities of these conditions  nine cases of granulomatous prostatitis and six cases of poorly differentiated carcinoma  with a panel of antibodies to cytokeratin  ae1 3   prostate specific antigen  psa   prostatic acid phosphatase  pap   lysozyme  antimacrophage m  and leukocyte common antigen  lca   in granulomatous prostatitis  histiocytes were not immunoreactive for pap  psa  or cytokeratin  however  histiocytes reacted to lysozyme in nine of nine cases  antimacrophage m in seven of nine cases  and lca in one of nine cases  tumor cells from all six carcinoma cases reacted with pap  psa  and cytokeratin  all failed to react with lysozyme  lca  and antimacrophage m  the authors conclude that granulomatous prostatitis and poorly differentiated carcinoma can be reliably distinguished with immunohistochemical methods  
class4	automated immunohistochemical estrogen receptor in fixed embedded breast carcinomas  the authors immunohistochemically assessed the presence of estrogen receptor  er  in formalin fixed  paraffin embedded tissue sections of 68 breast carcinomas by an automated method using pronase  calbiochem  la jolla  ca  predigestion and alkaline phosphatase detection  method 1   these results were compared with those obtained by an automated peroxidase antiperoxidase method with dnase pretreatment of fixed embedded sections  method 2   with er immunostain on frozen sections  method 3   and with biochemical results  dextran coated charcoal cytosolic  dcc  assay   compared with the dcc assay  methods 1  2  and 3 gave sensitivities of 54   25   and 89   respectively  the sensitivity for method 1 was increased to 74  in those cases with dcc results showing greater than 50 fmol mg protein  these findings indicate that er immunohistochemical studies on formalin fixed paraffin embedded tissues  as assayed by method 1  provide useful clinical information when the results are positive  a negative result  especially if surrounding normal elements are not positive  may indicate no receptors  receptor levels less than 50 fmol mg protein  or improper tissue preservation  in the absence of fresh tissue for er assay by dcc assay or of frozen sections for immunostaining  and with an understanding of its limitations  this method may be useful  
class4	ovarian myxoma  a study of two cases with long term follow up  two cases of the so called ovarian myxoma are reported  one was from a 13 year old girl who had a 31 year follow up and no evidence of recurrence  the second case  from a 65 year old woman  recurred intraperitoneally  19 years after the surgery  both tumors were myxoid  with round to stellate cells  immunohistochemical  electron microscopic  em   and dna flow cytometric  fcm  studies were performed on formalin fixed  paraffin embedded tissue of the second patient on both the primary tumor and the recurrence  tumor cells expressed vimentin and were focally positive for desmin and myoglobin  em findings suggested a fibroblastic differentiation  an aneuploid cell population was present in the recurrent tumor by dna fcm studies  only four other cases of so called ovarian myxoma were reported to date  and the follow up does not exceed 18 months  the authors conclude that the presence of aneuploidy and the late recurrence of one of their cases suggest that certain ovarian myxomas might behave like low grade sarcomas  the histogenesis of this tumor remains unsettled  but similarities were found with myxomas in other locations  
class4	gene rearrangements in the diagnosis of lymphoma leukemia  guidelines for use based on a multiinstitutional study  the demonstration of immunoglobulin or t cell receptor gene rearrangements in human lymphoproliferative processes with the use of dna hybridization has gained great popularity as a sensitive laboratory adjunct to diagnostic hematopathology  the fact that nearly all b  or t cell malignant lymphomas and leukemias have one or more rearranged antigen receptor genes provides a biologic basis for a diagnostic test  to formally analyze the sensitivity  specificity  and reproducibility of gene rearrangements in the diagnosis of human lymphoproliferative disease  the authors conducted a large  multiinstitutional study  through a blinded  controlled approach  gene rearrangement analysis of 275 cases was shown to carry a high correlation with conventional phenotyping and histologic diagnosis  with only minor false positive and false negative rates  significantly  no rearrangements were detected in normal lymphoid tissues or carcinomas  sarcomas  or melanomas  in a randomized study of 50 cases  laboratory results showed a high rate of interlaboratory agreement  regardless of the level of previous experience  furthermore  the reproducibility of interpretation of data  southern blot autoradiograms  of 192 cases showed high concordance among 11 observers from multiple laboratories  based on these findings  the authors propose a set of guidelines for interpretation of gene rearrangement analysis that  if carefully followed  renders this a highly reproducible  safe  and accurate addition to the diagnostic regimen for human lymphoproliferative processes  
class4	bone marrow findings after treatment with recombinant human interleukin 3  in a phase i ii study  bone marrow biopsy specimens and aspirates of 20 patients with malignant tumors but normal bone marrow  n   6   bone marrow failure resulting from chemotherapy  n   4   myelodysplastic syndrome  n   5   and aplastic anemia  n   5  were evaluated before and after patients were treated with recombinant human interleukin 3  rhil 3   this cytokine proved to be an effective hematopoietic growth factor with only mild side effects  the rhil 3 treatment led to increased overall bone marrow cellularity with trilinear stimulation of hematopoietic cells  except in most patients with aplastic anemia  in all patients  significant eosinophilia and  in some instances  bone marrow fibrosis developed  in addition to the increase in the number of circulating neutrophilic granulocytes  platelets  and reticulocytes  an increase of peripheral blood monocytes and lymphocytes was observed  the histologic and cytologic findings support the concept that rhil 3 stimulates the proliferation and differentiation of pluripotent hematopoietic progenitor cells  it appears to be a safe and efficient therapeutic modality in patients with bone marrow failure  additional clinical studies are needed to determine which patients will profit most from rhil 3 treatment  
class4	flow cytometric analysis of terminal deoxynucleotidyl transferase  terminal deoxynucleotidyl transferase  tdt  is a useful marker for lymphoid precursor cells  in this study  the authors used flow cytometry  fcm  to analyze tdt expression in human hematopoietic malignancies  cells were fixed in 0 5  formaldehyde  briefly exposed to nonionic detergent  and subsequently labeled with mouse monoclonal anti tdt antibodies followed by fluorescein conjugated antimouse igg and propidium iodide  pi   which was used for the simultaneous analysis of dna content  cells from 20 of 22 acute lymphoblastic leukemias  all   4 of 7 mixed lineage leukemias  2 of 21 acute myeloid and myelomonocytic leukemias  1 of 2 chronic myeloid leukemias in blast crisis  1 lymphoblastic lymphoma  and 1 thymoma were tdt positive  cells from 13 nonlymphoblastic lymphomas  3 myelodysplastic bone marrows  and peripheral blood mononuclear cells from 29 normal individuals were negative  an excellent correlation was seen between this assay  the conventional slide immunofluorescence technique  and an enzyme immunoassay method  the fcm assay detected as few as 2  blasts in mixing experiments of tdt containing leukemic cells with normal peripheral lymphocytes  furthermore  the combined analysis of tdt and dna allowed the recognition of aneuploid tdt positive cells in four cases of all  the high sensitivity  the quantitative information obtained  and the capability of simultaneously analyzing dna content make this method of tdt analysis more valuable than conventional techniques  
class4	renal function after tumor enucleation in a solitary kidney  whether extensive ablation of renal mass in humans leads to progressive glomerulosclerosis  proteinuria  and hypertension  as it does in animal models  is a matter of controversy  we have studied kidney function in six patients who underwent enucleation of a renal cell carcinoma in a solitary kidney  four patients had previously had a nephrectomy  the two others each had one atrophic  nonfunctioning kidney  serum creatinine levels before surgery were within the normal range  mean  99 9 mumol l  1 13 mg dl    two weeks after tumor enucleation  creatinine levels were significantly higher than the preoperative values  mean  124 6 mumol l  1 41 mg dl    the follow up period varied from 10 to 23 months  in all patients  kidney function improved during the following months  serum creatinine levels nearly reached preoperative values in all patients  mean  105 2 mumol l  1 19 mg dl    none of the patients showed a progressive deterioration in renal function or proteinuria  we found a modest increase in blood pressure in two patients who had been normotensive before surgery  in conclusion  tumor enucleation in a solitary kidney did not cause significant renal injury to the remnant kidneys in our patients  at least in the short term  
class4	local reactions to radioiodine in the treatment of thyroid cancer  purpose  to compare the rate of local complications resulting from radioiodine ablation of thyroid cancer in patients with a residual intact thyroid lobe to that in patients who had more extensive surgical treatment prior to radioiodine administration  patients and methods  we retrospectively studied 59 patients who had received 131i between 1979 and 1989  the patients were divided into two groups  depending on the extent of their previous surgical thyroid excision  group 1 comprised 10 patients with a lobectomy or hemithyroidectomy before the ablative radioiodine dose  and group 2 comprised 49 patients with more extensive thyroid excision  near total or subtotal thyroidectomy  before the radioiodine treatment  results  sixty percent of the 10 patients in group 1 experienced some degree of neck pain or tenderness following radioiodine ablation of their residual thyroid  in one case  the local reaction was very severe and accompanied by the development of transient hyperthyroidism  there was only a 6  local complication rate in the patients who had undergone more extensive thyroid excision before ablative therapy  p less than 0 001   and none had a severe reaction  conclusions  patients with only unilateral surgical excision before radioiodine therapy have a higher rate of local complications than do patients treated with more extensive surgery prior to radioiodine ablation  if radioiodine is to be employed in such patients  they should be informed of this possible complication  since evidence supports a dose effect in the pathogenesis of the complications  we recommend using a dose of less than 30 mci for the initial ablation in these patients even though it may be necessary to repeat this dose to complete thyroid ablation  
class4	efficacy of fludarabine  a new adenine nucleoside analogue  in patients with prolymphocytic leukemia and the prolymphocytoid variant of chronic lymphocytic leukemia  purpose  to describe the results of fludarabine therapy in patients with prolymphocytic leukemia  pll  and the prolymphocytoid variant of chronic lymphocytic leukemia  cll pro   patients and methods  seventeen patients with a diagnosis of pll or cll pro received fludarabine 30 mg m2 over 30 minutes daily for 5 days every 4 weeks alone  12 patients   or with prednisone  five patients   previously defined criteria for response were used  differences in response rates according to various characteristics were evaluated by chi square test  results  three patients  18   achieved complete remission  and three  18   had a partial remission  for an overall response rate of 35   responses were durable and occurred in all involved organ sites  lower response rates were observed in patients with anemia  thrombocytopenia  advanced rai stages  and primary resistance to prior therapy  toxicities were minimal except for febrile episodes associated with therapy  conclusion  fludarabine has shown encouraging results in these patients and deserves further investigation in combination with other active agents  and in the setting of front line therapy  
class4	two cases of adult t cell leukemia associated with acute pancreatitis due to hypercalcemia  we report two cases of adult t cell leukemia associated with acute pancreatitis and hypercalcemia  after sudden onset of epigastralgia  acute pancreatitis and hypercalcemia were found in both patients  there were no diseases that could explain the acute pancreatitis except for hypercalcemia probably due to adult t cell leukemia  thus we considered that hypercalcemia due to adult t cell leukemia had led to acute pancreatitis  this is the first report of such a complication in adult t cell leukemia  
class4	suddenly symptomatic brain tumors at altitude  high altitude cerebral edema can present with a wide variety of neurologic manifestations  these symptoms resolve with descent  the persistence of neurologic symptoms after descent suggests an intracranial lesion  brain tumors suddenly becoming symptomatic at altitude have not been reported previously  we report three cases of previously unsuspected brain tumors that suddenly became symptomatic at high altitudes  
class4	melanoma in pregnancy  the clinical course of malignant melanoma in pregnancy has been a subject of controversy  but current evidence indicates that it is similar to the clinical course in non pregnant patients  early detection and biopsy of localized disease is crucial because early treatment provides an excellent prognosis  surgical excision is the primary therapy for this disease  as the primary care provider for many women in the reproductive age group  obstetrician gynecologists have an opportunity to detect these lesions at their earliest stages when they are amenable to cure  overall  maternal metastases to the fetus and placenta are very rare events and do not warrant elective termination based on the maternal diagnosis  however  a thorough examination of the infant and placenta should be done in all cases of melanoma complicating pregnancy  after treatment  long term follow up is recommended  since most recurrences develop within 3 years after the diagnosis  it remains prudent to recommend that these patients avoid a subsequent pregnancy during this interval  
class4	surgical staging of cervical cancer  noninvasive radiologic methods to detect paraaortic lymph node metastases are reliable when combined with fna of enlarged lymph nodes  however  the sensitivity is low  and undetected microscopic metastases leads to treatment failure  these patients with paraaortic lymph node metastasis are not treated with extended field radiation  and they all die within 3 years  the ct scanning is probably the best diagnostic method to evaluate cervical cancer  because it can assess the primary tumor  the urinary tract  gastrointestinal tract  liver parenchyma  and retroperitoneum  it also permits the guidance of fna and the arrangement of radiation ports  surgical staging provides the direct assessment of the peritoneal cavity and the retroperitoneal spaces  metastatic tumor  including enlarged lymph nodes  can be resected  but this is of dubious benefit  the operative morbidity is acceptable  with fewer intestinal complications when the extraperitoneal approach is used  and long term morbidity is minimal when appropriate paraaortic radiation doses are employed  less than 5 000 cgy   surgical staging has provided data on the frequency of paraaortic lymph node metastasis by stage of cervical cancer  and thus  treatment strategies can be better developed  extended field radiation results in 5 year survival rates of 20 25  in patients with microscopic paraaortic lymph node metastasis  patients who would not survive without the treatment  however  surgical staging has produced only a modest boost in survival rates  because of the high rate of pelvic and systemic failure  when extended field radiation is used prophylactically or in patients with probable lymph node metastasis seen on radiographic studies  survival rates are similar to patients irradiated after surgical staging finds paraaortic lymph node disease  as our ability to predict  and detect nonsurgically  positive paraaortic node disease improves  extended radiation  or other adjuvant therapy  could be used more frequently without operation in patients who are at high risk for metastatic disease  in a study by haie et al  prophylactic paraaortic radiation was given to patients at high risk for paraaortic metastasis  in patients with a high probability of local disease control  paraaortic radiation significantly reduced the incidence of paraaortic and distant metastases  patients with known paraaortic lymph node metastases frequently have occult systemic metastases  in these same patients  pelvic failure is also common  thus  until effective systemic therapies emerge  a marked improvement in survival is unlikely in patients who have paraaortic lymph node metastasis  abstract truncated at 400 words   
class4	surgery or radiation for early cervical cancer  in summary  neither radiation nor surgery is clearly superior  the benefits of surgery include  1  emotional satisfaction that the tumor has been removed  2  accuracy of surgical staging  3  preservation of the ovaries  4  no secondary uterine cancer  a very uncommon problem   and 5  complications that are more readily correctable  radiation offers the major advantages of being useful in most patients regardless of age or medical condition and is the choice for large cancers  because stage ib cervical cancer is a very diverse pathological entity with a number of potential prognostic factors  including cell type  depth of invasion  tumor volume  lymphatic space involvement  and occult lymph node metastases   and because patients present with a number of other conditions  including excess weight  advanced age  prior pelvic surgery or infection  and severe medical illness   we are fortunate to have two good methods for treating cervical cancer  prospective randomized studies will be necessary in the future to better define specific advantages in the various clinical settings  but  in general  the following have proven most expedient  1  class i hysterectomy  for microinvasive cancer of 3 mm invasion or less without lymphatic space involvement  2  modified  extended hysterectomy  class ii  and pelvic lymphadenectomy for lesions of 3 mm and lymph vascular space involvement or when the lesion seems to just exceed 3 mm and for very early adenocarcinoma  3  an extended hysterectomy  class iii  and pelvic lymphadenectomy for larger ia2  ib  and iia lesions that are less than 4 cm  particularly for the pregnant or younger patient  and when ovarian conservation is desired  4  radiation therapy is used for lesions over 4 cm and for women with severe medical illness making extended hysterectomy too hazardous  5  combination therapy and chemotherapy are now reserved for study in poor prognosis patients with very large lesions  greater than 6 cm   occult metastases  and unfavorable histologic criteria  table 2   
class4	the management of malignant bone tumors in children and adolescents  a series of 205 pediatric patients affected by osteosarcoma  ewing s sarcoma  fibrosarcoma  and malignant fibrous histiocytoma of bone were treated from 1978 to 1988  ninety eight percent of the patients received chemotherapy and 63  had a surgical resection  sixty five percent of all patients were alive at 30 months and were considered disease free  the functional results after surgery were evaluated according to the musculoskeletal tumor society score  in all diaphyseal resections and resections of the upper extremity and pelvis  the results were excellent or good in 60  of the cases  in resections of the proximal femur  distal femur  or proximal tibia and reconstruction with nonexpansible prostheses  the results were excellent or good in 75   on the other hand  when arthrodeses of the lower extremity were used  only 14  of cases had a good result  this correlates with the resulting lack of articulation and serious limb shortening seen with progression of skeletal growth  
class4	dexamethasone nonsuppressible cortisol in two cases with aldosterone producing adenoma  forty one patients with aldosterone producing adenoma  apa  were subjected to a dexamethasone suppression test  dst  before surgery  serum cortisol and urinary excretion of 17 hydroxycorticosteroids were suppressed by dexamethasone in 39 patients  dst      in two patients  cases a and b   they were not suppressed  dst      clinical manifestations of the two dst    patients were similar to those of dst    patients  hypertension  hypokalemia  high serum aldosterone levels  and suppressed pra were found in all of the patients  the cut surfaces of the adenomas from all of the patients  including cases a and b  were golden yellow  which is typical of apa  however  atrophies of the adjacent normal tissues were evident exclusively in the two dst    patients  after removal of the affected adrenals  the serum cortisol level was suppressed by dexamethasone in one of the dst    patients  case b   these findings suggested autonomous cortisol production by apa  to evaluate whether cortisol could be produced from the adenoma tissue  the presence of several steroidogenic enzymes was studied by immunohistochemistry and mrna analysis in the adenomas and the adjacent nonneoplastic adrenals from the 2 dst    and 5 dst    patients  immunohistochemical analysis demonstrated that steroidogenic enzymes were expressed in apa tumor tissues from both dst    and dst    patients  in both groups  mrnas coding steroidogenic enzymes were present not only in the nonneoplastic but also in the tumor tissues  quantitative analysis of the mrna levels revealed that in the adrenals from dst    patients  the mrnas were more abundant in nonneoplastic tissue than in tumor tissue  however  in those from dst    cases  the mrnas were much more abundant in the tumor tissues than in the nonneoplastic tissues  these results indicate that tumor cells of the two dst    patients autonomously synthesized not only aldosterone but also cortisol  the diameters of the tumors from the two dst    patients exceeded 3 cm  while those from other dst    patients were smaller  in patients with large apa  adrenal insufficiency should be anticipated upon removal of the tumor  
class4	preliminary characterization of growth factors secreted by human pituitary tumors  to investigate the secretion of mitogenic factors by human pituitary tumors we have cultured cells from 54 adenomas in serum free medium  conditioned media from 28  52   elicited dose dependent stimulation of  3h thymidine incorporation into rat gh3 cells  22 338  above control   while 14  26   inhibited gh3 proliferation  stimulating activity was observed more frequently in nonfunctional tumor conditioned medium  73   n   22  than in secretory tumor conditioned medium  37   n   32   of 10 tumour conditioned media with mitogenic activity for gh3 cells  only 4 produced modest stimulation of hep2  human laryngeal carcinoma  cells  in contrast   3h thymidine incorporation into a431  human squamous carcinoma  and pc12  rat adrenal pheochromocytoma  cells was enhanced by each of 15 tumor conditioned media  up to 342  and 275   respectively   8 of which had shown stimulatory and 2 inhibitory effects on gh3 cells  gel filtration of pooled conditioned media from 10 nonfunctional tumors showed significant growth promoting activity for gh3 cells in fractions corresponding to mol wt of 2 3 and 11 18 kda  proliferative activity on a431 cells also eluted in two positions  one corresponded to the higher mol wt peak seen with gh3 cells  while the other  not observed with gh3 cells  was in the 3  to 6 kda range  these findings suggest that cells derived from human pituitary adenoma tissue synthesize and secrete several growth factors  each of which may have its own target cell specificities  these factors have yet to be characterized  but we suggest that they may have a role in stimulating the development or maintenance of human pituitary adenomas  
class4	endothelial markers in malignant vascular tumours of the liver  superiority of qb end 10 over von willebrand factor and ulex europaeus agglutinin 1  a new monoclonal antibody  qb end 10  raised against the cd34 antigen in human endothelial cell membranes and haemopoietic progenitor cells  was studied for its usefulness as a marker of neoplastic vascular cells in 21 angiosarcomas and seven malignant haemangioendotheliomas of the liver  qb end 10 was both more sensitive and more specific than von willebrand factor  vwf  and ulex europaeus 1 agglutinin  uea 1  in labelling endothelial cells and it did not cross react with epithelia as uea 1 often does  staining was uniformly strong and clear in all histological variants of these two tumours  qb end 10 should prove particularly useful in the differential diagnosis of malignant vascular tumours of the liver  
class4	interphase cytogenetics using biotin and digoxigenin labelled probes  iii  increased sensitivity and flexibility for detecting hpv in cervical biopsy specimens and cell lines  a monoclonal antibody to digoxin enabled sandwich techniques to be used for the detection of hybridised digoxigenin labelled probes in cultured cells and paraffin wax sections  this system has greater flexibility than alkaline phosphatase conjugated polyclonal antidigoxigenin antibody and permits the use of alternative detector enzymes  such as horseradish peroxidase and fluorescence labels  the apaap detection system that does not require the use of biotin can also be used in situations where endogenous biotin is a problem  the low level of background staining combined with precise substrate deposition of the amplified peroxidase system gives higher sensitivity and resolution  this permits localisation of closely adjacent chromosomal loci in interphase nuclei  the most sensitive peroxidase based digoxigenin detection system visualises two and a half to 12 copies of human papillomavirus  hpv  per nucleus  this system is also suitable for the analysis of low copy number hpv infection of cervical tissues  
class4	chromosomes in childhood acute lymphoblastic leukaemia  karyotypic patterns in disease subtypes  to define further the clinical importance of cytogenetic analysis in acute lymphoblastic leukaemia  all  a prospective study was performed on 139 unselected children  analyses were considered adequate in 104  of whom 35 were normal and 69 had clonal abnormalities  abnormalities were categorised according to banded chromosome analysis as well as chromosome count  karyotypes were correlated with clinical and laboratory features at diagnosis and with survival  of the successful analyses  thirty five  34   children had no abnormalities  this group contained an excess of t cell disease  twenty five  24   had a  characteristic  hyperdiploid karyotype and as a group had lower presenting white counts  a tendency to cd10  and periodic acid schiff positivity of the blast cells and smaller spleens  none was an infant and only one was over 10 years old  seven  7   children with t 9  22   t 8  14   or t 4  11  translocations were grouped together as  specific  translocations  collectively they had a significantly worse prognosis than the remainder  nine children developed central nervous system relapse  six of whom had either t 4  11  or abnormalities of 9p or 19p  a descriptive classification taking into account chromosome bonding pattern is cytogenetically more appropriate and may be more clinically useful than grouping children simply by chromosome number  as knowledge and techniques improve  the classification of cytogenetic abnormalities in all will need to be kept under frequent review  
class4	increased serum beta 2 microglobulin concentrations in hyperthyroid states  serum beta 2 microglobulin concentrations were determined in 21 untreated hyperthyroid patients  12 with graves  disease  and nine with toxic nodular adenoma  and in 20 healthy controls  all subjects had normal serum creatinine concentrations and urine analysis  both total and free thyroid hormones were significantly higher in the hyperthyroid groups than in controls  beta 2 microglobulin concentrations were significantly increased in both groups of hyperthyroid patients compared with controls  no difference was found in the thyroid hormone and beta 2 microglobulin concentrations between both sets of patients  the beta 2 microglobulin and thyroid hormone concentrations were not correlated  these data show that hyperthyroidism is another cause of increased beta 2 microglobulin production along with viral infections  immunologically mediated diseases  and malignant neoplasms  the increased serum beta 2 microglobulin concentration in thyroid hyperfunction is probably related to metabolic rate  even if autoimmunity might contribute to its overproduction  
class4	mechanical ventilation in medical and neurological diseases  11 years of experience  mechanical ventilation  mv  is imperative in many forms of acute respiratory failure  arf   the aim of this work was to review all episodes of mv in a medical intensive care unit  micu  during the 11 year period 1976 1986  four per cent  n   1008  of 24 899 admissions to the micu were treated with mv  the mean age of ventilator treated patients was 53     18 years  and obviously it increased during the period of study  the average duration of mv was 4 7 d  micu mortality  hospital mortality and 2 year mortality rates for patients subjected to mv were 33   38  and 46   respectively  the mortality rate did not change during the study period  cerebrovascular and malignant diseases carried the highest mortality rates  75 and 79   respectively  whereas mortality in patients ventilated because of drug overdose  n   313  was only 2   the results of this study confirm previously published findings concerning the outcome of mv  and we conclude that the effects of mv remain discouraging in medical and neurological patients  improved quality of ventilator therapy and monitoring  as well as continued research directed at the causes of arf  are equally important in reducing the mortality in arf  
class4	gastric lymphoma causing granulocytopenia and cold intolerance  with recovery after treatment  a 34 year old man was found to have granulocytopenia with a white blood count of 2 3 x 10 9  l 1  consisting of 10  segmented neutrophils  50  monocytes and 40  lymphocytes  a bone marrow aspirate showed 20  promyelocytes and 10  blasts with monoblastic features  and a smouldering myelomonocytic leukaemia was considered to be a possible diagnosis  in cold weather the patient experienced cold intolerance with acrocyanosis and small ulcerations on the ears  the test for heparin precipitable protein   cryofibrinogen   was strongly positive  during the following year  these signs and symptoms persisted  and the patient also developed constant moderate pain in the epigastric region  gastroscopy revealed a large lymphoma of the stomach  which was a high grade malignant centroblastic type of non hodgkin s lymphoma  after successful removal of the tumour  and six courses of potent cytostatic combinations  the patient recovered completely  and the granulocytopenia and cold intolerance disappeared  
class4	familial hypobetalipoproteinaemia complicated by cerebellar ataxia and steatocystoma multiplex  a 55 year old man with cerebellar ataxia and steatocystoma multiplex was found to have reduced serum concentrations of total cholesterol  betalipoprotein and apolipoprotein b  computed tomography revealed atrophy of the cerebellum and brain stem  of the six family members examined  four had hypobetalipoproteinaemia  and one had mild ataxia  similar skin lesions were noted in five male relatives  this case represents a rare combination of familial hypobetalipoproteinaemia  cerebellar ataxia and steatocystoma multiplex  
class4	lymphoma presenting as a popliteal mass in a patient with rheumatoid arthritis  a patient with hla b27 and rheumatoid factor positive rheumatoid arthritis presented with a painless swelling in his popliteal fossa  clinical features were atypical for a baker s cyst  and subsequent investigation showed this lesion to be a primary malignant lymphoma  
class4	the role of adjuvant chemotherapy following cystectomy for invasive bladder cancer  a prospective comparative trial  we assigned 91 patients with deeply invasive  pathological stage p3  p4 or n  and mo transitional cell carcinoma of the bladder  with or without squamous or glandular differentiation  to adjuvant chemotherapy or to observation after radical cystectomy and pelvic lymph node dissection  for most patients chemotherapy was planned as 4 courses at 28 day intervals of 100 mg  m 2 cisplatin  60 mg  m 2 doxorubicin and 600 mg  m 2 cyclophosphamide  a significant delay was shown in the time to progression  p   0 0010  with 70  of the patients assigned to chemotherapy free of disease at 3 years compared to 46  in the observation group  median survival time for patients in the chemotherapy group was 4 3 years compared to 2 4 years in the observation group  p   0 0062   in addition to treatment groups  important prognostic factors included age  gender and lymph node status  the number of involved lymph nodes was the single most important variable  we recommend adjuvant chemotherapy for patients with invasive transitional cell carcinoma after definitive surgical resection  
class4	spontaneous perinephric hemorrhage  imaging and management  we report on 10 patients with spontaneous perinephric hemorrhage associated with underlying disease  including renal cell carcinoma  5   angiomyolipoma  2   malignant melanoma  1   periarteritis nodosa  1  and severe portal hypertension  1   the etiology could not be identified with computerized tomography  ct  in 5 cases  50    including 2 renal cell carcinomas  1 angiomyolipoma  1 periarteritis nodosa and 1 portal hypertension  arteriography demonstrated underlying lesions in 4 of these 5 cases  80   including the case of vasculitis  ct combined with magnetic resonance imaging is accurate for the diagnosis of spontaneous perinephric hemorrhage but the underlying pathological condition is often undetectable in the acute phase due to the perinephric blood  ct should be the first study performed if this diagnosis is suspected  arteriography is recommended if a renal mass is not detected  if a mass is not identified with these 2 imaging studies and the patient is clinically stable  followup thin slice ct should be performed  
class4	partial nephrectomy for renal cell carcinoma  indications  results and implications  of 52 patients who underwent partial nephrectomy for tumor 44 were found to have renal cell carcinoma  the indications for this parenchyma sparing procedure were categorized according to the initial status of the contralateral kidney and included bilateral tumors or tumor in a solitary kidney in 16 patients  mandatory indications   unilateral carcinoma with compromise of the contralateral kidney by a benign disease process in 9  relative indications  and small peripheral tumor with a normal contralateral kidney in 19  elective indications   there were 4 recurrences that accounted for 3 deaths  all in patients with mandatory indications  all patients who underwent partial nephrectomy for relative or elective indications were without definite evidence of recurrent disease at last followup  over all mean 36 months   our results suggest that conservative surgery can often provide effective and advantageous therapy for renal cancer and we encourage further consideration of the role of partial nephrectomy as an alternative to radical nephrectomy in selected patients with small peripheral tumors and normal contralateral kidneys  
class4	a seromuscular stripping method to create a nipple valve without metal stapling for continent urinary reservoir  urinary continence with a kock or mainz pouch is achieved by a nipple valve of the invaginated ileum which is usually fixed with metal staples  however  metal staples can cause various complications as a foreign body  the seromuscular stripping method  a new technique to create a nipple valve  was applied to 17 patients with bladder cancer in the construction of a continent urinary reservoir by the ileocolonic pouch  mainz pouch   metal staples were not used  the results were satisfactory except for 2 patients who became incontinent because of prolapse of the nipple in one and insufficient valve function due to ischemic change of the nipple valve in the other  histology of the nipple valve from an autopsy case showed a good double layer nipple valve that functioned well to preserve continence  
class4	sensitivity of urinary quantitative immunocytology with monoclonal antibody 486 p3 12 in 241 unselected patients with bladder carcinoma  we investigated the sensitivity of quantitative immunocytology with our monoclonal antibody 486 p3 12 in 241 unselected patients with transitional cell carcinoma  immunocytology yielded a sensitivity of 91 8   89 4  and 92 9  for grade 1  2 and 3 tumors  respectively  standard cytology was positive in 59 2   63 8  and 84 7   respectively  deoxyribonucleic acid flow cytometry  used in the first 69 patients  was positive in only 27 7   48 6  and 57 1   respectively  
class4	oral or intravesical bacillus calmette guerin immunoprophylaxis in bladder carcinoma  a total of 71 patients with superficial transitional cell carcinoma underwent transurethral resection of bladder tumor  all patients had stage pta or pt1 transitional cell carcinoma or carcinoma in situ without other concurrent malignancies  the patients were assigned to 3 treatment groups  control group  transurethral resection discontinued within the study  oral bacillus calmette guerin  bcg  group  transurethral resection of bladder tumor plus bcg  moreau  and intravesical bcg group  transurethral resection of bladder tumor plus bcg  of 9 patients in the control group 8  89   experienced tumor recurrence during a mean followup of 20 months  of the 28 patients in the oral bcg group 11  39 3   had recurrence during a mean followup of 36 months  of the 34 patients in the intravesical group 6  18   had recurrence in a 24 month mean followup  the incidence of complications was higher in the intravesical  41 2   than in the oral bcg group  28 5    these results show that intravesical bcg is a more effective immunotherapy  however  oral bcg can be used in patients who do not accept intravesical bcg administration  
class4	ileocolic neobladder post cystectomy  continence and potency  incontinence and impotence are 2 of the primary complications associated with total bladder reconstruction after cystectomy for carcinoma  these and other features are addressed in 25 patients who underwent total neobladder reconstruction following cystectomy for transitional cell carcinoma  of these patients 20 had a urethral anastomosis  no patient had to wear a pad or device  enuresis was rare  when the radical cystoprostatectomy population was contrasted with a radical prostatectomy patient population  continence was achieved more rapidly in the neobladder group  potency was maintained in 15 of 21  71   evaluable patients  this ileocolic neobladder produces a large volume and low pressure  and provides excellent day and night continence  with preservation of the neurovascular bundle potency can be maintained in the majority of patients  
class4	impact of anatomical radical prostatectomy on urinary continence  urinary continence following an anatomical approach to radical prostatectomy was evaluated in 593 consecutive patients  547  92   of whom achieved complete urinary control  stress incontinence was present in 46 patients  8    of whom 34  6   wore 1 or fewer pads per day and 2  0 3   required placement of an artificial sphincter  no patient was totally incontinent  age  weight of the prostate  prior transurethral resection of the prostate  pathological stage and preservation or wide excision of the neurovascular bundles had no significant influence on preservation of urinary control  these data suggest that anatomical factors rather than preservation of autonomic innervation may be responsible for the improved urinary control associated with an anatomical approach to radical prostatectomy  
class4	correlation of ultrasound guided and digitally directed transrectal biopsies of palpable prostatic abnormalities  the authors evaluated 51 patients with palpable prostatic abnormalities detected during digital rectal examination  these findings consisted of a nodule or an area of induration  each palpable abnormality was confined to 1 prostatic lobe and there was no suggestion of extracapsular extension of neoplasm or systemic metastatic disease  all patients underwent 7 0 mhz  sagittal ultrasound guided transrectal biopsy followed by digitally directed transrectal biopsy  biopsies were obtained only from the area of interest  the procedure was performed in the outpatient clinic without use of sedation or anesthesia  digitally directed biopsies were positive for adenocarcinoma in 9 lesions  ultrasound guided biopsies detected adenocarcinoma in 23 lesions  including all those detected by the blind digitally directed technique  this study demonstrates greater diagnostic accuracy using 7 0 mhz  ultrasound guided techniques and its routine use is warranted in the evaluation of palpable prostatic abnormalities  
class4	radical prostatectomy and adjuvant radioactive gold seed placement  results of treatment at 5 and 10 years for clinical stages a2  b1 and b2 cancer of the prostate  between 1977 and 1988  131 patients with adenocarcinoma of the prostate underwent combined radical prostatectomy and intraoperative radioactive gold seed placement  of these 131 patients 80 were clinically assessed as having stage a2  12   b1  43  or b2  25  cancer and they are the subject of this review  the average dose of radioactivity administered to each patient was 96 6 mci  and mean followup was 65 months  median 64 months   no patient in this series received any other form of adjuvant therapy until disease recurrence was demonstrated  local recurrences were observed in 2 patients  2 5   in this series while distant recurrences were observed in 10  12 5    cancer specific survival free of disease at 5 years was 100  for clinical stage a2  91  for b1 and 75  for b2 cancers  the 10 year survival free of disease was 100  for clinical stage a2  82  for b1 and 68  for b2 cancers  covariants of clinical stage and seminal vesicle involvement influenced survival free of disease in a statistically significant manner  p less than 0 05  while pathological stage and degree of tumor differentiation did not  mild to severe complications were observed in 12 patients  15    intraoperative placement of radioactive gold seeds into unresected pelvic tissues surrounding the site of prostatectomy offers a theoretical advantage in treatment by delivering tumoricidal levels of irradiation to residual foci of cancer not appreciated at the time of surgery  our results suggest that increases in cancer specific survival free of disease over that previously reported for prostatectomy alone may be achieved through this combined treatment regimen  furthermore  it is our opinion that therapeutic gains can be achieved without the attendant increases in morbidity and treatment delay often associated with adjuvant external beam radiotherapy  
class4	preoperative endoscopic diagnosis of fibroepithelial polyp of the renal pelvis  a case report and review of the literature  benign fibroepithelial polyps of the renal pelvis are rare  with only 9 cases described previously in the literature  we report an additional case and suggest how nephrectomy may be avoided  
class4	nonspecific magnetic resonance appearance of renal oncocytomas  report of 3 cases and review of the literature  we report the magnetic resonance appearance of 3 cases of solitary renal oncocytomas  all lesions were of low to moderate signal intensity on t1 weighted images and became considerably brighter on the more heavily t2 weighted images  one lesion contained a large central area of cystic degeneration  while the other 2 were solid  a central stellate scar was present in the smaller of the 2 solid lesions  our observations lend further support to earlier reports on the nonspecific magnetic resonance features of oncocytomas  
class4	surgical management of renal cell carcinoma with extensive intracaval involvement using a venous bypass system suitable for rapid conversion to total cardiopulmonary bypass  renal cell carcinoma involves the vena cava in approximately 4  of the patients  presently surgical extirpation is the only form of therapy that can result in cure  recently management of extensive vena caval involvement has involved the use of cardiopulmonary bypass with circulatory arrest and hypothermia  we describe a technique using a venous bypass pump system  femoral vein to right atrium  for resection of renal cell carcinoma with suprahepatic vena caval extension  type ii   which avoids the risks and complications of cardiac arrest and hypothermia but allows for rapid conversion to total cardiopulmonary bypass should the intraoperative need arise  
class4	assessment of the critical level of androgen for growth response of transplantable human prostatic carcinoma  pc 82  in nude mice  the androgen dependent prostatic carcinoma of human origin  pc 82  was used as a model system to investigate the effect of various levels of androgen on the growth of prostatic tumor tissue  plasma testosterone levels in mice were correlated to tumor growth and intratumor concentrations of testosterone and 5 alpha dihydrotestosterone  pc 82 tumor burden remained stable at plasma testosterone levels of 0 8 nmol l   whereas tumor growth occurred at higher levels and tumor regression was observed at lower plasma levels  this critical level of testosterone corresponded with intratumor testosterone and 5 alpha dihydrotestosterone concentrations of six to 10 and three to four pmol gm  tissue  respectively  which are significantly above the levels found in castrated non supplemented animals  3 1 and 1 4 pmol gm  respectively   this indicates that remaining concentrations of dihydrotestosterone  which amount to two to three times the castrate level  are not stimulatory for tumor growth in the model of the androgen dependent pc 82 tumor  
class4	experimental intravesical therapy for superficial transitional cell carcinoma in a rat bladder tumor model  a rodent bladder cancer model that is induced by intravesical instillation of n methyl n nitrosourea  mnu  was characterized  cohorts of four to five week old female fisher 344 rats received four biweekly 1 5 mg  doses of intravesical mnu and were sacrificed at various intervals  by week 13 all animals had flat atypia and or papillary transitional cell tumors  and 67  of the lesions were moderately  grade ii  or poorly differentiated  grade iii   by week 20  83  had gross muscle invasive tumors that eventually killed the host  a cohort of 40 mnu treated animals was subsequently treated commencing at week 17 after initiation of mnu with one of three intravesical six week regimens  1  saline  2  bcg  tice strain   or 3  recombinant human tumor necrosis factor  rtnf  plus adriamycin  there was no difference in animal survival or tumor growth in any group of animals commencing therapy at week 17  a second cohort of 107 animals commenced therapy at 13 weeks after initiation of mnu with one of five intravesical six week regimens  1  intravesical bcg  tice strain   2  adriamycin  3  recombinant human tumor necrosis factor  rtnf   4  rtnf plus adriamycin  or 5  bcg plus adriamycin  bcg  rtnf or adriamycin alone had no effect on tumor growth  however  bcg plus adriamycin and rtnf plus adriamycin commencing at week 13 significantly inhibited tumor growth and progression  in conclusion  this autochthonous intravesical rodent transitional cell carcinoma model appears useful for the following reasons  1  it closely resembles human transitional cell carcinoma histologically and biologically in that all animals develop neoplastic changes in situ that progress to muscle invasion and kill the host  2  as with human bladder cancer these tumors do not respond to intravesical therapy if treated when tumor burden is large  however  tumor growth is inhibited when treated early  and 3  this model appears appropriate for screening and developing new intravesical treatments for superficial bladder cancer  
class4	the effects of interleukin 6 on tumor infiltrating lymphocytes derived from human renal cell cancer  tumor infiltrating lymphocytes  til  are a heterogeneous population of t cells with potent antitumor activity against a wide variety of tumors  til from renal cell cancer  rcc  typically exhibit diminished growth and antitumor activity after four weeks in vitro  we have therefore investigated effects of varying doses of interleukin 6  il 6   0  25  100 units ml   on in vitro expansion  proliferation  cytotoxicity  and expression of cell surface phenotypes of long term renal til cultures from three rcc patients  among the various conditions tested  three of three til cultures displayed a mild increase in cell expansion when grown in il 2 with the addition of 100 units ml  of il 6  two of three til cultures grown in il 2 and 100 u ml  of il 6 demonstrated enhanced proliferation as determined by 3h thymidine uptake  til could not be isolated or maintained in vitro when grown in the presence of il 6 alone without il 2  il 6 was also found to enhance the long term non specific cytotoxicity against an allogeneic nonrenal tumor target  no consistent effect on autologous tumor specific cytotoxicity was demonstrated  we conclude that il 6  when used in combination with il 2  may modestly enhance the long term growth of rcc derived til  
class4	bladder perforation resulting from the use of the neodymium yag laser  complications resulting from the use of the neodymium yag  nd yag  laser to treat superficial bladder cancer are uncommon and are usually associated with abnormally high laser power outputs  we report a case of bladder perforation in a human attributed to the nd yag laser used at a low power setting and comment on those factors that contributed to this complication  
class4	generation of  soft x rays  by using the free electron laser as a proposed means of diagnosing and treating breast cancer  the diagnosis and treatment of breast lesions may be markedly enhanced by the use of a unique new source of near monochromatic x rays  concentric beams of near monochromatic x ray photons may be generated by collision of the free electron laser  fel  electron beam with the optical beam in an interaction zone that delivers the x rays to a shirtsleeve environment  the absence of compton scatter and the photoelectric interaction within tissues improves conspicuity of lesions by two to six times  increased attenuation of x rays in malignant vs  normal tissues makes tumors more obvious  k edge subtraction allows chemical analysis of tumors in vivo  all at radiation doses that are one tenth to one fiftieth that delivered by the lowest dose mammographic x ray technique available  this allows for an increased sensitivity and specificity and permits prediction of histology  negating necessity for biopsies  selective bond breaking at depth in tissues as well as x ray activated photodynamic therapy are also being explored  
class4	endometrial ablation for the treatment of menorrhagia  a comparison of patients with normal  enlarged  and fibroid uteri  one hundred sixty one patients underwent endometrial ablation with the nd yag laser for the treatment of refractory menorrhagia  patients were divided into one of three groups  those with a normal sized uterus  those with an enlarged uterus  greater than 10 cm   and those with uterine fibroids  which had been documented clinically  ultrasonographically  or by a combination of hysteroscopy and laparoscopy or by one or the other  all patients were considered candidates for hysterectomy  both preoperatively and postoperatively  patients monitored their menstrual cycles and evaluated their flow according to predetermined categories of amenorrhea  light flow  normal flow  heavy flow  and severe flow  after treatment  68  of patients with normal sized uterus and 91  of patients with an enlarged uterus  greater than 10 cm  and 88  of patients with uterine fibroids became amenorrheic or had light flow  none of the patients in this last group have had to undergo hysterectomy  this study indicates that the patient with an enlarged or fibroid uterus may not have contraindications for endometrial ablation  endometrial ablation may be effective in at least temporarily controlling bleeding in those patients with enlarged or myomatous uterus  
class4	effective surgical adjuvant therapy for high risk rectal carcinoma background  radiation therapy as an adjunct to surgery for rectal cancer has been shown to reduce local recurrence but has not improved survival  in a previous study  combined radiation and chemotherapy improved survival significantly as compared with surgery alone  but not as compared with adjuvant radiation  which many regard as standard therapy  we designed a combination regimen to optimize the contribution of chemotherapy  decrease recurrence  and improve survival as compared with adjuvant radiation alone  methods  two hundred four patients with rectal carcinoma that was either deeply invasive or metastatic to regional lymph nodes were randomly assigned to postoperative radiation alone  4500 to 5040 cgy  or to radiation plus fluorouracil  which was both preceded and followed by a cycle of systemic therapy with fluorouracil plus semustine  methyl ccnu   results  after a median follow up of more than seven years  the combined therapy had reduced the recurrence of rectal cancer by 34 percent  p   0 0016  95 percent confidence interval  12 to 50 percent   initial local recurrence was reduced by 46 percent  p   0 036  95 percent confidence interval  2 to 70 percent   and distant metastasis by 37 percent  p   0 011  95 percent confidence interval  9 to 57 percent   in addition  combined therapy reduced the rate of cancer related deaths by 36 percent  p   0 0071  95 percent confidence interval  14 to 53 percent  and the overall death rate by 29 percent  p   0 025  95 percent confidence interval  7 to 45 percent   its acute toxic effects included nausea  vomiting  diarrhea  leukopenia  and thrombocytopenia  these effects were seldom severe  severe  delayed treatment related reactions  usually small bowel obstruction requiring surgery  occurred in 6 7 percent of all patients receiving radiation  and the frequencies of these complications were comparable in both treatment groups  conclusions  the combination of postoperative local therapy with radiation plus fluorouracil and systemic therapy with a fluorouracil based regimen significantly and substantively improves the results of therapy for rectal carcinoma with a poor prognosis  as compared with postoperative radiation alone  
class4	clinical importance of myeloid antigen expression in acute lymphoblastic leukemia of childhood  background  leukemic cells in 15 to 25 percent of patients with acute lymphoblastic leukemia  all  express myeloid antigens as well as lymphoid antigens  the latter reflecting b cell or t cell lineage   the relations of myeloid antigen expression to other features of all and to prognosis have been controversial  methods  we analyzed clinical and laboratory features present at diagnosis in 236 consecutive cases of all in children  immunophenotyping  including single  and dual fluorescence analyses  was used to classify leukemic cells as b or t lymphoblasts and also to identify myeloid antigen expression  the simultaneous expression of lymphoid associated antigens and at least one of three myeloid associated antigens  cd33  cd13  and cd14  on cells classified as l1 or l2 according to the french american british system  results  forty five of 185 patients with b lineage all had myeloid antigen expression  as did 8 of 41 patients with t lineage all  in 10 patients  the lineage could not be determined  myeloid antigen expression was associated with l2 morphology  p less than 0 05   but it did not correlate with other prognostic features recognized previously  multivariate analysis showed that myeloid antigen expression was an important predictor of relapse in childhood all and the most significant prognostic factor statistically  p less than 0 0001   a white cell count greater than or equal to 50 x 10 9  per liter at diagnosis was also an important and highly significant prognostic feature  p less than 0 001   after 40 months  the estimated disease free survival for patients with all was 84 percent for those without myeloid antigen expression and with a low white cell count  57 percent for those without myeloid antigen expression and with a high white cell count  47 percent for those with myeloid antigen expression and a low white cell count  and 26 percent for those with myeloid antigen expression and a high white cell count  p less than 0 00001   conclusions  myeloid antigen expression is an important independent predictor of a poor response to chemotherapy in childhood all  
class4	late cardiac effects of doxorubicin therapy for acute lymphoblastic leukemia in childhood background  cardiotoxicity is a recognized complication of doxorubicin therapy  but the long term effects of doxorubicin are not well documented  we therefore assessed the cardiac status of 115 children who had been treated for acute lymphoblastic leukemia with doxorubicin 1 to 15 years earlier in whom the disease was in continuous remission  methods  eighteen patients received one dose of doxorubicin  45 mg per square meter of body surface area   and 97 received multiple doses totaling 228 to 550 mg per square meter  median  360   the median interval between the end of treatment and the cardiac evaluation was 6 4 years  our evaluation consisted of a history  24 hour ambulatory electrocardiographic recording  exercise testing  and echocardiography  results  fifty seven percent of the patients had abnormalities of left ventricular afterload  measured as end systolic wall stress  or contractility  measured as the stress velocity index   the cumulative dose of doxorubicin was the most significant predictor of abnormal cardiac function  p less than 0 002   seventeen percent of patients who received one dose of doxorubicin had slightly elevated age adjusted afterload  and none had decreased contractility  in contrast  65 percent of patients who received at least 228 mg of doxorubicin per square meter had increased afterload  59 percent of patients   decreased contractility  23 percent   or both  increased afterload was due to reduced ventricular wall thickness  not to hypertension or ventricular dilatation  in multivariate analyses restricted to patients who received at least 228 mg of doxorubicin per square meter  the only significant predictive factors were a higher cumulative dose  p   0 01   which predicted decreased contractility  and an age of less than four years at treatment  p   0 003   which predicted increased afterload  afterload increased progressively in 24 of 34 patients evaluated serially  71 percent   reported symptoms correlated poorly with indexes of exercise tolerance or ventricular function  eleven patients had congestive heart failure within one year of treatment with doxorubicin  five of them had recurrent heart failure 3 7 to 10 3 years after completing doxorubicin treatment  and two required heart transplantation  no patient had late heart failure as a new event  conclusions  doxorubicin therapy in childhood impairs myocardial growth in a dose related fashion and results in a progressive increase in left ventricular afterload sometimes accompanied by reduced contractility  we hypothesize that the loss of myocytes during doxorubicin therapy in childhood might result in inadequate left ventricular mass and clinically important heart disease in later years  
class4	chemotherapy of brain metastases from lung carcinoma  a controlled randomized study  a controlled randomized study was carried out to evaluate the effects of chemotherapy in patients with brain metastases from lung carcinoma  one hundred patients were randomly divided into three groups at the time of diagnosis or after surgery for metastases  group a received radiotherapy alone  group b received radiotherapy and chloroethylnitrosoureas  methyl ccnu  100 120 mg m2  or acnu 80 100 mg m2  every 6 8 weeks   and group c received radiotherapy and a combination of chloroethylnitrosoureas and tegafur  300 mg m2  daily   of the 100 patients  88 could be evaluated  the reduction rates of the tumors of the patients in whom tumor was not surgically removed or not totally removed were compared  complete resolution of the tumor was noted in 29  69  and 63  of the patients in groups a  b  and c  respectively  tumor regression of greater than or equal to 50  was seen in 36  69  and 74  of the patients in groups a  b  and c  respectively  the difference in the response rates of groups a and c was statistically significant  p less than 0 05   median survival after the start of treatment for brain metastasis was 27  30 5  and 29 weeks in groups a  b and c  respectively  there was 1 long term survivor  more than 5 years  in group a  3 in group b  and 1 in group c  the main cause of death was deterioration attributable to the primary lesion or systemic metastasis  and no statistical difference was noted in survival time among the groups  
class4	interstitial irradiation and hyperthermia for the treatment of recurrent malignant brain tumors  between june 1987 and june 1989  29 recurrent malignant gliomas or recurrent solitary brain metastases in 28 patients were treated in a phase i study of interstitial irradiation and hyperthermia  patient age ranged from 18 to 65 years  and the karnofsky performance status scores ranged from 40 to 90   there were 13 glioblastomas  10 anaplastic astrocytomas  3 melanomas  and 3 adenocarcinomas  catheters were implanted stereotactically after computed tomography based preplanning  hyperthermia was administered before and after brachytherapy  using one to six 2450  or 915 mhz helical coil microwave antennas and one to three multisensor fiberoptic thermometry probes  the goal was to heat as much of the tumor as possible to 42 5 degrees c for 30 minutes  within 30 minutes after the first hyperthermia treatment  implant catheters were afterloaded with high activity iodine 125 seeds delivering tumor doses of 32 6 to 61 0 gy  most patients had no sensation of heating  complications included seizures in 5 patients  reversible neurological changes in 9 patients  a scalp burn in 1  and infections in 3  of 28 evaluable 2 month follow up scans  11 showed definite improvement in the radiological appearance of the tumor  4 were slightly improved  7 were stable  and 6 showed tumor progression  ten patients underwent reoperation for persistent tumor and or necrosis  eleven of 28 patients are alive 40 to 97 weeks after treatment  thirteen patients died of a brain tumor  2 died of extracranial melanoma metastases  1 died of new brain melanoma metastases  and 1 died of a pulmonary embolus  the median survival was 55 weeks overall  median survival has not yet been reached for the anaplastic astrocytoma subgroup  we conclude that interstitial brain hyperthermia using helical coil microwave antennas is technically feasible  the level of toxicity is acceptable  and the computed tomographic response rate is encouraging  
class4	expression of platelet derived growth factors  transforming growth factors  and the ros gene in a variety of primary human brain tumors  ribonucleic acid was isolated from a wide spectrum of central nervous system tumors to examine the expression of platelet derived growth factors  pdgf  a and b  tumor growth factors  tgf beta  1 and 2  and ros messenger ribonucleic acid  eight glioblastoma cell lines were examined as well as cell cultures from 22 tumor explants  the explants included 6 glioblastomas  4 anaplastic astrocytomas  5 astrocytomas  3 ependymal tumors  2 meningiomas  1 medulloblastoma  and 1 ganglioglioma  for comparison  2 nontumor glial cell cultures were included  the pdgf b chain was expressed in 5 of 8 glioblastoma cell lines  2 of 6 glioblastomas  and in 3 of 4 anaplastic astrocytoma explants  there was no pdgf b expression in 4 astrocytomas  3 ependymomas of varying malignancy  in the remainder of the tumors  or in the nontumor glial cells  the pdgf a chain was expressed in all of the tumors  with the exception of the malignant ependymoma and in both nontumor glial cell cultures  tgf beta 1 was expressed in all of the tumors and in nontumor glial cells  the expression of tgf beta 2 was expressed in many of the benign and malignant tumors and also in both nontumor glial cell cultures  the ros messenger ribonucleic acid was expressed in 1 of 5 glioblastoma cell lines and in 2 of 6 glioblastoma cell explants  but in none of the other tumors or in the nontumor glial cells  
class4	iatrogenic saphenous neuralgia  successful therapy with neuroma resection  we report the case of a patient with saphenous neuralgia secondary to iatrogenic trauma resulting from bypass surgery in the femoral popliteal region  early symptoms of this condition were medial calf and ankle pain  with no findings of motor and reflex abnormalities  exploration of the thigh 2 years later revealed a neuroma of the nerve in the distal dissection site  medial to the knee  resection of the neuroma alleviated this condition  it is noted that saphenous neuropathy is seen as a spontaneous entrapment syndrome as well as a complication of orthopedic and vascular procedures performed on the medial area of the knee  saphenous neuralgia is often not recognized by neurosurgeons  if the condition is intractable  it does respond to surgical therapy  
class4	spinal glioblastomas  report of seven cases and review of the literature  intramedullary glioblastomas are uncommon tumors  they occur chiefly in the cervicothoracic segments  have a slight tendency to occur in the early decades of life  and have a short clinical history before diagnosis  we report seven cases and discuss the salient features of these tumors  particularly the pathological features and treatment  in light of the relevant literature  
class4	spinal cord compression from a thoracic paraganglioma  case report  a 34 year old man with a 4 month history of midthoracic back pain sought treatment for a recent onset of lower extremity paresthesia and stiffness  a myelogram and computed tomographic myelogram disclosed an extradural block at the level of the 8th thoracic vertebral body with involvement of the pedicles  lamina  and spinous process  a posterior decompression of the spinal cord with subtotal resection of a highly vascular tumor was performed  the tumor was identified as a paraganglioma  in a second stage  the remainder of the tumor was embolized preoperatively  and gross total excision and sequential stabilization of the spine with a luque rectangle and sublaminar wires were performed  the patient has been symptom free and without signs of a recurrence in the spine for over 13 months  a large abdominal paraganglioma was recently resected from its probable origin from the adventitia of the abdominal aorta  
class4	reversible hearing loss from cerebellopontine angle tumors  we report two patients who presented with a dramatic recovery from severe sensorineural hearing loss after total surgical removal of cerebellopontine angle tumors  meningioma and jugular foramen neurinoma   the factors that differentiate these  non acoustic tumors  in relation to the prognosis for hearing are discussed  a surgical approach that maintains the labyrinthine structure and preserves the arachnoid membrane of the superior cerebellopontine angle cistern during tumor removal is stressed  
class4	malignant melanoma of the oral cavity  a case report  the oral cavity is a rare location for the development of primary malignant melanoma  less than 2  of all malignant melanomas develop in the region  a case report is presented  illustrating the management in the site of the palate  together with a review of the relevant literature  
class4	oral cancer  a survey of 566 cases from the university of connecticut oral pathology biopsy service  1975 1986  a survey of the university of connecticut oral pathology biopsy service was undertaken to analyze cases of oral cancer accessioned during the 12 year period  1975 through 1986 inclusive  of 33 429 total specimens accessioned  there were 546 malignant oral neoplasms diagnosed and reported  sixty five  11 5   originated from out of state  invasive intraoral squamous cell carcinoma was the predominant tumor  69 7  of total   whereas lip cancer constituted only 2 8  of all malignancies  minor salivary gland adenocarcinomas accounted for 11  of total malignancies whereas verrucous carcinoma  carcinoma in situ  and miscellaneous other forms of oral cancer accounted for the remainder  4 6   5 3   and 6 6   respectively   cases of invasive squamous cell carcinoma were further analyzed by year  sex distribution  location subsite  age at diagnosis  and histologic grade  with the exception of histologic grading  we found that the characterization of cases of squamous cell carcinoma within the biopsy service tended to parallel results from a separate but related statewide analysis of both oral cancer and intraoral squamous cell carcinoma from connecticut over a much longer time span  we concluded that the picture of oral cancer as characterized by cases within the university of connecticut oral pathology biopsy service is generally reflective of the disease on a statewide level  
class4	pathologic characteristics of human t cell lymphotropic virus  htlv  related extranodal orofacial lymphomas  eleven cases of extranodal orofacial lymphomas  eofl   consisting of four htlv related and seven htlv unrelated eofl  were investigated with respect to the immunohistochemical and clinical features  htlv related eofl were of t cell phenotype and were associated with a poorer prognosis than htlv unrelated eofl  most of which were of b cell origin  the appearance of giant cells with cerebriform nuclei was helpful in identifying htlv related eofl  the relatively high incidence of t cell type eofl in our series was considered to be related to the high percentage of htlv carriers in our district  an area endemic for adult t cell leukemia lymphoma  
class4	adult t cell leukemia lymphoma of the tongue  a case of posterior tongue lymphoma associated with adult t cell leukemia  atl  that occurred as a lesion in the lingual dorsal portion is reported in a 64 year old woman  initially  a diagnosis of hodgkin s lymphoma was considered as no findings associated with atl except lymphadenopathy and serum anti atla antibodies were present  combined radiotherapy and chemotherapy were administered with favorable results  however  4 months later  pneumocystis carinii pneumonia developed  and 2 months later  generalized lymphadenopathy and hypercalcemia evolved  at this time  a diagnosis of atl was made  the patient died of renal dysfunction 6 months after the initial presentation  in suspected cases of atl and malignant diseases of t cell lineage  namely  malignant lymphoma and mycosis fungoides  the presence of htlv 1 infection should be confirmed by testing for anti atla antibodies  
class4	peripheral ameloblastoma with clear cell differentiation  this report details a case of mandibular peripheral ameloblastoma having a clear cell component  the latter consisted of ovoid cells with vacuolated or clear cytoplasm and vesicular or pyknotic nuclei that may be disposed as discrete clusters or show direct transition from typical acanthomatous areas  comparison of this lesion with other odontogenic and nonodontogenic tumors that contain clear cells is discussed in the context of the differential diagnosis  
class4	ectatic blood vessels in port wine stains lack innervation  possible role in pathogenesis  the innervation pattern of port wine stains was investigated using indirect immunohistochemistry with antibodies to protein gene product 9 5  pgp 9 5   neuron specific enolase  nse   calcitonin gene related peptide  cgrp   and neurofilament  nf   the pathologically dilated vessels in the middle and deep dermis were found to have defective innervation with only single or no nerve fibers in their vicinity  while other structures in the skin showed a normal density of fibers  nse  and pgp like immunoreactive   li  nerve fibers were observed innervating vessels with a normal morphology and other structures in the skin  such as sweat glands and hair follicles  as free nerve endings and in nerve bundles  the nerve bundles were often seen to pass the ectatic vessels without giving off any branches  cgrp li nerve fibers were detected running toward epidermis  whereas no fibers were found around the ectatic vessels  nf li fibers were seen innervating normal vessels in dermis  while in relation to the dilated vessels  no or only occasional fibers were observed  the lack of innervation may be of importance for the development of the disease as a result of decreased tonus of the vessels and or a loss of neuronal trophic factors  
class4	composite reconstruction for chest wall and scalp using multiple ribs latissimus dorsi osteomyocutaneous flaps as pedicled and free flaps  a composite flap is presented based on the latissimus dorsi myocutaneous unit together with the underlying ninth to eleventh ribs  three patients are presented  in two  a full thickness chest wall defect was present  in one  a full thickness scalp and cranial defect was present  use of the composite osteomyocutaneous latissimus dorsi free flap as a pedicled flap in two patients and as a free flap in one patient resulted in successful definitive reconstruction in all with no complications  this procedure necessitates no transplantation of soft tissue prior to bone grafting to maintain local vascularity  so the simultaneous one stage reconstruction of an osseous soft tissue defect becomes possible easily  
class4	cerebral venous thrombosis  new causes for an old syndrome  the range of disorders affecting the cerebral veins and sinuses is increasing and now includes blood disorders  abnormalities in the patterns of blood flow  and infiltrative or inflammatory conditions  all of which may promote thrombosis  we describe 10 patients with cerebral venous thrombosis  two had protein s deficiency  one had protein c deficiency  one was in early pregnancy  and there was a single case of each of the following  dural arteriovenous malformation  intracerebral arteriovenous malformation  bilateral glomus tumours  systemic lupus erythematosus  wegener s granulomatosis  non hodgkin s lymphoma  the recognition of such diverse aetiology may be importance since clinical features are non specific  and may consist only of raised intracranial pressure  allowing confusion with  benign intracranial hypertension   the existence of effective treatment both for the thrombosis and for many of the underlying disorders makes early diagnosis essential  the prognosis of treated patients may be favourable  
class4	incidence  causes and mechanism of hypercalcaemia in a hospital population in hong kong  to determine the incidence and causes of hypercalcaemia in a hospital population in hong kong  all 29 107 samples received in the laboratory in one year were analysed for plasma calcium and albumin  and samples with a plasma calcium concentration adjusted for albumin greater than 2 55 mmol l were investigated  plasma calcium greater than 2 55 mmol l was found in 462 patients  repeat samples were received from 302 of these and hypercalcaemia was confirmed in 183  the main causes of hypercalcaemia were malignancy  72 1 per cent   tuberculosis  6 0 per cent   and primary hyperparathyroidism  5 5 per cent   in the malignant hypercalcaemia group  carcinoma of lung was the most common  31 8 per cent  and carcinoma of breast was uncommon  3 0 per cent   secondary deposits in bone were detected in 35 of the 122 solid tumours  in order to identify the mechanism of hypercalcaemia the contributions of renal tubular reabsorption and increased bone resorption to the plasma calcium concentration were calculated  increased tubular reabsorption was the main contributor to hypercalcaemia in primary hyperparathyroidism and carcinoma of liver  none of whom had bony metastases  and it contributed significantly to hypercalcaemia in carcinoma of lung without bony metastases and carcinoma of oesophagus  we conclude that in hong kong  a  primary hyperparathyroidism is uncommon   b  tuberculosis is an important cause and  c  humoral factors may be responsible for a relatively high proportion of cases of malignant hypercalcaemia  
class4	radiographic manifestations of anomalies of the brain  congenital brain anomalies are classified as developmental anomalies  effects of teratogens  errors of histogenesis  or sequelae of infections  the imaging options for delineation of these anomalies are many  a basic understanding of the disorder is central to the effective choice of imaging modality  this review begins with a brief overview of embryogenesis then reviews the common congenital brain anomalies encountered in infants  
class4	radiographic manifestations of congenital anomalies affecting the airway  congenital anomalies of the airway are generally uncommon  but a vast array of possibilities exists  some present life threatening emergencies at birth  and others go undiagnosed for years  clinical symptoms are often nonspecific  and radiographic evaluation is frequently requested to localize and characterize the lesion before endoscopy  surgery  or medical management  the most common intrinsic congenital anomalies causing airway compromise in infants include choanal atresia  mandibular hypoplasia  laryngomalacia  vocal cord paralysis  and congenital subglottic stenosis  the radiologist must be on the alert for unsuspected additional anomalies involving the airway  lungs  and esophagus  which occur with relative frequency  numerous extrinsic congenital masses of the head  neck  and mediastinum may compromise the airway  hemangiomas  lymphangiomas  and teratomas are more likely to be noted at birth  whereas branchial cleft cysts  thyroglossal duct anomalies  and dermoid cysts frequently present later  mass location and radiographic characteristics usually allow accurate preoperative diagnosis  intracranial involvement by nasal or nasopharyngeal masses  intrathoracic involvement by lower neck mass  and intraspinal involvement by posterior neck mass must always be sought for radiographically  persistence of respiratory symptoms after removal of such masses is not uncommon because tracheal deformity and laxity may take months or years to resolve  recent advances in cine ct and mr imaging promise to improve imaging of the airway in general and in the pediatric population in particular  significant limitations in imaging of the pediatric larynx remain  as a result  endoscopy continues to be the primary diagnostic tool for airway anomalies of this region  
class4	bronchopulmonary and neurenteric forms of foregut anomalies  imaging for diagnosis and management  bronchopulmonary foregut malformations encompass a great variety of anomalies that may arise from abnormal differentiation of the respiratory and alimentary tracts  abnormal separation of the two systems  or abnormal development of blood supply  perhaps singly or in combination  during early embryogenesis  the pulmonary and neurenteric forms share the common features of a pulmonary parenchymal opacification and or intrathoracic mass  with the addition of vertebral anomalies in the instance of the neurenteric malformations  plain radiographs serve as the starting point for diagnostic evaluation and sometimes are all that is needed  more often  though  the plain film findings suggest which road to follow in further imaging  no single imaging approach can be advocated for all patients  the lesion may be found initially  for example  on prenatal sonography  ultrasonography also can establish the cystic nature of a mass and may help define vascular supply  although it cannot yet be said to have supplanted angiography s role in evaluating suspected sequestrations  for most intramediastinal or intrapulmonary masses without associated vertebral anomalies  ct will satisfactorily establish the cystic nature and should afford a reasonably confident preoperative diagnosis of bronchogenic cysts or type 1 or 2 cystic adenomatoid malformations  type 3 cystic adenomatoid malformation  because of its relatively  solid  imaging characteristics  may not be diagnosed confidently by preoperative imaging  the finding of vertebral anomalies associated with a mediastinal mass especially warrants mr imaging to define intraspinal involvement  however  the association of vertebral or rib anomalies with apparent unilateral pulmonary agenesis or hypoplasia arouses suspicion of a bronchopulmonary foregut malformation that communicates with the gastrointestinal tract  and this uncommon situation calls for a barium examination  radionuclide scintigraphy has an ancillary role in assessing foregut anomalies  but many findings from scintigraphy are relatively nonspecific and anatomic definition is poor  scintigraphy may yield supportive information in cases of sequestration that have inconclusive findings as determined by plain radiographs and ct  
class4	immunohistochemical characterization of microvascular endothelial cells in primary b cell lymphoma of the gastrointestinal tract  microvascular endothelial cells  enc  in primary b cell lymphoma of the gastrointestinal tract were immunohistochemically studied  based on the morphological structure  the microvasculatures were divided into high endothelial cell vessels  hev  and flat endothelial cell vessels  fev   there were distinct phenotypic differences between hev and fev in lymphoma tissues  hev were characterized as okm1  okm5   accompanied by the cluster of non neoplastic t lymphocytes  and fev were okm1  okm5  not accompanied by t lymphocyte infiltration  factor viii related antigen was clearly identified in both enc  and major histocompatibility complex  mhc  class ii antigens and interleukin 1 were absent or only faintly visible on enc in lymphoma tissues  whereas they were expressed on enc in non lymphoma tissues  these findings suggest that microvascular enc in primary b cell lymphoma of the gastrointestinal tract lack a property as antigen presenting cells  and that hev are involved in the migration of non neoplastic t lymphocytes  
class4	the role of the physician in the late diagnosis of primary malignant tumors of the small intestine  survival from primary malignancies of the small intestine has not improved during the last four decades  one reason for this is the advanced stage of disease at the time of surgery  in order to determine why diagnosis is made late  we reviewed the records of all patients with small bowel malignancy diagnosed between 1967 and 1988  the time from the onset of symptoms to the first medical contact and the time from medical contact until diagnosis were evaluated in 77 patients  the average delay in diagnosis attributable 1  to the patient failing to report symptoms was less than 2 months  2  to the physician not ordering the appropriate diagnostic test was 8 2 months  and 3  to the radiologist failing to make the diagnosis was 12 months  thus  the major delay in diagnosis was after medical help was sought and not from the onset of symptoms to first medical consultation  physicians must increase their sensitivity to the subtle but persistent symptoms that necessitate a small bowel evaluation  
class4	the effects of vitamin k on the generation of des gamma carboxy prothrombin  pivka ii  in patients with hepatocellular carcinoma  the clinical significance of des gamma carboxy prothrombin  pivka ii  in hepatocellular carcinoma  hcc  was investigated in 112 patients with and without vitamin k administration  the positivity rate of pivka ii was significantly decreased in patients receiving vitamin k  28 5    compared with those without vitamin k administration  54 5   p less than 0 05   the plasma levels of vitamin k derivatives  phylloquinone  vk1   menaquinone 4  mk4   and menaquinone 7  mk7   measured were not decreased in patients with hcc  but were significantly increased in mk4 and vk1   mk4   mk7  the amount of pivka ii in plasma did not correlate with the plasma levels of vitamin k derivatives  however  pivka ii was decreased by the administration of vitamin k  and all of the six patients with more than 5 0 ng ml of vk1   mk4   mk7 were within normal limits  whereas half of 32 patients with less than that had abnormal levels of pivka ii  thus  it was suggested that pivka ii was not elevated due to vitamin k deficiency  but might result from the impaired metabolism or availability of vitamin k in the tumor  therefore  pivka ii should be measured without vitamin k administration  
class4	perforation and tumor formation of the intestine in primary amyloidosis  we report a case of primary amyloidosis with repeated bowel perforations  this patient also had localized amyloid deposition creating a tumorous region mimicking malignancy in the rectum  perforation of the intestine is common in systemic amyloidosis  the ischemic change due to amyloid infiltration into the vessel wall may lead to perforation of the affected bowel  amyloid tumors occur more often in localized amyloid than in systemic amyloidosis  macroscopically  it is difficult to distinguish amyloid tumor of the intestine from neoplasia  
class4	a community study of delay in presenting with signs of melanoma to medical practitioners  in the absence of more effective treatment for advanced tumors  early diagnosis and treatment of localized tumors is the most effective way of reducing the burden of illness associated with melanoma  this study examined the following factors  prevalence of signs of melanoma  a mole changing in size  shape  appearance  or color  itching or tingling  bleeding or weeping  becoming raised  in 1344 individuals in a randomly selected sample of 1075 households  the length of delay in seeking medical advice  the factors associated with either going to a medical practitioner or not going delaying  and the actions of the medical practitioners when first presented with these signs  the results indicate that a large proportion of the sample  11 9   n   156  had observed signs of melanoma in the previous 12 months  of the sample reporting signs that had first appeared in the previous 5 years  only 32  sought medical advice about the signs within the recommended period  of the sample either not seeking advice at all or delaying  49  reported that they thought the sign  wasn t serious would clear up   furthermore  30  of the sample either did not known or underrated the importance of early detection and treatment of lesions  these results indicate that there is a deficit in the knowledge of the general public about the signs of melanoma  the severity of the disease  and the possible risks associated with delay  
class4	nasal midline masses in infants and children  dermoids  encephaloceles  and gliomas  nasal dermoids  gliomas  and encephaloceles are uncommon congenital lesions that result from aberrant embryologic development  we have treated 46 children with these nasal lesions  in view of the potential intracranial connection  patients are at risk for intracranial infection  and early surgical correction is thus imperative  neuroimaging studies may help to predict intracranial involvement  
class4	somatostatin and analogues in the treatment of cancer  a review somatostatin is a naturally occurring cyclic tetradecapeptide that inhibits release of growth hormone and all gastrointestinal hormones  the beneficial effect of somatostatin in the treatment of certain hypersecretory disorders of hormone excess in well recognized  however its clinical usefulness has been limited in the past by its extremely short plasma half life  the development of long acting somatostatin analogues has provided clinically useful agents for treatment of hormone producing tumors  in addition to well known inhibiting effects on hormone release and actions  recent studies using experimental tumor models have demonstrated an antiproliferative effect of somatostatin and its analogues on growth of a variety of neoplasms  the exact role of somatostatin analogues in cancer therapy has yet to be established  however studies suggest that these agents could provide a useful and relatively nontoxic adjuvant therapy in the treatment of certain tumors  in this review  the oncologic application of somatostatin and possible mechanism of action are examined and current clinical and experimental studies are summarized  
class4	the potential role of postoperative hepatic artery chemotherapy in patients with high risk hepatomas  the relationship between operative findings of hepatoma and the postoperative prognosis was studied to clarify indications for adjuvant hepatic arterial chemotherapy after hepatectomy  the results of adjuvant hepatic arterial chemotherapy using 0 4 mg kg of doxorubicin and 0 12 mg kg of mitomycin c and infusion of 5 fluorouracil were reported  one hundred sixty patients who had undergone hepatectomy for hepatoma were studied  in the operative findings of hepatoma  with a surgical margin of less than 10 mm  intrahepatic metastasis  tumor embolus in the second or more proximal branch of the portal vein  or lack of capsule formation related to the prognosis were the risk factors for recurrence  in 132 patients with these risk factors the survival rate of 19 patients with adjuvant arterial chemotherapy was significantly higher than for the 113 patients without it  adjuvant hepatic arterial chemotherapy thus may be an effective therapy and should be studied prospectively in patients undergoing hepatectomy for high risk hepatoma  
class4	human liver regeneration after major hepatectomy  a study of liver volume by computed tomography  regeneration of the remnant liver after major hepatectomy in humans was studied by computed axial tomography  ct  in 12 noncirrhotic and five cirrhotic patients  liver volumes were measured by abdominal ct 3 days  10 days  3 months  6 months  1 year  and 1 5 years after resection  of the 17 patients  liver remnant volume was increased in 21 2      6 7  and 30 6      12 7  at 3 months and 6 months after resection  respectively  noncirrhotic livers were 28 4      9 5  and 48 4      17 8  larger at 3 and 6 months  for cirrhotic livers  the increase was 8 5      3 6  and 12 9      4 5   in five patients with right hepatectomy  65  resection   the liver remnant volumes were increased 38 4      11 7   48 0      16 2  and 95 1      4 5  at 3 months  6 months  and 1 year after resection  respectively  in seven patients with right partial hepatectomy  30  to 35  resection   the percentages were 7 4      3 2   21 8      8 4   and 63 9      18 3  and in five patients with left lateral segmentectomy  15  resection   they were 15 6      8 2   27 8      12 2   and 33 0      14 5  3 months  6 months  and 1 year after resections  respectively  noncirrhotic livers showed better regeneration than cirrhotic livers  complete regeneration took about 1 year  the noncirrhotic liver that underwent right lobectomy also needed 1 year to double its postresection volume  
class4	surgical management of 552 carcinomas of the extrahepatic bile ducts  gallbladder and periampullary tumors excluded   results of the french surgical association survey  five hundred fifty two cases of primary carcinoma of the extrahepatic bile ducts  gallbladder and periampullary tumors excluded  collected from 55 surgical centers were reviewed retrospectively  three hundred seven patients  56   had upper third lesions  proximal carcinoma   whereas 71  13   and 101  18    respectively  had middle third and lower third bile duct carcinomas  the remaining patients had diffuse lesions  resectability rates were 32  for upper third localization compared to 47  and 51  for middle third and lower third localization  respectively  the operative mortality rate for proximal carcinomas was significantly lower with resection  16   compared with palliative surgery  31    p less than 0 05   overall 1 year survival  operative deaths excluded  was 68  after tumor resection compared to 31  after palliative surgery  p less than 0 001   long term results after surgical resection correlated with local and regional extension of the disease  the results of this study show that resection of extrahepatic bile duct carcinomas  particularly in an upper third localization  often is associated with worthwhile long term survival  
class4	defining the role of subtotal colectomy in the treatment of carcinoma of the colon  seventy two patients with colon cancer were treated by primary subtotal colectomy  including 23 patients with acute and subacute left colon obstruction  there were two operative deaths and no cases of disabling diarrhea  one death occurred in the group with colon obstruction  other indications for subtotal colectomy included multiple polyps associated with the primary tumor  32   synchronous carcinomas  15   a previous transverse colostomy for obstruction  8   associated severe sigmoid diverticular disease  2   age less than 50 years with a positive family history  3   adherence of the sigmoid loop to a cecal tumor  2   and metachronous carcinoma  2   there were multiple indications in several patients  subtotal colectomy has a defined role in a wide variety of clinical settings associated with colon cancer  including management of obstruction of the left and sigmoid colon  particularly if the proximal colon cannot be evaluated before operation by colonoscopy or barium enema  segmental or regional colonic resections are appropriate if the entire colon can be evaluated before operation and no associated neoplasms are revealed  
class4	bronchoalveolar carcinoma  factors affecting survival  one hundred thirty four consecutive patients  65 men and 69 women  underwent pulmonary resection for bronchoalveolar carcinoma  mean age was 65 years  lobectomy was done in 100 patients  pneumonectomy in 10  segmentectomy in 5  and wedge excision in 19  only 10 patients had lymph node metastases  7 5    the neoplasm was solitary in 111 patients  82 8    97 were in stage i  4 were in stage ii  9 were in stage iiia  and 1 was in stage iiib  there were two operative deaths  1 5    thirty nine complications occurred in 31 patients  median follow up was 5 1 years  recurrent bronchoalveolar carcinoma developed in 45 patients  five  and 10 year survival for patients in stage i was 75 2  and 62 0   respectively  survival for patients with t1 n0 m0 neoplasms was identical to expected survival and was 90 5  at 5 years  as compared with 55 4  for patients with t2 n0 m0 disease  only 35 9  for patients with multiple bilateral disease  and 0 0  for patients with bilateral disease  p less than 0 0001   other significant factors adversely affecting survival included the presence of signs and symptoms  diffuse malignant invasion  mucin producing tumors  and the histological absence of scar  we conclude that bronchoalveolar carcinoma has a unique natural history that is more influenced by local neoplastic processes than by lymph node metastases  early aggressive pulmonary resection is safe and offers the potential for cure  the presence of bilateral cancer  however  is ominous  
class4	primary cysts and tumors of the mediastinum  a retrospective analysis was performed on 230 patients with primary cysts and tumors of the mediastinum seen at our institution from january 1944 to april 1989  we divided these patients into two groups  group 1 was seen before 1970 and group 2 was seen from january 1970 to april 1989  there was a significant increase in the prevalence of malignancy in group 2  47 2  versus 17 1   p less than 0 0001  due to an increase in the number of lymphomas  22 6  versus 3 5   p less than 0 001  and malignant neurogenic tumors  6 8  versus 1 1   p   0 0528   there was a significant increase in the number of malignant tumors in the anterior  59 5  versus 30 9   p   0 0022  and paravertebral  28 5  versus 2 8   p   0 0027  compartments in group 2  more patients with these tumors were symptomatic in group 2  63 6  versus 5   p   0 0422   there was an increase of ancillary diagnostic studies performed to evaluate these tumors  76 0  versus 34 5   p   0 0422   logistic regression analysis identified date of presentation  p less than 0 005   symptoms  p less than 0 01   size  p less than 0 005   and the anterior mediastinal compartment  p less than 0 005  as preoperative predictors of malignancy  the surgical approach to these tumors included more median sternotomy  30 1  versus 10 7   p   0 0008   anterior mediastinotomy  and cervical mediastinoscopy in group 2  1 1  versus 17 5   p   0 0002   long term results support surgical resection in benign lesions and an aggressive multimodality approach to malignant lesions  
class4	role of percutaneous fine needle aspiration biopsy in suspected intrathoracic malignancy  percutaneous fine needle aspiration  pfna  biopsy is an accepted technique for the diagnosis of suspected intrathoracic malignancy  but the appropriate indications for its use have not been clearly defined  to help establish guidelines  we performed a retrospective analysis of 188 patients who underwent pfna biopsy for suspected intrathoracic malignancy  biopsy led to a diagnosis in 72   135 188  of the patients  but in 27   50 188  samples were inadequate for cytological diagnosis  and in 2   3 188  samples were adequate but failed to yield a diagnosis  fifty three patients underwent surgical intervention  thus allowing histological confirmation of the cytological diagnosis  in patients with a diagnosis from pfna biopsy  operation confirmed malignancy in 97   37 38  and a specific cell type in 79   30 38   in patients without a diagnosis after biopsy  a malignancy was found in 73   11 15  at the time of operation  this suggests a high rate of accuracy when pfna biopsy provides a diagnosis  however  it also illustrates that a substantial percentage of pfna biopsy attempts fail to yield a diagnosis in patients ultimately found to have malignancies  this implies that pfna biopsy might best be reserved for patients who are not surgical candidates  
class4	carcinosarcoma of the lung with hypertrophic pulmonary osteoarthropathy  carcinosarcoma of the lung is a rare malignancy  endobronchial and parenchymal variants are classically described  clinicopathological features are often related to anatomical location  as is the case for most lung neoplasms  this case report details the surgical management of a carcinosarcoma in a patient seen with pulmonary osteoarthropathy  
class4	surgical management of carcinoid heart disease metastatic carcinoid tumor is often seen with flushing  diarrhea  and cardiac symptoms  the carcinoid syndrome  cardiac failure is often associated with major morbidity and mortality in carcinoid disease  in this report  a case of successful cardiac valvar surgical intervention has resulted in prolonged alleviation of cardiac symptoms and survival  
class4	adenocarcinoma arising in a foregut cyst of the mediastinum  a case of malignant transformation in a mediastinal cyst of the esophageal reduplication type is presented  the cyst had been recognized 39 years previously  but remained asymptomatic until sudden growth occurred  it was resected totally from the esophagus and the patient recovered well  a review of the literature showed that malignancy in mediastinal foregut cysts is extremely rare  
class4	inflammatory breast cancer  historically  the prognosis of inflammatory breast cancer has been poor  we conducted a retrospective review to evaluate the recent memorial sloan kettering cancer center experience  to evaluate the role of combination chemotherapy  and to compare the effect of surgery and radiation on local regional failure  fifty six patients with local regional inflammatory breast cancer diagnosed between 1975 and 1984 were identified  all were treated with combination chemotherapy  overall 5 year survival was 45  with a 5 year disease free survival rate of 37   twenty one patients were treated with induction chemotherapy followed by mastectomy and adjuvant chemotherapy  survival and disease free survival rates were similar to those achieved in patients treated with mastectomy followed by chemotherapy  residual cancer was found in all 21 patients treated with induction chemotherapy  with extensive disease present in 18  including six of seven complete responders  the local regional failure rate was 34   
class4	enhanced antitumor reactivity of tumor sensitized t cells by interferon alfa  tumor draining lymph node cells from mice bearing the methylcholanthrene induced mca 106 tumors can be sensitized in vitro to acquire antitumor reactivity  we examined the effect of interferon alfa on the function of cells that underwent in vitro sensitization in adoptive immunotherapy  interferon alfa increased the antitumor reactivity of in vitro sensitized cells in the treatment of mca 106 pulmonary metastases  this effect was evident in irradiated mice  indicating that a host response to the interferon alfa was not required  interferon alfa treatment increased class i major histocompatibility complex antigen expression on tumor cells and increased their susceptibility to lysis by in vitro sensitized cells  these results suggest that interferon alfa enhancement of adoptive immunotherapy was mediated by its effect on tumor cells  interferon alfa may be a useful adjunct to the adoptive immunotherapy of human cancer  
class4	prognostic significance of carcinoembryonic antigen in colorectal carcinoma  serum levels before and after resection and before recurrence  the use of carcinoembryonic antigen was evaluated in 425 patients with a mean follow up of 48 months  the preoperative and postoperative carcinoembryonic antigen levels were predictive of recurrence and survival independent of the tumor stage  in a multivariate regression analysis of age  location  tumor stage  and preoperative and postoperative carcinoembryonic antigen levels  the latter three factors were significant prognostic variables with respect to the adjusted survival  recurrent disease was found in 42  of patients  excluding patients with stage iv disease  the carcinoembryonic antigen level at recurrence was greater than 5 ng ml in 79  of the patients and in 89  of the intra abdominal recurrences  carcinoembryonic antigen level at recurrence was not predictive of postrecurrence survival except in the subgroup of locoregional disease  the life span in patients with liver and lung metastases was not influenced by carcinoembryonic antigen level at recurrence  preoperative and postoperative carcinoembryonic antigen levels can indicate a poorer prognostic group of patients with colorectal cancer who may benefit from adjuvant treatment  the carcinoembryonic antigen at recurrence can be used effectively to diagnose intra abdominal recurrences and project survival after development of local regional disease  
class4	technique of photodynamic therapy for disseminated intraperitoneal malignant neoplasms  phase i study  patients with disseminated intraperitoneal malignant neoplasms were given intra abdominal photodynamic therapy  patients received dihematoporphyrin ethers intravenously 48 to 72 hours before laparotomy at doses of 1 5 to 3 0 mg kg  at operation  as much tumor as possible was resected  red light  630 nm  was delivered to all peritoneal surfaces from an argon pumped dye laser at doses ranging from 0 2 to 3 0 j cm2 in an escalating fashion  viscera and peritoneal surfaces were anatomically isolated and exposed to light for intervals calculated to deliver the prescribed energy  light was delivered to mesentery and bowel by a flat cut optical fiber  while other areas  including diaphragm  viscera  omental bursa  gutters  and pelvis  were delivered light through a diffusing wand  twenty three patients  13 with ovarian cancer  eight with sarcoma  and two with pseudomyxoma peritoneii  underwent photodynamic therapy  five of eight patients cleared positive peritoneal cytologies after treatment  six patients remained clinically free of disease for up to 18 months  and five patients had treatment related complications  intraperitoneal phototherapy is technically feasible and deserving of clinical evaluation  
class4	prognostic factors in primary retroperitoneal soft tissue sarcomas  we analyzed independent treatment variables  age  sex  signs and symptoms  site  size  histopathologic findings  grade  and clinical presentation  and treatment dependent variables  resectability  type of operation  surgical margins  surgical boundaries  microscopic margins  adjuvant radiotherapy  and adjuvant chemotherapy  in 80 patients with primary retroperitoneal soft tissue sarcomas admitted from 1982 through 1988  both univariate and multivariate analysis of survival and disease free survival were performed  the major factor in survival outcome was the ability to completely resect the lesion  when the 62 patients who underwent complete resection were examined  the only independent prognostic factor for both survival and disease free survival was grade  we conclude that completeness of resection and grade of the lesion are primary determinants of survival  once all tumor is macroscopically removed  no advantage could be demonstrated by more extensive surgical resection or current adjuvant therapy  
class4	mechanism of surgical stress impairment of human perioperative natural killer cell cytotoxicity  natural killer  nk  cells are an important defense against intravascular tumor dissemination  tumor embolization can occur at surgery  so we tested whether surgical stress decreased perioperative nk cell cytotoxicity  and examined the underlying mechanism of suppression  patients with solid tumors underwent nk cell cytotoxicity assay just before and 24 hours after surgery in a 3 hour chromium 51 release assay  the nk cell cytotoxicity was significantly decreased postoperatively  we considered that surgical nk cell impairment might be due to  1  nk cell redistribution   2  presence of suppressor cells  or  3  direct  toxic  effects on nk cells  impaired nk cell cytotoxicity was not due to nk cell redistribution  because differential counts showed no significant changes in the percentage of large granular lymphocyte nk morphology  to isolate possible suppressor cells  postoperative cells from patients were selectively depleted of nk cells using anti leu 11b monoclonal antibody plus complement  these cells were then mixed with autologous preoperative cells  postoperative nk cell cytotoxicity was markedly impaired  but the postoperative nk depleted cells did not suppress preoperative nk cells  we conclude that nk cell functional impairment from surgical stress is due to direct  toxic  effects on nk cells rather than either nk cell redistribution or the generation of nk directed suppressor cells  
class4	radioimmunoguided surgery using iodine 125 b72 3 in patients with colorectal cancer  preliminary data using b72 3 murine monoclonal antibody labeled with iodine 125 suggested that both clinically apparent as well as occult sites of colorectal cancer could be identified intraoperatively using a hand held gamma detecting probe  we report the preliminary data of a multicenter trial of this approach in patients with primary or recurrent colorectal cancer  one hundred four patients with primary  suspected  or known recurrent colorectal cancer received an intravenous infusion of 1 mg of b72 3 monoclonal antibody radiolabeled with 7 4 x 10 bq of iodine 125  twenty six patients with primary colorectal cancer and 72 patients with recurrent colorectal cancer were examined  using the gamma detecting probe  78  of the patients had localization of the antibody in their tumor  this included 75  of primary tumor sites and 63  of all recurrent tumor sites  9 2  of all tumor sites identified represented occult sites detected only with the gamma detecting probe  the overall sensitivity was 77  and a predictive value of a positive detection was 78   a total of 30 occult sites in 26 patients were identified  in patients with recurrent cancer  the antibody study provided unique data that precluded resection in 10 patients  and in another eight patients it extended the potentially curative procedure  
class4	radical resection for carcinoma of the ampulla of vater  one hundred four consecutive patients who underwent radical resection for ampullary cancer between 1965 and 1989 were retrospectively reviewed  frequent clinical findings included jaundice  67    significant  greater than 10   weight loss  42    and anemia  27    eighty seven patients  84   underwent a subtotal pancreatectomy  and 17 patients  16   underwent a total pancreatectomy  the postoperative mortality was 5 7   six patients   and reoperation for postoperative complications was required in six patients  the 5  and 10 year survival rates were 34  and 25   respectively  eight patients died of tumor recurrence more than 5 years after resection  patient survival was significantly impaired by microscopic lymphatic invasion  regional nodal metastasis  tumor grade  and the epithelium of origin  in a multivariate analysis  only microscopic lymphatic invasion significantly reduced patient survival  radical resection for ampullary cancer can be performed with a low morbidity and mortality and should remain the procedure of choice for ampullary carcinoma  
class4	effect of splenectomy on morbidity and survival following curative gastrectomy for carcinoma  we performed a retrospective analysis of 392 patients who underwent curative resection of gastric adenocarcinoma to evaluate the impact of splenectomy on survival from gastric cancer and postoperative morbidity  twelve factors  including splenectomy  were associated with a poor prognosis by univariate analysis  multivariate analysis identified six of these factors  but not splenectomy  as independently predictive of death due to gastric cancer  the apparent adverse effect of splenectomy was due to its association with other significant risk factors  postoperative complications occurred more commonly in patients who underwent splenectomy than in those who did not  45  vs 21    patients in the splenectomy group also had a higher percentage of infectious complications than those in the nonsplenectomy group  75  vs 47    we conclude that splenectomy has no direct influence on survival  but that it increases the morbidity of curative gastrectomy and should be avoided unless the spleen is close to or invaded by the tumor  
class4	the use of a biodegradable mesh to prevent radiation associated small bowel injury  radiation associated small bowel injury occurs in up to 50  of patients receiving postoperative radiotherapy following pelvic cancer surgery  we describe our experience using a biodegradable mesh that allows the small bowel to be supported above the pelvic inlet and is totally absorbed following radiation therapy  between 1985 and 1989  45 procedures were performed in patients with carcinoma of the rectum  anterior resection in 15 patients  abdominoperineal resection in 23 patients  pelvic exenteration in six patients  and proctocolectomy in one patient   in 30 patients a polyglycolic acid  dexon  mesh was used  and in 15 patients a polyglactin 910  vicryl  mesh was used  forty four patients received postoperative radiotherapy  the mean      sem  dose was 56 8     18 4 gy  there were no immediate complications related to the mesh  follow up ranged from 12 to 53 months  median follow up  34 months   with the exception of two patients who had a polyglactin 910 mesh and who developed bowel obstruction due to adhesions under the anterior abdominal wall  there has been no documented incidence of clinical radiation associated small bowel injury  the use of the absorbable mesh may permit us to use higher doses of postoperative radiotherapy without the associated hazard of radiation associated small bowel injury  
class4	5 year results of cisplatin and fluorouracil infusion in head and neck cancer  as part of the developmental process for the head and neck intergroup trial of adjuvant chemotherapy for advanced resectable head and neck carcinoma  in 1981 the radiation therapy oncology group  philadelphia  pa  conducted two nonrandomized pilot studies using chemotherapy consisting of three courses of cisplatin and fluorouracil infusion  chemotherapy was administered prior to surgery in 42 patients  induction  and after surgery in an additional 29 patients  sequential   the populations were roughly comparable with respect to tumor site and stage  twelve of the 42 patients in the induction group and seven of the 29 in the sequential group are alive and with no evidence of disease at the last reported follow up  the median survival was 31 months in the sequential group vs 20 months in the induction group  only two of the 26 patients with less than a complete clinical response following induction chemotherapy are still alive  twenty seven of the 42 patients who received induction chemotherapy did not undergo surgery as initially planned  despite the lack of surgery  at 5 years the survival between the two groups was not significantly different  27  for the induction group vs 23  for the sequential group   
class4	circulating c1q binding macromolecules and their relationship to radiographic characteristics of laryngeal cancer  circulating macromolecules capable of binding the first component of complement  c1qbm  may represent subcellular components of tissue tumor debris generated from rapidly proliferating invasive disease  thirty eight patients were randomly selected from 74 untreated patients with laryngeal cancer on the basis of disease stage and c1qbm levels  c1qbm levels were correlated with computed tomographic evidence of tumor necrosis and or thyroid cartilage destruction  results show that patients with stage iii iv disease with tissue necrosis and or cartilage invasion had demonstrably higher c1qbm levels than did individuals with similarly staged disease with no evidence of these radiographically defined characteristics  120     81 micrograms ml vs 18     15 micrograms ml   the strongest association was reflected by the area of necrosis within regional lymph metastases  elevated c1qbm level in patients with stage iii iv laryngeal cancer thus reflects highly aggressive disease  which is less responsive to therapeutic intervention  
class4	radiotherapy  the mainstay in the treatment of early glottic carcinoma  early squamous cell carcinoma of the glottis may be effectively treated with surgery or radiation therapy  controversy exists as to whether radiation therapy effects survival at the expense of vocal function by ultimately requiring more total laryngectomies for salvage of local tumor recurrence  this study reviewed the medical records of 185 patients with t1 or t2  no invasive squamous cell carcinoma of the glottis treated with primary radiation therapy between 1969 and 1984  all patients were followed up for a minimum of 5 years after completion of therapy  one hundred sixty one patients met the criteria for local control analysis  radiation therapy controlled disease in 93   105 of 113  of patients with t1 lesions and 73   38 of 48  of those with t2 tumors  ultimate control of disease for t1 and t2 lesions  including surgical salvage  was 111  98   of 113 and 44  92   of 48 patients  respectively  the rate of successful surgical salvage was 75   t1  and 70   t2   the t2 lesions with impaired vocal cord mobility or anterior commissure disease were identified as being at increased risk for recurrence after primary radiation therapy  overall voice preservation was 90   our data demonstrate that radiation therapy effects disease free survival rates that are comparable to those produced by surgery  without sacrificing voice  although a small percentage of patients with selected early glottic lesions may be more effectively treated with primary conservation surgery  these data do not support a change in philosophy concerning primary treatment of early glottic cancer with radiation therapy  
class4	primary sarcomas of the major salivary glands  sarcomas arising in the major salivary glands are rare  this article presents the clinicopathologic features of 11 patients with primary sarcomas of the parotid gland  eight men and three women aged 7 to 75 years  mean age  42 years   the 11 sarcomas were histologically typified as follows  three malignant fibrous histiocytomas and two each of neurosarcomas  rhabdomyosarcomas  fibrosarcomas  and osteosarcomas  four patients experienced disease recurrences  and seven patients developed metastases  seven patients died of their sarcomas  with a mean survival time of 30 months  four patients were alive from 5 to 12 years  one each with angiomatoid malignant fibrous histiocytoma  embryonal rhabdomyosarcoma  fibrosarcoma  and neurosarcoma   prognosis correlated with size of the neoplasm  type of sarcoma  and histologic grade  in this respect  salivary gland sarcomas behaved in identical fashion to their soft tissue counterparts  
class4	effective destruction of cervical intraepithelial neoplasia  cin  3 at 100 degrees c using the semm cold coagulator  14 years experience a total of 1628 women with cin 3 treated with the semm cold coagulator between 1975 and 1989 was followed primarily by cytology  the standard suitability criteria for ablation were adhered to except that patients were treated at their first visit when the colposcopist expected that the diagnosis would be no worse than cin 3  overall 97  of the women were treated at their first visit  in 30 women  2   the histology was glandular or worse than expected  but 22 of these showed no persistent cervical disease subsequently  follow up was achieved for 87  at 10 years  in actuarial terms the primary success rate was 95  at 1 year and 92  at 5 years  it was similar for all age groups  repeat cold coagulation for persistent recurrent cin 3 was less successful and is not advised  the outcome for 226 pregnancies established after treatment is known  the rates for miscarriage  preterm or operative delivery were not increased  cold coagulation of cin 3 at 100 degrees c as performed by us is as effective as any other treatment and calls into question the need for more expensive practices  
class4	a randomized control trial of two cervical spatulas the sampling efficacy of the ayre and rocket cervical spatulas was compared in a randomized controlled trial involving 533 women who were attending a colposcopy clinic either for investigation of cytological abnormality or for review after treatment of cin  smears were compared with respect to the presence of cytological abnormality and two types of normal cervical epithelial cells  endocervical and immature metaplastic cells  which are considered indicators of adequate cytological sampling  smears taken with the rocket spatula were significantly less likely to contain immature metaplastic cells  95  ci on difference in proportion  5 30    but more likely to contain endocervical cells  95  ci 16 36    no significant difference was found in the proportion of smears containing one or other type of indicator cell or in the yield of abnormal smears  it is concluded that the rocket spatula offered no advantage when used in these circumstances  this study illustrates how spurious conclusions of sampling efficacy can be drawn if only one type of indicator cell is used as an endpoint  
class4	vaginal epithelial abnormalities in patients with cin  clinical and pathological features and management  of 4147 women who had cin treated by laser at the regional gynaecological oncology centre  queen elizabeth hospital  gateshead  103  2 5   had co existing vaginal epithelial abnormalities  cin 3 was the histological diagnosis most often associated with vaginal lesions  the upper vagina was almost always involved  in 67  the lesion in the cervix appeared to be confluent with that in the vagina  even when the lesions were confluent  biopsies form the cervical and vaginal components did not always show the same grade of intraepithelial neoplasia and in some biopsies they showed different lesions  laser treatment appears to be effective for the vaginal lesions and is therefore recommended although  in selected patients  careful follow up alone may suffice  
class4	treatment of anovulation due to polycystic ovarian syndrome by laparoscopic ovarian electrocautery  our experience of ovarian electrocautery for the treatment of polycystic ovarian syndrome  pcos  in ten women is described  we found that nine responded favourably  either ovulating spontaneously or becoming more responsive to ovulation induction  there was a significant and persistent fall in serum testosterone levels  and a transient fall with subsequent rise in inhibin  we recommend that laparoscopic ovarian electrocautery is considered as an alternative to ovulation induction with gonadotrophins  in women with pcos who fail to respond to clomiphene citrate  
class4	the immunoperoxidase localization of tumour markers in ovarian cancer  the value of cea  ema  cytokeratin and dd9  primary tumours from 40 patients with epithelial ovarian cancer  treated at st thomas s hospital over a 10 year period  were studied for the immunocytochemical expression of the following tumour markers in formalin fixed paraffin embedded material  carcinoembryonic antigen  cea   epithelial membrane antigen  ema   cytokeratin  cam 5 2   and dd9  an indirect immunoperoxidase staining technique was used  all of the tumours were positive for ema and cam 5 2  and 30  of them were positive for both cea and dd9  the absence of cea and dd9 may be of value in differentiating between metastatic abdominal adenocarcinomas of ovarian origin and those of gastrointestinal origin  but no indication of prognosis was obtained using these epithelial markers  the strong and widespread staining of all the tumours for ema suggests that this may be a useful marker for detecting metastatic or recurrent disease by immunoscintigraphy  
class4	hormone replacement therapy and survival after surgery for ovarian cancer objective  to evaluate whether hormone replacement therapy affects survival in women who have undergone bilateral salphingo oophorectomy because of epithelial ovarian cancer  design  retrospective analysis by review of patients  notes and questionnaires completed by general practitioners to compare the overall survival and disease free survival in patients with ovarian cancer who did or did not receive hormone replacement therapy after diagnosis  data were analysed by cox regression  with hormone replacement therapy as a time dependent covariate because patients who received hormone replacement did so at different times after diagnosis  setting  gynaecological oncology unit of royal marsden hospital  patients  373 patients aged 50 years or younger who attended the hospital from 1972 to 1988  all of the women had undergone bilateral salpingoophorectomy for epithelial ovarian cancer  in all  78 had received hormone replacement therapy  starting at a median of four months after diagnosis  intervention  a questionnaire was sent to the general practitioners of all patients who were not recorded as having received hormone replacement therapy  main outcome measures  overall survival and disease free survival  results  there was no significant difference in survival between women receiving hormone replacement therapy and those not receiving it after accounting for the effects of other known prognostic factors  stage of cancer  differentiation of tumour  histological results  and time to relapse   the relative risk of dying in those who received hormone replacement therapy was 0 73  95  confidence interval 0 44 to 1 20   in addition  there was no significant difference in disease free survival  relative risk in those receiving hormone replacement therapy was 0 90  95  confidence interval 0 52 to 1 54   conclusions  this study shows that hormone replacement therapy is unlikely to have a detrimental effect on the prognosis of patients with ovarian cancer  but this would be shown conclusively only by a randomised controlled trial  
class4	misinterpretation of the upper parathyroid adenoma on thallium 201 technetium 99m subtraction scintigraphy  pre operative thallium technetium subtraction scintigraphy of 50 patients with primary hyperparathyroidism  which was subsequently proven on histology to be due to an adenoma  was compared with operative findings  six scans were negative and seven uninterpretable  of the remaining 37 patients  34 had correct scan prediction of the anatomical locations of the adenomas  on examination of the origins of the adenomas  all six scintigraphic predictions of upper adenomas corresponded to tumours arising from the upper gland found at operation  of the 25 lower predictions  there was one false positive and 16 were correct  i e  of lower gland origin  but eight were found to originate from the upper gland  this misinterpretation is though to be due to the prolapse of an adenoma arising from the upper gland towards the lower pole of the thyroid  thereby mimicking a lower lesion on the scan  
class4	ultrasound in the investigation of the right iliac fossa mass  patients presenting with a right iliac fossa  rif  mass are a diagnostic problem  the objective of this study was to assess the role of ultrasound  us  in their investigation  a prospective series of 50 patients presenting with a clinically suspected rif mass was examined by us and the finding correlated with the final diagnosis  there was a positive finding in 34 patients  68    ultrasound correctly identified the organ of origin in 33  97   and was able to guide the patients  further management  in 12 cases no abnormality was found in the rif  of which 11 had no positive findings at follow up and one was shown to have an unrelated abnormality at laparotomy  in four cases the findings were due to normal variants  ultrasound is the imaging modality of first choice in patients presenting with a rif mass  
class4	carcinoma of the breast  measurement and the management of treatment  i  the value of the data  this is the first of a series of papers in which we shall explore some insights into the biological changes which accompany the treatment of human tumours which may be obtained through estimation of volume changes in relation to treatment  we have adopted a working hypothesis that regression slopes reflect the composition of individual tumours and  indirectly  their intrinsic growth rate rather than the effectiveness of treatment  the breast has proved to be a suitable site for measurement and our interpretation of the results has led to the development of a new style of management for carcinoma of the breast  measurement based sequential therapy  mbst   in this paper the method of measurement and detailed statistical evaluation of the quality of the data from 262 patients  263 tumours  is presented  exponential regression lines have been fitted to describe volume changes in relation to treatment by radiation  chemotherapy and hormones  a simple classification of steepness of slopes is introduced  
class4	selective uptake of toxic nucleoside  125iudr  by resistant cancer  we report uptake of a thymidine analogue 125 iodine 5 iodo 2  deoxyuridine  125iudr  by nude mice bearing human xenografts of choriocarcinoma or colonic cancer  when 125iudr was given alone  uptake by intestinal tissues was 5 10 times greater than by the tumours as measured by tissue gamma counting  this ratio was reversed when hydroxyurea or cytosine arabinoside were used as inhibitors of ribonucleotide reductase and were given in combination with 5 fluorouracil or methotrexate to inhibit thymidine synthesis shortly before injecting 125iudr  counting the radioactivity in tissues removed 24 hours after 125iudr gave tumour to highest normal tissue ratios of up to 15 1  but the corresponding nuclear grain counts  which is probably a more reliable indicator of selective uptake into dna  were in excess of 100 1  the addition of unlabelled iudr to the regimen only reduced the uptake of 125iudr when given in relatively large amounts  for this approach to be exploited it is concluded that the tumour must be resistant at the cell level to the inhibitor of dna synthesis either de novo or as a result of prior exposure to it  this inhibitor can then be used to block uptake of the potentially toxic nucleoside analogue by normal renewal tissues while it is taken up by the resistant cancer cells  by inhibiting synthesis of the corresponding normal nucleosides with inhibitors to which the cancer cells are not resistant  incorporation of the toxic analogues into tumour dna was enhanced  although 125iudr is a convenient agent for exploring this approach and is highly cytotoxic when incorporated in dna  the clinical potential of reverse role chemotherapy probably lies with the development of toxic non radioactive nucleoside analogues  
class4	tissue dose estimates following the selective uptake of 125iudr and other radiolabelled thymidine precursors in resistant tumours  for the purposes of evaluation of the therapeutic potential of the radiohalogenated thymidine analogue 125iudr  estimation of the radiation dose to the tumour cells and normal tissues is important  to determine the dose to any tissue from the radionuclide 125i is not simple  since the major emissions are very short range auger electrons  the cytotoxicity of 125i is strongly dependent on the position of the decay relative to the dna  the principal target for cell sterilization  estimates of the cytotoxicity of 125i based on the traditional mird recommended formulation  icru report 32  1979  may produce gross underestimates if it is incorporated into the dna via the thymidine precursor 125iudr  in this work  tissue count and autoradiography  arg  data from studies by bagshawe et al were used to estimate tissue doses following the administration of 125iudr to ls174 t  a colorectal carcinoma  and cc3  a choriocarcinoma  tumour bearing animals  after a hydroxyurea block of the normal tissue turnover  the tumour cell toxicity is estimated from arg data on the degree of 125i incorporation into the cell nucleus  major drawbacks with 125i for this type of therapy are the long 60 day half life  leading to radiological and waste disposal problems and the extreme short range of the radiotoxic effects  possible alternative radiohalogens  13i  77br  131i and 211at  are suggested in place of 125i in the thymidine analog iododeoxyuridine  dose calculations are performed and cytotoxicities estimated on the assumption that their biological retention characteristics are the same as for 125iudr  
class4	importance of the omentum in the development of intra abdominal metastases  areas of trauma are preferred sites for metastatic tumour growth  in extensive intra abdominal tumour recurrence the omentum is invariably involved  the importance of the omentum in the development of tumours at sites of intra abdominal trauma has been investigated  colonic anastomoses were performed in hooded lister rats with and without omentectomy  animals received intraluminal or intraperitoneal injections of a syngeneic tumour  with intraluminal injection  tumour occurred at the anastomosis and in the omentum in 38 and 43 per cent of animals respectively but following omentectomy the values were 14 and 9 per cent  omental remnant   with intraperitoneal administration tumour occurred in 53 per cent at the anastomosis and in 79 per cent in the omentum compared with 16 and 29 per cent  in omental remnant  following omentectomy  in this model a reduced ability of an anastomosis to support  seeded  tumour following removal of the omentum is demonstrated and the development of local recurrence from spilled tumour cells during operation may be enhanced by  or be dependent on  the proximity of the omentum  
class4	evaluation of the results of oesophagectomy for oesophageal cancer  the long term results of standard techniques of oesophagectomy were examined in 127 patients with squamous cell carcinoma of the oesophagus  a near total oesophagectomy with a cervical anastomosis was performed in 93 patients and an oesophagogastrectomy with an intrathoracic anastomosis was carried out in 34 patients  one hundred and eight patients had a curative oesophagectomy and 19 patients had a palliative resection  eight patients received radiotherapy to the tumour bed  there were 15 deaths in hospital and the overall 5 year survival rate including perioperative deaths was 13 2 per cent  survival was adversely affected by incomplete excision of macroscopic tumour  p less than 0 001   positive regional lymph nodes  p less than 0 05  and distant lymphatic metastases  p less than 0 02   the 5 year survival rate of patients with tumour invasion beyond the oesophageal wall  t3  and negative nodes was 20 per cent  postoperative irradiation had no effect on the survival of patients with gross residual tumour  complete clearance of microscopic tumour was achieved in 50 per cent of patients with t3 tumours and this group did not benefit from adjuvant radiotherapy  survival in patients undergoing curative oesophagectomy with residual microscopic tumour  however  was significantly improved by irradiation of the tumour bed  p less than 0 01   these results suggest that the survival of patients can be increased significantly by the excision of all gross tumour and by identification of those who will benefit from local radiotherapy  
class4	prolonged intermittent clamping of the portal triad during hepatectomy  from 112 consecutive hepatectomies for malignant tumours performed with intermittent portal triad clamping  we have retrospectively selected the 20 cases in which clamping exceeded 90 min  intermittent portal clamping of prolonged duration was used because of abnormal liver texture in 13 cases  mainly patients who had received intra arterial chemotherapy  and or because of technically difficult hepatectomy  the mean s d   duration of intermittent portal clamping was 109 18  min and in two cases it exceeded 140 min  148 and 150 min   there was no postoperative mortality and the rate of postoperative morbidity was 35 per cent  postoperative changes in biochemical liver tests were not major and transient hepatic failure occurred in only one patient following subtotal resection of the liver  we conclude that intermittent portal clamping is a useful manoeuvre in partial hepatectomy when resection is difficult or prolonged  or when the liver parenchyma is abnormal  such clamping may be used for longer than 120 min without major complications  
class4	detection of colorectal liver metastases using intraoperative ultrasonography  intraoperative ultrasonography of the liver has been carried out in 99 patients undergoing surgery for colorectal cancer  palpation of the liver  preoperative abdominal ultrasonography and computed tomography scanning were also performed in all patients  metastases were identified in 26 of the 99 patients  26 per cent   intraoperative ultrasonography diagnosed more metastases than palpation  abdominal ultrasonography or ct scanning  identifying metastases in 24 of the 26 patients  including six patients in whom the metastases were not detected by any other technique  identification and localization of impalpable liver metastases is therefore possible using intraoperative ultrasonography  
class4	proliferation characteristics of human colorectal carcinomas measured in vivo  the cell proliferation kinetics of 100 human colonic and rectal adenocarcinomas have been studied in vivo by bromodeoxyuridine infusion and multiparameter flow cytometry  a total of 97 patients  three with synchronous tumours  consented to receive a single bolus dose of 250 mg between 2 4 and 16 h before curative or palliative surgery  by this method  the ploidy pattern  the total and aneuploid labelling indices  li   the s phase duration  ts  and the potential doubling time  tpot  can be estimated  of the tumours 48 were diploid and 52 were aneuploid  the mean and median total li of 100 tumours were 9 0 per cent  range 0 7 22 2 per cent   the mean aneuploid li was 12 1 per cent  median 12 0 per cent  range 2 0 25 5 per cent   and was significantly higher than the total li  p   0 01   the labelling index alone is not a sufficient indicator of proliferation  because the ts also varies within and between tumours  the intertumour range of the ts varied from 4 0 to 28 6 h  the mean was 14 1 h and the median was 13 1 h  the mean tpot was 5 9 days  median 3 9 days  with a range of 1 7 21 4 days  no correlation was found between any kinetic parameters and the dukes  classification or histological classification  the correlation between proliferation and prognosis will be established in due course  
class4	primary papillary carcinoma of a thyroglossal duct cyst  report of a case and literature review  thyroglossal duct cysts are the most common anomaly in thyroid development  they are twice as frequent as branchial cleft abnormalities and  in children  are second only to enlarged cervical lymph nodes as the cause of neck mass  generally  duct cysts are benign  but 1 per cent of cases may be malignant  from the world literature  114 cases of malignant thyroglossal cysts were available for review  with the addition of our own case  we discuss 115 instances of duct cysts  the different types of neoplasia described included thyroid papillary carcinoma in 81 7 per cent  mixed papillary follicular carcinoma in 6 9 per cent  squamous cell carcinoma in 5 2 per cent  follicular and adenocarcinoma in 1 7 per cent each  and malignant struma  epidermoid carcinoma and anaplastic carcinoma in 0 9 per cent each  of the 115 cases surveyed  35 thyroid glands were examined microscopically  of these  four  11 4 per cent  contained malignant foci  whether these are primary malignancies of the thyroglossal duct cysts or metastases is discussed  
class4	solitary thyroid nodule  a prospective evaluation of nuclear scanning and ultrasonography  the aim of this study was to assess prospectively the value of thyroid nuclear scans and ultrasound examination in the preoperative investigation of patients with a solitary thyroid nodule  total thyroid lobectomy for a solitary thyroid nodule was performed in 68 cases  each patient had a thyroid isotope scan  except two women who were pregnant  and thyroid ultrasound examination  there were 10  15 per cent  malignant nodules  11  16 per cent  benign neoplastic nodules and 47  69 per cent  benign non neoplastic nodules  all of the patients with malignant nodules who were scanned had a solitary cold nodule on thyroid scan  as did 40  69 per cent  of those with benign solitary nodules  ultrasound examination of the thyroid suggested correctly that one of 16  6 per cent  cystic lesions  four of 16  25 per cent  complex solid cystic lesions and three of 18  17 per cent  of solid lesions were malignant  one lesion reported as multinodular on ultrasonography and one reported as normal also turned out to be malignant  thyroid isotope scans and ultrasound do not accurately differentiate between benign and malignant conditions and their routine use in the investigation of a solitary thyroid nodule should be abandoned  
class4	dna aneuploidy in follicular thyroid neoplasia  the potential value of dna aneuploidy  in distinguishing benign from malignant follicular thyroid neoplasms  was studied  the nuclear dna content of 65 follicular thyroid neoplasms  52 adenomas and 13 carcinomas  was determined by flow cytometric analysis of paraffin embedded material  in 58 cases preparations were technically satisfactory  in 22 follicular neoplasms dna analysis was also performed on fresh material obtained by fine needle aspiration of surgical specimens  cell cycle analysis was performed on both fresh and fixed specimens  an aneuploid dna profile was found on analysis of fixed tissue in eight of 45  18 per cent  follicular adenomas and four of 13  31 per cent  follicular carcinomas  dna aneuploidy was also found in six of the 22  27 per cent  fresh preparations from follicular adenomas  the frequency of dna aneuploidy in apparently benign and malignant follicular neoplasms was similar  follicular thyroid neoplasia are best regarded as a single entity with a low incidence of local and distant spread  all follicular neoplasia are therefore best excised  
class4	further evaluation of radical surgery following radiotherapy for advanced parotid carcinoma  a series of 30 patients who have been treated for advanced carcinoma of the parotid gland using radiotherapy followed by radical surgery is presented  three patients deteriorated during preoperative radiotherapy and remained unfit for surgery  the remaining 27 underwent radical parotidectomy with block dissection of the neck  twelve patients received additional radiotherapy after operation  of those patients undergoing surgery  three have been lost to follow up  17 have died and seven remain alive  the period of follow up ranges from 3 to 133 months  fourteen patients remained free of recurrent disease at death or when last seen  and six patients developed a local recurrence at a medium period of 10 5  range 3 36  months after surgery  for all 30 patients  the cumulative proportion surviving for 5 years was 30 per cent  
class4	axial myoclonus of propriospinal origin  three patients are described with nonrhythmic repetitive axial myoclonic jerks causing symmetric flexion of the neck  trunk  hips and knees  no electrophysiological evidence of a cortical or brainstem reticular origin for the myoclonus was found  in the first patient the axial jerks only occurred spontaneously  the latencies of recruitment of spinal segments during a jerk indicated that the discharge arose in the mid thoracic cord and then slowly spread at about 5 ms 1 up and down the cord to involve rostral and caudal segments  no structural lesion was identified in this patient  in the second patient spontaneous and reflex axial jerks developed following the excision of a cervical haemangioblastoma  in the stimulus induced jerks the relative latencies of muscles innervated by rostral and caudal spinal segments suggested that the myoclonus originated between the upper cervical and midthoracic cord  in the final patient  emg activity during spontaneous and stimulus induced jerks commenced in the rectus abdominis  and was followed by later activity in muscles innervated by rostral spinal segments  suggesting that the myoclonus originated in the midthoracic cord  no structural lesion was identified in this patient  electrophysiological evidence is used to argue a spinal origin for these axial jerks in all 3 cases  there are striking features common both to this form of human myoclonus and to long propriospinal pathways identified in animals  the new concept of propriospinal myoclonus is suggested  
class4	hemodialysis for acute renal failure in patients with hematologic malignancies  objective  to assess the prognosis of patients with hematologic malignancies in acute renal failure who require hemodialysis  design  retrospective study  setting  icu  patients  forty three consecutive patients  methods  prognostic analysis using both univariate and multivariate  stepwise regression  methods  results  fifteen  35   patients recovered from acute renal failure and 12  28   were discharged from the icu  the prognosis of patients with acute renal failure linked to sepsis is poorer than the prognosis of the patients with acute renal failure from other etiologies  only one patient survived in the former group  n   26  and 11 in the latter group  n   17   p less than  0001 in multivariate analysis  when accompanied by associated respiratory failure  mortality rate was higher  93  vs  33   p less than  0001   the simplified acute physiology score  saps  calculated within the first 24 hr of admission was significantly  p less than  001  related to mortality when the saps was greater than or equal to 13  the presence of neutropenia and the type of hematologic malignancy were not related to a worse prognosis  tolerance to hemodialysis appeared good  and complications were rare  
class4	the value of radioimmunoguided surgery in first and second look laparotomy for colorectal cancer  radioimmunoguided surgery  rigs  using an anti cea  a5b7  monoclonal antibody has been assessed in 52 patients  43 primary excisions and nine second look procedures  undergoing surgery for colorectal carcinoma  the antibody localized in 97 8 percent of primary tumours and in 88 8 percent of the principal tumor in second look procedures  additional information concerning the extent of primary tumor was obtained in 11 of 43 patients  25 5 percent  undergoing excision of primary carcinoma and five of nine patients  55 percent  in the second look series  incorrect information was obtained about the extent of the primary tumour in six patients  11 3 percent   whereas no incorrect information was obtained during second look procedures  rigs correctly predicted the subsequent dukes  staging in 77 percent of first look cases  sensitivity 65 percent  specificity 90 percent   although accurate identification of individual nodes was impossible  the technique influenced the surgical procedure performed in 2 of 43 cases  4 6 percent  in primary surgery and in three of nine patients undergoing second look laparotomy  33 percent   rigs in primary colorectal carcinoma may provide additional information concerning extent of locally advanced tumors in particular and the principle that the subsequent surgery may be influenced has been established  the technique appears to have a greater role in second look procedures where it may help determine the extent of recurrent tumour  larger follow up series are required to define how the additional information provided by this technique may best be exploited  
class4	nuclear shape as a prognostic discriminant in colorectal carcinoma  in search for a more reliable prognostic discriminant  a retrospective analysis of 100 cases of colorectal carcinoma having undergone curative resection and followed for at least 5 years were assessed by nuclear morphometry  each case was staged according to the dukes  classification as well as graded histologically  for all patients in this series  the perimeter  area  and nuclear shape factor of 50 interphase nuclei were determined for each carcinoma  the information was obtained through the use of an image analysis system by tracing the nuclear profiles  magnification 1000x  as digitized on a video screen  the nuclear shape factor was defined as the degree of circularity of the nucleus  a perfect circle recorded as 1 0  a nuclear shape factor greater than 0 84 was associated with poor outcome  multiple regression models showed that the single nuclear parameter of the shape factor was the most highly significant predictor of survival  p less than 0 0001   this variable remained highly significant even when corrected for sex  age  histologic grade  and dukes  classification  these findings indicate that a nuclear shape factor greater than or equal to 0 84 as determined by nuclear morphometry is an independent morphometric nuclear variable of great importance in the prognosis of large bowel carcinoma  
class4	primary de novo adenocarcinoma of the colon measuring 8 mm in diameter with lymph node metastases  report of a case  colonic adenocarcinomas measuring less than 10 mm are rare  herein  we report a carcinoma measuring 8 mm in diameter associated with subserosal extension through a  locus minoris resistentiae  and metastases to lymph nodes  an association not previously reported  no residual adenomatous tissue was found  suggesting a de novo carcinoma  
class4	dysplasia and dna aneuploidy in a pelvic pouch  report of a case  a patient with an 18 year history of ulcerative colitis was operated on with colectomy  mucosal proctectomy  ileoanal anastomosis  and an s type pelvic pouch due to intractable chronic continuous disease  the patient was followed by endoscopic controls and biopsy sampling from the pouch at regular intervals  a gradual development of severe atrophy in the ileal mucosa was followed by the development of low grade dysplasia  at the most recent endoscopic control  4 years after the construction of the pouch  biopsies were sampled also for flow cytometric dna analyses  dna aneuploidy was detected in a biopsy from the center of the pouch  and a biopsy taken immediately adjacent showed low grade dysplasia  these findings underline the importance of endoscopic follow up after construction of a pelvic pouch and focus attention to the potential of malignant transformation of the mucosa  
class4	development and characterization of a new  highly specific antibody to the human chorionic gonadotropin beta fragment  in addition to high concentrations of hcg  pregnancy urine contains even higher concentrations of a fragment of the hcg beta subunit  this biologically inactive material complicates immunological measurement of hcg  since it cross reacts with many polyclonal and monoclonal antibodies to the hcg beta subunit that are employed for assays of hcg in urine  although we and others have developed antibodies to this fragment  specific measurement of the fragment in the presence of free hcg beta has remained difficult due to intrinsic cross reactivity of these antibodies with the intact hcg beta  rather than attempt to increase specificity by assay optimization  we developed a new  highly specific monoclonal antibody  designated b210  which cross reacts less than 0 1  with the free hcg beta subunit in both liquid and solid phase immunoassay formats  we have used this new monoclonal antibody in immunoradiometric assays to measure specifically the hcg beta fragment in urine throughout pregnancy as well as in the sera of two individuals with cancers producing the hcg beta subunit  we discovered that the hcg beta fragment can bind three monoclonal antibodies simultaneously  indicating that although the epitope for antibody b210 is a new determinant exposed on the hcg beta fragment and not on intact hcg or on free hcg beta subunit  the hcg beta fragment retains at least two other hcg beta related epitopes intact  i e  those that bind monoclonal antibodies b108 and b201  
class4	calcium transport by plasma membranes from a glucose responsive rat insulinoma  inside out plasma membrane vesicles from a glucose responsive rat insulinoma showed an atp  and mg2    dependent uptake of ca2   the km  concentration giving half maximal activity  for ca2  was 60 nm  in the presence of 0 4 microm free ca2   the km for atp was 15 microm  and the km for mg2  was 4 microm  glucose  30 mm  decreased ca2  uptake by 50   while other insulin secretagogues had no effect  except for glyceraldehyde  which stimulated ca2  uptake  calmodulin increased the uptake of ca2   while trifluoperazine and vanadate inhibited the uptake  the ca2     and mg2    dependent atpase from this tumor has a 10  to 20 fold higher requirement for ca2   which suggests that this enzyme is not responsible for ca2  transport  rather  ca2  transport activity represents only a small fraction of the total ca2    atpase activity  the physiological importance of ca2  transport in insulin secretion is evident from the inhibition of ca2  uptake by glucose  which leads to a decrease in ca2  efflux from the cell  this inhibition would lead to an increase in intracellular free ca2  and insulin release  
class4	transcriptional regulation of ferritin messenger ribonucleic acid levels by insulin in cultured rat glioma cells  recent data have shown that ferritin  a ubiquitous protein  has a role as a regulator of cellular differentiation  in the present study we have investigated the expression of ferritin mrnas in cultured c6 cells  a rat glioma cell line  in response to insulin  which has an important role in cellular growth and differentiation  insulin stimulated steady state levels of both ferritin heavy chain and ferritin light chain mrnas  an increase in the level of ferritin heavy or light chain mrna was detected after 2 h of incubation with insulin  and a plateau was reached after 48 h for heavy chain mrna and after 72 h for light chain mrna  the responses were dose dependent and were maximal at 100 nm for both mrnas  treatment of cells with actinomycin d showed that insulin had no effect on the posttranscriptional stability of these mrnas  actinomycin d inhibited insulin induced accumulation of both mrnas  suggesting transcriptional stimulation of ferritin genes by insulin  a nuclear run on assay showed that the insulin induced increase in ferritin heavy chain mrna was due to an increase in the rate of gene transcription  we also demonstrated that insulin like growth factor i  igf i  increased ferritin heavy and light chain mrna levels in a dose dependent fashion  and that the maximum effect was obtained at a concentration of 10 nm on both mrna levels  igf i was not only 10 fold more potent  but the absolute level of maximum stimulation was also about 2 fold greater than that for insulin  the combination of insulin  100 nm  and igf i  10 nm  showed no additive effect  the results suggested that the ferritin heavy and light chain genes are transcriptionally regulated by insulin and influenced by igf i  
class4	regulation of insulin  epidermal growth factor  and transforming growth factor alpha levels by growth factor degrading enzymes  the mechanisms by which growth factors are degraded and the role this process plays in the regulation of cell growth are not well understood  insulin degradation is believed to be mediated by a specific metalloprotease  insulin degrading enzyme  ide   we have previously shown that ide can also degrade transforming growth factor alpha  tgf alpha   but not epidermal growth factor  egf   in vitro  this selectivity was surprising  since tgf alpha and egf are structurally similar and bind to the same receptor with comparable affinities  using a spectrum of protease inhibitors  we have now analyzed the degradation of tgf alpha  egf  and insulin by human hepatoma hepg2 cells  the results suggest that bacitracin sensitive metalloproteases are involved in the degradation of tgf alpha and egf as well as insulin  and that the degradation of tgf alpha  but not egf  is mediated in part by ide  inhibiting the activity of these metalloproteases decreased growth factor depletion  suggesting that these enzymes play an important role in the control of extracellular growth factor levels  the existence of separate degradative pathways for egf and tgf alpha may explain how the two factors exert differential effects in some systems  and degradation of tgf alpha by ide would provide a possible mechanism for interaction between the insulin and tgf alpha egf signalling systems  
class4	effects of hepatitis b virus  alcohol drinking  cigarette smoking and familial tendency on hepatocellular carcinoma  independent and interactive effects related to the development of hepatocellular carcinoma were assessed using a community based case control study for hepatitis b virus  habitual alcohol drinking  cigarette smoking  peanut consumption and history of hepatocellular carcinoma among the immediate family  all 200 male newly diagnosed hepatocellular carcinoma patients were recruited consecutively through the period of study as the case group from two teaching medical centers in northern and southern taiwan  healthy community residents matched one to one with cases on age  sex  ethnic group and residential area were selected as the control group  the carrier status of hbsag and hbeag was determined by blind radioimmunoassays  and other risk factors were obtained through standardized interviews according to a structured questionnaire  conditional logistic regression analysis showed a significant association between hepatocellular carcinoma and the carrier status of hbsag and hbeag with an odds ratio of 16 7 and 56 5  respectively  for carriers of hbsag alone and for carriers of both hbsag and hbeag  there was a dose response relationship between cigarette smoking and hepatocellular carcinoma with an odds ratio of 1 1  1 5 and 2 6  respectively  for those who smoked 1 to 10  11 to 20 and more than 20 cigarettes a day  a significant association with hepatocellular carcinoma was also observed for the habitual alcohol consumer with an odds ratio of 3 4  those whose immediate family had a history of hepatocellular carcinoma were more likely to have the disease develop  with an odds ratio of 4 6  however  the frequency of peanut consumption was not significantly associated with hepatocellular carcinoma  
class4	transcatheter oily chemoembolization in the management of advanced hepatocellular carcinoma in cirrhosis  results of a western comparative study in 60 patients  transcatheter oily chemoembolization is widely used as palliative therapy for inoperable hepatocellular carcinoma in high incidence asiatic areas  to assess its usefulness in the western form of this cancer  30 french patients were treated between 1987 and 1990 by intraarterial hepatic injection of a lipiodol doxorubicin emulsion followed by embolization with 0 5 to 1 mm gelatin sponge particles  the number of procedures ranged from one to five  all patients had advanced  symptomatic and inoperable hepatocellular carcinoma  okuda s staging  i  n   8  ii  n   14  iii  n   8   none was found under systematic screening  all had underlying cirrhosis  child pugh s class  a  n   15  b  n   12  c  n   3  that was alcoholic in origin in 27 cases and posthepatitic b in origin in 3 cases  the results of the treatment were assessed by comparison with a group of 30 untreated patients admitted to the same unit between 1984 and 1987  patients of both groups were closely matched for clinical presentation  global disease staging and precise anatomical extension  the overall 1  and 2 yr survival rate was 59  and 30   respectively  for the treated patients vs  0  at 1 yr for the untreated patients  the latter all died from local disease with end stage liver failure and or uncontrollable variceal bleeding  in the former  the three patients with child s class c cirrhosis died after the first procedure  during the follow up  range   3 to 26 mo   11 additional patients died  8 from metastatic generalization  
class4	usefulness of pulsed doppler ultrasound in detection of angiographically evident recurrence of hepatocellular carcinoma after arterial embolization treatment  because hepatocellular carcinoma treated by transcatheter arterial embolization often regains its size  routine follow up is necessary  the usefulness of pulsed doppler ultrasound for detection of this type of recurrence was compared with ultrasonography and computed tomography in 21 such hepatocellular carcinomas  of 15 hepatocellular carcinomas diagnosed by angiography as showing recurrence  four were detected with ultrasonography and five were detected with computed tomography  doppler signals were obtained in the peripheral portions corresponding to tumor vessels or stains on angiograms in 14 of these 15 hepatocellular carcinomas  but they were undetectable in six hepatocellular carcinomas with no recurrence  all signals disappeared after transcatheter arterial embolization  one false negative hepatocellular carcinoma with pulsed doppler ultrasound showed faint tumor stains on angiograms  these were also negative on ultrasonography and computed tomography  pulsed doppler ultrasound may be superior to ultrasonography and computed tomography as a routine procedure to detect the recurrence of hepatocellular carcinoma treated by transcatheter arterial embolization  
class4	mucin production by human colonic carcinoma cells correlates with their metastatic potential in animal models of colon cancer metastasis  patients with mucinous colorectal cancers characteristically present with advanced disease  however  the relationship between mucin production by colon cancer cells and their metastatic potential remains unclear  we therefore sought to define the relationship between mucin production by human colon cancer cells and metastatic ability by employing animal models of colon cancer metastasis  ls lim 6  a colon carcinoma cell line with high liver metastasizing ability during cecal growth in nude mice produced twofold more metabolically labeled intracellular mucin and secreted four  to fivefold more mucin into the culture medium compared to poorly metastatic parental line ls174t  this was accompanied by a similar elevation in poly a   rna detected by blot hybridization with a human intestinal mucin cdna probe  and increases in mucin core carbohydrate antigens determined immunohistochemically  variants of ls174t selected for high  hm 7  or low  lm 12  mucin synthesizing capacity also yielded metastases after cecal growth and colonized the liver after splenic portal injection in proportion to their ability to produce mucin  inhibition of mucin glycosylation by the arylglycoside benzyl alpha n acetyl galactosamine greatly reduced liver colonization after splenic portal injection of the tumor cells  these data suggest that mucin production by human colon cancer cells correlates with their metastatic potential and affects their ability to colonize the liver in experimental model systems  
class4	acquired cisplatin resistance in human ovarian cancer cells is associated with enhanced repair of cisplatin dna lesions and reduced drug accumulation  studies were undertaken to investigate acquired resistance to cisplatin in human ovarian cancer cells  the cell lines a2780 and a2780 cp70 were studied to assess their respective characteristics of drug accumulation and efflux  cytosolic inactivation of drug  and dna repair  all experiments were performed using 1 h drug exposures  the a2780 cp70 cell line was 13 fold more resistant to cisplatin than a2780 cells  when studied at their respective ic50 doses  drug accumulation rates were similar for the two cell lines  however  the resistant cell line was twofold more efficient at effluxing drug  which was associated with reduced total drug accumulation for equivalent micromolar drug exposures  at equivalent levels of total cellular drug accumulation  the two cell lines formed the same levels of cisplatin dna damage  suggesting that cytosolic inactivation of drug does not contribute to the differential in resistance between these cell lines  resistant cells were also twofold more efficient at repairing cisplatin dna lesions in cellular dna and in transfected plasmid dna  we conclude that in these paired cell lines  alterations in drug uptake efflux and in dna repair are the major contributing factors to acquired resistance to cisplatin  
class4	evidence that tumor necrosis factor plays a pathogenetic role in the paraneoplastic syndromes of cachexia  hypercalcemia  and leukocytosis in a human tumor in nude mice  recently  we have established a human squamous cell carcinoma of the maxilla  called mh 85  associated with hypercalcemia  leukocytosis  and cachexia in culture  mh 85 tumor cells caused the same paraneoplastic syndromes in tumor bearing nude mice  we found that there was a sixfold increase in splenic size in mh 85 tumor bearing mice  this increase paralleled tumor growth and was reversed by surgical removal of the tumor  splenectomy in nude mice 1 wk before or 6 wk after tumor inoculation resulted in a decrease in tumor growth  and impairment of hypercalcemia  leukocytosis  and cachexia  in mh 85 tumor bearing animals that had been pretreated by splenectomy  intravenous injection of fresh normal spleen cells caused an immediate reversal of leukocytosis  hypercalcemia  and cachexia  since the presence of cachexia in both the patient and the mice carrying the tumor suggested tumor necrosis factor  tnf  may be overproduced  we injected polyclonal neutralizing antibodies raised against murine tnf into tumor bearing mice  there was a rapid and reproducible decrease in blood ionized calcium  accompanied by suppression of osteoclast activity  no changes in blood ionized calcium were seen in mice injected with normal immune sera  in addition  there was an increase in body weight and decrease in white cell count  plasma immunoreactive tnf was increased almost fourfold in tumor bearing nude mice compared with control nude mice  although tnf activity was undetectable in mh 85 culture supernatants  cells of the macrophage lineage  including spleen cells  released increased amounts of tnf when cultured with mh 85 tumor conditioned media  these results suggest that splenic cytokines such as tnf may influence the development of the paraneoplastic syndromes of hypercalcemia  leukocytosis  and cachexia in these animals  as well as tumor growth  they also show that paraneoplastic syndromes may be due to factors produced by normal host cells stimulated by the presence of the tumor  
class4	biology of basal cell carcinoma  part i   basal cell carcinoma is the most common malignancy in humans  although rarely metastatic  it is capable of significant local destruction and disfigurement  this two part article reviews the current understanding of basal cell carcinoma biology  part i examines significant clinical  histologic  and ultrastructural features that relate to invasive potential  genetic characteristics  including tumor growth rate  chromosomal abnormalities  and oncogene presence  are discussed  and expression of important cell and matrix proteins  including keratin  fibronectin  and hla antigens  are reviewed  further topics to be explored in part ii include host immunologic responses  theories of pathogenesis  and valuable second line therapeutic regimens for treatment of multiple cancers  
class4	the reliability of frozen sections in the evaluation of surgical margins for melanoma  as the width of surgical margins declines  histologic evaluation of the margins is needed to assess the completeness of excision of a malignant melanoma  we studied 221 specimens in 59 patients and compared the interpretations of frozen and paraffin sections from the same block  frozen sections had a sensitivity of 100  in detecting melanoma when present and a specificity of 90   
class4	epidermotropic eccrine porocarcinoma  three cases of epidermotropic eccrine porocarcinoma are summarized and compared with reported cases  all patients had a long standing tumor on a lower extremity that rapidly metastasized to the skin and proximal lymph nodes  the histologic picture was consistent with an intraepidermal eccrine sweat gland carcinoma  
class4	lobulated intradermal nevus  report of three cases  we report the cases of three patients with lobulated intradermal nevi  biopsy specimens showed similar findings  that is  fatty infiltration within nests of nevus cells  neuroid differentiation of nevus cells  and dermal fibrosis  our cases probably represent an unusual form of regressing melanocytic nevus  
class4	late metastases of cutaneous melanoma  case report and literature review  the development of delayed metastases  although rare  is well documented in patients with invasive cutaneous melanoma  only 24 cases  including ours  are clearly documented in the literature  we describe a 56 year old woman who had an acral lentiginous melanoma of the right hand  thickness 1 2 mm   thirteen years after excision and postoperative irradiation  a subcutaneous metastasis developed in the right arm  one year later the patient died with disseminated bone metastases  this case  as with most of those with delayed metastases  has typical features  female sex  location at a site other than the back  arm  neck  or scalp  and primary tumor thickness between 1 2 and 2 5 mm  
class4	multiple granular cell tumors associated with giant speckled lentiginous nevus and nevus flammeus in a child  we describe an 11 year old girl in whom multiple cutaneous granular cell tumors were associated with a giant speckled lentiginous nevus and an extensive nevus flammeus  an association between granular cell tumors and pigmented skin lesions has been reported twice previously and supports a neural origin for these tumors  an abnormality of neural crest development is proposed to explain the coexistence of three uncommon and unusually extensive cutaneous disorders in this patient  this case may represent a further variant of phakomatosis pigmentovascularis  
class4	xeroderma pigmentosum lesions related to ultraviolet transmittance by clothes  xeroderma pigmentosum is associated with severe actinic degeneration of the skin  our patient with xeroderma pigmentosum showed increasing actinic damage in some areas covered by clothes  we therefore performed a complete evaluation of the patient s exposure to ultraviolet radiation  this included transmission measurements of the patient s clothes  glasses  and car windows  the transmission of uvb  280 to 320 nm  by the clothes varied from none to 17 8   the transmitted uvb radiation was proportional to the clinical manifestations of xeroderma pigmentosum  the patient s wardrobe was changed  and uva blocking film was applied to the windows of the car and house  a decline in manifestations was seen after 18 months of improved ultraviolet protection  
class4	abnormal epidermal changes after argon laser treatment  a 26 year old woman with a congenital port wine stain on the forehead was treated three times at 2 month intervals with an argon laser  six months after the last treatment  moderate blanching and mild scaling confined to the treated area was observed  a biopsy specimen of the treated area revealed a significant decrease in ectatic vessels  however  epidermal changes similar to those of actinic keratosis with disorganized cell layers and marked cytologic abnormalities were seen  analysis of peripheral blood lymphocytes for a defect in dna repair was negative  multiple  argon laser induced photothermal effects may be responsible for the changes observed in our case and may lead to premalignant epidermal transformation  
class4	unusual presentation of squamous cell carcinoma of the middle ear and mastoid  an unusual case of squamous cell carcinoma of the middle ear and mastoid in which syncope was a major presenting feature is reported  no such case has been reported in the literature  a possible explanation is offered  
class4	radiation induced cranial nerve palsy  hypoglossal nerve and vocal cord palsies  cranial nerve palsies are an unexpected complication of radiotherapy for head and neck tumours  we present a case of this radiation induced cranial palsy  an 18 year old female with nasopharyngeal carcinoma developed a right hypoglossal nerve palsy 42 months after cancericidal doses of radiotherapy  in addition  she developed a bilateral vocal cord palsy 62 months after therapy  follow up over four years has demonstrated no evidence of tumour recurrence and no sign of neurological improvement  
class4	massive metastasis from squamous carcinoma of the tonsil  squamous carcinomas of the oro pharynx are associated with a high incidence of distant metastases at post mortem  a case of a massive distant metastasis from a squamous cell carcinoma of the tonsil is presented  this occurred despite excellent local control  the pathology and the possible management implications are discussed  
class4	paraneoplastic limbic encephalitis  clinico pathological correlations  three new cases of limbic encephalitis in association with malignancy are reported  the literature on this condition is reviewed and the clinical  laboratory and histopathological features of cases proven at necropsy are correlated  the possible pathogenic mechanism of this disorder is discussed  
class4	the history of nitrite in human nutrition  a contribution from german cookery books  in order to settle the question of when saltpetre  nitrate  came in use as an additive to human food  a number of historic cookery books from germany and austria were reviewed  obviously  the change from vegetable dyes to saltpetre for the coloring or color preservation  respectively  of meat occurred between 1600 and 1750  probably near 1700  the addition of sugar which favours the reduction of nitrate to the active agent nitrite became common practice during the 19th century  thus some historic parallels to the appearance of colorectal cancer  multiple sclerosis and rheumatoid arthritis in the medical literature became apparent  
class4	systematic computer aided search of optimal staging system for colorectal cancer  two hundred and ninety eight patients with curatively resected colorectal cancer were classified into 12 categories according to the depth of tumour penetration  t1 t4   and lymph node status  n0 n2   using a computer  these categories were grouped into 2 12 stages in every possible combination  so a total of 146 975 logical classifications were generated  the optimal model was selected for each group of classifications with equal stage number  thus giving the greatest prognostic information on 5 year survival according to the akaike criterion  the results showed that  1  13  of the total classifications  including 85  of the 3 stage classifications  were better than the dukes system in predicting our patients  outcomes   2  the t level was a stage determinant even more important than the n level  and  3  major changes in prognosis occurred at more advanced stages than the classical  turning points   we conclude that in order to find an optimal staging of cancer  systematic computer aided search through all the possible classifications is necessary  using the appropriate database  
class4	a cost minimization study of cancer patients requiring a narcotic infusion in hospital and at home  we conducted a retrospective  non randomized  cost minimization study  from the perspective of the ministry of health  to compare the cost of managing cancer patients who required narcotic infusions  in hospital and at home  our medical costs averaged  369 72 per inpatient day and  150 24 per outpatient day  saving  219 48 per diem  1988 canadian dollars   while narcotic costs were the same for any given patient in both settings  sensitivity analysis showed that no reasonable changes in the quantity and cost of services reduced our savings by more than 50   during incremental analysis  savings increased as more outpatient days were managed by our centre  from  0 00 for 318 days  to more than  500 000 for over 2000 days per annum  as this program has been extremely cost effective and preferred by our patients  other hospitals and central funding agencies might consider establishing a regional outpatient narcotic infusion program to reduce their costs  
class4	usefulness of epidurally evoked cortical potential monitoring during cervicomedullary glioma surgery  this report describes a patient with an intramedullary ependymoma at the region of the cervicomedullary junction in whom there was an abolition of somatosensory evoked potentials following median nerve stimulation  during intraoperative monitoring of cortical potentials elicited by epidural cervical cord stimulation  the tumor was removed  posterior epidural stimulation appeared to depolarize more ascending fibers than did stimulation of a single peripheral nerve  we recommend that  in cases of operations in this vital area  epidurally evoked cortical potentials be monitored intraoperatively  
class4	the influence of drug interval on the effect of methotrexate and fluorouracil in the treatment of advanced colorectal cancer the importance of the interval between methotrexate  mtx  and fluorouracil  5 fu  was studied in 168 patients with previously untreated  measurable  advanced colorectal cancer  they were randomized to receive mtx 200 mg m2  followed by 5 fu 600 mg m2 either 24 hours  arm a  or 1 hour  arm b  after mtx  all patients received leucovorin  lv  24 hours after mtx  10 mg m2 orally every 6 hours for six doses  the regimen was repeated every 2 weeks  with 5 fu escalation as tolerated  arm a was significantly better than arm b with respect to overall response rate  29  v 14 5   p    026   time to progression  ttp  median  9 9 months v 5 9 months  p    009   and survival  median  15 3 months v 11 4 months  p    003   significant differences between arms were not found in response rate  median ttp  or median survival for the subgroup of patients with rectal primaries who comprised 20  of the patients in each arm  significant factors prognostic for survival were performance status and number of metastases  as well as treatment  age did not influence survival  toxicity was similar in both arms and was primarily gastrointestinal  more mucositis was seen in arm a  there were four toxic deaths secondary to neutropenia and infection  one from arm a and three from arm b  and three other deaths  two from arm a and one from arm b  that were possibly drug related  the combination of mtx with lv rescue and 5 fu is an active regimen in advanced colorectal cancer  its efficacy is increased in colon  but not rectal cancer  when the interval between mtx and 5 fu is long  24 hours  rather than short  1 hour   
class4	clonogenic growth in vitro  an independent biologic prognostic factor in ovarian carcinoma a retrospective analysis was performed to investigate the prognostic value of growth in a human tumor clonogenic assay system for 84 ovarian cancer patients  a significant difference in survival probability  determined by the method of kaplan meier  was found by univariate analysis between patients with ovarian carcinoma whose tumors manifested clonogenic growth  defined as growth of greater than or equal to five colonies per plate  and patients whose tumors did not grow  clonogenic growth in vitro was associated with worse prognosis  p    007  log rank test   a number of generally accepted prognostic factors  international federation of gynecology and obstetrics  figo  stage  p    003   residual tumor mass  p less than  001   and grade  p    011   were also of prognostic importance in our patient population  multivariate analysis  based on the cox regression model  identified clonogenic growth as a significant independent prognostic parameter in ovarian carcinoma  p    031   in addition to the conventional risk factors  estimation of survival of individual patients was best accomplished by combining the factors of residual tumor mass  p less than  05   age  p less than  01   and clonogenic growth  p less than  05   in sequence of decreasing potential of risk   
class4	second line platinum therapy in patients with ovarian cancer previously treated with cisplatin  in an effort to critically define the incidence and clinical characteristics of secondary responses to cisplatin based therapy in patients with ovarian cancer previously treated with a cisplatin based program  a retrospective review was undertaken of patients at the memorial sloan kettering cancer center who received greater than or equal to two cisplatin carboplatin based programs  eighty two patients were identified who met the entry criteria of having had a cisplatin free interval  cfi  of more than 4 months between the completion of their first regimen and the institution of a second cisplatin carboplatin program  of the 72 assessable patients  10 had no measurable disease  and a laparotomy was not performed to assess response   31  43   responded  including 10 surgically defined complete responses  s crs   the overall response rates  and s cr rate   based on duration of cfi  were 5 to 12 months  27   5    13 to 24 months  33   11    and more than 24 months  59   22    twenty nine patients  35   received noncisplatin carboplatin containing treatments between the cisplatin programs  patients without any treatment for more than 24 months from the completion of their initial therapy experienced a 77   17 of 22  response rate and a 32   seven of 22  s cr rate  in conclusion  secondary responses to cisplatin carboplatin based treatment are common in patients with ovarian cancer who have previously responded to the agents and increase in frequency with greater distance from the initial therapy  
class4	human growth hormone and insulin like growth factor 1 enhance the proliferation of human leukemic blasts  as the number of long term survivors of childhood leukemia increases  growth retardation has emerged as a significant complication  treatment of these children with growth hormone  gh  has been suggested and sporadically implemented  we  therefore  studied the effect of human gh  hgh  and its by product insulin like growth factor 1  igf 1  on the growth of leukemic cells in vitro  under serum free conditions hgh and igf 1 induced a significant dose dependent proliferative effect on promyelocytic leukemia  hl60  and burkitt s lymphoma  daudi  cell lines  anti hgh antibodies negated the stimulatory effect of hgh and anti igf 1 serum abrogated the growth promoting effect enhanced by igf 1  similar statistically significant stimulatory properties were found when freshly obtained marrow cells from four of five acute lymphoblastic leukemia  all  of childhood and four acute myelogenous leukemia  aml  patients were studied in all and aml blast cell clonogenic assays  all colonies increased numerically by 72   p less than  025  and aml colonies by 92   p less than  01  in the presence of hgh at concentrations of 2 5 x 10 2  and 3 0 x 10 2  ng ml  respectively  igf 1 stimulated all and aml blast colony growth at concentrations ranging from 0 05 to 0 5 ng ml by up to 105   p less than  025  and 65   p less than  03   respectively  our in vitro data suggest that circulating hgh and igf 1 may promote leukemic blast cell replication in vivo  and the supplemental administration of hgh to leukemia patients in remission must be carefully monitored for early relapse  
class4	abnormal growth patterns and adult short stature in 115 long term survivors of childhood leukemia  significant growth retardation was found in 115 survivors of childhood acute lymphoblastic leukemia  all  who had completed their growth  these children were diagnosed before 12 years of age and treated on four protocols in a single institution  all received either cranial  n   78  or craniospinal  n   37  prophylactic irradiation  patients  heights at diagnosis were within expected ranges  but final heights were greater than or equal to 1 sd below population means in 74  of cases and greater than or equal to 2 sd in 37   effects on growth were more pronounced for children who had received craniospinal irradiation  but decrements were also significant in the cranial irradiation group  with adult heights greater than or equal to 2 sd below population norms in 32   growth retardation was significantly greater  p less than  0001  in children who had earlier disease onset  growth deceleration occurred not only during chemotherapy but during a later period that followed an interval of improved growth in many cases  thus  late decrements in growth may be missed in studies that do not follow patients until they have attained final heights  these findings indicate that abnormally short stature among survivors of all merits further clinical and research attention  
class4	a phase i clinical trial of 2 chlorodeoxyadenosine in pediatric patients with acute leukemia  to evaluate its toxicity and clinical efficacy in children with relapsed or refractory leukemia  we performed a phase i trial of 2 chloro 2  deoxy adenosine  2 chlorodeoxyadenosine  2 cda  given as a continuous 5 day infusion at doses of 3 to 10 7 mg m2 d  in this study of 31 children with acute leukemia  the only dose limiting toxicity was myelosuppression  at the highest dose level  three of seven patients developed fatal systemic bacterial or fungal infections  at dose levels above 6 2 mg m2 d  significant oncolytic responses occurred in all patients  in addition  there was a significant correlation between both the responsiveness by cell type and dose of 2 cda  such that more oncolytic responses were noted in acute myeloid leukemia  aml  patients than acute lymphoblastic leukemia  all  patients  p    02   although this was a phase i trial in heavily pretreated patients with refractory disease  two aml patients treated at 5 2 and 10 7 mg m2 d  respectively  had complete hematologic responses  and one patient treated at 10 7 mg m2 d had a partial response  in addition  there was a dose response relationship in all patients with improved cytoreduction of peripheral blast cells at higher doses of 2 cda  in vitro evaluation of 2 cda uptake and anabolism by leukemic blast cells from 22 patients demonstrated that 2 chloro 2  deoxyadenosine  cld amp  and 2 chloro 2  deoxyadenosine 5  striphosphate  cldatp  reached concentrations close to steady state levels within 1 hour  intracellular nucleotide disappearance rates were high with half lives of 1 29 and 2 47 hours for cldamp and cldatp  respectively  this suggests that continuous infusion is necessary to maintain the desired plasma concentration  the results of this study confirm the antileukemic activity of 2 cda and the lack of prohibitive nonhematologic toxicity  phase ii trials in patients with aml and all are warranted  
class4	treatment of relapsed non hodgkin s lymphomas with dexamethasone  high dose cytarabine  and cisplatin before marrow transplantation  combination chemotherapy is capable of curing many patients with newly diagnosed intermediate  and high grade non hodgkin s lymphomas  nhl   but treatment of relapsed nhl remains problematic  bone marrow transplantation  bmt  offers the best chance for disease free survival  but interim chemotherapy is often necessary while awaiting bmt  especially for patients with bulky disease  we report here 39 patients  median age  44 years  who failed primary therapy with doxorubicin based regimens and subsequently were treated with one to six cycles of dexamethasone  40 mg intravenous  iv  every day on days 1 to 4  cisplatin 100 mg m2 by continuous infusion on day 1  and cytarabine 2 g m2 iv every 12 hours x two doses on day 2  dhap  before the planned bmt  histologies included 16 diffuse large cell  six diffuse mixed  five diffuse small cleaved  four lymphoblastic  and eight other  twenty eight patients had stage iv disease  13 had b symptoms  and 20 had an elevated lactate dehydrogenase  ldh   patients had been treated with a median of three previous chemotherapy regimens  sixty one percent of patients had high tumor burdens according to the md anderson criteria  objective responses to dhap were seen in 26 patients  67   including nine complete responses  crs   23   and 17 partial responses  prs   44    and responses lasted a median of 7 5 months  myelosuppression was the major toxicity  but there were no treatment related deaths  to date  17 patients have undergone subsequent bmt with a projected 3 year disease free survival of 15   we conclude that the dhap regimen is effective short term salvage therapy for relapsed nhl patients  but the long term prognosis of multiply relapsed patients remains poor  
class4	second primary cancer following hodgkin s disease  updated results of an italian multicentric study  the risk of second primary cancer  spc  was evaluated in 947 patients treated for hodgkin s disease  hd  during the period january 1969 to december 1979  the median follow up of this series was 10 5 years  range  9 to 19   treatment categories included radiotherapy  rt  alone  115 patients  12    chemotherapy  cht  alone  161 patients  17    combined rt plus cht  381 patients  40    and salvage treatment for resistant or relapsing hd  290 patients  30 6    fifty six spcs were observed  occurring between 1 and 17 years from initial treatment  among these  secondary acute nonlymphoid leukemia  s anll  was the most frequent spc  23 cases   secondary non hodgkin s lymphoma  s nhl  occurred in 5 patients  whereas a secondary solid tumor  s st  was observed in 28 patients  the calculated actuarial risk      se  of developing spc was 5 0       0 9   and 23 1       5 8   at 10 and 19 years  respectively  concerning treatment modalities and s anll risk  no cases were observed in the radiotherapy group  whereas cht plus rt and salvage groups showed the highest actuarial risk  this was  in fact  at 10 and 19 years  3 1       0 9   and 8 1       4 0   in the former group  and 1 8       1 0   and 16       9 0   in the latter  a statistically significant difference was observed when the cht plus rt group was compared with cht and rt groups  p    04   concerning the relationships with chemotherapeutic regimens  12 s anll cases occurred in the mechlorethamine  vincristine  procarbazine  and prednisone  mopp  plus rt group  and only one case in the group receiving doxorubicin  bleomycin  vinblastine  and dacarbazine  abvd  plus rt  a statistically significant difference of s anll actuarial risk was found comparing patients receiving mopp plus rt to all other treatment groups  p    04   with respect to s st  the actuarial risk at 10 and 19 years was 2 0       0 6   and 13 0       3 8    respectively  no significant differences were found among groups treated with different modalities  these data were confirmed by a multivariate analysis  which indicated treatment modality and age as independent variables for s anll and s st development  respectively  based on the prolonged follow up analysis  the actuarial spc risk at 10 years hereby reported should reflect the real spc incidence in our series  
class4	the pattern of intrathoracic hodgkin s disease assessed by computed tomography  computed tomography  ct  was used to define the sites of intrathoracic abnormality in hodgkin s disease  determine a pattern of progression of disease in the thorax  and establish the place of this pattern of spread in the differential diagnosis of thoracic abnormalities  one hundred eight patients with newly diagnosed hodgkin s disease were studied by chest ct  seventy seven patients had intrathoracic abnormalities  the pattern seen was one of contiguous spread from the anterior mediastinal paratracheal area to the other mediastinal lymph node groups  aortopulmonary  subcarinal  posterior mediastinal  and internal mammary   to the hila  and then into the lung by extension or as discrete nodules  involvement of the pleura  pericardium  or chest wall occurred only after the anterior mediastinal paratracheal mass had enlarged to greater than 30  of the thoracic diameter  the probability that this pattern of contiguous lymph node spread occurred by chance alone was very small  hodgkin s disease spreads from the anterior mediastinal paratracheal area in a contiguous manner  exceptions are unusual enough that when they occur  diagnoses other than hodgkin s disease are more likely  
class4	multiple myeloma  vmcp vbap alternating combination chemotherapy is not superior to melphalan and prednisone even in high risk patients  the efficacy of alternating vincristine  melphalan  m   cyclophosphamide  prednisone vincristine  carmustine  doxorubicin  and prednisone  vmcp vbap  polychemotherapy was compared with the m and prednisone  mp  regimen as induction treatment in multiple myeloma  mm   three hundred four mm patients entered this study between march 1983 and july 1986  the analysis was performed in december 1989  the treatment groups did not show significant differences with respect to major prognostic factors  median overall survival was 33 8 months  in the vmcp vbap and mp arms  after 12 induction chemotherapy cycles  59 0  and 47 3   p less than  068  of the patients achieved an m component reduction greater than 50   no significant difference was observed in the two treatment arms in terms of remission duration  21 3 v 19 6 months  p less than  66  and survival  31 6 v 37 0 months  p less than  28   patients younger than 65 years did not show any advantage from the alternating polychemotherapy  at diagnosis  the plasma cell labeling index  li  and serum beta 2 microglobulin  beta 2 m  were evaluated in 173 and 183 patients  respectively  a significantly reduced survival was observed for patients with li greater than or equal to 2   16 4 months  or beta 2 m greater than or equal to 6 mg l  20 4 months   even in these poor risk subgroups  vmcp vbap was not superior to mp  
class4	concurrent cisplatin  infusional fluorouracil  and conventionally fractionated radiation therapy in head and neck cancer  dose limiting mucosal toxicity  after a preliminary dose finding study involving 12 patients with advanced or locally recurrent head and neck cancer  27 patients were treated on a phase ii protocol  using fluorouracil 350 mg m2 d by continuous intravenous  iv  infusion over 5 days  followed on the sixth day by a 2 hour iv infusion of cisplatin 50 mg m2  administered during the first and fourth weeks of radiation therapy to total doses between 60 and 64 gy  using 2 gy daily fractions  eight of these 27 patients had american joint committee on cancer staging  ajcc  stage iii disease  and 12 had stage iv disease  four had recurrent disease after surgery  three year follow up is now available  twenty one  77 8   remitted completely following treatment  and 11 remain free of local and regional relapse at 3 years  four have developed systemic metastases  following successful salvage treatment in two cases  estimated determinate survival at 3 years is 64   acute toxicity was manageable with this regime  eleven instances of grade 3 radiation therapy oncology group european organization for research and treatment of cancer  rtog eortc  mucositis were observed  which caused interruptions to radiotherapy in only four cases  no late sequelae have so far been recorded  it is concluded that the protocol described is tolerable but probably did not cause a greater number of locoregional  cures  than would have been expected following conventional radiotherapy alone in this group of patients  the use of infusional fluorouracil with concurrent conventionally fractionated radiation therapy and cisplatin infusion results in mucositis that limits the dose of fluorouracil to levels that are probably subtherapeutic  
class4	phase ii trial of piritrexim in metastatic melanoma using intermittent  low dose administration  a phase ii trial of piritrexim  2 4 diamino 6 2 5 dimethoxybenzyl  5 methyl pyrido  2 3d  pyrimidine  301u74  ptx  was conducted for patients with metastatic malignant melanoma using an intermittent  low dose oral administration schedule  ptx was administered at a starting dose of 25 mg orally three times per day for 5 days weekly for 3 weeks followed by 1 week of rest  thirty one patients were entered onto the study  among 31 patients assessable for response  there were two complete responses  crs  and five partial responses  prs  for a response rate  cr plus pr  of 23   95  confidence limit  10  to 42    five responses occurred in soft tissue lesions  and two responses occurred in lung lesions  the initial dose schedule was well tolerated  the dose limiting toxicity was myelosuppression  ptx administered in this schedule appears to be active against malignant melanoma  further clinical trials to confirm these results are underway  
class4	occurrence of hypercalcemia and leukocytosis with cachexia in a human squamous cell carcinoma of the maxilla in athymic nude mice  a novel experimental model of three concomitant paraneoplastic syndromes  hypercalcemia and leukocytosis may occur in conjunction as paraneoplastic syndromes associated with malignant disease  here we describe a human squamous cell carcinoma of the maxilla that was associated with hypercalcemia and leukocytosis  and also cachexia  the primary tumor was surgically removed and established in permanent cell culture  when either primary tumors or cultured tumor cells were inoculated into nude mice  the nude mice developed the same paraneoplastic syndromes as those which occurred in the patient from whom the tumor was originally derived  the plasma calcium was increased two and one half fold and the wbc count 30 fold  and the body weight was decreased by 45  in tumor bearing animals  each of these paraneoplastic syndromes was alleviated by surgical excision of the tumor  indicating that the paraneoplastic syndromes were due to a factor or factors produced by the primary tumor  the development of each of these paraneoplastic syndromes in nude mice correlated positively with the other two syndromes  we examined the organs of tumor bearing mice and found striking histopathologic abnormalities in the bones  spleen  and liver  but no infiltration with tumor cells  the bones showed marked evidence of osteoclastic bone resorption  this model of a human tumor associated with the hypercalcemia leukocytosis paraneoplastic syndrome  together with cachexia  should make it possible to determine the mechanisms responsible for these paraneoplastic syndromes and their relationship to each other  
class4	a phase i clinical  plasma  and cellular pharmacology study of gemcitabine  a novel deoxycytidine analog  gemcitabine  2  2  difluorodeoxycytidine  dfdc    has been studied in a phase i clinical and pharmacology trial  doses ranging from 10 to 1 000 mg m2 were administered over 30 minutes weekly times 3 weeks every 4 weeks  the maximum tolerated dose  mtd  was 790 mg m2  the dose limiting toxicity was myelosuppression  with thrombocytopenia and anemia quantitatively more important than granulocytopenia  nonhematologic toxicity was minimal  two responses in patients with adenocarcinomas of the colon and lung were documented  the maximum dfdc plasma concentration  reached after 15 minutes of infusion  was proportional to the total dose administered  elimination  due mainly to deamination  was rapid  terminal half life  t1 2   8 0 minutes  and dose independent  the deamination product 2  2  difluorodeoxyuridine  dfdu  was eliminated with biphasic kinetics characterized by a long terminal phase  t1 2  14 hours   it was the sole metabolite detected in urine  the concentration of dfdc 5  triphosphate in circulating mononuclear cells increased in proportion to the dfdc dose at infusions between 35 and 250 mg m2  no further increment in dfdc 5  triphosphate  dfdctp  was observed at higher doses  which resulted in plasma dfdc concentrations greater than 20 mumol l  350 to 1 000 mg m2   suggesting saturation of dfdc 5  phosphate accumulation  the recommended dose for phase ii clinical trials in solid tumors is 790 mg m2 wk  
class4	bone metastases  pathophysiology and management policy  the pathophysiology and options for management of bone metastases as well as criteria for determining response to therapy are reviewed  bone metastases are frequently one of the first signs of disseminated disease in cancer patients  in the majority of patients  the primary tumor is in the breast  prostate  or lungs  although almost all patients will die of their disease  a proportion of the patients will survive for several years  treatment is primarily palliative  the intention is to relieve pain  prevent fractures  maintain activity and mobility  and  if possible  to prolong survival  therapeutic options include local treatment with radiotherapy and or surgery  and systemic treatment using chemotherapy  endocrine therapy  radioisotopes  agents such as diphosphonates  which inhibit resorption of bone  as well as analgesic and antiinflammatory drugs  the mechanisms by which pain is relieved by several of these therapies remain unclear but actions beyond a simple tumoricidal effect appear to be important  there have been few randomized trials comparing the therapeutic options  and the criteria for assessing response to therapy have  in general  been poorly defined  there is a need for rigorous clinical investigations that assess the efficacy of the various therapeutic possibilities by using well defined and validated criteria of response  
class4	interleukin 2  prospects for lymphocyte mediated destruction of pediatric malignancies  immunologic therapy of cancer was speculated on at the turn of the century  in animals  in vitro  and most recently in patients  irrefutable evidence has been obtained that lymphocyte responses can have a reproducible and beneficial antitumor effect  these results indicate that  biologic response modification  may truly become a fourth modality for cancer treatment  to be integrated into the standard approaches of radiation  chemotherapy  and surgery  to what extent these immune approaches may enable eradication of microscopic amounts of residual diseases in children who would otherwise have a recurrence of their malignancies remains the critical issue for testing over the next decade  enthusiasm regarding this approach is abundant  but critical evaluation of all clinical trials is essential to best focus these mechanisms into effective therapy  
class4	endometrial cancer  biochemical and clinical correlates  some endometrial cancers and endometrial adenocarcinoma cell lines show amplified expression of proto oncogenes  fos  fms  myc  myb  neu  and erb b  and augmented production of growth factors  colony stimulating factor 1  epidermal growth factor  transforming growth factor alpha  and transforming growth factor beta  and epidermal growth factor receptor  oncogene expression  the presence of estrogen and progesterone receptors  and the fraction of cells in s phase are useful biochemical prognostic indicators of clinical outcome  and markers recognized by monoclonal antibodies are available for use in following the clinical course of the disease and responses to treatment  in vivo and in vitro studies on normal and neoplastic tissues are providing evidence of paracrine influences on epithelial cell proliferation  long term administration of tamoxifen as adjuvant therapy for breast cancer has recently been found to increase the risk for development of endometrial cancer  
class4	radiotherapy alone versus combined chemotherapy and radiotherapy in nonresectable non small cell lung cancer  first analysis of a randomized trial in 353 patients  we report the results observed in a large  randomized study that compared the effects of radiotherapy alone  the standard therapy  with those of a combination of radiotherapy and chemotherapy in nonresectable squamous cell and large cell lung carcinoma  the radiation dose was 65 gy in each group  and chemotherapy included vindesine  cyclophosphamide  cisplatin  and lomustine  in this study  177 patients received radiotherapy alone  group a   and 176 patients received the combined treatment  group b   the 2 year survival rate was 14  in group a and 21  in group b  p    08   the distant metastasis rate was significantly lower in group b  p less than  001   local control was poor in both groups  17  and 15   respectively  and remained the major problem  
class4	alternating hepatic intra arterial floxuridine and fluorouracil  a less toxic regimen for treatment of liver metastases from colorectal cancer  hepatic intra arterial  hia  infusion of floxuridine  fudr  via an implanted pump has shown promise in the treatment of colorectal cancer metastasized to the liver  however  the potential benefit of this therapy may be offset by the high incidence of treatment limiting biliary toxicity  although weekly hia bolus of fluorouracil  5 fu  is effective against metastatic colorectal cancer to the liver with no biliary toxicity  it is limited by systemic side effects  in december 1986  we began a phase ii trial of alternating hia fudr and 5 fu via the implanted pump in an attempt to extend the duration of treatment by obviating the limiting biliary  fudr  and systemic  5 fu  drug toxic effects  patients received continuous hia fudr at 0 1 mg kg of body weight per day on days 1 through 8 followed by an hia bolus of 5 fu at 15 mg kg given via the pump sideport on days 15  22  and 29  with the cycle repeated every 35 days  sixty eight patients were enrolled in this trial  and 64 were fully evaluable  of the 64 patients  30  47   previously had received chemotherapy  major response  complete response plus partial response  was observed in 32  50   of 64 patients  and the median survival from pump implantation in all patients was 22 4 months  in contrast to the experience with the single agent hia fudr regimen  no patient had treatment terminated because of drug toxicity  alternating hia fudr and 5 fu has efficacy similar to that of hia fudr given alone  but when closely monitored and adjusted appropriately  is not associated with toxic effects requiring treatment termination  
class4	cancer registry problems in classifying invasive bladder cancer  a slide review of diagnostic pathologic tissue obtained from 364 bladder cancer cases  identified through the iowa surveillance  epidemiology  and end results  seer  program in 1983  classified 97  26 6   of these cases as invasive bladder cancers  these findings contrasted sharply with the iowa seer program classification that coded 289  79 4   of these cases as invasive bladder cancers  these results were validated further by the hazard ratio of 4 54  95  confidence interval  2 57 to 8 03  among invasive relative to noninvasive bladder cancer cases when the slide review findings were used  in contrast  the hazard ratio was only 1 70  95  confidence interval  0 76 to 3 79  when the iowa seer program findings were used  the traditional method used by the national cancer institute s seer program to deal with this problem is described and its implications are discussed  
class4	preferential localization of human adherent lymphokine activated killer cells in tumor microcirculation  the efficacy of adoptive immunotherapy for solid tumors with lymphokine activated effector cells presumably depends on the ability of these cells to localize adequately in tumor tissues  we present here the first quantitative study of the in vivo movement of fluorescently labeled adherent lymphokine activated killer  a lak  cells  these cells were injected intra arterially along with low dose interleukin 2 into normal  mature granulation  tissue and an implant of vx2 carcinoma grown in the rabbit ear chamber  a small proportion of a lak cells accumulated preferentially in the tumor microcirculation in vivo because of an increased frequency of long term adhesive interactions with the tumor vasculature  stasis of blood flow in the tumor vasculature was observed 1 to 2 days after injection  subsequent necrosis of the tumors was observed  along with diffuse infiltrates of lymphocytes  monocytes  and granulocytes in the interstitial space within the tumor  development of necrosis despite low ratios of effector cells to target cells suggests that in addition to direct cytotoxicity  the response to adoptive immunotherapy is mediated via the tumor vasculature  this novel mechanism for adoptive immunotherapy must be taken into account in the development of improved strategies for cancer treatment  
class4	mortality among workers at oak ridge national laboratory  evidence of radiation effects in follow up through 1984  published erratum appears in jama 1991 aug 7 266 5  657  white men hired at the oak ridge  tenn  national laboratory between 1943 and 1972 were followed up for vital status through 1984  n   8318  1524 deaths   relatively low mortality compared with that in us white men was observed for most causes of death  but leukemia mortality was elevated in the total cohort  63  higher  28 deaths  and in workers who had at some time been monitored for internal radionuclide contamination  123  higher  16 deaths   median cumulative dose of external penetrating radiation was 1 4 msv  638 workers had cumulative doses above 50 msv  5 rem   after accounting for age  birth cohort  a measure of socioeconomic status  and active worker status  external radiation with a 20 year exposure lag was related to all causes of death  2 68  increase per 10 msv  primarily due to an association with cancer mortality  4 94  per 10 msv   studies of this population through 1977 did not find radiation cancer mortality associations  and identical analyses using the shorter follow up showed that associations with radiation did not appear until after 1977  the radiation cancer dose response is 10 times higher than estimates from the follow up of survivors of the bombings of hiroshima and nagasaki  japan  but similar to one previous occupational study  dose response estimates are subject to uncertainties due to potential problems  including measurement of radiation doses and cancer outcomes  longer term follow up of this and other populations with good measurement of protracted low level exposures will be critical to evaluating the generalizability of the results reported herein  
class4	cancer in populations living near nuclear facilities  a survey of mortality nationwide and incidence in two states  reports from the united kingdom have described increases in leukemia and lymphoma among young persons living near certain nuclear installations  because of concerns raised by these reports  a mortality survey was conducted in populations living near nuclear facilities in the united states  all facilities began service before 1982  over 900 000 cancer deaths occurred from 1950 through 1984 in 107 counties with or near nuclear installations  each study county was matched for comparison to three  control counties  in the same region  there were 1 8 million cancer deaths in the 292 control counties during the 35 years studied  deaths due to leukemia or other cancers were not more frequent in the study counties than in the control counties  for childhood leukemia mortality  the relative risk comparing the study counties with their controls before plant start up was 1 08  while after start up it was 1 03  for leukemia mortality at all ages  the relative risks were 1 02 before start up and 0 98 after  for counties in two states  cancer incidence data were also available  for one facility  the standardized registration ratio for childhood leukemia was increased significantly after start up  however  the increase also antedated the operation of this facility  the study is limited by the correlational approach and the large size of the geographic areas  counties  used  it does not prove the absence of any effect  if  however  any excess cancer risk was present in us counties with nuclear facilities  it was too small to be detected with the methods employed  
class4	esophageal ultrasound and the preoperative staging of carcinoma of the esophagus  esophageal ultrasound allows the esophageal wall to be viewed as five discrete layers  lymph nodes are easily identified  and their size  shape  margin  and internal structure can be assessed  this provides an alternative method of preoperative  clinical  evaluation of the primary tumor  t  and the regional lymph nodes  n  of patients with carcinoma of the esophagus  esophageal ultrasound was attempted in the clinical staging of 28 patients with carcinoma of the esophagus  six patients  21   were not assessed because of the inability to pass the esophageal ultrasound probe through the malignant stricture  the staging system for carcinoma of the esophagus developed by the international union against cancer and the american joint committee on cancer was used  twenty two patients had the true t determined by pathologic review of the resected esophagus  esophageal ultrasound correctly identified t in 13 patients  59  accuracy   in four patients  18   the disease was overstaged by esophageal ultrasound  all these patients had early t1 tumors confined to the submucosa  in five patients  23   the disease was understaged by esophageal ultrasound  all of these patients had advanced tumors  four t3 and one t4  that invaded beyond the esophageal wall  seven of the nine incorrect esophageal ultrasound determinations were called t2  three t1  three t3  one t4   which suggests that the borders of the muscularis propria require careful attention when evaluated by esophageal ultrasound  twenty patients had the true n determined by pathologic review of the resected specimen  esophageal ultrasound correctly identified n in 14 patients  70  accuracy   three patients were falsely identified as having n1 disease and three were falsely identified as having n0 disease  the sensitivity  specificity  positive predictive value  and negative predictive value for n assessment by esophageal ultrasound were 70   esophageal ultrasound provides an alternative method of visualization of the esophageal wall and regional lymph nodes  our early experience shows promise for esophageal ultrasound in the clinical staging of carcinoma of the esophagus  
class4	use of immunoglobulin gene rearrangements to show clonal lymphoproliferation in hyper reactive malarial splenomegaly in africa  hyper reactive malarial splenomegaly  hms   which is also known as tropical splenomegaly syndrome  can be associated with a prominent lymphocytosis in blood and bone marrow that is difficult to distinguish clinically from chronic lymphocytic leukaemia  cll   the observation that some patients with hms become resistant to treatment with anti malarial drugs has led to the suggestion that hms may evolve into a malignant lymphoproliferative disorder  to test this hypothesis  22 ghanaian patients with hms and or lymphocytosis were categorised by degree of response to proguanil according to standard clinical criteria  and dna was extracted from peripheral blood cells and screened for rearrangements of the jh region of the immunoglobulin gene with a dna probe  clonal rearrangements of the jh region were found in all 3 patients with no response  in none of 13 patients with sustained response  and in 2 of 6 patients with moderate response or relapse on proguanil therapy  the detection of such rearrangements  and hence clonal lymphoproliferation in individuals with clinical features intermediate between hms and cll  supports the hypothesis that hms may evolve into a malignant lymphoproliferative disorder  
class4	muscle fibre type and habitual snoring  although anatomical abnormalities of the upper airway have been recorded in some patients with obstructive sleep apnoea  osa   a muscle tone dysregulation also seems to have an important role in this disorder  since habitual snoring is the initial stage of osa  the structural characteristics of upper airway muscles  medium pharyngeal constrictor muscle  mpcm   from 13 men  9 non snorers and 4 habitual snorers  were studied  mpcm fibre structure in non snorers was broadly similar to that in normal limb muscles  with the exception that fibre diameters were smaller for all fibre types  compared with limb muscles  mpcm had a smaller proportion of type iib fibres and a higher proportion of types i and iia fibres  mpcm in habitual snorers had an abnormal distribution of fibre types  low percentage of type i and type iib fibres and high percentage of type iia fibres  compared with non snorers  p less than 0 001  and the type iia fibres were hypertrophic  no myopathic or neurogenic changes were seen  two possible hypotheses explain the abnormal distribution of fibre types in snorers  first  a constitutionally determined reduction of slow alpha motor neurons induces an adaptive transformation of type iib to type iia fibres and a hypertrophy of type iia fibres  or  second  motor neurons change their patterns of discharge and  hence  of activation  and modify fibre type distribution of mpcm as an adaptation to the anatomical characteristic of upper airway and habitual snoring  
class4	lack of effect of pregnancy on outcome of melanoma  for the world health organisation melanoma programme to determine the effect of pregnancy on prognosis in melanoma we investigated 388 women treated for stage 1 primary cutaneous disease during their childbearing years  85 women had been treated before any pregnancy  92 during pregnancy  143 after they had completed all pregnancies  and 68 between pregnancies  women who had received treatment while pregnant had primary tumours of significantly greater thickness than did those in the other three groups  p   0 002   other possible confounding factors  site  age  parity  did not differ between the groups  once tumour thickness was controlled for  survival rate of women in whom melanoma was diagnosed and treated while they were pregnant did not differ from that in the other three groups  cox regression analysis showed no differences between the three groups of women who were not pregnant at diagnosis  women with melanoma should be advised about pregnancy on the basis of thickness and site of tumour and evidence of vascular spread  and not hormonal status  
class4	prognostic factors in craniofacial surgery  from 1979 to 1989  21 patients underwent craniofacial resection for malignancies involving the anterior skull base  histologic types included 8 squamous cell carcinomas  3 chondrosarcomas  2 melanomas  2 basal cell carcinomas  2 adenocarcinomas  2 poorly differentiated carcinomas  1 malignant schwannoma  and 1 malignant hemangiopericytoma  survival was 57   with follow up of 41 months  a 50  complication rate included osteomyelitis  cerebrospinal fluid rhinorrhea  meningitis  brain abscess  epidural abscess  and syndrome of inappropriate antidiuretic hormone  recurrent disease occurred in 9 patients  41    the most reliable predictor being dural invasion indicated preoperatively by ct scan or at operation  patients demonstrating dural involvement  n   9  had a 22  survival rate  while patients without  n   12  had a survival rate of 83   the impact of dural invasion on long term survival is emphasized  though complications were frequent  long term results were favorable  
class4	the internal oblique iliac crest free flap in composite defects of the oral cavity involving bone  skin  and mucosa  the reconstruction of oromandibular defects following ablative surgery is a challenging undertaking  when the defect involves skin as well as mucosa  the challenge becomes even greater  the internal oblique iliac crest osteomyocutaneous free flap is particularly useful for reconstruction of through and through composite defects due to the inclusion of two separate soft tissue flaps on the same vascular pedicle  we report our experience with this flap in the reconstruction of 10 patients with such defects  the utility  and the limitations of this form of reconstruction are discussed in detail  
class4	detection of epstein barr virus dna in formalin fixed paraffin embedded tissue of nasopharyngeal carcinoma using polymerase chain reaction and in situ hybridization  the polymerase chain reaction method for amplification of dna in formalin fixed  paraffin embedded tissue sections was used to detect epstein barr virus dna in nasopharyngeal carcinomas from japanese patients  thirty one cases of nasopharyngeal carcinoma and 8 cases of lymph node metastasis of nasopharyngeal carcinoma were studied  detection rates of epstein barr virus in various types of nasopharyngeal carcinoma according to the world health organization classification were as follows  10 of 10 undifferentiated carcinomas  8 of 13 nonkeratinizing carcinomas  and 5 of 7 keratinizing carcinomas  eight lymph node metastases  for which the primary was positive for epstein barr virus  also contained epstein barr virus dna  by in situ hybridization using a biotinylated epstein barr virus probe  it was clearly demonstrated that epstein barr virus dna was localized in the nuclei of the neoplastic cells  the clinical features of nasopharyngeal carcinoma with or without epstein barr virus were not different  these results demonstrate that nasopharyngeal carcinoma in japanese patients is closely associated with epstein barr virus infection  similar to nasopharyngeal carcinoma of other endemic and nonendemic areas  
class4	paraneoplastic vasculitic neuropathy  a treatable neuropathy  paraneoplastic vasculitic neuropathy has been recently described  we report the first case of this disorder which responded both clinically and electrophysiologically to cyclophosphamide treatment  a 54 year old woman with a history of metastatic endometrial carcinoma in remission had asymmetrical polyneuropathy  electrophysiological findings consistent with a diffuse axonal neuropathy  high sedimentation rate and spinal fluid protein  and microvasculitis with axonal degeneration on nerve biopsy  the patient was treated with 150 mg of cyclophosphamide daily with gradual clinical and electrophysiological improvement  
class4	activation of epstein barr virus latent genes protects human b cells from death by apoptosis  epstein barr virus  ebv   a human herpesvirus  establishes a persistent asymptomatic infection of the circulating b lymphocyte pool  the mechanism of virus persistence is not understood but  given the limited lifespan of most b cells in vivo  it seems most likely that ebv infected cells must gain access to the long lived memory b cell pool  here we show in an in vitro system that ebv  through expression of the full set of eight virus coded  latent  proteins  can protect human b cells from programmed cell death  apoptosis   the deletion mechanism which normally restricts entry into memory  we have found that ebv positive burkitt s lymphoma  bl  cell clones retaining the original tumour cell phenotype and expressing only one of the virus latent proteins  the nuclear antigen ebna 1  are extremely sensitive to apoptosis  in this respect they resemble the tumour s normal cell of origin found in the germinal centres of lymphoid tissue  by contrast  isogenic bl cell clones which have activated expression of all eight ebv latent proteins are resistant to the induction of apoptosis  the ebv latent proteins should therefore be seen not just as activators of b cell proliferation but  perhaps more importantly  as mediators of enhanced b cell survival  
class4	location of port wine stains and the likelihood of ophthalmic and or central nervous system complications  of 310 patients with port wine stains  68  had more than one dermatome involved  85  had unilateral and 15  had a bilateral distribution of their port wine stain  at the time of examination  8  of all patients with trigeminal port wine stains had evidence of eye and or central nervous system  cns  involvement  extensive involvement  with port wine stain over the trunk and extremities as well as the head and neck  was observed in 12   patients who did not have port wine stains on the areas served by branches v1 and v2 of the trigeminal nerve had no signs or symptoms of eye and or cns involvement  port wine stains of the eyelids  bilateral distribution of the birthmark  and unilateral port wine stains involving all three branches of the trigeminal nerve were associated with a significantly higher likelihood of having eye and or cns complications  twenty four percent of those with bilateral trigeminal nerve port wine stains had eye and or cns involvement compared with 6  of those with unilateral lesions  all those who had eye and or cns complications had port wine stain involvement of the eyelids  in 91  both upper and lower eyelids were involved  whereas in 9  only the lower eyelid was involved  none of those with upper eyelid port wine stains alone had eye and or cns complications  in addition  3  75   of the 4 subjects with seizures alone had bilateral port wine stain involvement  a third group  these with unilateral v1  v2  and v3 port wine stains  had eye and or cns complications in 3  19   of 16 subjects  
class4	the nursing role in limb salvage surgery  limb salvage surgery has proven itself as a valuable option for sarcoma patients  the reconstruction options are vast and include metallic implants  allografts  and a combination of both  the nursing implications for these patients are unlimited  the patient needs to be educated and assessed closely for complications such as infections  nonunion of the allograft  and limited mobility  although the nursing care is more complicated  the rewards with working with these patients are great  
class4	what to do when an x ray film suggests lung cancer  the chest film is one of the most common methods of detecting lung cancer  which often appears as solitary nodules or hilar masses  once the diagnosis is established  the most effective treatment can be determined and staging of the tumor can be done  surgical resection is the only cure for non small cell carcinoma  although radiotherapy and chemotherapy may shrink some tumors  because 90  of all cases are caused by smoking  a preventive approach to the disease is crucial  screening of high risk patients  ie  smokers with airflow obstruction  using chest films and sputum cytology may aid this approach  
class4	why patients delay seeking care for cancer symptoms  what you can do about it  patient delay in seeking care for cancer symptoms is common and well documented by research studies  fear and denial  lack of information about cancer  and financial considerations all contribute to this delay  patient education may be an important factor in decreasing the length of delay and thereby improving treatment outcome  by making good use of opportunities for patient education  primary care physicians may positively influence the prognosis of several types of cancer  particularly breast cancer and malignant melanoma of the skin  
class4	effects of epidermal growth factor and analogues of luteinizing hormone releasing hormone and somatostatin on phosphorylation and dephosphorylation of tyrosine residues of specific protein substrates in various tumors  analogues of somatostatin  ss  and luteinizing hormone releasing hormone  lh rh  activate tyrosine phosphatases in mia paca 2 human pancreatic cancer cell line membranes and inhibit growth  we compared the substrates phosphorylated by epidermal growth factor  egf  to those dephosphorylated by the ss analogue rc 160  d phe cys tyr d trp lys val cys trp nh2  and  d trp6 lh rh in cancer cell lines such as mia paca 2  human pancreatic cancer   hcpc  hamster cheek pouch carcinoma   a 549  human lung cancer   ht 29  human colon cancer   and r3230ac  breast cancer   egf phosphorylated proteins of 170  65  and 60 kda and analogues of ss and lh rh promoted the dephosphorylation of these proteins in mia paca 2 and hcpc cell lines  the egf receptor is 170 kda  pp60src  60 kda  is known to be a substrate for egf receptor  the lh rh receptor is also 60 kda  the effects of rc 160 and  d trp6 lh rh were quantitatively different  examinations of ht 29  a 549  and r3230ac cancer cell lines revealed no phosphorylation by egf or dephosphorylation by rc 160 and  d trp6 lh rh  in addition to the 170   65   and 60 kda proteins  35 kda proteins were also phosphorylated in some cancer cell lines  this work demonstrates that analogues of ss and lh rh can reverse the effects of egf biochemically as well as functionally  
class4	characteristics of erythroleukemia cells selected for vincristine resistance that have accelerated inducer mediated differentiation  the induction of murine erythroleukemia cells  melc  ds19 sc9  to terminal differentiation by hexamethylenebisacetamide  hmba  is characterized by a latent period of 10 12 hr before onset of commitment to terminal cell division and increased transcription of globin genes  melc variants  derived from this parental cell line  selected for resistance to vincristine  vc   can be induced to differentiate with little or no latent period  this study shows that accelerated hmba induced commitment is characteristic of melc with a low level  2  to 5 fold  of vc resistance in four independently derived cell lines  both resistance to vc and accelerated differentiation are stable phenotypes for at least 50 passages  approximately 5 months  in the absence of vc  low level vc resistant melc do not display increased levels of p glycoprotein or mdr1  mdr2  and mdr3 mrnas  nor do they exhibit cross resistance to colchicine or doxorubicin  these cells do show  i  increased level of protein kinase c activity   ii  reduced accumulation of  3h vc  and  iii  restoration of vc sensitivity in the presence of verapamil  melc selected for higher levels of vc resistance  approximately 500 fold  do express high levels of p glycoprotein and the mdr3 gene  during hmba induced differentiation  ds19 sc9 decrease  3h vc accumulation  but p glycoprotein content does not change  a vc transport associated protein  also critical for the process of induced differentiation  may be constitutively present in vc resistant melc  accounting for their enhanced sensitivity to inducer  this protein accumulates by exposure of vc sensitive cells to hmba  contributing to their differentiation and decreased level of vc accumulation  
class4	effects of site directed mutagenesis at residues cysteine 31 and cysteine 184 on lecithin cholesterol acyltransferase activity  native lecithin cholesterol acyltransferase  lcat  phosphatidylcholine sterol acyltransferase  phosphatidylcholine sterol o acyltransferase  ec 2 3 1 43  protein  and lcat in which either or both of the enzyme free cysteines had been replaced with glycine residues by site directed mutagenesis  has been expressed in cultured chinese hamster ovary cells stably transfected with the human lcat gene  the mass of lcat secreted  determined by immunoassay  did not differ in the native and mutant species  lcat specific activity was also unchanged in the mutant species  in particular  the cysteine free double mutant  in which cys 31 and cys 184 had both been replaced  was fully active in the synthesis of cholesteryl esters  this result is not consistent with a catalytic role for lcat free cysteine residues  the classical inhibitor of lcat activity  5 5  dithiobis 2 nitrobenzoic acid   dtnb   which strongly  89   inhibited the native enzyme  had partial  45   inhibitory activity with mutant enzyme species containing a single  sh residue  while the double mutant was not significantly inhibited by dtnb  these data are interpreted to suggest that cys 31 and cys 184 are vicinal both to each other and to the  interfacial binding site  at residues 177 182  and that dtnb exerts its effect by steric inhibition  
class4	transfection of c6 glioma cells with connexin 43 cdna  analysis of expression  intercellular coupling  and cell proliferation  c6 glioma cells express low levels of the gap junction protein connexin 43 and its mrna and display very weak dye coupling  when implanted into the rat cerebrum  these cells quickly give rise to a large glioma  to investigate the role of gap junctions in the tumor characteristics of these cells  we have used lipofectin mediated transfection to introduce a full length cdna encoding connexin 43  several transfected clones were obtained that exhibited various amounts of connexin 43 mrna transcribed from the inserted cdna  immunocytochemical analysis revealed an increase in the amount of connexin 43 immunoreactivity in the transfected cells  being localized at areas of intercellular contact as well as in the cytoplasm  the level of dye coupling was also assessed and found to correlate with the amount of connexin 43 mrna  when cell proliferation was followed over several days  cells expressing the transfected cdna grew more slowly than non transfected cells  these transfected cells will be useful in examining the role of gap junctions in tumorigenesis  
class4	translocation breakpoint of acute promyelocytic leukemia lies within the retinoic acid receptor alpha locus  acute promyelocytic leukemias  apls  are characterized by a reciprocal balanced translocation that involves chromosomes 15 and 17  t 15 17    we report the isolation and characterization of one of the two reciprocal break sites and demonstrate that the chromosome 17 breakpoint lies within the retinoic acid receptor alpha locus  nucleotide sequencing of the 15 17 cross over junction on 15q  showed that the retinoic acid receptor alpha gene is truncated within its first intron  370 base pairs upstream from the splicing donor site of exon ii  such a recombination would be expected to generate abnormal rar alpha mrna and protein  southern blot analysis of a number of apls with chromosome 15  and 17 derived dna probes revealed similar 15 17 recombinations in the majority of other apls  our data are strong evidence that the retinoic acid receptor alpha gene plays a crucial role in the leukemogenesis of apl  
class4	differentiation of hl 60 leukemia by type i regulatory subunit antisense oligodeoxynucleotide of camp dependent protein kinase  a marked decrease in the type i camp dependent protein kinase regulatory subunit  ri alpha  and an increase in the type ii protein kinase regulatory subunit  rii beta  correlate with growth inhibition and differentiation induced in a variety of types of human cancer cells  in vitro and in vivo  by site selective camp analogs  to directly determine whether ri alpha is a growth inducing protein essential for neoplastic cell growth  human hl 60 promyelocytic leukemia cells were exposed to 21 mer ri alpha antisense oligodeoxynucleotide  and the effects on cell replication and differentiation were examined  the ri alpha antisense oligomer brought about growth inhibition and monocytic differentiation  bypassing the effects of an exogenous camp analog  these effects of ri alpha antisense oligodeoxynucleotide correlated with a decrease in ri alpha receptor and an increase in rii beta receptor level  the growth inhibition and differentiation were abolished  however  when these cells were exposed simultaneously to both ri alpha and rii beta antisense oligodeoxynucleotides  the rii beta antisense oligodeoxynucleotide alone has been previously shown to specifically block the differentiation inducible by camp analogs  these results provide direct evidence that ri alpha camp receptor plays a critical role in neoplastic cell growth and that camp receptor isoforms display specific roles in camp regulation of cell growth and differentiation  
class4	computed tomography and the tnm classification of lung cancer  computed tomography  ct  of the thorax and upper abdomen was prospectively evaluated in 84 patients with potentially operable lung cancer  invasion into the thoracic wall and the mediastinal structures was not accurately demonstrated by ct  for metastatic mediastinal lymph nodes  the sensitivity and specificity of ct were  respectively  86  and 61  and the positive and negative predictive indices 49  and 91   for t1  t2 and t3 tumours the negative indices were 100   96  and 71   positive predictive index did not differ between squamous cell carcinoma and adenocarcinoma  adrenal metastases were ct suspected in 17 cases and liver metastases in eight  but were verified by ultrasonography in only one and four cases  ct should be used in preoperative investigation of lung cancer  irrespective of stage  demonstration of thoracic wall or mediastinal invasion need not exclude tumour resection  preoperative mediastinoscopy is indicated if ct shows nodal metastases or if there are signs of tumour invasion  but not in ct negative t1 or t2 tumour  abdominal metastases indicated by ct should be investigated with ct guided needle biopsy  
class4	titrated intravenous barbiturates in the control of symptoms in patients with terminal cancer  patients with terminal cancer may have a series of severe and dehumanizing physical and psychologic symptoms  to improve symptom control in the final days and hours of life  we administer intravenous barbiturates continuously to provide heavy sedation or continuous somnolence  titrated dosage is then reduced to a minimum  after a desired steady state has been achieved  improved symptom control is provided  and the patient s dignity is maintained until death  
class4	scalp pilomatrix carcinoma as an extra axial mass  we report the ct  mri  and angiographic findings in a case of pilomatrix carcinoma that had invaded the temporal bone and presented itself as an extra axial mass  even though bone destruction was better shown with ct  the tumor mass with its meningeal and tentorial extension was seen more clearly with mri  the arteriogram demonstrated a unique vascular supply from the external carotid artery  
class4	benign cystic teratoma manifested as an umbilical hernia  we have reported a case of dermoid tumor manifested as an umbilical hernia  resection led to complete recovery  
class4	stomatococcus mucilaginosus catheter related infection in an adolescent with osteosarcoma  ours is apparently the first reported pediatric case of stomatococcus mucilaginosus bacteremia  it is the second reported case of s mucilaginosus catheter associated infection  but the first case successfully treated without removing the central venous catheter  this unusual organism should be added to the list of opportunistic pathogens that can be isolated from immunocompromised pediatric patients  
class4	management of soft tissue sarcomas of the extremities  the management of soft tissue sarcomas has undergone and continues to undergo important changes  the purpose of this report is to review the presentation  diagnosis  and natural history of soft tissue sarcomas  in so doing  the importance of a careful and rigorous method of evaluation will be emphasized  furthermore  the results of multidisciplinary treatment  with a goal towards limb salvage  will be reviewed  with appropriate and timely intervention  selected patients with pulmonary metastases may still experience long term survival  throughout this review  the importance of early and continuing multidisciplinary treatment and evaluation will be emphasized  
class4	possible transmission of serum hepatitis in liver surgery with the ultrasonic dissector  when the ultrasonic dissector is used during liver surgery  the possibility exists of the transmission of virus to the attending hospital personnel because of unavoidable splashing of the irrigating solution  it becomes apparent from this study that the titer of hepatitis b surface antigen in the aspirated irrigating solution is almost the same level as that in the serum  we therefore strongly recommend that eye shields should be used in hepatic surgery when the ultrasonic dissector is in use  
class4	effects of hypovolemia and transfusion on tumor growth in mca tumor bearing rats  pretransplant blood transfusion has been shown to significantly affect the outcome of renal transplantation  evidence regarding the association of blood transfusions with growth or recurrence of solid tumors is still conflicting both in clinical and in experimental studies  although diminished survival has been suggested in several studies  to determine the influence of blood transfusions and hypovolemia  as separate or combined factors  on tumor growth  we evaluated the weight of a subcutaneously implanted sarcoma  methylcholanthrene induced  in 35 rats  after reaching 1  tumor burden  day 0   the animals were separated into two groups  hypovolemia  shed volume  15 ml kg  or normovolemia  these groups were further divided according to resuscitation  oo  no resuscitation   bl  receiving syngeneic blood stored in citrate phosphate dextrose for 4 days  15 ml kg   sl  receiving 0 9  sodium chloride  45 ml kg   tumor dimensions were determined daily by external measurement  and tumor weight was calculated  hypovolemia exerted a significant influence on tumor growth  independent of the resuscitation modality  the rats that received blood transfusions showed an increased rate of tumor growth  compared to the animals that received saline solution or no treatment  no interaction was noted between the effects produced by hypovolemia and blood transfusion  we conclude that the hypovolemic event enhanced tumor growth independently of the resuscitation  and transfusion of citrate phosphate dextrose blood stored for 4 days did influence tumor growth in this model  we suggest that the effect of blood transfusion in patients with cancer has to be redefined to account for the influence of possible hypovolemic events  
class4	cystic dilatation of the cystic duct  a new type of biliary cyst  a case of a patient with a congenital cyst that was localized solely to the cystic duct is presented  we propose including this anomaly in the biliary cyst classifications  which currently include choledochal and intrahepatic and extrahepatic biliary cysts  the diagnosis and management of this new type of cyst in addition to other types of biliary cysts are discussed  
class4	malignant melanoma of the biliary tract  a case report  a 58 year old man was seen with obstructive jaundice and discomfort in the upper abdomen  computed tomographic and ultrasound examinations revealed a soft tissue mass in the gallbladder  cholecystectomy and choledochotomy revealed a soft black mass in the gallbladder and a second one in the intrapancreatic portion of the common bile duct  each was diagnosed as malignant melanoma  subsequently  a whipple resection of the pancreas  duodenum  and distal bile duct revealed a melanoma circumferentially invading and obstructing the distal common duct  no lymph node or distant metastasis was identified  repetitive searches for another primary site have been negative  the tumor apparently originated in the biliary tract  the patient remains almost well 2 years after diagnosis  
class4	inflammatory pseudotumor of the liver  inflammatory pseudotumor of the liver is an extremely rare entity  because of its unusual clinical presentation and confusing histologic picture  a diagnosis of malignancy is frequently made  thus the surgeon is closely involved with the case and extensive procedures are not uncommon  however  this lesion is benign and will even regress spontaneously  making radical surgical procedures contraindicated  the difficulty lies in establishing an accurate diagnosis and the histologic pitfalls of this particular process  conservative therapy can then be applied  avoiding surgical morbidity  
class4	congenital cyst of common bile duct  an unusual cause of obstructive jaundice  congenital cysts  sometimes referred to as nonparasitic biliary cysts  are not unusual findings in the liver parenchyma  but they have not been previously described in the common bile duct  this clinical report describes a 41 year old woman with obstructive jaundice that was caused by congenital cysts  the patient had obstruction of the middle portion of the common bile duct  therefore the major differential diagnostic considerations were cholangiocarcinoma  cancer of the pancreas  or true biliary cysts  congenital cysts  retention cysts  and neoplastic cysts cannot be differentiated from other true cysts preoperatively  diagnosis can only be established by microscopic examination after surgical excision  
class4	lymphoma of the gastric stump  report of a case  we report a case of primary lymphoma on a previously resected stomach in a 62 year old man  the patient was treated 22 years earlier with a partial gastrectomy and billroth ii reconstruction for a benign gastric ulcer  the rarity of this entity and its possible relationship with pseudolymphoma or lymphoid nodular hyperplasia is discussed  and the literature is reviewed  
class4	gleason s histologic grading as clinical prognostic marker in patients with advanced prostatic carcinoma  we have found that the gleason s histologic grading system is a good clinical marker to predict long term response and prognosis in symptomatic stage d 2 adenocarcinoma of the prostate  in this retrospective study  56 cases were reviewed and correlated with bone scan  acid phosphatase  and symptomatology following bilateral orchiectomy  
class4	simultaneous presentation of adenocarcinoma of prostate and transitional cell carcinoma of bladder  simultaneous presentation of transitional cell carcinoma of the bladder and adenocarcinoma of the prostate is not uncommon  twenty two patients were diagnosed as having simultaneous or concurrent presentation of prostate and bladder carcinomas between january 1970 and july 1986  the overall five year survival was 40 percent  with patients presenting with prostate cancer doing better  50   than those with bladder cancer  32    retrospective review of these cases suggests that primary therapy should be directed to the most advanced cancer  incidental prostate cancer may be  cured  with a cystoprostatectomy and  when indicated  radiation therapy added postoperatively for the bladder cancer  eleven patients presented with stage a prostate cancer  10 of the 11 were treated for their bladder cancer  treatment was usually radical cystoprostatectomy with or without postoperative radiation  none died of prostate cancer  patients presenting with advanced stage prostate cancer have had recurrence or have died of the cancer  
class4	results of surgical treatment of kidney cancer with solitary metastasis to contralateral adrenal  a large series of patients were reviewed in two major teaching institutions  and patients with a carcinoma of the kidney with a solitary metastatic deposit in the contralateral adrenal were identified  their survival was analyzed and compared with the survival of those patients having a solitary metastatic deposit in other organs  
class4	management of symptomatic lymphocele via percutaneous drainage and sclerotherapy with tetracycline  lymph collections following pelvic surgery are usually asymptomatic  but may occasionally produce symptoms requiring invasive therapy  we have successfully obliterated a large lymphocele by employing percutaneous drainage and instilling tetracycline  
class4	renal cell metastases versus liver hemangioma  we present the case of a man with presumed metastatic renal cell carcinoma based on radiologic examination and weight loss  who refused treatment of any kind for one year  a surgical exploration to control hematuria revealed a stage i tumor  
class4	squamous cell carcinoma of prostate  a primary squamous cell carcinoma occurring in the prostate of a sixty nine year old man is described  a radical excision that included cystoprostatectomy  total penectomy  scrotectomy  pubic symphysiectomy  and abdominoperineal resection of rectum was done  the patient died of systemic metastases six months after diagnosis  review of the literature suggests that such a cancer of the prostate is rare  highly aggressive  and responds poorly to any mode of therapy  histogenesis of this tumor remains controversial  however  it probably does not originate from the prostatic acinar cells  
class4	giant sclerosing leiomyoma of bladder presenting as chronic renal failure  the clinical and pathologic features of a case of giant sclerosing leiomyoma of the bladder in a male polynesian patient are reported  the presenting complication of chronic renal failure due to tumor envelopment of both ureters and consequent bilateral renal obstruction appears to be unique in the literature  
class4	ureteral stump carcinoma incidentally found at cystectomy for bladder cancer  we report on a sixty five year old man with hematuria secondary to superficial bladder cancer  because of previous urethral trauma  a complete transurethral resection of his bladder tumor could not be done  he  therefore  underwent cystectomy  at which time we incidentally found a transitional cell carcinoma of the left ureteral stump that had been left from a previous left nephrectomy for a world war ii related injury  this case underscores the importance of a thorough investigation of the complete urinary tract in a patient with hematuria or other urinary tract symptoms even if an obvious cause is found for his symptoms  
class4	tumor targeted chemotherapy with lipid contrast medium and macromolecular anticancer drug  smancs  for renal cell carcinoma  twenty five patients with renal cell carcinoma were treated with a lipophilic macromolecular drug  poly stylene co maleic acid  conjugated neocarzinostatin  smancs  dissolved in lipid contrast medium  lipiodol   the drug was injected by catheterizing the renal artery and another feeding artery in 24 patients  and in the common hepatic artery in 1 patient with metastases to the liver after a radical nephrectomy  the procedure of selective arterial administration of 3 20 mg ml of smancs lipiodol was simple to perform and was required once every two to three weeks  total dose of smancs for each patient varied from 3 to 57 mg  both smancs and lipiodol accumulated more selectively in tumor than in any other tissue and remained in the neovasculature and extracapillary space for a long time  ct pattern of the remaining oil contrast medium in the tumor was characterized by the high density area localized mainly in the periphery of the tumor around the central necrosis  when hyperviscosity lipiodol  lipiodol hv  was used as lipid contrast medium  it remained more persistently in the tumor and disappeared more slowly than lipiodol  moreover  the pronounced anticancer effect was recognized when smancs lipiodol hv was administered compared with only smancs lipiodol  severe side effects  such as myelosuppression  unendurable pain  paralytic ileus  etc   were not observed  this targeting chemotherapy may be of great significance for advanced renal cell carcinoma  
class4	hypercalcemia in malignancy  the pathogenesis of hypercalcemia in malignancy has been enigmatic until recent years  since the realization in 1980 that bioassays for parathyroid hormone detected a cross reacting substance in malignancy  progress has been remarkably rapid  a parathyroid hormone related protein was purified and identified by molecular cloning as a 141 amino acid peptide with limited homology to parathyroid hormone itself  nonetheless  both peptides activate the parathyroid hormone receptor to produce hypercalcemia  it is now clear that the parathyroid hormone related protein is the cause of hypercalcemia in most solid tumors  particularly squamous and renal carcinomas  new assays for the hormone as well as the related peptide have greatly simplified the differential diagnosis of hypercalcemia  at the same time  new agents for the treatment of hypercalcemia are becoming available  most notably the bisphosphonate drugs  
class4	giant cell tumor of bone  giant cell tumor is the second most common benign tumor of bone  plain radiographs may demonstrate distinctive features but can also be misleading  the diagnosis may be aided by the use of other imaging modalities  such as bone scan  computed tomography and angiography  the recurrence rate is high  but some of the newer treatments seem to be associated with better outcomes  
class4	lack of effect of chronic administration of oral beta carotene on serum cholesterol and triglyceride concentrations  previous studies suggest that chronic oral administration of retinol and other retinoids causes elevation of plasma triglyceride concentrations  the effects of chronic oral administration of beta carotene  a carotenoid partially metabolized to retinol  on plasma lipid concentrations have not been well studied  therefore  we studied 61 subjects over 12 mo while they were enrolled in a skin cancer prevention study in which patients were randomly assigned to receive either placebo  n   30  or 50 mg beta carotene d orally  n   31   at study entry and 1 y later  fasting blood samples were obtained for measurement of triglycerides  total cholesterol  hdl cholesterol  retinol  and beta carotene  retinol concentrations changed minimally in both groups  beta carotene concentration increased an average of 12 1     47 nmol l in the placebo group and 4279     657 nmol l in the active treatment group  both groups experienced similar small increases in triglyceride and total cholesterol concentrations and small decreases in hdl cholesterol  daily oral administration of 50 mg beta carotene d did not affect plasma lipid concentrations  
class4	beta carotene s effects on serum lipoproteins and immunologic indices in humans  doses of beta carotene for cancer prevention trials have been chosen based on epidemiologic data  mechanisms of the putative antineoplastic effects by beta carotene are unknown but may involve modulation of the immune system  we measured plasma carotenoid concentrations and selected immunologic indices at baseline and at 2 and 4 wk in 50 healthy humans  5 groups of 10 each  ingesting 0  15  45  180  or 300 mg beta carotene d for 1 mo in this randomized placebo controlled  open label  parallel study  plasma beta carotene concentrations were markedly increased by 2 wk and were correlated with dose  beta carotene concentrations plateaued between 2 and 4 wk except for the 300 mg group  thus  we developed a dose concentration curve to optimize beta carotene dose selection to achieve target plasma concentrations  we were unable to identify any effects of beta carotene ingestion on the immunologic indices studied  but modest increases in high density lipoprotein cholesterol were observed in all beta carotene treated groups  
class4	hypercalcemia with excess serum 1 25 dihydroxyvitamin d in lymphomatoid granulomatosis angiocentric lymphoma  hypercalcemia has been described in a variety of granulomatous and lymphoproliferative disorders in association with elevated serum levels of 1 25 dihydroxyvitamin d  in such cases  hypercalcemia appears to be the consequence of excessive production of 1 25 oh 2d by the lymphocyte macrophage line  the authors report a patient with lymphomatoid granulomatosis angiocentric lymphoma who developed hypercalcemia with extreme elevation in serum 1 25 oh 2d  therapy with steroids reduced the serum calcium and 1 25 oh 2d levels to normal  hypercalcemia has not previously been reported in lymphomatoid granulomatosis angiocentric lymphoma  the distinctive features of this malignancy  and the derangement in the metabolism of 1 25 oh 2d in lymphoproliferative disorders in general  are discussed  
class4	pericardial metastasis from testicular seminoma  appearance and disappearance by echocardiography  at the time of initial diagnosis  testicular malignancy is usually limited to the testicle and infradiaphragmatic lymph nodes  metastases initially follow the retroperitoneal lymph channels and subsequently extend to the supradiphragmatic lymph nodes in the mediastinum and supraclavicular fossa  testicular metastases to the pericardium are rare and usually asymptomatic  these lesions are most commonly identified at autopsy  therefore  the actual incidence is unknown  the authors report a 32 year old man with testicular carcinoma  who developed asymptomatic pericardial metastases without concomitant supradiaphragmatic nodal or pulmonary metastases  they review the efficacy of echocardiography in diagnosis and follow up or pericardial metastasis  
class4	in vivo phosphorus 31 magnetic resonance spectroscopy of human uveal melanomas and other intraocular tumors  we studied the feasibility of using the surface coil probe technique for the noninvasive in vivo study of ocular tumors by phosphorus 31 magnetic resonance spectroscopy  the characteristic organophosphate metabolites of suspected uveal melanomas before proton beam irradiation were determined qualitatively by phosphorus 31 magnetic resonance spectroscopy in vivo using a three turn surface coil  spectra of choroidal hemangioma  osteoma  and metastasis were also obtained in vivo and compared with those of uveal melanomas  analysis of spectra performed at 1 5 t showed significant peaks of phosphomonoesters  inorganic phosphate  phosphodiesters  phosphocreatine  and adenosine 5  triphosphates  the unusually high concentration of phosphodiesters may be considered as a marker for uveal melanomas and other choroidal tumors  by analyzing the ratio of phosphocreatine to phosphodiesters spectral area values  we interpreted qualitatively spectra of intraocular tumors to differentiate malignant tumors from benign lesions  nevertheless  the main limitation of interpreting the spectra was their contamination by signals from surrounding tissues  
class4	incidence of prominent corneal nerves in multiple endocrine neoplasia type 2a  we studied the increased visibility of corneal nerves inside an 8 mm diameter central corneal area in 14 patients with multiple endocrine neoplasia type 2a  one patient with multiple endocrine neoplasia type 2b  five patients with nonhereditary medullary thyroid carcinoma  ten patients with anterior keratoconus  and ten normal subjects  we used a grading system  grade 0 through grade 4  for nerve visibility based on slit lamp biomicroscopic examination and photographic documentation  all 20 normal eyes showed either grade 0 or grade 1  which indicated no pathologic thickening of corneal nerves  sixteen of the 28 eyes  57   with multiple endocrine neoplasia type 2a  however  were evaluated as grade 2 or higher  which indicated thickened corneal nerves  the incidence of high nerve visibility in eyes with multiple endocrine neoplasia type 2a was significantly greater compared to normal eyes  p less than  0001   anterior keratoconus  p less than  0001   and nonhereditary medullary thyroid carcinoma  p    0012   furthermore  eight of the 28 eyes  29   with multiple endocrine neoplasia type 2a showed markedly prominent corneal nerves  grade 3 and 4   a prominence similar to those seen in eyes with multiple endocrine neoplasia type 2b  there was no definite relationship among prominent nerve  age of the patient  and occurrence of pheochromocytoma  these findings suggest that over half of all patients with multiple endocrine neoplasia type 2a show corneal nerves pathologically thickened to different degrees  
class4	histopathologic evidence of fibrovascular ingrowth four weeks after placement of the hydroxyapatite orbital implant  we studied the histopathologic findings after placement of an orbital hydroxyapatite implant in a patient  the implant was placed after enucleation for a choroidal melanoma and was removed four weeks later because histopathologic examination of the enucleated globe disclosed tumor invasion of the optic nerve that necessitated further orbital tissue removal  our histopathologic findings confirm that there is significant ingrowth of fibrovascular tissue in these implants  even within weeks of implantation  
class4	ovarian granulosa stromal cell tumors are characterized by trisomy 12  eleven ovarian granulosa stromal cell tumors including 1 thecoma  2 fibromas  6 fibrothecomas  and 2 granulosa cell tumors  were karyotyped after direct harvest and or short term tissue culture  bilateral fibrothecomas from one patient appeared to lack cytogenetic aberrations  the remaining nine tumors were characterized by trisomy for chromosome 12  cytogenetic aberrations in the two granulosa cell tumors were much less complex than those described previously in undifferentiated carcinomas  accordingly cytogenetic analyses might be useful in distinguishing these categories  the consistent occurrence of trisomy 12 in different varieties of granulosa stromal cell tumors suggests a common mechanism of oncogenesis within this diverse group of neoplasms  that mechanism probably involves promotion of low grade  orderly cell proliferation  
class4	development of intrapancreatic transplantable model of pancreatic duct adenocarcinoma in syrian golden hamsters  intrapancreatic and subcutaneous  sc  inoculation of cultured pancreatic cancer cells  derived from an induced primary pancreatic cancer in a syrian hamster  resulted in tumor take in all recipient hamsters  the intrapancreatic allografts grew rapidly  were invasive  and metastasized into the lymph nodes and liver in 2 of 9 cases  in comparison  sc tumors grew relatively slower and formed a large encapsulated mass without invasion and metastases  histologically  tumors of both sites showed fairly well differentiated adenocarcinomas of ductal ductular type resembling the induced primary cancer  similar to the primary induced pancreatic cancers  tumor cells of both allografts expressed blood group related antigens  including a  b  h  le b   le y   le x   and tumor associated antigen tag 72  the tumor cells did not express le a   ca 19 9  17 1a  or du pan 2  the expression of these antigens was retained in the metastases and presented the same patterns of reactivity as the allografts  thus intrapancreatic transplantation provides a rapid model for production of pancreatic cancer with morphologic similarities to human pancreatic cancer  
class4	evaluation of hepatocellular carcinoma aggressiveness by a panel of extracellular matrix antigens  invasion and metastasis requires a series of interactions between malignant cells and the extracellular matrix  ecm   antigen markers that relate to these interactions were evaluated for prognostic correlation in human hepatocellular carcinoma  basement membrane type iv collagen  civ   type iv collagenase  civase   laminin  and laminin receptors  lrs   all ecm antigens previously proposed to be modulated in association with tumor aggressiveness  were immunohistochemically investigated in 30 cases of hepatocellular carcinomas  hccs   the pattern of antigen expression was correlated with 1  36 months  clinical follow up and 2  the pathologic grade  as a means of estimating the proliferation fraction  an additional antigen  ki67  was also studied in this series  there were major differences in the distribution of civ and laminin  and in the quantity of civase   lr   and ki67 positive cells associated with grade and prognosis  a smaller quantity of civ and laminin and a higher number of civase   lr   and ki67 positive cells were detected in the poorly differentiated compared with the well differentiated hccs  the tumors with lower immunoreactivity for civ and laminin components accompanied by a higher number of civase   lr   and ki67 positive cells fall into a group with the poorest overall survival  p less than 0 006   the panel of antigens is proposed as a useful prognostic tool for evaluating hcc tumor aggressiveness  
class4	epithelial cells immortalized by human papillomaviruses have premalignant characteristics in organotypic culture  three hpv 16  and four hpv 18  immortalized human foreskin keratinocyte cell lines were analyzed on organotypic epidermal raft cultures at various passage levels  this culture system allowed normal cultured keratinocytes to stratify and differentiate in a manner similar to normal epidermis  all seven hpv immortalized cell lines displayed epidermal morphologies on organotypic cultures  which were clearly abnormal and resembled premalignant lesions in vivo  features of premalignant lesions that were shared by all of the hpv immortalized cell lines included disorganized tissue architecture  mitotic cells present throughout the living layers of the epidermal sheet  abnormal mitoses  enlarged nuclei  and variable cell size and shape  most hpv immortalized cell lines were stable in terms of epidermal morphology with long term passage in culture  two of the hpv 18  immortalized cell lines  however  lost all morphologically apparent terminal squamous differentiation potential after long term passage in monolayer culture  these results strongly support the idea that immortalization of squamous epithelial cells in culture by hpv transforming genes generates a morphologically premalignant cell  
class4	expression of vla alpha 2  vla alpha 6  and vla beta 1 chains in normal mucosa and adenomas of the colon  and in colon carcinomas and their liver metastases   very late antigen   vla  proteins are members of the integrin superfamily with cell surface receptor function and are involved in the cell cell matrix interaction  they are heterodimers with a common beta 1 chain and different alpha chains counted through vla 1 to vla 6  the vla 2 complex  alpha 2 beta 1  was found to act as collagen receptor on platelets and the vla 6 complex  alpha 6 beta 1  as laminin receptor  using monoclonal antibodies and an indirect immunoperoxidase method  we investigated the expression of vla alpha 2  vla alpha 6  and vla beta 1 chains in 20 normal colonic mucosa samples  in 20 colonic adenomas  and in 96 carcinomas together with 10 accompanying liver metastases  all three proteins were expressed throughout the colonic epithelium  except for vla alpha 2  which was present in the cryptic gland but was absent on the mucosal surface in some cases  in general  adenomas were strongly positive for the vla proteins but 3 of 20 cases showed focal vla alpha 2 negative areas  the carcinomas revealed considerable heterogeneity of vla alpha 2 expression  ie  59 tumors were completely positive  35 tumors revealed a focal loss of antigen  and 2 cases were negative  this reduced antigen expression was statistically associated with dukes  stage c d  p   0 003   vla alpha 6 was expressed throughout in all tumors  vla beta 1 was found extensively expressed in 77 carcinomas  partially expressed in 17 carcinomas  and was absent in 2 carcinomas  as compared to their primary tumors  liver metastases showed roughly corresponding patterns of antigen expression  the down regulation loss of vla proteins in a subset of epithelial colon tumors might cause a disturbed cell cell cell matrix interaction that might augment the invasive property of their cells  
class4	basal cell specific and hyperproliferation related keratins in human breast cancer  in normal breast tissue and in noninvasive breast carcinomas  various keratin 14 antibodies were reactive predominantly with the basal myoepithelial cell layer  although mainly in terminal and larger ducts luminal cells sometimes also were stained  a similar reaction pattern was found with an antibody directed against keratin 17  although this antibody was more often found negative than keratin 14 in the pre existing myoepithelial cells in intraductal carcinomas  furthermore antibodies reactive with hyperproliferation related keratins 6 and 16 were used  one of these  ll025  was completely negative in normal breast tissue and noninvasive breast carcinomas  however 10  of the invasive carcinomas were diffusely or focally positive with this latter antibody  while in 18 of 115 cases of invasive breast carcinomas studied  a basal cell phenotype was detected  a relatively high concordance was found between the carcinomas immunostaining with the basal cell and the hyperproliferation related keratins  but not between these markers and the proliferation marker ki 67  this supports the conclusion that basal cells in breast cancer may show extensive proliferation  and that absence of ki 67 staining does not mean that  tumor  cells are not proliferating  
class4	elective diagnostic laparoscopy  laparoscopy developed as a science at the turn of the century  and many scientists assisted in the evolution of this technique  however  it was many years before the multiple trocar system was developed that allowed internal organs to be moved and biopsies to be obtained  this has led to the development of numerous indications for elective diagnostic laparoscopy  adequate preparation and attention to instrumentation ensure the safety of this operation  elective diagnostic laparoscopy is a useful adjunct to many other diagnostic modalities such as  for instance  the assessment of abdominal pain  abdominal masses  fever of unknown origin  and gastrointestinal bleeding  in many other circumstances  such as the assessment of oncology cases  this modality is superior to conventional radiology because biopsy specimens may be obtained  if the procedure is correctly performed  the diagnostic yield is extremely high and the morbidity and mortality are low  the role of this important technique should not be underestimated by today s practicing surgeon  
class5	epidemiology in bone and joint infection  the studies of community acquired infection indicate the importance of the environment in which the host pathogen interaction takes place  whereas the high incidence rates at the extremes of life are compatible with a hypothesis of diminished immune competence  the varying rates of acute osteomyelitis during growth  and its predominantly metaphyseal site  suggest that further studies of the molecular biology of this rather specific infection would be revealing  molecular biology has a role  too  in improving understanding of the epidemiology of resistance and pathogenicity in hospital acquired infections  although antibiotic prescription and other medical practices influence the environment profoundly  we should remember that we may be experiencing long term trends beyond our present understanding  as more and more reconstructive bone and joint surgery is carried out  careful observational epidemiology remains a vital tool  
class5	animal models of osteomyelitis  knowledge  hypothesis  and speculation  each animal model has provided insights  particularly important was the considerable resistance of bone to infection without manipulation  no morrhuate  fracture  rod  wax  or prosthesis   such perturbations allow bone infection with much smaller inocula  typical inocula decreases are 1000 to 10 000 fold  staphylococci may have a selective advantage in bone because of specialized or tropic binding  perhaps to cartilage or collagen  osteoclast induced resorption of hydroxyapatite might explain the distribution of some osteomyelitis  increased osteoclast activity could link the susceptible metaphyseal regions  the repetitively traumatized diabetic foot  a history of blunt bone trauma  fracture  and perhaps even nearby soft tissue infection  diagnosis remains difficult  gallium 67 and indium111 labeled wbc probably deserve additional investigation  therapeutic failures in the rabbit and rat models mirror clinical experience  clindamycin  rifampin  and quinolones are promising  neither systemic nor local antimicrobial prophylaxis is well studied yet  
class5	musculoskeletal infection  microbial adhesion  and antibiotic resistance  osteomyelitis and intra articular infection are septic diseases that present pathogenic features characteristic of molecular mechanisms involving adhesion to substrata  in this review  mechanisms of microbial adhesion to bone and cartilage as substrata are presented and related to host tissue response and to antibiotic treatment  
class5	the diabetic foot  soft tissue and bone infection  diabetic patients  as a consequence of various neurologic  vascular  and metabolic perturbations  are at high risk for developing infections of the soft tissue and bones of the feet  the microbial etiology of soft tissue in infections is best determined by cultures of a tissue curetting or aspiration  rather than a swab  aerobic gram positive cocci are the major pathogens in diabetic foot infections  these may be the sole isolate s  in acute uncomplicated infections  but they are usually accompanied by aerobic gram negative bacilli or anaerobes in chronic or previously treated infections  carefully selected patients with mild infections can be treated as outpatients with oral antibiotics  but others require hospitalization and broad spectrum parenteral antibiotics  bone infections are frequently diagnosed on the basis of roentgenographs and nuclear medicine scans  but these methods are often inaccurate  and bone cultures should be obtained whenever possible  
class5	hyperbaric oxygen as adjunctive therapy for osteomyelitis  mechanistically  hyperbaric oxygen  hbo  appears useful for the treatment of osteomyelitis  hbo increases the oxygen tension in infected tissue  including bone  an adequate oxygen tension is necessary for oxygen dependent killing of organisms by the polymorphonuclear leukocytes and for fibroblast activity leading to angiogenesis and wound healing  hbo has a direct bacteriocidal or bacteriostatic effect on anaerobic organisms  in addition  hbo augments the killing of pseudomonas aeruginosa by the aminoglycoside  tobramycin  at the university of texas medical branch at galveston  adjunctive hbo is used for the cierny mader stage 3b and 4b osteomyelitis  
class5	diagnostic imaging of osteomyelitis  there are many imaging procedures for diagnosing osteomyelitis  each with unique strengths and weaknesses  plain radiographs are inexpensive and can be very accurate but may provide a delayed diagnosis  computed tomography and magnetic resonance imaging are both excellent at differentiating soft tissue infection from osteomyelitis  computed tomography  magnetic resonance imaging  and bone scans are accurate diagnostic tools for use when the bone has not be violated by surgery  trauma  or other structural alterations  when such changes are present  an indium 111 leukocyte or indium 111 polyclonal antibody study may be necessary for accurate diagnosis  
class5	antibiotic therapy for osteomyelitis  antibiotic therapy for osteomyelitis has dramatically changed within the past twenty years  the diagnostic criteria for osteomyelitis remain confusing to practicing physicians  bone biopsy culture is now the standard for determining specific antimicrobial therapy  many of the newest and most potent antimicrobials are now used to treat the increasingly broad bacterial spectrum of etiologies of osteomyelitis  there are tremendous economic incentives for outpatient and or oral therapy  the third generation cephalosporins and the new fluoroquinolones have replaced older  more toxic regimens  especially those containing aminoglycoside used to treat gram negative osteomyelitis due to susceptible organisms  
class5	surgical approaches in osteomyelitis  use of laser doppler flowmetry to determine nonviable bone  the surgical management of osteomyelitis includes radical debridement on nonviable bone  laser doppler flowmetry is a method for directly assessing the functional microcirculation in bone  the early results of the use of this technique as a surgical adjunct in the management of osteomyelitis are promising  
class5	acute osteomyelitis in children  although relatively uncommon  osteomyelitis is an important disease because of the potential for chronicity or permanent sequelae  diagnostic methods  the spectrum of the disease  and clinical situations that merit special consideration are reviewed in this article  
class5	infectious arthritis  any patient who presents with an acute monarticular arthritis  especially a new asymmetric effusion with underlying joint disease  should be suspected of having a bacterial process  because synovial fluid findings  leukocyte counts and glucose  may not be predictive of infection  bacteriologic analysis by smear and culture is necessary in the evaluation of any new synovial effusion  a chronic monarticular process is highly likely to be infectious also  but mycobacterial or fungal etiologies frequently require appropriate culture of synovial tissue in addition to processing fluid  acute polyarticular syndromes are seen as manifestations of disseminated gonococcal infections  dgi  and certain viral infections in adults  diagnostic clues include historic and physical findings  exposure history and type of rash   the major pathogen in adults remains staphylococcus aureus  so initial therapy is directed at this organism unless urinary tract infection is present also  proper recommended therapy for dgi is ceftriaxone because penicillin resistant strains are present in many urban centers  early recognition and treatment of bacterial arthritis may prevent poor outcome  particularly in elderly patients or those with underlying joint diseases  for chronic mycobacterial or fungal infections  surgery may need to be combined with medical management  
class5	vertebral osteomyelitis  vertebral osteomyelitis can be caused by a variety of microorganisms  the hematogenous pyogenic form is characteristically a disease of people over age 50  predominantly in the male population  and most frequently caused by s  aureus  in ivdas  however  younger patients and a heavier predominance of males are seen  and p  aeruginosa is one of the most commonly seen pathogens  the disease is generally monomicrobial  unless it is secondary to a contiguous process such as a pressure sore  in which polymicrobial infection with participation of anaerobes is the general rule  lumbar  greater than thoracic  greater than cervical involvement is the rule in the general population  but cervical spine involvement is frequently seen more often than thoracic involvement in ivdas  diabetic patients are over represented among patients with vertebral osteomyelitis  and they also have a tendency for higher morbidity and mortality  simultaneous involvement of adjacent vertebral end plates and the intervening disk is the general rule  the vertebrae are generally involved  and the posterior elements of the spine are involved infrequently  posterior element involvement is seen more commonly in actinomycosis  coccidioidomycosis  and neoplasms  newer diagnostic modalities  such as ct  mri  and radionuclide scans  may detect the disease earlier than conventional radiographs  immunobilization by bed rest and appropriate antimicrobial therapy are generally sufficient in the therapy of pyogenic  as well as tuberculous  vertebral osteomyelitis  in selected circumstances  such as in the presence of marked instability of the spine  the presence of new neurologic deficits  or with progression of previous neurologic deficits  surgical intervention may be necessary  with prompt diagnosis and proper management  the prognosis should generally be good  
class5	zygomatic approach to skull base lesions  a modification of the preauricular skull base approach is described  after sectioning and downward displacement of the zygomatic arch  the coronoid process of the mandible is dissected and sectioned at its base  the temporal muscle  with its coronoid insertion  is then retracted upward  this approach provides direct and unobstructed access to the temporal and infratemporal fossae  adequate vascularity of the temporal muscle is maintained  the exposure encompasses the internal carotid artery in the neck for vascular control  extensive reconstruction is eliminated  the described technique was used in seven patients with lesions of the skull base  there was no operative mortality  and morbidity consisted of temporary restriction of mandibular opening in two patients  
class5	postlaminectomy ossified extradural pseudocyst  case report  a large ossified spurious meningocele accompanied by recurrent lumbar disc herniation occurred 7 years after posterior intervention for laminectomy and discectomy in a 53 year old man  the cyst wall  histologically composed of mature bone tissue  was sparsely covered with connective tissue and lined with fibrocyte  or fibroblast like cells on the inside  the ossified pseudocyst was presumed to have originated from a minute defect in the dura mater which occurred at the time of the first operation  
class5	a simple technique of posterior wiring in traumatic instability of the mid to lower cervical spine  technical note  wiring without bone fusion in the treatment of traumatic cervical instability is an uncommon procedure  the authors describe a semirigid wiring technique for stabilizing the acute injured movement segment in the mid and lower cervical spine  results are briefly discussed  
class5	adaptive and remodeling changes in the fractured mandibular condyle after open reduction using the kirschner pin  six cases of fracture of the mandibular condyloid process in which there was osteosynthesis using the kirschner pin were followed radiographically for more than 1 year  tracings were made to analyze the remodeling process  the clinical course of all patients was satisfactory  without functional disturbance or asymmetries of the mandible  
class5	treatment of the retained permanent molar  the effect of five different treatments for retained permanent molars was evaluated in 59 patients to develop a rational guideline for adequate therapy  the results showed that a prosthetic buildup is the proper treatment if retention develops after the growth spurt  because in these cases the extent of infraocclusion is slight and relatively stable  if retention develops before the growth spurt  immediate removal of the retained molar followed by orthodontic treatment is the way to maximal success  when retention develops during the growth spurt  the tooth affected has to be observed at 6 month intervals  in such a case  no active treatment is indicated if the neighboring teeth show no tilting and the extent of infraocclusion is minor and stable  in all other cases  the teeth affected have to be removed  followed by orthodontic closure of the edentulous space  finally  all patients must be screened regularly  because in this investigation  new cases of retention were observed relatively frequently  
class5	management of delayed union and nonunion of maxillary osteotomies  delayed union and nonunion of maxillary osteotomies are unusual  but have been seen with a variety of surgical moves  management of these problems can be divided into early and late therapy  four cases are presented illustrating some of these methods of treatment  
class5	composite temporalis pedicle flap as an interpositional graft in temporomandibular joint arthroplasty  a preliminary report  fifteen temporomandibular joint patients were evaluated preoperatively and postoperatively to evaluate the effectiveness of a composite  fascia  muscle and periosteum  temporalis pedicle flap as an interpositional disc replacement  a modified craniomandibular index  cmi  and symptom severity index  ssi  were used to assess clinical and subjective symptoms  eighteen months postoperatively there was a significant reduction in the cm and ss indices  p less than  001   with significant clinical improvement of the mandibular range of motion  p less than  05   however  a significant reduction of translation  p less than  01  was evident indicating that the increased mandibular opening was owing to a compensatory rotational movement  this study indicates that the composite temporalis pedicle flap is a good autogenous tissue for the reconstruction of the temporomandibular joint  
class5	tissue response to composite ceramic hydroxyapatite demineralized bone implants  this study evaluated the tissue reactions to two materials  ceramic hydroxyapatite  cha   and a composite material of demineralized bone powder  dbp  and cha  ratio of 4 1  in a collagen vehicle  the materials were tested in a subcutaneous pocket  a mandibular onlay  and in a calvarial onlay model  specimens were evaluated histologically at 7  10  14  and 21 days postimplantation  ceramic hydroxyapatite  implanted subcutaneously  elicited a fibrous response with minimal inflammation  but did not induce bone formation  in specimens of subcutaneously implanted composite material  induced bone was evident in association with the dbp  in cha onlay specimens  there was a small amount of reactive bone extending from the host bone into the implant  in composite onlays  bone filled the entire body of the implant  the results of this study indicate that cha particles were not osteoinductive in heterotopic sites and that osteoconductive ingrowth was minimal in onlays  bone was induced by dbp even when mixed with cha particles and implanted in subcutaneous and intraosseous sites  it was concluded that composite implants may provide a means of combining the osteoinductive properties of dbp with the bulk and structural support of osteoconductive cha particles  
class5	bone response to hydroxyapatite particles of different shapes in rabbit tibia  four holes drilled in rabbit tibia were filled with different commercial hydroxyapatite products  all particles caused a mild inflammatory reaction  which disappeared in 2 months  the line between the new and original bone was visible even after 6 months  no differences in healing pattern were discovered for the various products  when bone cavities are filled with hydroxyapatite particles  the shape of the particles does not seem to affect the healing process  
class5	invasive squamous cell carcinoma of the mandible presenting as a chronic osteomyelitis  report of a case  a case of invasive squamous cell carcinoma of the mandible initially thought to be chronic osteomyelitis is reviewed  discussion of the origin of the tumor and several imaging techniques used for differentiating maxillofacial infection from neoplasm are discussed  the difficulty of diagnosis of chronic painful maxillofacial lesions illustrates the need for a high degree of suspicion concerning any inflammatory lesion not responding to appropriate therapy  accurate diagnosis and treatment of such lesions most often necessitates microscopic examination  
class5	assessment of proplast teflon disc replacements  published erratum appears in j oral maxillofac surg 1991 feb 49 2  220  this retrospective study reports the findings in the follow up of 31 temporomandibular joints in which proplast teflon  vitek inc  houston  tx  replacements were used  among the problems noted were pain  malocclusion  restricted opening  and degenerative changes in the condyle and fossa  
class5	a protocol for management of temporomandibular joint ankylosis  a management protocol for temporomandibular joint  tmj  ankylosis consisting of 1  aggressive resection  2  ipsilateral coronoidectomy  3  contralateral coronoidectomy when necessary  4  lining of the tmj with temporalis fascia or cartilage  5  reconstruction of the ramus with a costochondral graft  6  rigid fixation  and 7  early mobilization and aggressive physiotherapy is presented  the protocol was retrospectively evaluated in the first 14 patients  18 involved tmjs  treated and followed postoperatively for at least 1 year  the facial asymmetries present in all unilateral cases remained corrected  the mean maximum postoperative interincisal opening at 1 year was 37 5 mm  292 36  mean increase   lateral excursions were present in 16 of 18 joints  vs 0 of 18 joints preoperatively   and pain was present in 2 of 18 joints  vs 13 of 18 preoperatively   the results of this study indicate that this protocol is effective for treatment of tmj ankylosis  
class5	factors associated with soft  and hard tissue compromise of endosseous implants  this prospective analysis identifies factors associated with endosseous implant removal as well as factors associated with implant morbidity resulting in nonscheduled patient visits  treatment of the latter conditions is discussed  the most important factors identified for implant success were surgery without compromise in technique  placing implants into sound bone  avoiding thin bone or implant dehiscence at the time of implant placement  avoiding premature implant exposure during the healing period  establishing a balanced restoration  and insuring appropriate follow up hygiene care  in the posterior mandible  the presence of keratinized gingiva was strongly correlated with optimal soft  and hard tissue health  
class5	magnetic resonance imaging appearance of the muscles in childhood dermatomyositis  documentation of muscle involvement in a child thought to have dermatomyositis may require the performance of invasive procedures such as electromyography and or muscle biopsy  we describe four patients with dermatomyositis in whom magnetic resonance imaging  mri  demonstrated the muscle involvement  the involved muscles had increased signal intensity on the t2 weighted images  se 2500 80  and normal appearance on the t1 weighted images  se 600 20   the involvement of the muscles was not uniform  there was good correlation between the distribution of muscle involvement by mri and functional testing  follow up mri scans in patients with favorable outcome demonstrated that the affected muscles had returned to normal signal intensity  although the mri findings are not specific  in the proper clinical context they may be helpful in establishing the diagnosis of dermatomyositis  mri may also be used in establishing an appropriate muscle biopsy site  in addition  mri may be used for monitoring the progress of the disease  
class5	heat induced radial segmentation of leukocyte nuclei in patients with polymyalgia rheumatica and other inflammatory diseases  heat induced radial segmentation of leukocyte nuclei is an in vitro phenomenon accompanying inflammatory diseases  we studied 62 patients with suspected polymyalgia rheumatica  pmr  to determine  whether heat induced radial segmentation can help in discriminating pmr from other conditions  at the initial presentation patients with pmr had more radial segmentation formation than patients with other inflammatory conditions  prednisone induced a rapid and marked decrease in radial segmentation formation in patients with pmr  this latter finding was much less marked in patients with other inflammatory conditions  we conclude that heat induced radial segmentation at the initial presentation and during prednisone treatment can help in discriminating pmr from other inflammatory conditions  
class5	cd5 positive b lymphocytes in seronegative juvenile arthritis  we investigated the levels of circulating cd5  b cells in 43 patients with seronegative  hla b27 negative juvenile arthritis  7 patients with juvenile dermatomyositis  dm  and 16 children with systemic lupus erythematosus  sle   we found that cd5  b cell levels were high in juvenile arthritis  p less than 0 01   normal in juvenile dm and decreased in sle  p less than 0 01  compared to 33 age matched controls  in juvenile arthritis  the increase of cd5  b cells appeared to be independent of discuss activity and was present in all the onset types except in a subset of patient with late onset pauciarthritis  
class5	a modification of the health assessment questionnaire for the spondyloarthropathies  published erratum appears in j rheumatol 1991 feb 18 2  305  a functional status measure was developed by adding 5 items to the health assessment questionnaire  haq s   and compared to anthropometric measures of spinal mobility  forty four patients with spondylitis were evaluated by the haq s and measures of spine flexibility  finger to floor  smythe test  neck rotation  and chest expansion   modification of the haq raised the mean difficulty score by 29  from 0 38  sd   0 49  to 0 49  sd   0 51   indicating increased ability to capture functional limitations  neck rotation correlated most strongly with the haq s score  r    0 57   which suggests an important role for this measure in clinical management and followup of spondylitis  
class5	trigger finger in young patients with insulin dependent diabetes  two hundred and fifty patients with juvenile diabetes mellitus aged 3 38 years  were examined for trigger finger  thirteen patients  5   were found to have trigger finger  10 women and 3 men aged 14 38 years  mean 26 years   the ring  middle fingers  and thumb were the most affected  two patients had bilateral trigger finger  there was a significant correlation between duration of diabetes and trigger finger  p less than 0 001  but no correlation with the control of diabetes  our work indicates for the first time the prevalence of trigger finger in young patients with insulin dependent diabetes mellitus  
class5	prevalence of tendinitis and related disorders of the upper extremity in a manufacturing workforce  a cross sectional survey of a randomly selected population of 2 261 textile workers form an overall population of 8 539 eligible workers was performed to evaluate the prevalence of tendinitis in related upper extremity disorders  of the sample  2 047 respondents  91 3   participated in a nurse screening history and examination  1 091  53   had no upper extremity symptoms or abnormalities on examination  959  47   with positive findings were examined by trained physicians  of these  347  36 5   were found to have no abnormality  whereas  548  57 3   workers were assigned a diagnosis  of these 227 were considered to fall into the categories of tendinitis  n   69  or related disorders  n   158   the projected prevalence of tendinitis and related disorders for the overall group was 11 6   carpal tunnel syndrome 1 1   epicondylitis 2 0   tendinitis 3 5   shoulder condition 2 3   ganglion 2 3   neck conditions 4 0    tendinitis was less frequent in the older age group and those employed for a longer time  the prevalence of tendinitis was found to be statistically higher in physically demanding job categories  ninety four percent of ailments were of mild or moderate severity  although our study provides prevalence data for these conditions in a large manufacturing workforce across several job categories  
class5	an unusual manifestation of paget s disease of bone  spinal epidural hematoma presenting as acute cauda equina syndrome  neurologic sequelae of paget s disease of bone include involvement of the spinal cord or cauda equina due to mechanical compression by enlarged vertebrae  ischemia caused by a spinal artery  steal syndrome or neoplasm  we describe a patient with paget s disease of bone who presented with acute cauda equina syndrome due to a spinal epidural hematoma  clinicians need to recognize this entity since surgical intervention may result in a favorable outcome  
class5	a self report articular index measure of arthritic activity  investigations of reliability  validity and sensitivity  a self report measure of rheumatoid arthritic activity developed from the articular index described by thompson  silman  kirwan  and currey  1987   was tested for reliability  validity  and sensitivity to therapeutic change  concurrent validity was demonstrated by a significant correlation   icc   0 83  between the self report measure and a standard thompson index completed by a rheumatologist  test retest reliability was demonstrated by significant correlations  icc   0 88  icc   0 77  between repeated administrations of the self report form in 2 independent samples  the self report measure demonstrated sensitivity to therapeutic change when completed by patients both before and after intraarticular corticosteroid injection  the rheumatologist s index correlated significantly with c reactive protein but the self report form did not  
class5	connective tissue disease in southeast georgia  a community based study of immunogenetic markers and autoantibodies  hla antigens  c4 allotypes and t cell antigen receptor  tcr beta dna polymorphisms were determined in a community based study of connective tissue diseases  ctd   hla b8  dr3 and c4a null phenotypes occurred frequently in caucasian patients with ctd  especially those with systemic lupus erythematosus  sle   but were also more commonly found among healthy white controls of this southeast georgia community  tcr beta gene polymorphisms also showed differential segregation patterns between patients with sle and scleroderma  high frequencies of ana and anti ssdna antibodies occurred among apparently healthy family members and local controls  genetic factors predisposing to ctd in a community setting appear to be similar to those reported from referral centers  
class5	the heterogeneity of anticentromere antibodies in immunoblotting analysis  we tested anticentromere antibody positive sera from 37 patients by immunoblotting techniques  three antigenic polypeptides were recognized when immunoblotted against protein extracts from hela cell nuclei or from chromosomal segments enriched with centromere region  these were a 17 kda  cenp a recognized by 34 sera   an 80 kda  cenp b recognized by 33 sera   and a 140 kda polypeptide  cenp c recognized by 26 sera   there was no disease specific pattern of antigenic polypeptides  although raynaud s phenomenon was frequent in patients with anti cenp b reactivities  p less than 0 01   the heterogeneity of the anticentromere antibody response in japanese patients shows anticentromere antibody may not be a disease specific autoantibody and diagnostic marker  
class5	pyoderma gangrenosum complicating felty s syndrome  the case of a 54 year old woman with felty s syndrome whose course was complicated by mucocutaneous lesions clinically typical of pyoderma gangrenosum is described  necrotizing sinusitis and saddle nose deformity were distinctive clinical features  lymphocytic vasculitis and rheumatoid nodule formation observed within panniculus at the base of a cutaneous lesion and in a nasal mucosal lesion were unexpected histopathologic findings  
class5	presentation of breast carcinoma as volkmann s contracture due to skeletal muscle metastases  metastases to the skeletal muscles are extremely rare  they usually occur during the course of a pulmonary or digestive carcinoma  we describe a case of breast carcinoma presenting with forearm muscle metastases and volkmann s type contracture  
class5	rapidly progressive calcific periarthritis occurring in a patient with lupus nephritis receiving chronic ambulatory peritoneal dialysis  we present a patient who developed rapidly progressive calcific periarthritis while receiving chronic ambulatory peritoneal dialysis  she developed chronic renal failure on the basis of lupus nephritis  hydroxyapatite crystals were isolated from periarticular deposits and identified using phase contrast light microscopy and electron microscopy  conservative management using phosphate binding agents and nonsteroidal antiinflammatory drugs was unsuccessful and lesions were excised surgically  
class5	the prophylactic use of antibiotic impregnated beads in open fractures  four hundred four compound fractures were reviewed in 339 patients treated between august 1983 and november 1987  the 252 males and 87 females had a mean age of 33 years  range  14 86   one hundred twenty seven  31 4   fractures were classified as grade i  153  38 9   as grade ii  and 124  30 7   as grade iii by gustilo s classification  the mean injury severity score was 15  range  9 57   three hundred thirty four of the open fractures  82 7   were managed with antibiotic impregnated bead chains  tobramycin  and systemic antibiotic prophylaxis  cefazolin  tobramycin  and penicillin   seventy open fractures  17 3   received systemic antibiotic prophylaxis  cefazolin  tobramycin  and penicillin  without supplemental use of the antibiotic beads  all open fractures underwent acute irrigation and debridement  in the 404 fractures 46 5  of wounds were closed primarily  12 9  underwent delayed primary closure  7 9  were left open  and 32 7  were temporized by the antibiotic bead pouch technique until definitive flap coverage and skin grafting were performed  of the 404 fractures evaluated  17  4 2   developed an acute wound infection  of these wound infections  eight  11 4   were in the group managed with systemic antibiotics alone  by comparison  nine  2 7   of open fractures treated with combined systemic antibiotics and antibiotic impregnated beads developed an infection  chronic osteomyelitis developed in 18 of 404 open fractures  4 5    ten  14 3   open fractures which developed osteomyelitis were managed with systemic antibiotics whereas eight  2 4   fractures managed with systemic antibiotics and antibiotic impregnated beads developed a chronic infection  
class5	vitamin d and bone  recent studies of the effects of vitamin d on bone include characterization of the receptors for 1 25  oh 2d3 in bone and bone derived cells  the receptors show similar affinities in the different tissues  the receptor concentration is affected by the stage of the cell cycle  glucocorticoid treatment affects the number of receptor sites  the most extensively studied effects of 1 25  oh 2d3 on macromolecular synthesis in bone have been on collagen  where both anabolic and antianabolic effects are found  differences in the response may reflect the state of differentiation of the cells  significant effects are seen on osteocalcin synthesis  although the role of this protein in vitamin d action on bone is still unclear  1 25  oh 2d3 influences the activity of alkaline phosphatase and 25 oh d3 24 hydroxylase in bone  receptors for growth factors  and production of cytokines may be influenced by 1 25  oh 2d3 treatment  although some of these findings would be consistent with direct anabolic effects of vitamin d or its metabolites on bone  such a process has yet to be integrated into the complete picture of vitamin d action at physiological and pharmacological levels in vivo  recent studies are consistent with earlier results that indicate that hypercalcemic effects of 1 25  oh 2d3 are mediated by a direct effect on bone  studies with analogs of 1 25  oh 2d3 suggest that the stimulation of bone resorption can be dissociated from effects on differentiation of cells of the monocyte lineage  
class5	accelerated transmural gradients of energy compound metabolism resulting from left ventricular hypertrophy  eighteen dogs underwent transmural left ventricular biopsies for adenosine triphosphate and suturing of the noncoronary cusp  creating valvular aortic stenosis  three months after aortic stenosis and the subsequent development of left ventricular hypertrophy  animals underwent repeat transmural left ventricular biopsies followed by total myocardial ischemia at 37 degrees c  left ventricular tissue samples for adenosine triphosphate and lactate levels were determined at 15 minute intervals and compared with 15 control animals  no significant difference between subendocardial and subepicardial adenosine triphosphate levels was found between left ventricular samples taken before left ventricular hypertrophy and 3 months after left ventricular hypertrophy  significant differences in adenosine triphosphate utilization occurred between subendocardial and subepicardial layers in control and left ventricular hypertrophy myocardium  however  the gradient between the subendocardium and the subepicardium was significantly increased by left ventricular hypertrophy  p less than 0 05   significant differences also occurred within the same layer when left ventricular hypertrophy and control groups were compared  during total ischemia  lactate concentration was significantly greater within the subendocardium than within the subepicardium in left ventricular hypertrophy  the onset of ischemic contracture was 48 2     2 1 minutes in left ventricular hypertrophy versus 62 3     1 8 minutes in control hearts  p less than 0 01   subendocardial intramyocardial pressure increased significantly earlier than subepicardial in both left ventricular hypertrophy and control hearts  adenosine triphosphate was used  and lactate accumulated more rapidly in animals with a more pronounced hemodynamic gradient  these data show that after left ventricular hypertrophy  adenosine triphosphate stores in the subendocardium and the subepicardium are unchanged from control values  yet the rates of adenosine triphosphate utilization and lactate accumulation during total ischemia are significantly increased  furthermore  the subendocardial to subepicardial gradient of adenosine triphosphate utilization during ischemia found in normal hearts is markedly increased by left ventricular hypertrophy  
class5	le fort i osteotomy approach to the skull base  horizontal osteotomy allows the surgeon to safely down fracture the maxilla for wide exposure of the central skull base  this surgical approach is easily extended posteriorly in the midline to include the clivus and the arch of c1  providing 8 cm of horizontal anterior exposure and 5 cm of posterior  wide operative exposure and a low rate of complications afford superior functional and cosmetic preservation in removing tumors of the central cranial base  
class5	spinal bone loss and ovulatory disturbances background  osteoporosis develops in women with estrogen deficiency and amenorrhea who lose bone at an accelerated rate  it is not known to what extent bone loss differs between ovulatory women with regular menstrual cycles who are training intensely and those who are sedentary  methods  we measured the density of cancellous spinal bone from the 12th thoracic vertebra to the 3rd lumbar vertebra by quantitative computed tomography on two occasions one year apart in 66 premenopausal women 21 to 42 years of age  all the women had two consecutive ovulatory cycles immediately before entering the study  twenty one women were training for a marathon  22 ran regularly but less intensively  and 23 had normal levels of activity  the lengths of the women s menstrual cycles and luteal phases  diet  exercise levels  and hormonal levels were also determined  we defined ovulatory disturbances as anovulatory cycles and cycles with short luteal phases  results  the mean      sd  spinal bone density in the 66 women decreased 3 0     4 8 mg per cubic centimeter per year  2 0 percent per year   p less than 0 001   amenorrhea did not develop in any woman during the year of observation  only 2 7 percent of the cycles were greater than 36 days long   ovulatory disturbances occurred in 29 percent of all cycles  however  bone loss was strongly associated with these disturbances  r   0 54  24 percent of the variance   the 13 women who had anovulatory cycles lost bone mineral at a rate of 6 4     3 8 mg per cubic centimeter per year  4 2 percent per year   the women training for a marathon had menstrual cycles similar to those of the women in the other two groups  conclusion  decreases in spinal bone density among women with differing exercise habits correlated with asymptomatic disturbances of ovulation  without amenorrhea  and not with physical activity  
class5	pre trigeminal neuralgia  eighteen patients who subsequently developed typical trigeminal neuralgia experienced a prodromal pain termed  pre trigeminal neuralgia   these patients described their prodromal pain as a toothache or sinusitis like pain lasting up to several hours  sometimes triggered by jaw movements or by drinking hot or cold liquids  typical trigeminal neuralgia developed a few days to 12 years later  and in all cases affected the same division of the trigeminal nerve  six additional patients experiencing what appeared to be pre trigeminal neuralgia became pain free when taking carbamazepine or baclofen  recognition of pretrigeminal neuralgia makes it possible to relieve the pain with appropriate medications and avoid unnecessary irreversible dental procedures  
class5	effect of estrone sulfate on postmenopausal bone loss  estrogen replacement therapy confers many beneficial effects to postmenopausal women  such as slowing the rate of bone loss and decreasing the risk of coronary artery disease  this multicenter  placebo controlled study evaluated the lowest effective daily dose of estrone sulfate  0 3  0 625  or 1 25 mg  combined with 1000 mg elemental calcium supplementation for preventing bone loss in the immediate supplementation for preventing bone loss in the immediate postmenopausal period  spinal bone mineral density was measured using quantitative computed tomography  compared with baseline  bone mineral density increased significantly  p less than  05  after 12 months of 0 625 mg daily    1 9   or 1 25 mg daily    2 5    the difference between the 0 625 mg and 1 25 mg doses was not statistically significant  estrone sulfate administration  0 625 and 1 25 mg  produced significant changes in various lipid measurements at both the 6  and 12 month observation points  the prevalence rates for adverse events were comparable among the estrone sulfate groups and the placebo group  estrone sulfate 0 625 mg daily  combined with 1000 mg elemental calcium supplementation  was the minimum effective dosage to prevent loss of spinal bone mineral density in postmenopausal women over a 12 month period  
class5	premature alveolar bone loss in erdheim chester disease  erdheim chester disease is a rare histiocytosis also known as lipoid granulomatosis  oral findings have not been reported previously to our knowledge  this case report documents evidence of oral sequelae of erdheim chester disease  a patient whose course was followed for 10 years at the national institutes of health had premature alveolar bone resorption  he underwent full mouth extraction at age 29 years because of severe periodontitis  histopathologic evidence of erdheim chester disease was demonstrated in the periodontal soft tissues  in the ensuring years  accelerated resorption of the residual ridges precluded the use of conventional dentures  we recommend early preventive dental management for patients with erdheim chester disease  
class5	dental abnormalities associated with familial expansile osteolysis  a clinical and radiographic study  familial expansile osteolysis is a rare and possibly unique form of hereditary bone dysplasia with dental manifestations that has affected 42 members of a northern ireland family for five generations  twenty seven family members  aged 3 to 60 years  were examined clinically and radiographically  and it was found that cervical and or apical root resorption is an early manifestation of the dysplasia  of the 20 family members with skeletal manifestations of familial expansile osteolysis  16 showed root resorption  root resorption may therefore be a good prognosticator for later bone involvement  
class5	differences between florid osseous dysplasia and chronic diffuse sclerosing osteomyelitis  florid osseous dysplasia  fod  is confused in the literature with chronic diffuse sclerosing osteomyelitis  two cases of each condition are presented to demonstrate the differences between them  in fod  there are multiple lobulated sclerotic masses in several quadrants of the jaws  usually in black females  in some cases  the sclerotic masses are exposed to the oral cavity  resulting in a secondary osteomyelitis  periapical cemental dysplasia is often found in association with fod  chronic diffuse sclerosing osteomyelitis is a primary inflammatory condition of the mandible  patients have cyclic episodes of unilateral pain and swelling  the affected region of the mandible exhibits a diffuse opacity with poorly defined borders  although women are affected more often than men  black persons are not particularly susceptible  
class5	the radiologic morphology of asymptomatic temporomandibular joints  a high frequency of remodeling changes was demonstrated radiographically in a series of 200 female patients with asymptomatic temporomandibular joints  fewer than 10  of joints were completely radiologically  normal   generally  there was an increasing incidence of changes with increasing age and for edentulous patients  but these relationships were by no means direct or mutually exclusive  
class5	the radiologic morphology of painful temporomandibular joints  a high frequency of remodeling changes was demonstrated radiographically in a series of patients having pain in the temporomandibular joint region  radiologic morphologic differences between painful and asymptomatic temporomandibular joints were in frequency rather than type  caution should be taken not to overestimate the significance of radiologic abnormality in patients with pain in the temporomandibular joint region  
class5	bone trabecular pattern analysis in down syndrome with the use of computed panoramic radiography  part ii  visual pattern analysis with the frequency and gradational enhancement  visual pattern analysis of mandibular bone trabeculation of 51 patients with down syndrome and 78 normal persons was performed by using rotational panoramic radiography with a laser scan system  the findings for patients with down syndrome were consistent with geromorphism  one of the somatic characteristics of down syndrome  
class5	silicone rubber fossa implant removal via partial arthrotomy followed by arthroscopic examination of the internal surface of the fibrous capsule  thirteen temporomandibular joints were examined arthroscopically for evaluation for fibrous encapsulation of silicone elastomer disk replacement implants  partial arthrotomies were performed with removal of silicone rubber implants  followed by arthroscopic examination of the internal surfaces of the fibrous capsule as a pseudodisk and to verify the continuity of the fibrous barrier between the condyle and the fossa  
class5	a histologic evaluation of the accuracy of tmj diagnostic arthroscopy  sixty seven temporomandibular joints with internal derangement were examined with arthroscopy  and synovial biopsies were taken for histologic evaluation  histologically  in 10 cases  the synovium appeared to be normal in appearance  24 cases had moderate to severe synovitis  11 cases showed hyperplastic synovitis  13 cases showed synovial fibrosis  and foreign body granuloma was found in 9 cases  correlation between arthroscopic observation and histologic findings disclosed an 89 1  specificity and 100  sensitivity  
class5	triple bone labeling of canine mandibles  fluorescence microscopy was used for evaluation of new bone formation in 16 canine mandibles augmented with hydroxylapatite  ha  granules  three fluorochromes were injected at different time intervals during therapeutic radiation treatment  oxytetracycline  dcaf  and alizarin complexone were given intravenously to mark the bone level at these times  respectively  oxytetracycline  which defined the baseline of bone at implantation of ha  was detectable in 42  of animals that were irradiated and in no animal of the nonirradiated control group  the marker dcaf  designating levels of bone at the start of radiation  was demonstrated in 92  of irradiated animals  and in 75  of animals in the control group  the uptake of alizarin complexone determined the level of bone found at the end of irradiation  this marker was demonstrated in 50  of the dogs irradiated and in 75  of the control dogs  bony trabeculae were found between and at the surface of the ha granules  new generation of bone directly on the ha granule and in the surrounding haversian systems as part of normal bone turnover was demonstrated to take place more than 5 months after implantation of ha  
class5	temporomandibular joint dysfunction and selected health parameters in the elderly  little research has focused on temporomandibular joint dysfunction  tmjd  in the elderly  the present study describes relationships between tmjd and selected health parameters in a population of 75  to 94 year old roman catholic sisters  nuns   mental  physical  and oral assessments made on 117 sisters identified 26 with tmjd  among all sisters  tmjd was not associated with age  education  mental impairments  hand coordination  handgrip strength  mobility  or use of walking aids  in 75  to 84 year old sisters  tmjd was positively associated with self reported arthritis  p   0 12   edentulism  p   0 09   and the presence of complete dentures  p   0 05   and negatively associated with the number of teeth present  p   0 05   especially the posterior teeth  these associations were weaker in 85  to 94 year old sisters  this study suggests that tmjd is associated with the presence of complete dentures and a low number of teeth  especially the posterior teeth  
class5	diffuse sclerosing osteomyelitis of the mandible  a new concept of its etiology  diffuse sclerosing osteomyelitis of the mandible is a disease of unknown etiology  the clinical and radiographic findings suggest an infectious origin  but bacteriologic and histologic findings do not support this concept  analysis of clinical symptoms  localization of the condition  and posttreatment findings in a group of 27 patients suggest a chronic tendoperiostitis due to muscular overuse as an etiologic factor in diffuse sclerosing osteomyelitis of the mandible  this hypothesis was supported by the initial results of muscle relaxation treatment in 13 of these patients  
class5	peripheral giant cell granuloma  evidence for osteoclastic differentiation  nine cases of peripheral giant cell granuloma of the oral cavity have been immunohistochemically analyzed to assess the nature of the giant cells  giant cells were unreactive when tested with antibodies recognizing myelomonocytic and macrophage markers  lysozyme  mac 387  ham 56  but showed strong immunoreactivity with mb1  an antibody reactive with osteoclasts  it is concluded that giant cells characterizing giant cell granuloma exhibit a phenotype distinct from other giant cells found in sites of chronic inflammation and may be true osteoclasts  
class5	progressive osseous destruction as a complication of hiv periodontitis  a pathologic condition is described  characterized by rampant necrosis of gingival mucosa  periodontium  and related osseous structures associated with systemic infection with the human immunodeficiency virus  hiv   it is believed that this condition is an extension beyond the normal clinical course of hiv periodontitis  hiv p  and manifests itself in three progressive stages   1  hiv associated gingivitis   2  hiv p  and  3  an extension of hiv p to osseous necrosis  two cases of osseous destruction attending hiv p are reported  one of which led to initial diagnosis of hiv infection  they represent the final stage of disease progression with localized necrosis of gingiva  periodontium  and alveolar bone  
class5	periapical lesions of mandibular bone  difficulties in early diagnostics  it is often difficult to establish a correct diagnosis on the basis of initial clinical and roentgenologic symptoms in mandibular bone disease  in this paper these problems are discussed  and some suggestions are made to overcome them  the discussion is based on cases of osteogenic sarcoma  histiocytic lymphoma  and chronic osteomyelitis  the patients were a boy and two middle aged women  all of them with primary clinical symptoms of pain and swelling  diffuse roentgenologic changes in mandibular bone  uncertain response to treatment  and an unusual progress of the disease  
class5	fine detail panoramic radiography by free focus radiography  a clinical demonstration of diagnostic radiographs  previous comprehensive clinical studies have shown that free focus radiography  ffr  may be used to improve image detail and diagnostic value in panoramic radiography of the teeth and jaws  this study demonstrated the clinical image quality in fine detail panoramic ffr surveys relative to conventional surveys made by rotational panoramic or intraoral radiography  cases of particular diagnostic interest with respect to common dental disease and changes in the jaws were included  the radiographic area of diagnostic interest depicted in ffr surveys generally resembled that of conventional dental radiographic surveys with the use of intraoral films rather then those of conventional rotational panoramic surveys  
class5	tibial nonunions  treatment tactics with the ilizarov method  the key to the success of the ilizarov method is that the rigid systems  such as plates and traditional external fixators that bypass the nonunion  have been replaced by the axially elastic system of ilizarov  the cyclic axial telescoping mobility  not rigidity  at the nonunion or fracture site is an important requirement for the formation of reparative callus  as we gain more experience with the method  we find ourselves capable of solving increasingly more difficult problems with a level of success rarely  if ever  achieved with more conventional methods  
class5	the use of the ilizarov concept with the ao asif tubular fixateur in the treatment of segmental defects  for the treatment of segmental defects of less than 4 cm  cancellous autografting remains the treatment of choice  pedicled or free cortical grafts  fibula  ribs  iliac crest  often are not strong enough  particularly when used in the femur  allografts  especially appealing because of the theoretic unlimited supply  should not be considered for segmental diaphyseal defects because they remain dead spacers  remodelled only very slowly and incompletely  and are often complicated by late infection  the technique of distraction histogenesis used by putti and anderson  improved and further differentiated towards corticotomy and fragment transport by ilizarov  is a further possibility of treating long  segmental bone defects  already clinical and experimental data clearly show that the effect of distraction histogenesis can be obtained using many different types of external fixators  therefore  we should use as simple a fixator construction as possible  the standard unilateral sagittal frame we suggest is derived from a two tube ao fixator using only a few additional elements  the majority of cases with segmental defects and minor additional axial or rotational deformities  which can be corrected primarily  can be treated with such a fixator  the quality of the regenerate may be improved with a motorized  continuous transport system and by better soft tissue coverage using early flaps  interface healing is very probably improved by cancellous grafting and internal fixation after the transport period  thus decreasing the fixator time  
class5	treatment of malunions and mal nonunions of the femur and tibia by detailed preoperative planning and the ilizarov techniques  internal fixation has been the mainstay of treatment for post traumatic deformities  external fixation has been used for correction of deformity in malunions and mal nonunions  treatment goals of achieving complete deformity correction with restoration or improvement of function were successful in this very complex group of malunions despite the numerous problems  obstacles  and complications of treatment  
class5	pauwels osteotomy for nonunions of the femoral neck  the concept of the pauwels osteotomy seems to be a valuable method of treating nonunions of the femoral neck  if there is concomitant avascular necrosis  the involved area should be small and the patient younger than 60 years old  
class5	amenorrhea  osteopenia  and the female athlete  athletic amenorrhea is a problem because it is associated with an increased risk of injuries and potentially an increased risk of osteoporosis in later life  this article gives suggestions for the evaluation of the athlete with amenorrhea and for treatment protocols  primary care physicians should routinely screen female adolescent athletes for amenorrhea and  if athletic amenorrhea is present  initiate treatment or referral for treatment for this important problem with short  and long term complications  
class5	the le fort iii advancement osteotomy in the child under 7 years of age  this is a longitudinal study of 12 patients with craniofacial synostosis syndromes  crouzon s  apert s  pfeiffer s  who underwent le fort iii advancement under the age of 7 years  average age 5 1 years  range 4 0 to 6 7 years   the average follow up was 5 0 years and included clinical  dental  and cephalometric examinations according to a prescribed protocol  the study demonstrated that the procedure could be safely performed in the younger child with an acceptable level of morbidity  there was a remarkable degree of postoperative stability of the maxillary segment  however  although vertical  inferior  growth or movement of the midfacial segment was demonstrated  there was minimal  if any  anterior or horizontal growth  any occlusal disharmony developing during the period of follow up could be attributed to anticipated mandibular development and could be corrected by orthognathic surgery  the roles of surgical overcorrection and anterior pull headgear therapy after release of intermaxillary fixation are also discussed  the le fort iii osteotomy is justifiably indicated during early childhood for psychological and physiologic reasons  
class5	polyurethane foam covered implants and capsular contracture  a laboratory investigation  experiments were conducted in rabbits comparing polyurethane foam covered implants with otherwise identical smooth silicone gel implants  using five objective methods of measurement of capsular contracture  no significant difference could be identified  the foam covered implants consistently developed capsular contracture  although in most cases this was of mild degree and would not have been clinically significant  in the two foam covered implants with hard contractures  there was no evidence of hematoma or separation of the foam  
class5	recurrent anterior dislocation of the ulnar nerve at the cubital tunnel  recurrent anterior dislocation of the ulnar nerve at the cubital tunnel is reported in two patients  this was due to traumatic attenuation of the flexor carpi ulnaris retinaculum  the mechanism of injury in both patients was a fall with the shoulder abducted and the elbow acutely flexed  both patients had relief of their neurologic symptoms following anterior submuscular transposition of the ulnar nerve  
class5	temporal bone  three dimensional ct  part ii  pathologic alterations  three dimensional  3d  surface renderings were obtained from routine axial computed tomographic  ct  images in 15 patients with a variety of complex temporal bone abnormalities  the 3d ct reformations served as an adjunct to conventional sectional ct examination  while no diagnosis was substantially changed because of the 3d ct images  they did provide a more global perspective in cases of large tumors and fractures and at the postmastoidectomy site  three dimensional ct surface reformations are now practical and may be potentially useful for visualizing temporal bone lesions characterized by complex destructive change  
class5	scapholunate advanced collapse  a common wrist abnormality in calcium pyrophosphate dihydrate crystal deposition disease  scapholunate advanced collapse  slac  is a pattern of wrist malalignment that has been attributed to posttraumatic or spontaneous osteoarthritis of the wrist  its features  however  also have been observed in patients with idiopathic calcium pyrophosphate dihydrate  cppd  crystal deposition disease  to determine the frequency and characteristics of slac in this disease  the authors reviewed wrist radiographs in 168 well documented cases of this disorder  forty four of the cases  26   revealed wrist abnormalities typical of slac  associated findings included bilateral involvement  63    calcification in or near the triangular fibrocartilage  70    scapholunate widening or dissociation  70    and arthropathies of the trapezioscaphoid  57    metacarpophalangeal  second through fifth   52    first carpometacarpal  40    and radiolunate  14   joints  results strongly suggest that cppd crystal deposition disease is one of the major causes of slac  furthermore  radiolunate arthropathy was found in 14  of the patients with slac and cppd crystal deposition disease  which is different from other observations  
class5	a prospective necropsy study of arthritis in acquired immunodeficiency syndrome  thirty two knee and 23 sternoclavicular joints from 35 subjects with acquired immunodeficiency syndrome were examined prospectively at necropsy  there were two instances of opportunistic infectious arthritis  one caused by staphylococcus aureus  the other by sporothrix schenckii  in five other subjects  para articular bone was infiltrated by granulomatous or neoplastic sequelae of the human immunodeficiency virus infection  there was no immunohistochemical  p24 antigen  or other evidence for existence of a specific acquired immunodeficiency syndrome arthritis  
class5	large cell orbital lymphoma in a patient with acquired immune deficiency syndrome  case report and review despite the protean ocular manifestations of acquired immune deficiency syndrome  aids   orbital involvement is rare and only one previous case of orbital non hodgkin s lymphoma  nhl  has been documented  we report a second case of nhl  large cell  of the orbit in a 28 year old patient with a 4 year history of aids and review the context in which this lesion presented  
class5	a new dynamic lumbrical simulating splint for claw hand deformity  the claw hand deformity  resulting from low ulnar or combined low ulnar and median nerve palsy  is an incapacitating situation  the splint described herein reverses the clawing by substituting for the lumbricals and interossei  if started early  it not only prevents the permanent stiffness of fingers in the claw position  but also effectively restores function without hampering day to day work because it is a surface splint  
class5	hemodialysis related amyloidomas of bone  lytic bone lesions secondary to amyloid deposition are a recently described complication of long term hemodialysis  the authors refer to these tumorlike deposits as amyloidomas in a review of the subject and four proved cases  this entity typically appears as multiple well defined  juxta articular lytic lesions without matrix calcification  the duration of hemodialysis is probably the greatest risk factor for development of these intraosseous amyloidomas  ultrastructurally  this new type of amyloid originates from beta 2 microglobulin  a low molecular weight serum protein that is not filtered by standard dialysis membranes  
class5	occult posttraumatic osteochondral lesions of the knee  prevalence  classification  and short term sequelae evaluated with mr imaging  the prevalence  characterization  and classification of acute  post traumatic  occult subcortical fractures of the knee  identified at magnetic resonance  mr  imaging  were evaluated prospectively in 120 consecutive patients first seen with acute posttraumatic hemarthrosis of the knee  occult subcortical femoral and tibial fractures were identified in 72  of patients  a modified mr imaging classification is suggested based on a combination of the appearances of such lesions at mr imaging and their short term osteochondral sequelae  among 67  of a cohort of 21 patients first seen with what have been described as occult geographic subcortical fractures  osteochondral sequelae were seen at follow up mr imaging 6 12 months later  the evidence from this study indicates that specific subcategories of occult subcortical knee fractures are associated with an inordinately high prevalence of osteochondral sequelae  especially significant cartilage damage  
class5	primary bone tumours of the thoracic skeleton  an audit of the leeds regional bone tumour registry  an audit of the leeds regional bone tumour registry found that primary bone tumours of the thoracic skeleton constituted 90 of the 2004 cases  4 5    thirty seven per cent occurred in the ribs  32  in the scapulae  11  in the thoracic vertebrae  11  in the sternum  and 9  in the clavicles  malignant tumours were more common than benign  54 v 36  and occurred in an older population  mean ages 47 and 31 years   the scapula was the most common site for malignant lesions and the ribs the most common site for benign tumours  chondrosarcoma was the commonest tumour in older patients  fibrous dysplasia and plasmacytoma in the middle age group  and eosinophilic granuloma in children  presenting symptoms were a poor guide to whether the lesion was malignant or not  this and the small proportion of correct preoperative diagnoses indicate the need for early biopsy  bone tumour registries provide a valuable source of cumulative information about uncommon tumours and facilitate accurate diagnosis  teaching  and research  
class5	eosinophilic granuloma of the lung presenting as a solitary pulmonary nodule  a symptomless 58 year old man had an eosinophilic granuloma of the lung that presented as a solitary pulmonary nodule rather than the usual diffuse reticulonodular shadow on the chest radiograph  only one previous case presenting in this way has been described  
class5	traumatic synovitis analysed by arthroscopy and immunohistopathology  the synovitis induced in previously healthy subjects by knee joint trauma was investigated at arthroscopic surgery performed after 3 70 days  synovitis was confined to the areas of the synovial membrane bordering the cartilage lesion and displayed a varied intensity of inflammation  biopsies were sampled under direct vision from the area of the peak inflammatory intensity within each joint and analysed by immunohistopathology  only sparse lymphocytic infiltration and a slight increase of lining cell layers were found in the biopsies after as long as 70 days  the restricted extent and limited intensity of the inflammatory changes contrast with previous findings in rheumatoid arthritis  however  the arthroscopic and immunohistopathological signs of synovitis were no different  
class5	intestinal flora of patients with rheumatoid arthritis  induction of chronic arthritis in rats by cell wall fragments from isolated eubacterium aerofaciens strains  the composition of the obligate anaerobic intestinal flora of patients with rheumatoid arthritis  ra  differed from that of healthy subjects  hs   total numbers of aerobes as well as anaerobic coccoid rods were found elevated when compared with hs  eubacterium species were found in all stool samples of both groups  bifidobacterium species were present in seven  ra  and eight  hs  out of 10 subjects  from the flora of two ra patients and two hs eubacterium species were isolated and identified  cell wall fragments from four e  aerofaciens strains  two from ra  two from hs  were tested for arthritis induction in rats  all four strains induced chronic arthritis which was histologically confirmed  we concluded that in the normal intestinal flora of ra patients eubacterium species are present in high numbers  i e  greater than 10 9  g faeces   cell walls from isolated e  aerofaciens strains had arthropathic properties  
class5	post traumatic osteoarthritis  a medico legal minefield  a consensus view has been obtained from 108 colleagues about four major questions relating to post traumatic osteoarthritis  oa  posed by a retired judge  in determining the likelihood of oa developing after a fracture  several factors must be taken into account  these include whether the fracture goes through the joint  the resulting angular deformity  the degree of soft tissue damage  the ensuing laxity of the joint  the presence of generalized oa  the involvement of nearby blood vessels supplying the bones of the joint and possibly the degree of immobilization  lower limb joints are more likely to develop arthritis after injury than arm joints as they carry more load  although it would be wrong to think that arm joints were not load bearing   occupation is a further factor  age is thought to be important  with the elderly more at risk immediately  but the younger having longer in which to develop the disease  younger people are less likely to develop post traumatic oa  unless there is involvement of the epiphysis or residual angular deformity  whilst in animals and in some fractures  degenerative changes begin immediately after damage to the joint  in most adults they take at least 2 years  the span is 2 5 years in more severe cases  including fractures of the joint line with a step in the surface  and associated dislocation  otherwise it may take 10 years  most of these data are anecdotal or obtained from retrospective surveys  there is great need for prospective work in this field  
class5	remitting seronegative symmetrical synovitis with pitting oedema in young adults  a subset of rheumatoid arthritis or a distinct syndrome  three young adult patients with seronegative symmetrical polysynovitis affecting the peripheral joints with pitting oedema of both dorsum of hands and feet are described  all of these patients had a benign course and resolved completely within 10 15 months of the onset  none developed any deformities or erosions and or relapse of arthritis after prolonged follow up  
class5	natural and recombinant human il 1 receptor antagonists block the effects of il 1 on bone resorption and prostaglandin production  inhibitory factors towards il 1 have been identified in the urine and in the supernatants of human monocyte cultures and have been shown to act as receptor antagonists  we have investigated whether a natural inhibitor purified from human urine  uil 1ra  and a recombinant molecule expressed using the gene for an il 1 antagonist isolated from monocytes  ril 1ra  can alter responses to human ril 1 alpha in organ cultures of fetal rat long bones and neonatal mouse calvariae  the two preparations probably contained similar or identical molecules  because an antibody to ril 1ra reacted with uil 1ra by western blot analysis  uil 1ra and ril 1ra specifically blocked stimulation of bone resorption by ril 1 in both culture systems  as well as the increase in pge2 production in cultured calvariae  resorptive effects of parathyroid hormone and tnf alpha were not blocked  the uil 1ra preparation had some intrinsic resorbing activity  but on gel chromatography this appeared in fractions that eluted earlier than uil 1ra  concentration ratios of ril 1ra to ril 1 as low as 10 could block the resorptive response of fetal rat long bones  whereas concentration ratios of 100 to 1000 were required to block il 1 action on neonatal mouse calvariae  the inhibitory effects appeared to be competitive  because increasing concentrations of il 1 overcame the block of bone resorption in both systems and the inhibition of pge2 production in calvariae  
class5	basilar impression in osteogenesis imperfecta tarda  case report  a case is presented of basilar impression secondary to osteogenesis imperfecta tarda  associated with hemifacial spasm and brain stem compression syndrome  the symptoms improved with posterior fossa decompression and posterior fusion  
class5	septic hip in pelvic fracture with urologic trauma  case report  urologic injuries occur in 10  of pelvic fractures and hip sepsis is a rare complication  the symptoms of a septic hip are often not as dramatic when found in the setting of an acute pelvic fracture and may be overlooked  a case is presented with a review of the literature  early recognition and aggressive surgical debridement are important to prevent the long term sequelae of septic arthritis  
class5	the operative management of basilar impression in osteogenesis imperfecta  four patients with osteogenesis imperfecta and neurologically significant basilar impression have been treated over the past 8 years  the experience has resulted in changes in our therapeutic strategy for this particularly difficult problem  these cases are discussed with respect to the disease process  neurological involvement  radiological findings  and modes of surgical therapy  the errors in management as well as the success resulting from our learning experience are described  currently  we recommend the extensive removal of the anterior bony compression by a transoral approach  this should be followed by a posterior rigid fixation that transfers the weight of the head to the thoracic spine  in an effort to prevent further basilar invagination  
class5	cryptic osteoid osteoma of the cranium  case report  osteoid osteoma is an uncommon benign tumor of bone that rarely involves the cranium  if often causes local pain that is worse at night  characteristically relieved by aspirin  and does not correlate with the size of the lesion  the diagnosis depends on skull radiographs and computed tomography  this report describes a case in which radiographs showed nothing abnormal  the diagnosis and operative localization were accomplished with radionuclide bone scanning  thus  the possibility of radiographically cryptic lesions must be considered in the evaluation of atypical head pain syndromes  
class5	disorders of calcium and phosphorus homeostasis  calcium and phosphorus are  respectively  the fifth and sixth most abundant elements in the body  both play vital roles in a multitude of physiologic systems  because the great bulk of these elements is found in the skeleton  a large part of the discussion of calcium and phosphorus metabolism focuses on skeletal disorders  the impact of which falls heavily on young children  this article reviews the physiology of calcium and phosphorus  the skeletal and systemic consequences of disorders of vitamin d nutrition and metabolism  and the metabolic bone disease of prematurity  
class5	microcomputer reconstruction for analysis of spinal deformity and lung volume in hypokyphotic scoliosis  current techniques for imaging chest deformity are limited to two dimensional representations  and clinical testing for lung volume measurements are based on pulmonary function studies that are effort dependent  the authors evaluated spine deformity and lung volume by using a new three dimensional microcomputer imaging technique  results from preoperative and postoperative chest computed tomograms underwent boundary detection by expert human observers  data were then processed by polygon surface tiling to create three dimensional color images of the spine and lungs for display  this computer technique allowed  1  visualization of the anatomic relationships from any angle  2  assessment of spinal deformity in relation to lung volume  and 3  measurement of individual lung volumes  three dimensional microcomputer imaging is a useful technique in objectively measuring lung volume and assessing postoperative changes  
class5	cobb angle versus spinous process angle in adolescent idiopathic scoliosis  the relationship of the anterior and posterior deformities  the standard clinical measurement for adolescent idiopathic scoliosis is the cobb angle  measured from the end plates of the end vertebral bodies in a standing radiograph  this measurement of anterior column structures describes the anterior spinal deformity  the posterior spinal deformity can be described by the  spinous process angle   measured from a curve joining the tips of the spinous processes  a computer model  and a radiographic study of cobb angle  spinous process angle and vertebral rotation show that adolescent idiopathic scoliosis results in larger angulations of the anterior elements than posterior elements  this helps to explain some of the inherent limitations of posterior instrumentation  including cotrel dubousset instrumentation  and of noninvasive posterior surface measurement systems  
class5	digital radiography can reduce scoliosis x ray exposure  digital radiology is a new computerized system of acquiring x rays in a digital  electronic  format  it possesses a greatly expanded dose response curve that allows a very broad range of x ray dose to produce a diagnostic image  potential advantages include significantly reduced radiation exposure without loss of image quality  acquisition of images of constant density irrespective of under or over exposure  and reduced repeat rates for unsatisfactory films  the authors prospectively studied 30 adolescents with scoliosis who had both conventional  full dose  and digital  full  one half  or one third dose  x rays  they found digital made ap and lateral image with all anatomic areas clearly depicted at full and one half dose  digital laterals were better at full dose and equal to conventional at one half dose  cobb angles were easily measured on all one third dose ap and on 8 of 10 one third dose digital laterals  digital clearly depicted the risser sign at one half and one third dose and the repeat rate was nil in this study  indicating digital compensates well for exposure errors  the study indicates that digital does allow radiation dose to be reduced by at least one half in scoliosis patients and that it does have improved image quality with good contrast over a wide range of x ray exposure  
class5	results of treatment of idiopathic scoliosis with the charleston bending orthosis  the authors present a preliminary retrospective review of the treatment of 32 patients with idiopathic scoliosis with the charleston bending thoracolumbosacral orthosis  tlso   a new  low profile spinal orthosis  at the onset of treatment  the patients  mean age was 12 5 years and the mean risser stage was 0 4  females achieved menarche at an mean of 1 8 months after starting orthotic treatment  single structural curves were treated in all patients  at this time  2 patients have failed treatment  their curves progressing 12 degrees and 8 degrees  respectively  an additional 11 patients have successfully completed treatment  having reached skeletal maturity with no more than 5 degrees of curve progression  their mean curve change was a 2 2 degrees decrease  the other 19 patients remain under treatment  the charleston bending tlso is worn only during nighttime sleeping hours  it is well tolerated  with excellent patient compliance and low psychological stress  and it may be as successful at curve control as other orthoses  experience with more patients and longer follow up is needed  
class5	surface electrical stimulation versus brace in treatment of idiopathic scoliosis  surface electrical stimulation using the scolitron device was applied to 40 adolescent patients for treatment of idiopathic scoliosis  adequate follow up was available for 30 of these patients  the overall failure rate was 15 of 30 or 50   due to curve progression while using the scolitron  these patients either went on to a fusion  9 of 15  or were changed to a brace  6 of 15   the remaining 15 patients were considered successes with no curve progression  10 of 30 or 33   or successful failures with slight curve progression not requiring a change in treatment  5 of 30 or 17    none of the various parameters analyzed were found to be useful indicators of successful treatment using the scolitron device  electrical stimulation was found to be ineffective in preventing curve progression for idiopathic scoliosis  
class5	influence of bone mineral density on the fixation of thoracolumbar implants  a comparative study of transpedicular screws  laminar hooks  and spinous process wires  posteriorly directed load to failure testing of four different types of spinal implants was performed in individual t5 to s1 vertebra harvested from seven fresh frozen human cadaveric spines  the implants tested were  1  drummond spinous process wires  2  harrington laminar hooks  3  cotrel dubousset transpedicular screws  and 4  steffee vsp transpedicular screws  the ultimate failure of each implant was compared with the bone mineral density of each vertebra to determine which implants  if any  were particularly advantageous in osteoporotic vertebrae  before biomechanical testing  the spines were analyzed in vitro by dual photon absorptiometry to determine the bone mineral densities  gm cm2  of each vertebra  the mean tensile loads to failure for each of the implants tested were as follows  cotrel dubousset transpedicular screws  345 newtons  spinous process wire button  382 newtons  steffee transpedicular screws  430 newtons  and laminar hooks  646 newtons  the difference between the loads to failure for laminar hooks and the other implants was significant  p less than 0 05  using one way analysis of variance  the overall correlation coefficient for bone mineral density with ultimate load to failure was 0 30  p less than 0 001   the correlation coefficients were 0 47  p less than 0 001  for spinous process wires alone  0 096  not significant  for laminar hooks alone  0 37  p less than 0 001  for cotrel dubousset pedicle screws  and 0 48  p less than 0 001  for steffee pedicle screws  of the four different implants tested  laminar hooks were most resistant to failure from posteriorly directed forces  
class5	the use of fibrin sealant to reduce blood loss during cotrel dubousset instrumentation for idiopathic scoliosis  the increased complexity of cotrel dubousset instrumentation has  as an unexpected side effect  a potential increase in blood loss  a prospective randomized study was undertaken to test the hypothesis that application of a fibrin sealant to exposed cancellous bone can significantly reduce blood loss during cotrel dubousset instrumentation for idiopathic scoliosis  a significant difference was demonstrated in total body loss  loss per level fused  and loss per kilogram of body weight when comparing the sealant group with random controls  a significant difference was demonstrated in loss per level fused when comparing the sealant control with a historical control group  thirty three patients were randomly assigned to the fibrin sealant or nonsealant groups  another 10 patients operated on before planning the study were included as historical controls  the sealant was used to control bleeding at the bone graft donor site and in the spine after decortication  all patients underwent cotrel dubousset instrumentation for idiopathic scoliosis  there were no significant differences between groups with respect to degree of curvature  number of levels fused  age or weight of patient  or operating time  total blood loss in the sealant group averaged 672 ml compared with 894 ml in the sealant control group  no patient in the sealant group required homologous blood  given the increasing awareness of the complications of blood transfusion  the authors conclude that fibrin sealant is a useful adjunct to spinal surgical technique  
class5	fusion levels and hook patterns in thoracic scoliosis with cotrel dubousset instrumentation  this study reports the results of treatment of adolescents with king types 2  3  and 4 idiopathic curves using cotrel dubousset instrumentation  imbalance was seen in types 2 and 4 curves when distraction direction hook patterns crossing the thoracolumbar junction were employed  imbalance was not seen when a modified hook pattern employing compressing forces across the thoracolumbar junction was employed  no imbalance was observed in type 3 curves using the basic right thoracic curve hook pattern  in type 4 curves  a second modified hook pattern is required to obtain improved correction and balance  the mechanism of production of imbalance is explained by a three dimensional analysis of the deformity and of the forces generated by the cotrel dubousset system  
class5	sagittal plane analysis in idiopathic scoliosis patients treated with cotrel dubousset instrumentation  one hundred sixty patients with idiopathic scoliosis underwent preoperative and postoperative sagittal plane analysis of the thoracic spine  thoracolumbar junction  and lumbar spine  the data suggest that mild to moderate improvements in thoracic hypokyphosis are possible  when crossing the thoracolumbar junction  reversal of rod bend and reversal of hooks on the derotation rod appears to provide the most physiologic sagittal contour  cotrel dubousset instrumentation to the mid and distal lumbar spine can preserve and  at times  enhance lumbar lordosis  
class5	decompensation after cotrel dubousset instrumentation of idiopathic scoliosis  spinal decompensation after corrective surgery for scoliosis appears to be a significant problem after cotrel dubousset instrumentation  cdi   cdi produces torsional changes in the instrumented and uninstrumented spine that could result in spinal imbalance  preoperative and postoperative three dimensional analysis including computed tomography  ct  scans to measure vertebral rotation and segmental rotation were performed to evaluate the importance of torsional changes  moe king type ii deformities had a substantially greater risk of imbalance  deformities instrumented over fewer spinal segments were less likely to decompensate  specifically  instrumentation excluding the mobile transition segment  determined by maximum segmental rotation and segmental cobb angle  was likely to decompensate  derotation and deformity correction excessive in relation to preoperative side bending flexibility and segmental rotation frequently resulted in imbalance  spinal imbalance after cdi can be reduced by avoiding overcorrection and inclusion of mobile transition segments  
class5	immediate complications of cotrel dubousset instrumentation to the sacro pelvis  a clinical and biomechanical study  the authors reviewed the early complications in all patients fused to the sacro pelvis using cotrel dubousset instrumentation at the texas scottish rite hospital  sixteen patients were studied with an average follow up of 13 months  three methods of sacro pelvis fixation were evaluated  iliosacral screws  sacral screws  and a technique whereby the caudle ends of the cotrel dubousset rods were fashioned and inserted into the posterior iliac crest using the galveston technique  seven of the 16 sets of sacral screws  44   failed during and after surgery  two of the 7 sets of iliosacral screws failed postoperatively  28    no failures occurred in the 8 sets of cotrel dubousset rods placed with the galveston technique  seven of the nine medical complications observed  77   occurred in the sacral screw group  using calf spines  a biomechanical evaluation of each system was undertaken to determine strength of fixation  each system was failed in flexion 3 times  the sacral screws were the weakest  pulling directly out of the sacrum at 40 n m  cotrel dubousset rods inserted with the galveston technique were the strongest  experiencing rod deformities before flexion failure at 70 n m  iliosacral screws were of intermediate strength failing by rotation on the axis of the screws or pulling directly out of the ilium at 55 n m  the authors conclude that using cotrel dubousset rods inserted with the galveston techniques was the strongest and safest method of sacro pelvis fixation of the three tested  
class5	surgical treatment of scoliosis in a spinal muscular atrophy population  seventy eight patients were diagnosed with spinal muscular atrophy between 1969 and 1988  scoliosis developed in 34 of these patients  an incidence of 60   thirty one patients could be retrospectively reviewed by chart review or interview  the average follow up was 11 5 years  onset of scoliosis averaged 8 8 years  twenty two patients were treated nonsurgically and nine surgically  patients had improved sitting balance and endurance after surgery  complications of surgery included loss of correction in one patient  one pseudarthrosis  and one patient who required prolonged ventilatory support  the prolonged survival of patients with spinal muscular atrophy justifies aggressive orthopaedic management of scoliosis to prevent progression of deformity and improve sitting comfort  
class5	combined anterior and posterior fusion for spinal deformity in myelomeningocele  since 1973  50 of 54 children have been treated by the author with a combined anterior and posterior fusion  twenty males and 34 females  ranging in age from 1 to 16 years  have been followed for a mean period of 5 5 years  sixteen patients with a kyphosis averaging 113 degrees  range  77 to 170 degrees  had correction of deformity to a mean of 35 degrees  thirty seven patients with a scoliosis averaging 73 degrees  range  20 to 135 degrees  had correction to an average of 34 degrees  range  0 to 75 degrees   there were 4 cases of deep wound infection successfully treated with drainage and antibiotics and only one case required implant removal after fusion maturation  a pseudarthrosis was noted by radiograph in 6 patients  3 of whom had isolated asymptomatic lumbosacral pseudarthroses  three patients had pseudarthrosis at the thoracolumbar junction  these required repair and were successfully treated by supplemental posterior fusion resulting in an overall pseudarthrosis rate of 5 7   anterior fusion of the dysraphic spine allows greater correction of both spinal deformity and pelvic obliquity in addition to contributing significant strength to the fusion mass  segmental spinal instrumentation with sublaminar and pedicular wiring to custom contoured luque rods provides excellent correction and immediate postoperative stability  
class5	delayed anterior decompression in patients with spinal cord and cauda equina injuries of the thoracolumbar spine  forty nine patients with complete and incomplete injuries of the spinal cord or cauda equina who had undergone anterior decompression at a minimum of 3 months after injury were examined  follow up was from 12 months to 19 years  postoperative neurologic improvement occurred in 46 5  of patients with incomplete injuries  if the surgery was performed less than 2 years after injury  neurologic improvement occurred in 68  with an improvement in frankel grade of 32   bladder function improved in 27  of patients and if operated on less than 2 years after injury improvement occurred in 43   conus medullaris decompression resulted in a 50  improvement  there was an 83  improvement in the pattern of pain after decompression  of 23 patients with preoperative spasticity  10 improved but 6 were worse after surgery  
class5	factors affecting fusion rate in adult spondylolisthesis  the authors examined factors affecting fusion rate in the surgical treatment of 89 consecutive adult patients with spondylolisthesis  two factors significantly improved fusion rate  combined anterior and posterior fusion and rigid postoperative immobilization in the cast  in 65 patients with isthmic spondylolisthesis  the fusion rate was raised from 70  when posterior fusion alone was used to 88  when combined anterior and posterior fusion was used  in 20 patients with degenerative spondylolisthesis  frequent use of combined anterior and posterior fusion contributed to a high overall fusion rate of 95   among patients with isthmic spondylolisthesis  postoperative cast immobilization resulted in a higher fusion rate of 90  compared with a fusion rate of 63  obtained after brace immobilization  
class5	normal dystrophin in mcleod myopathy  dystrophin and its gene were studied in a patient with mcleod syndrome  this x linked recessive myopathy has been localized to xp21  as has the duchenne muscular dystrophy gene locus  which codes for dystrophin  histopathological study of the patient s muscle showed mild subclinical myopathy  immunological studies of dystrophin in two separate biopsy specimens and analysis of dystrophin gene dna from a blood sample did not detect an abnormality  this suggests that the duchenne muscular dystrophy gene  albeit close to the mcleod locus  is not involved in mcleod myopathy  
class5	clinical and pathologic studies of twenty six patients with penetrating foreign body injury to the joints  bursae  and tendon sheaths  foreign body synovitis has been neglected in the rheumatology literature  we describe 26 patients in whom arthritis  bursitis  or tenosynovitis appeared within 1 day to 7 years after an initial injury by a penetrating foreign body  twenty two patients presented with acute synovitis  which was followed by chronic or recurrent inflammation mimicking septic arthritis  osteomyelitis  monarticular juvenile rheumatoid arthritis  bone tumor  or apatite deposition disease  foreign bodies were not seen in 5 inflammatory synovial fluids studied  but were seen in the synovium or periarticular tissues of 17 patients  excisional biopsy was required in most patients for precise diagnosis and treatment  
class5	magnetic resonance imaging of sacroiliac joint inflammation  a consecutive series of 27 patients with symptoms compatible with sacroiliitis underwent magnetic resonance imaging  mri  of the sacroiliac joints  the diagnostic sensitivity of mri was similar to that of computed tomography or conventional radiography  however  mri seems to have the potential of providing unique information about the disease process in sacroiliitis by demonstrating abnormalities in subchondral bone and periarticular bone marrow  the results of this study suggest that early inflammatory changes in sacroiliitis occur in the subchondral structures of the sacroiliac joints  
class5	yersinia enterocolitica in the synovial membrane of patients with yersinia induced arthritis  using a monospecific rabbit antibody against yersinia enterocolitica outer membrane protein 1  we examined synovial biopsy specimens from 7 patients with yersinia induced arthritis  yersinia were demonstrated in the synovial membrane by indirect immunofluorescence in 4 patients with yersinia induced arthritis  but not in 6 control patients with salmonella induced arthritis or with rheumatoid arthritis  these findings suggest the persistence of yersinia in the joints of patients with yersinia induced arthritis  
class5	chondrons from articular cartilage  iii  morphologic changes in the cellular microenvironment of chondrons isolated from osteoarthritic cartilage  chondrons were isolated from human and canine osteoarthritic cartilage using low speed homogenization techniques  changes in chondron morphology were evaluated using differential interference contrast microscopy  phase contrast microscopy  and histochemical and ultrastructural methods  chondrocyte viability was assessed using fluorescein diacetate staining  and chondron metabolism was investigated using autoradiography  the results suggest that initial changes in the collagen and proteoglycan distribution within the chondron are followed by chondrocyte proliferation to form clusters  these techniques offer the potential to study cell matrix interactions in degenerative osteoarthritis  
class5	progression of osteoarthritis of the hand and metacarpal bone loss  a twenty year followup of incident cases  we examined the prospective relationship between metacarpal bone mass and osteoarthritis  oa  of the hand  using incidence data from the historical cohort in the tecumseh community health study  tecumseh  mi   women were examined for radiographic evidence of oa and for bone mass twice  20 23 years apart  1962 1965 and 1985  683 subjects with an age range of 55 74 in 1985   two measures of oa were evaluated  the highest score assigned to any of the 32 wrist hand joints  and the sum of scores for all wrist hand joints  after adjustment for age  women who were classified as having oa  by either measure of oa  in 1985 were more likely to have more cortical area at baseline  which indicates greater bone mass  women who developed oa in the 23 year period were more likely to experience a significantly greater widening of the medullary cavity over time  an indicator of increased bone resorption  women with increasing levels of oa involvement also had an increased likelihood of greater cortical area loss  we conclude that women who later developed oa were more likely to have higher baseline bone mass than women who did not develop oa  but these women also had a greater likelihood of bone loss over time  
class5	suppression of type ii collagen induced arthritis by monoclonal antibodies  some mouse monoclonal antibodies raised against chicken type ii collagen suppressed or delayed the onset of chicken type ii collagen induced arthritis in dba 1 mice  this was correlated with the suppression of anti mouse type ii collagen antibody responses following immunization with chicken type ii collagen  the epitopes recognized by the suppressive antibodies were found to be present on cyanogen bromide  cb  digested collagen peptides cb 11 and cb 12  this was also confirmed by the finding that administration of the cb 11 or cb 12 peptide suppressed the induction of arthritis  
class5	double blind  placebo controlled study of three month treatment with lymecycline in reactive arthritis  with special reference to chlamydia arthritis  we conducted a double blind  placebo controlled  randomized study of 3 month treatment with lymecycline  a form of tetracycline  in reactive arthritis  rea   lymecycline therapy significantly decreased the duration of the illness in patients with chlamydia trachomatis triggered rea  but not in other rea patients  in 2 rea patients  c trachomatis was found in the throat  an uncommon locale for this organism  our results suggest that it is important to verify the triggering microbe and that it is beneficial to treat chlamydia arthritis patients with a prolonged course of tetracycline  
class5	induction of arthritis in rats by aqueous suspensions of mycobacteria without the use of oil  we report for the first time the induction of arthritis by an aqueous  rather than an oil  suspension of killed tubercle bacilli  this was accomplished in the highly susceptible dark agouti strain of rats  by intraperitoneal injection during the healing phase of chemically induced peritonitis  the same procedure  injection after the induction of peritonitis  augmented the incidence of arthritis produced by bovine type ii collagen and freund s complete adjuvant  enhanced delivery of antigen from the peritoneal cavity to regional lymph nodes in the postinflammatory state was responsible for this increase in the induction of arthritis  
class5	septic arthritis of the c1 c2 lateral facet joint and torticollis  pseudo grisel s syndrome  we present the case of a 76 year old man who experienced the sudden development of fever  rightsided neck pain and stiffness  and torticollis  a soft tissue mass was noted on the right side of his neck  but his head was tilted to the left  computed tomography scans  with reformatted sagittal and coronal images  of the patient s cervical spine revealed destructive changes of the right lateral masses of c1 and c2 and the clivus  and a well delineated peridontoid soft tissue mass  confirmed by magnetic resonance imaging   after the second episode of right sided hemiparesis  he underwent transoral surgical exploration  with anterior decompression and odontoidectomy  histologic examination of the surgical material revealed granulation tissue  fibrosis  and chronic inflammation  consistent with abscess formation with invasion and compression of the spinal cord and bone  this case suggests that nonreducible rotational head tilt to the side opposite the side of lateral mass collapse should raise the suspicion of a possible infection  
class5	application of the polymerase chain reaction and immunofluorescence techniques to the detection of bacteria in yersinia triggered reactive arthritis  leukocytes in synovial fluid and peripheral blood samples from patients with yersinia triggered reactive arthritis were analyzed after dna amplification using the polymerase chain reaction  the primers applied were specific for the virulence plasmid coded 1cre genes of yersinia enterocolitica o 3 and yersinia pseudotuberculosis iii  no yersinia dna was observed within the synovial fluid cells or peripheral blood cells by polymerase chain reaction techniques  however  yersinia antigens were detected in the synovial fluid cells by immunofluorescence techniques  these results suggest that only parts of the causative agents  not the entire microbe  can enter the joint and initiate the inflammation that leads to a reactive arthritis  
class5	complete heart block and severe aortic incompetence in relapsing polychondritis  clinicopathologic findings  we describe a patient with relapsing polychondritis who developed fatal cardiac involvement comprising complete heart block  acute aortic incompetence  and cardiovascular collapse  pathologic studies showed fibrosis of the cardiac conducting system and necrotizing inflammation of the aortic valve  features not previously described in relapsing polychondritis  as well as evidence of coronary artery vasculitis  
class5	tired  weak  or in need of rest  fatigue among general practice attenders objectives  to determine the prevalence and associations of symptoms of fatigue  design  questionnaire survey  setting  london general practice  participants  611 general practice attenders  main outcome measures  scores on a fatigue questionnaire and reasons given for fatigue  results  10 2  of men  17 167  and 10 6  of women  47 444  had substantial fatigue for one month or more  age  occupation  and marital status exerted minor effects  subjects attributed fatigue equally to physical and non physical causes  physical ill health  including viral infection  was associated with more severe fatigue  women rather than men blamed family responsibilities for their fatigue  the profile of persistent fatigue did not differ from that of short duration  only one person met criteria for the chronic fatigue syndrome  conclusions  fatigue is a common complaint among general practice attenders and can be severe  patients may attribute this to physical  psychological  and social stress  
class5	effects of radiation therapy on skeletal growth in childhood  ionizing radiation was used to treat childhood cancer long before the advent of chemotherapy  and it took little time for physicians to appreciate the deleterious effects it had on skeletal growth  the cause of this complication results predominantly from alteration of chondroblastic activity  this may stem directly from irradiation at the epiphyseal plate or indirectly from irradiation of glands that secrete growth mediating hormones  the complication can go far beyond the obvious physical afflictions and extend into the psychologic domain  rendering deeper  more permanent scars  presently  many of these effects are predictable  reducible  and treatable without compromising the cure that so often depends on the use of irradiation  because of the complexities of childhood cancer therapy  strategies aimed at diminishing these effects are challenging  it is imperative that these effects be understood so that they can be reduced in current patients and prevented in future patients  
class5	osteolytic monostotic paget s disease of the fifth lumbar vertebra  a case report  osteolytic monostotic paget s disease or osteitis deformans of the fifth lumbar vertebra occurred in a 55 year old woman  an isolated lytic process involving the entire vertebral body and posterior elements and an open biopsy showed extensive remodeling with cement lines  myelofibrosis  and osteoclastic resorption typical of paget s disease  
class5	scapular allografts  a report of two cases  some malignant tumors of the scapula can be adequately treated by limb sparing  partial  or total scapulectomy  however  resection of the glenoid portion of the scapula and total scapulectomy result in an unsightly shoulder  in an attempt to minimize the functional impairment and restore stability and cosmesis  scapular glenoid allografts offer a reasonably good biologic replacement  this report describes the cases of a 45 year old woman and a 32 year old man in whom massive osteoarticular allografts were used  in one patient  good stability  cosmesis  and function were restored after resection of the glenoid portion  in the other patient  shoulder stability  cosmesis  and limited function were restored after total scapulectomy  no reports of scapular allografts seem to have been previously published in the literature  
class5	nonhemophilic hemosiderotic synovitis of the shoulder  a case report  in a nonhemophilic 72 year old man  a persistent degenerative hemarthrosis of the shoulder joint was associated with a complete tear of the rotator cuff  extensive  rusty synovial pigmentation and hyperplasia  hemosiderotic synovitis  mimicking pigmented villonodular synovitis  pvs  were noted at surgery  spontaneous hemarthrosis of the shoulder includes rapid onset of severe pain  limitation of movement  subsequent appearance of a bruise on the affected shoulder and arm  and radiological evidence of joint degeneration  hemosiderotic synovitis results from chronic intraarticular bleeding  with the breakdown of trapped hemoglobin  iron containing hemosiderin is stored in synovial tissue producing rusty discoloration and proliferative reaction  the classic cytoarchitecture of pvs has additional subsynovial nodular proliferation of mononuclear cells  hemarthrosis may produce significant structural alteration of joints  its prompt recognition and the awareness of underlying causes should lead to earlier diagnosis  appropriate therapy  less joint destruction  and better outcomes  
class5	tuberculous tenosynovitis of the wrist  two case reports  tuberculosis was first described in 1756 by acrel in a case report  subsequent reports of musculoskeletal tuberculosis documented the uncommon occurrence of hand and wrist involvement  the two cases presented here demonstrate the difficulty in eradicating the organism even with modern regimens of chemotherapy  intraoperative gram s stain and frozen sections were useful to rule out other etiologies  firm diagnosis must be established by tissue culture  the first case appeared cured after thorough initial debridement and had no recurrence for 36 years  while recurrences are common in patients treated with debridement alone  most appear within one year after the index procedure  the amount of time that elapsed in this case is unusual and serves as a sobering reminder that tuberculosis may recur at a time distant from the initial procedure  the second patient had tuberculosis diagnosed elsewhere and was treated twice with antituberculous chemotherapy  although the first course of therapy for six months may have been inadequate  the second course with multiple drugs for 18 months would certainly be considered adequate  yet he had a recurrence in his wrist eight months after completing treatment  these two cases illustrate the fastidious nature of the mycobacterium tuberculosis organism and the need for a combined treatment protocol of meticulous surgical debridement and combined chemotherapy  
class5	extensor tendon rupture after osteoarthrosis of the wrist associated with nonrheumatoid positive ulnar variance  rupture of the extensor tendon after osteoarthrosis of the wrist associated with nonrheumatoid  positive ulnar variance is uncommon  eight cases were seen in the last five years  they included five men and three women  whose ages ranged from 54 to 82 years  average  70 years   in all the cases  roentgenograms revealed osteoarthrotic changes in the wrist and dorsal subluxation or dislocation of the ulnar heads  seven cases had operations  friction with the dorsally subluxated or dislocated ulnar head and the osteophytes surrounding it caused these tendons to rupture  it was impossible to use end to end sutures  so tendon transfers or tendon grafts were performed  the patients were evaluated one to four years after surgery  three patients complained of some disability in their daily lives  notably  limited flexion of their fingers  it is important that during surgery the reconstructed tendons should not be strained excessively  
class5	growth disturbance in legg calve perthes disease and the consequences of surgical treatment  seventy two patients with legg calve perthes disease were studied to assess the interference with proximal femoral growth as a result of the disease itself and of surgical treatment  twenty five patients were treated nonoperatively  20 were treated by femoral varus derotation osteotomy  and 27 by innominate osteotomy  all patients were studied clinically for evidence of abductor weakness and leg length discrepancy  they were also studied roentgenographically for evidence of femoral head deformity and trochanteric overgrowth  the overall results showed a 6  incidence of leg length discrepancy greater than 2 cm after both operative and nonoperative treatment  the articulo trochanteric distance  atd  was less than  5 mm in 23  of patients  of which 43  had a positive trendelenburg sign  a significantly lower mean atd was found in patients treated by femoral varus osteotomy  which should be avoided in patients over eight years of age  the study also demonstrated a strong association between coxa magna and growth disturbance of the proximal femoral physis manifesting itself as either a leg length discrepancy or as a low atd  the significant effects of growth disturbance after treatment must be considered  as well as the sphericity of the healed femoral head  in the final assessment in legg calve perthes disease  
class5	bilateral femoral retroversion associated with acetabular dysplasia  a case report  retroversion of the proximal femur is associated with a number of acquired conditions but is unusual in a congenital form  it is even more unusual to be associated with acetabular dysplasia  a 38 year old woman with bilateral hip pain had roentgenographic evidence of acetabular dysplasia with valgus neck shaft angles  physical findings were consistent with femoral retroversion  and computed tomography demonstrated 28 degrees of retroversion on both sides  symptomatic relief was obtained with bilateral varus internal rotation osteotomies of the proximal femur  to date  a case of retroverted femora associated with acetabular dysplasia seems not to have been reported in the literature  
class5	total hip arthroplasty in ankylosing spondylitis  total hip arthroplasty was performed on 29 hips in 19 patients diagnosed with ankylosing spondylitis over a 13 year period  the results were analyzed retrospectively with an average follow up period of more than four years  complete pain relief was achieved in 97   and significant gains were made in ambulatory capacity  the limited gains in total range of motion  average improvement 75 degrees  were felt to be primarily due to the high incidence of brooker class iii and iv myositis ossificans  23   and long standing soft tissue contractures  
class5	the appearance of the piriformis muscle syndrome in computed tomography and magnetic resonance imaging  a case report and review of the literature  the piriformis syndrome  ps  is a controversial cause of hip pain because of the lack of objective findings to support the diagnosis  computed tomography  ct  and magnetic resonance  mr  imaging revealed ps in a 27 year old woman  this case may be one of the first reports in the literature on a piriformis muscle enlargement documented by ct and mr imaging  
class5	long term results of posterior release surgery for severe flexion contracture of the knee in patients with rheumatoid arthritis  twelve knees in nine rheumatoid patients with severe flexion contractures were evaluated clinically and roentgenographically for an average of 17 2 years  range  six to 25 years  after posterior release surgery  preoperatively  the average extension in the 12 knees was 42 5 degrees  and postoperatively it was 10 8 degrees  even though patients were able to walk postoperatively  the majority had knee pain when they extended their knees soon after surgery  seven knees required further surgery after correction of the flexion deformity  the average time before reconstructive surgery after posterior release was 11 1 months  in the treatment of severe flexion deformities of the knee in patients with rheumatoid arthritis  posterior release surgery was effective only in correcting the deformity  posterior subluxation of the tibia  knee pain  and instability occurred soon after surgery  therefore  patients may require additional reconstructive surgery soon after the posterior release  
class5	autograft versus allograft for benign lesions in children  benign bone lesions in children are often so large in size that there is not an adequate amount of bone available for an autograft to fill the resultant cavity after surgical curettage  this study compared autografts and allografts with respect to the time required and the success of graft incorporation  fifty four patients with 61 lesions were studied  lesions were classified as small volume  less than 60 cc  or large volume  more than 60 cc  and were separated into four groups  small volume autograft  large volume autograft  small volume allograft  and large volume allograft  allografts appeared comparable to autografts when small volume lesions were treated  the healing time was slightly longer for allografts with an average period of 21 months versus 27 months for autografts  autografts were superior to allografts in rate and completeness of healing for solitary large lesions  this increased efficacy presumes a somewhat older child in which an adequate amount of bone is available for an autograft  a young child with multicentric or polyostotic lesions can still achieve successful incorporation with allografts  in this study  38  healed completely and 29  healed partially  allografts have a distinct place in the treatment of benign bone lesions in children  
class5	simple bone cysts  the effects of methylprednisolone on synovial cells in culture  ten years ago  a protocol using depo medrol injections was developed for the treatment of unicameral bone cysts  this concept  designed by tumor surgeons and based on theory  has been cautiously approached  however  reproducible results have gradually increased clinical acceptance  understanding the healing process has been restricted because of the lack of an experimental model  in an attempt to elucidate this mechanism of healing  a cell culture model was used to investigate the effects of methylprednisolone on synovial cells  initially  three doses of the drug were tested and maximal changes were noted with the concentration of 40 mg ml  changes were then quantified by morphology  dna assay  cell protein analysis  and electron microscopy  results suggest that methylprednisolone may have a direct effect on the cellular component of unicameral bone cysts  
class5	acute eosinophilic pulmonary disease associated with the ingestion of l tryptophan containing products  a series of four patients with pulmonary infiltrates  pleural effusions  hypoxemia  peripheral eosinophilia  and symptoms of dyspnea  fatigue  and weakness is reported  lung tissue obtained in three patients revealed interstitial pneumonitis  small to medium vessel mixed cell vasculitis  and alveolar exudate of histiocytes and eosinophils  all patients reported ingestion of l tryptophan containing products at a time when an association between l tryptophan and the eosinophilia myalgia syndrome was established  this clinical pattern of pulmonary involvement may be part of the continuum of the eosinophilia myalgia syndrome  the pathophysiology of this syndrome and the relationship with the ingestion of l tryptophan containing products have not yet been identified  
class5	bowel dysfunction in fibromyalgia syndrome  fibromyalgia and irritable bowel syndrome frequently coexist  in this study  we utilized a previously validated self administered questionnaire to assess the prevalence of symptoms of bowel dysfunction and irritable bowel syndrome in 123 patients with fibromyalgia as compared to 54 patients with degenerative joint disease  djd  and 46 normal controls  ninety  73   of the fibromyalgia patients reported altered bowel function as compared to 20  37   djd patients and none of the normal controls  p less than 0 001   ninety nine patients  81   reported normal alternating with irregular bowel pattern  and 77  63   had alternating diarrhea and constipation  in contrast  only 24  44   of djd patients and six  13   of controls had regular alternating with irregular bowel pattern and only 12  22   of the djd patients and none of the healthy controls had alternating constipation and diarrhea  p less than 0 01   other bowel dysfunction complaints noted in the fibromyalgia group were abdominal gas  59    nausea  21    diarrhea  9    and constipation  12    seventy nine  64   fibromyalgia patients reported frequent abdominal pain that was stress related 47  of the time  laxative use was frequent in the fibromyalgia group  19   and absent in the other two groups  fifty percent of fibromyalgia patients  compared to 28  of djd patients  felt that their bowel complaints were worse during exacerbations of their joint disease  p less than 0 05   in conclusion  patients with fibromyalgia have a high prevalence of gastrointestinal complaints that should be carefully assessed  if the diagnosis of ibs is confirmed  appropriate treatment may improve patients  symptoms  although this approach requires further study  
class5	metabolic and health complications of obesity  overnutrition manifested by obesity has emerged as a major health problem in affluent countries  in spite of increased interest in fitness  obesity is on the increase in the united states  this is particularly so among children and adolescents  although obesity is associated with many risk factors for diseases  the mechanisms whereby it enhances disease risk are not fully understood  such an understanding is needed to develop strategies for management of these conditions  in this report we suggest that overnutrition produces clinical diseases only in individuals who already possess a metabolic weakness or  defect  in a given system  in the absence of such underlying defects  overnutrition  or obesity  is well tolerated  one of the most common consequences of obesity is dyslipidemia  that is  elevations of very low density lipoprotein  vldl  triglycerides and low density lipoprotein  ldl  cholesterol and low concentrations of high density lipoprotein  hdl  cholesterol  the major effect of overnutrition on lipoprotein metabolism is to stimulate the production of vldl  for patients who have an underlying defect in lypolysis of vldl triglycerides  hypertriglyceridemia will develop in the obese state  for those who have defective clearance of ldl  obesity will accentuate hypercholesterolemia  both of these effects can be explained by overproduction of vldl  due to obesity  combined with a genetic defect in clearance of vldl or ldl  the mechanism whereby obesity causes a lowering of hdl cholesterol is uncertain  although it could enhance removal of hdl by an excess of adipose tissue  another disease associated with obesity is cholesterol gallstones  the presence of obesity more than doubles the risk for gallstones  two underlying factors increase the danger for gallstones  a deficiency of hepatic secretion of bile acids and a tendency for formation of cholesterol crystals in bile  overnutrition promotes the synthesis of whole body cholesterol  and the only route for excretion of this excess cholesterol is through the biliary tree  abstract truncated at 400 words   
class5	apolipoprotein  apo  e inhibits the capacity of monosodium urate crystals to stimulate neutrophils  characterization of intraarticular apo e and demonstration of apo e binding to urate crystals in vivo  factors that modulate the ability of monosodium urate crystals to stimulate leukocytes could regulate gouty inflammation  lipoproteins that bear apo b 100 and apo e bind to urate crystals and suppress crystal neutrophil interaction  in this study  we observed that urate crystals  coated with apo e of monocyte origin  had a diminished ability to stimulate neutrophils  apo e was also detected on the surface of urate crystals recovered from gout patients  thus  we analyzed apo e in noninflammatory synovial fluid  and found it to be associated with particles of heterogeneous size and of predominantly alpha and pre beta electrophoretic mobility  local articular synthesis of at least a portion of synovial fluid apo e was suggested because  a  the synovial fluid plasma concentration ratio of apo e was significantly higher than that for both apo b and apo a i  which are not widely synthesized by extrahepatic tissues   b  cultured rheumatoid synovial cells in first passage secreted apo e   c  a portion of synovial fluid apo e was heavily sialylated  we conclude that synovial fluids contain apo e that appears partly of local origin  apo e binds to urate crystals and could modulate gouty inflammation  
class5	cartilage expression of a type ii collagen mutation in an inherited form of osteoarthritis associated with a mild chondrodysplasia  in a family who expressed severe dominantly inherited osteoarthritis  the underlying mutation was traced by genomic sequencing to a single base change which predicts an amino acid substitution of cysteine for arginine at residue 519 of the triple helical domain of the type ii collagen molecule  ala kokko  l   c  t  baldwin  r  w  moskowitz  and d  j  prockop  1990  proc  natl  acad  sci  usa  87 6565 6568   in the present study we examined whether this predicted protein phenotype was evident in articular cartilage obtained from an affected family member who underwent hip surgery  the cartilage collagen was solubilized by cnbr digestion  cysteine residues were labeled by reduction and alkylation with 14c iodoacetate  collagen cnbr peptides were fractionated by ion exchange and reverse phase column chromatography  one peptide from the alpha 1 ii  chain  alpha 1 ii  cb8  was found to be radiolabeled  tryptic peptides were prepared from it and identified by microsequence analysis  the results show that approximately one quarter of the alpha 1 ii  chains present in the polymeric extracellular collagen of the patient s cartilage contained the arg519 to cys substitution  the protein exhibited other abnormal properties including disulfide bonded alpha 1 ii  dimers and signs of posttranslational overmodification  the premature cartilage failure and osteoarthritis are presumably a result of the abnormal type ii collagen being expressed in the cartilage matrix  
class5	the neuromuscular pathology of the eosinophilia myalgia syndrome  the eosinophilia myalgia syndrome  ems  is a recently reorganized disorder in patients ingesting pharmacologic doses of l tryptophan  we studied the lesions of skeletal muscle  peripheral nerve and skin in 12 cases of ems  perimyositis was severe in four  moderate in two  mild in three and absent in three cases  the lesions contained many eosinophils  t helper cells  mast cells and activated macrophages  type 2 myofiber atrophy was present in five cases and in one  this was the only pathologic finding  severe epineurial inflammation was seen in the three sural nerve biopsies  indirect evidence for peripheral neurologic involvement in three other cases consisted of inflammation surrounding intramuscular nerve twigs  two cases  and neurogenic atrophy  one case   phlebitis accompanied the connective tissue inflammation in five cases and endarteritis in one  fasciitis was present in three of four skin biopsies and dermal fibrosis in one  
class5	a preliminary report of arthroscopic findings following acute condylar trauma standard therapy in orthopedics dictates that joints with suspected hemarthrosis be considered for irrigation or exploration  especially when immobilization is part of the treatment plan  in this preliminary report  14 patients who had condylar subcondylar fractures underwent superior joint space arthroscopy as part of the evaluation and treatment of their fractures  in all but two patients  blood was found in the superior joint space  length of time from injury to time of examination correlated with the quantities of blood found  the severity and direction of the blow seemed to influence the findings in the joints  synovial ecchymosis was a consistent finding  the disc appeared to be grossly intact and within the glenoid fossa in all cases  even when the condyle was grossly displaced  these findings raise questions about the role of direct disc injury as a source of postoperative temporomandibular joint  tmj  symptoms  as well as about the practice of immobilization of fractures immediately after trauma  further studies will be necessary to compare the treatment results in patients who have had arthroscopy versus those who have not  
class5	a report of fluorosis in the united states secondary to drinking well water  a 54 year old female resident of wellston  okla  was found to have osteosclerosis on a routine chest roentgenogram  subsequent investigation disclosed the cause of her osteosclerosis to be fluorosis secondary to the ingestion of well water containing 429 mumol l of fluoride  recommended levels  11 to 58 mumol l   water samples were also obtained from the 12 wells on properties adjacent to the index case  in three other wells  all at similar depths as the well of the index case  the fluoride concentration of the water was greater than 212 mumol l  urine samples from members of the four households who obtain their drinking water from these wells contained elevated urinary fluoride levels  thus  fluorosis may develop in certain areas of the united states as a result of the natural occurrence of fluoride in the groundwater  consequently  in known endemic areas  it would appear reasonable to measure the fluoride concentration of the well water at the time of drilling  
class5	in vivo muscle magnetic resonance spectroscopy in the clinical investigation of mitochondrial disease  we have investigated the sensitivity and specificity of a rapid phosphorus magnetic resonance spectroscopy  mrs  protocol for detecting metabolic abnormalities in vivo in skeletal muscle of patients with mitochondrial disease  we examined 17 patients with mitochondrial myopathies  sixteen had only mild or minimal myopathic signs and symptoms  phosphorus magnetic resonance spectra from the resting gastrocnemius muscles showed an abnormal intracellular energy state  marked by an increased intracellular inorganic phosphate concentration  in 14 17  in 3 17  this was associated with a decreased phosphocreatine concentration  we also studied 20 patients with other diseases of muscle  inflammatory myopathies  metabolic myopathies  muscular dystrophies  and myasthenia gravis  that can present with similar clinical features  spectra showed increased intracellular inorganic phosphate concentrations in 6 20  all of these muscle diseases were associated with evidence of muscle fiber necrosis  abnormalities in the muscle energy state in these cases may be due to secondary mitochondrial dysfunction  except for cases of polymyositis and dermatomyositis  these 6 other myopathies could be readily distinguished from the mitochondrial myopathies on the basis of the clinical examination and blood tests  we conclude that phosphorus mrs of resting muscle is practical in a clinical setting and has a useful sensitivity and specificity for mitochondrial myopathies when used in conjunction with standard noninvasive tests  
class5	centronuclear myopathy heterogeneity  distinction of clinical types by myosin isoform patterns  we studied muscles from 3 patients with centronuclear myopathy  cnm  by immunocytochemistry using myosin heavy chain  mhc  specific monoclonal antibodies to determine whether subtypes of cnm express prenatal mhc and to assess if there is an arrest in development of these muscles  muscle from a woman with childhood onset cnm did not express prenatal mhc  yet this prenatal mhc was strongly expressed in the muscle fibers of 2 brothers with x linked cnm  this finding represents the 1st immunocytochemical evidence of the expression of a prenatal myosin isoform in nonregenerating postnatal human muscle and suggests that the x linked form of cnm differs from the other types because of a true arrest in maturation of the muscle  
class5	the effect of spine fusion on respiratory function in duchenne muscular dystrophy  serial measures of respiratory function were made in 17 patients with duchenne muscular dystrophy who underwent segmental spine fusion and in 22 patients who did not  no significant differences were observed between the 2 groups  operated vs  nonoperated  in terms of declining respiratory function  nonetheless  all operated patients reported either improved sitting comfort  appearance  or both  thus  our results suggest that there are distinct benefits from segmental spine fusion  however  there was no salutary effect upon respiratory function either in the short term or after up to 5 years follow up  
class5	magnetic stimulation of the motor cortex in cervical spondylosis  we report a new technique of transcranial magnetic stimulation of the motor cortex to measure conduction within central motor pathways of 67 patients with cervical spondylosis or disk herniation  there were upper motor neuron signs in 34 patients  51   and x ray evidence of cervical cord compression in 44  66    muscle action potentials  maps  to cortical stimulation were abnormal in 84  of patients with  and 22  of those without  radiologic signs of cervical cord compression  median nerve somatosensory evoked potentials were altered in only 25  of patients  the frequency of map alterations correlated with upper motor neuron signs  in 5  11   of the 44 patients with x ray evidence of cervical cord compression  subclinical cord compression was disclosed by cortical stimulation  in 10 patients restudied 3 months after surgical decompression  normalization of central motor conduction time did not occur  indicating permanent damage to the cervical cord  
class5	clinical evaluation of the iti  f type  hollow cylinder implant  in 1976 the hollow cylinder implant was introduced  a number of articles have been published about the iti implant system  in this article  short term results of 102 iti f type implants in 40 patients are reported  the results showed this one stage implant to be at least comparable to other well known implant systems  
class5	massive osteolysis of the maxillofacial bones  report of two cases  two cases of massive osteolysis were encountered  one affecting the mandible and the other the maxilla and mandible  only 13 cases have been reported so far in the existing literature for massive osteolysis of the mandible  it is indeed a rare disease  our two cases were surgically treated and were clinically and histopathologically assessed  
class5	coronoid process elongation in rhesus monkeys  macaca mulatta  after experimentally induced mandibular hypomobility  a cephalometric and histologic study  the present study provided an experimental model that allowed a cephalometric and histologic analysis of craniofacial growth in monkeys with induced translatory impairment of the mandibular condyle  cauterization was performed anterior to the joint in nine experimental rhesus monkeys  while eight animals served as control subjects  the experimental procedure produced mandibular hypomobility in six animals  in three by means of temporomandibular joint ankylosis and in three by means of dense scar tissue formation anterior to the joint  in the remaining three experimental animals no restriction of mandibular mobility was created  mandibular hypomobility was found to induce elongation of the coronoid process and was also associated with bone deposition in the gonial region  in contrast  normal remodeling of the gonial region was found in the experimental animals with normal range of movements and in the control animals  
class5	african burkitt s lymphoma  case report and light and electron microscopic findings  an african burkitt s lymphoma occurred in a 9 year old american boy who had jaw tumors  proptosis  and abdominal masses  histologically  the tumor consisted of a monotonous overgrowth of undifferentiated lymphocytes with a  starry sky  appearance  the differential diagnosis of african versus american form and burkitt s lymphoma versus non burkitt s lymphoma is discussed  
class5	the role of an autoantigen  histidyl trna synthetase  in the induction and maintenance of autoimmunity  patients with systemic autoimmune diseases make specific autoantibodies that are directed against self structures  according to one view  these autoantibodies arise as a result of an immune response to foreign antigens such as infectious agents that share  by molecular mimicry  common structures with host proteins  an alternative view is that the target autoantigen itself initiates  selects  and sustains autoantibody synthesis  we show here that anti jo 1 autoantibodies directed against histidyl trna synthetase in the human autoimmune muscle disease polymyositis undergo  in addition to spectrotype broadening and class switching  the sine qua non of an immune response to the target antigen  affinity maturation to that antigen  we demonstrate further that these autoantibodies  unlike anti synthetase antibodies induced in mice immunized with heterologous antigen  bind only nonlinear epitopes on the native human synthetase that remain exposed when the enzyme is complexed to trna his   these data suggest that the native target autoantigen itself has played a direct role in selecting and sustaining the autoantibody response and sharply restrict the time and the way in which a molecular mimic might act to provoke autoantibodies  
class5	skeletal manifestations of ectopic or inappropriate endocrine and metabolic syndromes  a variety of tumors and nontumorous lesions were used to illustrate some of the biologic  clinical  and pathologic aspects of inappropriate or ectopic endocrine and metabolic syndromes that have musculoskeletal repercussions  it is clear  both from the discussion and case material  that many mechanisms of ectopic endocrine syndromes have yet to be clarified  elaborate techniques are available for hormonal estimations  but their routine use is prohibitively expensive and relatively unrewarding  cells of a given lesion may be functionally heterogeneous or may fail to elaborate active products in substantial amounts  different cells may produce similar peptides  while the same cells can produce more than one  despite these difficulties  recognition of ectopic endocrine syndromes remains crucial to diagnosis and patient management  and thus corroboration or correlation must often rest on a cruder basis  in fact  the clinical significance of basic laboratory data  e g   pth elevation  may vary  as pth may be immunoreactive but biologically inactive  as another example  hypercalcemia associated with myeloma may be variously related to coexistent hyperparathyroidism  renal disease  dehydration  or humoral osteolysis  therefore  roentgenographic evidence of bone destruction or skeletal stigmata of hyperparathyroidism imbues laboratory data with greater significance  paraneoplastic syndromes are of particular concern to the radiologist  as multiple systemic manifestations  occurring either synchronously or metachronously  may suggest the presence of an underlying or unifying lesion or even of a specific type of neoplasm  they may precede detection of neoplasms by months to years and can develop at any time during their course  paraneoplastic syndromes may  furthermore  parallel the course of a lesion and be used as indicators of remission or recurrence  conversely  those unassociated with overt symptoms possess endocrine markers that can reinforce sometimes silent skeletal stigmata  familiarity with representative secretory products influencing the musculoskeletal system per se may often clarify seemingly innocuous and sometimes asymptomatic skeletal findings  alert imagers may  therefore  detect  infer  or suspect particular syndromes when they present in a specific sequence or mosaic  conversely  when apprised of their existence  imagers should know where their related effects may be sought or anticipated  such relationships  sometimes serendipitously discovered  may be valuable assets in clinical diagnosis and patient management in both suspected and unsuspected cases  
class5	radiologic manifestations in the musculoskeletal system of miscellaneous endocrine disorders  the manifestations of endocrine derangements in the musculoskeletal system in infancy and childhood are disturbances in growth and maturation and in adulthood are disturbances in maintenance and metabolism  hypercortisolism during skeletal immaturity suppresses growth  in the adult  hypercortisolism leads to osteoporosis  osteonecrosis  and muscle wasting  deficiency of growth hormone during skeletal development results in short stature  an excess of growth hormone in a skeletally immature individual results in gigantism  an excess in a skeletally mature individual results in acromegaly  patients with gigantism have extreme height with normal body proportions  musculoskeletal manifestations of acromegaly include soft tissue thickening  vertebral body enlargement  characteristic hand and foot changes  and enthesal bony proliferation  hyperthyroidism causes catabolism of protein and loss of connective tissue  which manifest as muscle wasting  deficient levels of thyroid hormone cause defects in growth and development  severe growth retardation from congenital hypothyroidism is rare because neonatal screening recognizes the disorder and leads to early treatment  the skeletal manifestation of hypergonadism in children is precocious growth and early skeletal maturation  although the initial precocious growth spurt results in a tall child  early closure of the growth plates results in a short adult  hypogonadism in the prepubertal child results in delayed adolescence and delayed skeletal maturation  diabetes mellitus in childhood results in decreased growth  a phenomenon presumed to be secondary to nutritional abnormalities  generalized osteoporosis and short stature are common  in the adult  generalized osteoporosis may accompany insulin dependent diabetes mellitus if obesity is absent  calcification of interdigital arteries of the foot is common in diabetics and uncommon in other conditions  additional skeletal manifestations relate to complications of diabetes such as peripheral neuropathy and diabetic foot disease  
class5	inherited diseases of bone density in children  in this article the radiographic manifestations of various genetic diseases predominately affecting bone mineralization are considered  osteogenesis imperfecta and other diseases of diffuse osteopenia  hereditary rickets and rachiticlike conditions  and osteopetrosis and other diseases of increased bone density are emphasized  recognition of the radiographic manifestations allows accurate diagnosis  therapeutic intervention when possible  and determination of recurrence risk for genetic counseling  
class5	metabolic bone disease  morphometry  the history of the development of radiologic morphometric techniques is traced  emphasizing their pathophysiologic background and relevance to possible therapies  the techniques are described and longitudinal and comparative studies assessed  technical limitations of the various methods are presented  
class5	the pathology of metabolic bone disease  the skeletal manifestations of the diverse group of metabolic bone diseases are mediated through the altered function of osteoblasts and osteoclasts and abnormal rates of mineralization  appropriate understanding of their pathologic conditions requires familiarity with the normal anatomy and physiology of the skeleton  the accurate identification of metabolic bone disease frequently demands histologic confirmation and sophisticated analysis of undecalcified bone specimens labeled with tetracycline by histomorphometric techniques  these procedures allow the assessment of many morphologic features that characterize specific disease states  the most common types of metabolic bone diseases are acquired disorders  nonetheless  rare forms frequently are genetically based and cause intrinsic alterations in the bone cell populations  
class5	radiographic appearance of osteopenia  the radiographic appearance of bone is the result of two physiologic processes  the resorption of bone and the remodeling of bone in response to the stresses applied to it  the relative rates of these two processes will determine the structural and  therefore  the radiographic appearance of the affected bone  
class5	osteoporosis  current techniques and recent developments in quantitative bone densitometry  knowledge about the proper use and interpretation of bone densitometry studies and an understanding of appropriate medical interventions are not universal among physicians  nor are instrumentation and technical performance of bone density studies of uniformly high quality  indeed  this deficiency of medical and technical expertise is the principal deterrent to widespread implementation of our recommended clinical applications at this time  nonetheless  given the current impetus to disseminate information about osteoporosis  to make newer instrumentation more readily available  and to limit the cost of these techniques  we anticipate that our recommendations may soon become standard medical practice  
class5	osteoporosis  osteoporosis  a condition of decreased bone tissue that increases the likelihood of fracture  places a significant burden on our society in terms of health cost and morbidity  the most common type of osteoporosis is involutional  and two subtypes are recognized  type 1 and type 2  type 1  or postmenopausal  osteoporosis is most commonly seen in perimenopausal and postmenopausal women from ages 51 to 75  estrogen deficiency is the most dominant factor in the pathogenesis of this disorder  type 2  or aging related  osteoporosis is seen in elderly women and men aged 70 or more  bone loss in this group is related to aging  estrogen deficiency  negative calcium balance  and a variety of environmental and genetic factors  the best approach to the management of osteoporosis is to develop a lifelong strategy that maximizes peak bone mass and minimizes aging related and postmenopausal bone loss  estrogen is the only medication approved for the prevention of bone loss that is in general use  other strategies to prevent bone loss  and maximize peak bone mass  include adequate calcium intake  adequate exercise  and avoidance of excess alcohol  tobacco  and caffeine use  
class5	hyperparathyroidism  since the introduction of routine automated measurements of serum calcium levels in the 1970s  the detection of primary hyperparathyroidism has risen considerably  nevertheless  the severe bone changes described by von recklinghausen are still quite rare  the apparent rise in incidence is accounted for by the discovery of a large group of predominantly asymptomatic elderly patients who have mild primary hyperparathyroidism  because the diagnosis is most often confirmed through laboratory tests  radiologic studies are now most useful in assessing the severity of the disease  the presence of bone changes is an accepted indication for parathyroid surgery in primary hyperparathyroidism  for patients with asymptomatic disease in whom nonsurgical treatment may be considered  radiographic evaluation is one of several techniques that may be used to assess progression  high resolution radiographs of the hands are most valuable in this regard  accelerated bone mineral loss  as measured by quantitative techniques  will probably play a significant role in the future  radiographic follow up of patients with renal disease and secondary hyperparathyroidism is equally important  as increased bone or soft tissue changes may indicate a need for therapeutic change  radiographically identifiable changes of hyperparathyroidism consist mainly of various types of accelerated bone resorption  multifocal subperiosteal resorption is generally considered to be pathognomonic of hyperparathyroidism  subligamentous  subchondral  endosteal  and intracortical resorption are also important manifestations of accelerated bone turnover  the earliest bone changes are visible in the hands and should be searched for especially carefully in the phalanges and terminal tufts  only occasionally will changes be found elsewhere in the skeleton when hand changes are not present  
class5	rickets and osteomalacia are still around  the terms rickets and osteomalacia describe gross  histologic  and radiologic abnormalities common to more than 50 diseases that vary in cause and clinical presentation  rachitic and osteomalacic syndromes seen in current clinical practice usually are resistant to vitamin d forms and are most often caused by phosphate loss or 1 25 oh 2d deficiency  or both  radiographic identification of rachitic or osteomalacic syndromes and accurate diagnosis of a particular cause is essential  as many patients  conditions can be improved or cured with proper therapy  
class5	motor evoked potentials in patients with cervical spine disorders  measurements of motor evoked potentials by means of fractionated magnetic stimulation of motor pathways to the upper limbs was performed as part of the clinical assessment in 268 patients with cervical spine disorders  seventy two percent of the 127 patients with degenerative changes of the cervical spine  67  of the 55 patients with rheumatoid arthritis  ra   and 57  of the 51 patients with trauma of the cervical spine showed a pathologic delay of central motor latency  cml   the data suggest that this method has a high sensitivity and therefore is recommended in the diagnosis of cervical spine disorders in patients with suspected compression of neural structures  
class5	the neurologic workup in patients with cervical spine disorders  care must be exercised in interpreting the clinical and radiologic findings when assessing patients with cervical spondylosis and involvement of neural structures for surgery  if the clinical picture cannot logically be explained by the radiologic findings  further investigation is indicated to exclude a coexistent disorder  investigations may include electrophysiologic tests  transcranial magnetic stimulation  cerebrospinal fluid  csf  analysis  and magnetic resonance imaging  mri   only then can the indication for surgical intervention be properly determined  
class5	anterior cervical discectomy and fusion  a retrospective review of 94 patients who had undergone anterior cervical discectomy and fusion was performed to analyze the result in patients who had a diagnosis of posterolateral spondylosis  disc herniation  or both  although in 23 of 94 patients additional adjacent asymptomatic levels of spondylosis were noted  only the symptomatic levels were addressed in the 94 cases  postoperatively two cases of dysphagia were noted  as well as a 4  pseudarthrosis rate  there was an 88  good or excellent result when no additional spondylosis was present  but only a 60  good or excellent result when just the symptomatic levels were addressed  leaving unoperated adjacent levels of spondylosis  
class5	surgical management of cervical soft disc herniation  a comparison between the anterior and posterior approach  anterior cervical fusion was initially described in the 1950s for cervical spondylotic radiculopathy  the indications for this procedure in the management of soft disc herniation have not been clearly defined  in addition  controversy exists as to whether a cervical soft herniation should be managed by an anterior approach or a posterior cervical laminotomy foraminotomy  the authors report the results of a prospective study comparing anterior discectomy and fusion to posterior laminotomy foraminotomy for the management of soft cervical disc herniation  twenty eight patients underwent anterior discectomy and fusion  robinson horseshoe graft  while 16 patients underwent posterior laminotomy foraminotomy  the disc herniations were classified into two types  type i were single level anterolateral herniations  33 patients  while type ii were central soft disc herniations  11 patients   clinically  patients with type i herniations manifested signs and symptoms of radiculopathy while patients with type ii herniations manifested signs of myelopathy or neck pain and bilateral upper extremity paresthesias in 4 patients  confirmatory studies were myelography in 12 patients  myelography combined with computed tomography  ct  in 26 patients  and magnetic resonance imaging  mri  in 6 patients  for type i herniations  17 patients underwent anterior fusion while 16 patients had a posterior laminotomy foraminotomy  the 11 patients classified as type ii herniation all underwent anterior discectomy and fusion  there were 27 men and 17 women  the age range was 21 to 52 years  mean  41 years   the follow up was 1 6 to 8 2 years  mean  4 2 years   
class5	functional stability of the canine cervical spine after injury  a three month in vivo study  although clinical instability is an in vivo problem  most spinal instability criteria are either subjective or are based on in vitro experiments  the authors performed an in vivo experiment using a canine model to study the natural history of spinal instability as a function of healing time up to 12 weeks  three injuries were produced surgically  sham  laminectomy at c4  and bilateral facetectomy at c4 c5  three 1 5 mm steel balls were implanted into c3 to c6 vertebrae at the time of surgery  standardized functional flexion extension stereoradiographs of the cervical spine were obtained before injury  immediately after injury and at 0 5  1  1 5  2  3  4  5  6  7 5  9  and 12 weeks postinjury and immediately after killing the animals  in general  the authors found decreased ranges of motion  rom  at the c4 c5 level  compared with the pre injury values  for all injuries  but most significantly for the facetectomy  the maximum decrease occurred between 0 and 0 5 weeks postinjury  between 2 and 12 weeks  there was recovery in the rom  especially for the two less severe injuries  the changes in the rom at each spinal level were explained by simultaneous presence of a destabilizing factor  caused by the three different injuries with the sham as the least and the facetectomy as the most destabilizing injury  and a stabilizing mechanism of muscle spasm in the beginning and of healing and other adaptive responses in the late phase after injury  because of the significant differences between the canine model and the human cervical spine  the present findings should be extrapolated to the human situation with caution  
class5	evaluation of current extrication orthoses in immobilization of the unstable cervical spine  an experiment was designed to evaluate the comparative stabilizing efficacy of several widely used semi rigid orthoses applied to unstable fresh cadaver cervical spines subject to load  cadaver specimens were surgically destabilized at the c4 5 segment  lateral radiographs of the destabilized spine were obtained before and after collar placement and after the application of a 5 pound flexion force  data analysis employing a one way analysis of variance showed no statistically significant difference in the necloc s  philadelphia collar s  or the stifneck s ability to stabilize the cervical spine against a deforming flexion force  p greater than 0 05   they all provide translational stability while allowing angular changes to occur with application of the flexion force  the philadelphia collar halo system is statistically superior to all three of the aforementioned collars in prevention of both translation and sagittal rotation  p less than 0 05   
class5	anterior cervical plate fixation with the titanium hollow screw plate system  a preliminary report  morscher  of switzerland  has developed an anterior cervical spine plate system  thsp  that does not require screw purchase of the posterior cortex  this design eliminates potential neurologic complications usually associated with the anterior plate system  but maintains the mechanical advantages of internal fixation  the authors reviewed 13 consecutive patients in whom the thsp system was applied  indications for the use of this device included acute trauma in three patients  trauma of more than 6 weeks  duration in five patients  and spondylosis in five patients  fifteen plates and 58 screws were placed  with no screws purchasing the posterior cortex  postoperative immobilization varied from no immobilization to four poster brace  with a mean follow up of 13 months  all 13 patients went on to fusion  one patient had screws placed in the disc rather than in bone and went on to malunion  in all other patients  radiographs did not demonstrate screw migration  screw bone lucency  graft dislodgement  or malunion  no patient suffered neurologic injury as a result of this device  the thsp system facilitates reliable fusion with minimal complications  its use should be considered in multilevel anterior spine defects  posttraumatic cervical kyphosis  and cervical fractures with posterior disruption requiring anterior fusion  
class5	recurrent childhood myoglobinuria  recurrent heritable childhood myoglobinuria is a potentially fatal entity  mortality up to 35   in which prompt diagnosis and treatment are critical  sixty childhood cases have been reported between 1910 to 1988  most with undiagnosed etiologies  we have studied an additional 40 cases referred to cpmc  1980 1988   suggesting that this condition is largely underdiagnosed or unreported  we have found important differences between the childhood and adult onset cases  of 77 cases of adult onset recurrent myoglobinuria  45  have been diagnosed biochemically  in contrast  only 30  of the 60 childhood cases from the literature have been diagnosed  11 with cpt deficiency and 7 with various glycolytic defects  and only 5 of our 40 childhood cases have been diagnosed  all with cpt deficiency  the 100 combined childhood cases can be divided into an exertional group  type i  with exertion as the leading precipitating factor  46 literature and 10 cpmc cases   a toxic group  type ii  with infection and or fever as the primary precipitant  14 literature and 23 cpmc cases   and 7 undefined cases  the type i group resembles the adult onset group in which exercise is also the leading precipitating factor  there is a slight female predominance  male female   1 1 3  in the toxic group vs  a marked male predominance in the exertional and adult groups  4 1   only 4 of 37 cases  11   of the toxic group are diagnosed  all with cpt deficiency  vs  19 of 56 cases  34   of the exertional group  12 cpt  7 glycolytic  and 45  of the adult group  the toxic group is also differentiated by a higher mortality rate and by the presence of additional clinical features  including ictal bulbar signs  8 of 18   encephalopathy  4 of 19   and seizures  2 of 7   as well as persistent cardiac abnormalities  developmental delay  4 of 17   and dysmorphic features  2 of 9   these clinical characteristics clearly differentiate the childhood from the adult cases and suggest the presence of more generalized disease processes and different biochemical etiologies  a study of the heritable causes of myoglobinuria is important because identification of the biochemical defect may elucidate the pathogenetic mechanism of the myoglobinuria and facilitate the development of rational treatment strategies aimed at circumventing or correcting the metabolic block  
class5	acute osteomyelitis in children  reassessment of etiologic agents and their clinical characteristics  one hundred thirty five children with acute osteomyelitis were identified by chart review during a 7 year period  january 1  1980  through december 31  1986  bacteriologic causes were detected in 75  55   of the patients  staphylococcus aureus  haemophilus influenzae type b  and pseudomonas aeruginosa were identified in 34  25    16  12    and eight  6   children  respectively  staphylococcus aureus occurred in all age groups  h influenzae type b occurred only in children younger than 3 years and was the number one cause of disease in this group  pseudomonas aeruginosa occurred exclusively in children older than 9 years  children with h influenzae type b had clinical and laboratory findings that were almost indistinguishable from a matched group of children with osteomyelitis due to other known bacteria  although children with h influenzae type b tended to have more joint effusions  63  vs 27    less lower extremity disease  22  vs 70    and fewer positive cultures from bone or joint aspirates  41  vs 89    unlike most pediatric cases of osteomyelitis  the ones due to p aeruginosa did not represent the hematogenous route of infection  penetrating injury to the foot was present in every case  children with p aeruginosa infections were older than 9 years  100    predominantly male  88    often afebrile  83    and never bacteremic  these data provide guidelines for the initial work up and management of osteomyelitis in children  
class5	pneumococcal osteomyelitis and arthritis in children  a hospital series and literature review  twenty nine children with pneumococcal osteomyelitis and or arthritis  11 of whom had osteomyelitis  were treated at cook county hospital  chicago  ill  in the past 20 years  they were mostly normal children with a single focus of infection  they represented more than 5  of the hospitalized children with a systemic pneumococcal infection  most of the pneumococcal isolates were serotyped  serotype 19  in particular  seemed to be unusually common in these children  twenty three of the 29 children with pneumococcal osteomyelitis and or arthritis had been hospitalized in the past 15 years  these 23 children were compared with 161 hospitalized children who had bone and joint infections with other isolated bacteria  the children with pneumococcal osteomyelitis and or arthritis were indistinguishable from most of the other children  except by age  all but three of the children with pneumococcal osteomyelitis and or arthritis were between the ages of 3 and 24 months  in this age group  pneumococcus was the common isolate from children with osteomyelitis  and second only to haemophilus influenzae from children with bacterial arthritis  pneumococcal osteomyelitis and or arthritis has never been rare  the medical literature describes at least 245 other children  most of whom were younger than 2 years  
class5	neural arch stenosis and spinal cord injury in thanatophoric dysplasia  bony abnormalities caused by thanatophoric dysplasia affect the base of the skull and the vertebrae as well as the ribs and appendicular long bones  we present our findings in a full term infant with thanatophoric dysplasia in whom the posterior fossa  the rostral vertebral column  and the neuraxis at and adjoining the craniovertebral junction were studied by dissection  roentgenography  and histologic examination  in this infant  malformations of the vertebral laminae  most prominent in the basiocciput and atlas vertebra  led to compression of the rostral cervical spinal cord  causing gliosis and focal necrosis  stenosis of the foramen magnum and spinal canal may contribute to the ventilatory insufficiency that often causes death in patients with thanatophoric dysplasia  we suggest that the causes of death in patients with thanatophoric dysplasia and other severe forms of osteochondrodysplasia should be sought in neuraxial injury rather than attributed solely to pulmonary hypoplasia  
class5	pearson syndrome and mitochondrial encephalomyopathy in a patient with a deletion of mtdna  a patient is described who has features of pearson syndrome and who presented in the neonatal period with a hypoplastic anemia  he later developed hepatic  renal  and exocrine pancreatic dysfunction  at the age of 5 years he developed visual impairment  tremor  ataxia  proximal muscle weakness  external ophthalmoplegia  and a pigmentary retinopathy  kearns sayre syndrome   muscle biopsy confirmed the diagnosis of mitochondrial myopathy  analysis of mtdna from leukocytes and muscle showed mtdna heteroplasmy in both tissues  with one population of mtdna deleted by 4 9 kb  the deleted region was bridged by a 13 nucleotide sequence occurring as a direct repeat in normal mtdna  both pearson syndrome and kearns sayre syndrome have been noted to be associated with deletions of mtdna  they have not previously been described in the same patient  these observations indicate that the two disorders have the same molecular basis  the different phenotypes are probably determined by the initial proportion of deleted mtdnas and modified by selection against them in different tissues  
class5	analysis of the chondroitin sulfate proteoglycan core protein  cspgcp  gene in achondroplasia and pseudoachondroplasia  achondroplasia and pseudoachondroplasia are autosomal dominant skeletal dysplasias resulting in short limbed dwarfism  histologic and ultrastructural studies of the cartilage in pseudoachondroplasia and in homozygous achondroplasia have suggested a structural abnormality in chondroitin sulfate proteoglycan  cspg   a major structural protein in the extra cellular matrix  the gene encoding cspg core protein  cspgcp  is thus a logical  candidate gene  for analysis in these conditions  cdna probes encoding cspgcp were used to identify restriction fragment length polymorphisms  rflps  in dna from a panel of control individuals  no gross alterations at the cspgcp locus were noted in dna from 37 individuals with achondroplasia and 5 individuals with pseudoachondroplasia  in addition  allelic frequencies of the rflps were not significantly different among controls and patients with either condition  in one three generation family with achondroplasia  close linkage of the cspgcp locus and the skeletal dysplasia was excluded using a bgl ii polymorphism  similarly  in a three generation family with pseudoachondroplasia  the cspgcp gene was not tightly linked to the disease phenotype  these results indicate that mutations at the chondroitin sulfate proteoglycan core protein locus do not cause achondroplasia or pseudoachondroplasia in these families  
class5	multiple orbital tumors were cavernous hemangiomas  two distinct masses in the left orbit were incidentally found in a 48 year old woman during a computed tomographic scan done to evaluate neurologic complaints  initial diagnostic considerations focused on a lymphoproliferative disorder or other systemic disease  orbitotomy revealed two discrete tumors  both cavernous hemangiomas  although uncommon  cavernous hemangioma should be considered in the differential diagnosis of the patient with multiple orbital lesions  
class5	acute rheumatic fever in west virginia  not just a disease of children  rheumatic fever is a poststreptococcal disease that is receiving renewed attention by the medical community  we describe a recent increase in the number of observed cases of acute rheumatic fever  arf  in west virginia  this is the fifth report of a recent increase in the incidence of arf in the ohio valley area in the last 4 years  in contrast to the other reports  nearly two thirds of our cases of arf were in adults  more than half of whom had suffered previous bouts of arf  in these adults with recurrences  none was taking prophylactic penicillin at the time of presentation  carditis was present in seven adults  two without a history of carditis  arthritis was present in all adult patients  these data indicate a possible geographic phenomenon related to the increased number of observed cases of arf and document that arf is not simply a disease of childhood  furthermore  our findings highlight the need for extended penicillin prophylaxis for secondary prevention of arf  especially for those with an increased risk of acquiring a streptococcal upper respiratory tract infection  
class5	treatment of flexor tenosynovitis of the hand   trigger finger   with corticosteroids  a prospective study of the response to local injection  we developed a protocol to maximize medical therapy for  trigger finger   fifty eight patients with 77 episodes of flexor tenosynovitis of the hand that was resistant to rest  therapy with nonsteroidal anti inflammatory drugs  and or splinting were treated with single or multiple injections of depo methylprednisolone acetate or triamcinolone acetonide  patients were prospectively followed up for an average of 4 6 years  results showed that symptoms and signs resolved in 61  after a single injection  recurrent episodes  after prolonged pain free intervals  occurred in 27  and were effectively re treated with injection  in 12  of cases  either injection failed or early recurrence required surgical release  local adverse reactions to injection  including pain at the injection site  stiffness  ecchymosis  or atrophy of subcutaneous fat  were self limited  no episodes of postinjection infection or tendon rupture occurred  the medical management of flexor tenosynovitis with local corticosteroid injection s  is effective in nearly 90  of cases and is free from serious adverse reactions  
class5	gonococcal osteomyelitis  case report and review of the literature  we report the 11th case of gonococcal osteomyelitis in the postantibiotic era  this case demonstrates the classic presentation of osteomyelitis associated with gonorrhea  a subacute illness with minimal systemic symptoms  in addition  we present radiologic evidence of the pathogenesis of this unusual osteomyelitis from a contiguous joint infection  
class5	expanded clinical evaluation of lovastatin  excel  study results  i  efficacy in modifying plasma lipoproteins and adverse event profile in 8245 patients with moderate hypercholesterolemia in the expanded clinical evaluation of lovastatin  excel  study  a multicenter  double blind  diet  and placebo controlled trial  we evaluated the efficacy and safety of lovastatin in 8245 patients with moderate hypercholesterolemia  patients were randomly assigned to receive placebo or lovastatin at a dosage of 20 mg once daily  40 mg once daily  20 mg twice daily  or 40 mg twice daily for 48 weeks  lovastatin produced sustained  dose related  p less than  001  changes as follows  for dosages of 20 to 80 mg d   decreased low density lipoprotein cholesterol level  24  to 40    increased high density lipoprotein cholesterol level  6 6  to 9 5    decreased total cholesterol level  17  to 29    and decreased triglyceride level  10  to 19    the national cholesterol education program s low density lipoprotein cholesterol level goal of less than 4 14 mmol l  160 mg dl  was achieved by 80  to 96  of patients  while the less than 3 36 mmol l  130 mg dl  goal was achieved by 38  to 83  of patients  the difference between lovastatin and placebo in the incidence of clinical adverse experiences requiring discontinuation was small  ranging from 1 2  at 20 mg twice daily to 1 9  at 80 mg d  successive transaminase level elevations greater than three times the upper limit of normal were observed in 0 1  of patients receiving placebo and 20 mg d of lovastatin  increasing to 0 9  in those receiving 40 mg d and 1 5  in those receiving 80 mg d of lovastatin  p less than  001 for trend   myopathy  defined as muscle symptoms with a creatine kinase elevation greater than 10 times the upper limit of normal  was found in only one patient  0 1   receiving 40 mg once daily and four patients  0 2   receiving 80 mg d of lovastatin  thus  lovastatin  when added after an adequate trial of a prudent diet  is a highly effective and generally well tolerated treatment for patients with moderate hypercholesterolemia  
class5	muscle conditioning in late poliomyelitis  to study the adaptability of postpolio muscles  12 subjects  mean age 54 years  participated in a high intensity resistance exercise program  seventy five percent met the criteria for postpolio syndrome  isometric and isokinetic strength and muscle endurance were measured  polio affected muscles were identified in muscle biopsies  the biopsies were also used for measurements of enzymatic activities and for histochemical and histopathologic analyses  pretraining strength values were less than half those of healthy controls  mean fiber areas were twice those of healthy controls  and oxidative enzyme activity was low  after training  a significant increase in isometric  mean 29   and isokinetic  mean 24   strength was observed and maintained for some time  this demonstrates remaining adaptability in muscles already compensated from long standing polio  
class5	corticosteroid injections in adhesive capsulitis  investigation of their value and site  forty eight patients with frozen shoulder for less than six months were assigned at random to receive three shoulder injections into the subacromial bursa or glenohumeral joint at weekly intervals  the treatment groups were  1  intra articular methylprednisolone and lidocaine   2  intrabursal methylprednisolone and lidocaine   3  intra articular lidocaine   4  intrabursal lidocaine  the same physical therapy program was carried out for all patients  assessments of pain and range of motion were performed by a physical therapist who was uninformed about the nature of the injection therapy  there was no significant difference in outcome between intrabursal injection and intra articular injection  injection of steroid with lidocaine had no advantage over lidocaine alone in restoring shoulder motion  but partial  transient pain relief occurred in two thirds of the steroid treated patients  
class5	open depressed skull fracture missed on computed tomography  a case report  a case of an open depressed skull fracture that was missed on standard computed tomographic  ct  scan is presented  the fracture was seen on a ct generated lateral scout film  and after repositioning the gantry  further ct images clearly showed the fracture and underlying brain injury  the authors recommend that all patients with head trauma undergoing head ct have either a ct generated lateral scout film or a lateral skull radiograph to assess the vertex of the skull  an area poorly visualized on standard axial images  
class5	topical treatment of necrotic foot ulcers in diabetic patients  a comparative trial of duoderm and mezinc  an open randomized controlled study was carried out of 44 diabetic patients with necrotic foot ulcers treated with adhesive zinc oxide tape  mezinc  or with an adhesive occlusive hydrocolloid dressing  duoderm   fourteen of the 21 patients treated with mezinc had their necrotic ulcers improved by at least 50  compared to six out of 21 with the hydrocolloid dressing  p less than 0 025   fifteen patients showed an increase in the area of necrosis during the course of the 5 week study and of these  10 had been treated with the hydrocolloid dressing  
class5	reduction of graft failure by a monoclonal antibody  anti lfa 1 cd11a  after hla nonidentical bone marrow transplantation in children with immunodeficiencies  osteopetrosis  and fanconi s anemia  a european group for immunodeficiency european group for bone marrow transplantation report  forty six infants and children suffering from either inherited immunodeficiency disorders  wiskott aldrich syndrome  functional t cell immunodeficiency with or without hla class ii expression deficiency   malignant osteopetrosis  or fanconi s anemia received hla nonidentical bone marrow transplantation  bmt  from related donors  bone marrow was t cell depleted to reduce the risk of graft versus host disease  gvhd   to prevent graft failure  a mouse monoclonal antibody specific for the cd11a lymphocyte function associated antigen 1  lfa 1  molecule was infused into the patients  eleven patients received five infusions of 0 1 mg kg every other day from day  3 to  5  thirty five patients received 0 2 mg kg daily from day  3 to  6  the overall sustained engraftment rate was 72  instead of 26 1  in a historical control group of 24 patients similarly treated except for the infusion of the anti lfa 1 antibody  no late rejection occurred  the t cell depletion method  e rosetting or campath im plus complement  resulted in different rate of engraftment  83 3  v 57 9   respectively  p    05   engraftment rate was slightly but not significantly influenced by the degree of hla incompatibility between donor and recipient  acute gvhd of grade ii or more occurred in 35 5  of the patients and the rate of chronic gvhd was 12 9   the overall actuarial survival rate with a functional graft is 47 3  with a mean follow up of 28 0 months for patients with immunodeficiency and osteopetrosis  while none of the four patients with fanconi s anemia survived  the development of full t cell functions took on the average 6 months and of full b cell functions 10 months  significant infectious problems developed in the majority of the patients during the posttransplant course  epstein barr virus induced b cell proliferative syndromes were observed in seven patients  six of whom had wiskott aldrich syndrome  correction of immunodeficiency was comparable in terms of kinetics and quality with that observed in patients with severe combined immunodeficiency undergoing hla nonidentical bmt  correction of osteopetrosis appears not to be different from what has been observed after hla identical bmt  the in vivo use of an anti cd11a lfa 1 antibody as an additional immunosuppressive therapy in hla nonidentical bmt may thus promote engraftment and survival with correction of the primary disease in a significant number of patients with life threatening immunodeficiency and osteopetrosis  but not with fanconi s anemia  
class5	cytogenetic evidence of clonality in a case of pigmented villonodular synovitis  pigmented villonodular synovitis is an uncommon benign lesion that is characterized by diffuse synovial proliferation  based on animal models  this lesion has been conjectured previously to be reactive in nature  in this report  the authors present the histologic and cytogenetic findings for a pigmented villonodular synovitis that was excised from the right knee of a 47 year old man  trisomy 7 was observed in 24 of 75  35   metaphases obtained from short term culture of cells from this tumor  these findings suggest that some cases of pigmented villonodular synovitis represent clonal  neoplastic proliferations  
class5	chondrosarcomas of the synovium  chondrosarcoma of the synovium  either primary or secondary to synovial chondromatosis  is rare  ten cases of synovial chondrosarcoma were studied  four from the mayo clinic files and six from the authors  consultation files   two were considered primary  in five cases there was evidence of preexisting synovial chondromatosis  and in the remaining three  there was a suggestion of preexisting disease  several histologic features were found that were helpful to diagnose malignancy  the most important ones were loss of the  clustering  growth pattern typical of synovial chondromatosis  myxoid change in the matrix  areas of necrosis  and spindling at the periphery of chondroid lobules  pulmonary metastasis developed in five of nine patients  three of these patients died  
class5	late effects of treatment for wilms  tumor  a report from the national wilms  tumor study group  the national wilms  tumor study  nwts  was initiated in 1969  one of its objectives was to modulate treatments according to risk factors to minimize the number and severity of treatment related short term and long term iatrogenic complications  the nwts has therefore incorporated a long term follow up study  ltfs  within its framework to monitor late effects  the ltfs is confined to relapse free survivors alive 5 years or longer after initial surgery  and data are collected using specifically designed forms  a total of 787 patients registered on nwts 1 or nwts 2  1969 to 1979  were eligible  of whom 680  86   were available for analysis regarding musculoskeletal  cardiovascular  and neuropsychologic status  and the presence of benign and malignant tumors  patients with early stage disease who were treated with radiation had scoliosis reported  along with other musculoskeletal abnormalities  32 versus 2   nearly seven times as often as did the members of the cohort population who did not undergo radiation  35 of 57 versus 5 of 53  respectively   the difference in cardiovascular problems recorded in survivors who did and did not receive adriamycin  adria laboratories  columbus  oh   2 4 versus 1 1 per 100 person years at risk  had borderline statistical significance  p   0 06   no excess in neuropsychologic events was reported for those given the neurotoxin vincristine  when considering patients with disease of all stages  all 5 second malignant tumors occurred in the 623 patients who underwent radiation  rt patients   benign tumors were also more frequent in rt patients than in those patients who did not undergo radiation  41 of 486 or 8  versus 4 of 194 or 2    continuing study of this unique body of patients is needed  especially for those given adriamycin  because of the known long interval needed for latent cardiomyopathy to become clinically manifest in some patients  
class5	multidisciplinary treatment of primary orbital rhabdomyosarcoma  a single institution experience  orbital rhabdomyosarcoma accounts for one fourth of the primary tumors in the head and neck region  modern treatment modalities have led to a 2 year survival rate of about 90  in these patients  however  new therapeutic trials are designed to reduce complications and salvage more than 90  of orbital cases  between 1979 and 1990  12 children affected by primary orbital rhabdomyosarcoma have been diagnosed and treated at the university of naples  ten of them have been uniformly treated by biopsy  followed by immediate radiation and combined chemotherapy  all 12 patients are alive and free of detectable disease  from a minimum of 7 months to a maximum of 123 months after diagnosis  in all children  ocular structures have been spared and the complications observed until now have been few  the above results suggest that the association of immediate radiation therapy and chemotherapy might represent an optimal tool for treatment of orbital rhabdomyosarcoma  
class5	bracing for patellar instability  knee pain secondary to problems with patellar tracking is common  the initial treatment for these problems is conservative  patellar orthotics have been used extensively to treat a variety of extensor mechanism problems  millions of health care dollars are spent annually on the use of these braces  there are many different patellar orthotics on the market today  the use and design of most of these devices are unclear and often lack a solid biomechanical foundation  the practical mechanical function of these braces is to reduce the lateral displacement of abnormal patellofemoral tracking  orthotics that are designed and tested using practical biomechanical principles for applying a medially directed force to the patella seem to have a role in treating patients with knee pain secondary to patellar malalignment and instability  well defined and controlled clinical studies of the use of patellar braces are lacking  
class5	t plasty modification of the bankart procedure for multidirectional instability of the anterior and inferior types  forty patients who had a diagnosis of multidirectional instability of forty two shoulders had a modified bankart operation in which a t shaped incision was made in the anterior portion of the capsule  with advancement of the inferior flap superiorly and of the superior flap medially  all of the patients had been injured during athletic activities  some degree of anterior labral injury was present in thirty eight of the forty two shoulders  half of the patients had generalized ligamentous laxity  the patients were followed for an average of three years  range  two to seven years   four patients had episodes of instability after the operation  three had a single episode of posterior subluxation during throwing  one had recurrent posterior subluxation that subsequently was treated by posterior stabilization  and one had anterior subluxation while he was diving from a high board  the average loss of external rotation after the operation was 5 degrees with the arm at the side and 4 degrees with the arm abducted 90 degrees  satisfaction of the patient was rated excellent for forty  95 per cent  of the shoulders  good for one shoulder  and fair for one shoulder  however  throwing athletes found that they were unable to throw a ball with as much speed as before the operation  
class5	familial predisposition for herniation of a lumbar disc in patients who are less than twenty one years old  the parents of sixty three patients who were less than twenty one years old and who had operatively confirmed herniation of a lumbar disc were interviewed regarding a history of sever back pain  sciatica  and herniated disc  to determine whether aggregation of herniation of a lumbar disc occurs in families of patients in this young age group  the parents of sixty three additional patients who had a non spinal orthopaedic diagnosis  control group  were matched for age and sex with the study group and were given the same interview  of the patients who had herniation of a lumbar disc and were less than twenty one years old  32 per cent had a positive family history for that lesion compared with 7 per cent of the control group  the relative risk of development of herniation of a lumbar disc before the age of twenty one years is estimated to be approximately five times greater in patients who have a positive family history  the results indicate a familial basis for herniation of a lumbar disc in patients who are less than twenty one years old  
class5	magnetic resonance imaging of the shoulder  sensitivity  specificity  and predictive value  the sensitivity  specificity  and predictive value of magnetic resonance imaging in the diagnosis of lesions of the rotator cuff  glenohumeral capsule  and glenoid labrum were evaluated in ninety one patients and fifteen asymptomatic volunteers  magnetic resonance imaging demonstrated 100 per cent sensitivity and 95 per cent specificity in the diagnosis of complete tears  and it consistently predicted the size of the tear of the rotator cuff  there was a definite correlation between atrophy of the supraspinatus muscle and the size of a complete  chronic tear of the rotator cuff  the sensitivity and specificity of magnetic resonance imaging in the differentiation of tendinitis from degeneration of the cuff were 82 and 85 per cent  and in the differentiation of a normal tendon from one affected by tendinitis with signs of impingement the sensitivity and specificity were 93 and 87 per cent  the formation of spurs around the acromion and acromiocalvicular joint correlated highly with increased age of the patient and with chronic disease of the rotator cuff  the sensitivity and specificity of magnetic resonance imaging in the diagnosis of labral tears associated with glenohumeral instability were 88 and 93 per cent  the study showed that high resolution magnetic resonance imaging is an excellent non invasive tool in the diagnosis of lesions of the rotator cuff and glenohumeral instability  
class5	tests for posterolateral instability of the knee in normal subjects  results of examination under anesthesia  an apparently normal knee was examined in each of 100 subjects while they were under general or epidural anesthesia for an unrelated operation  the lachman  anterior drawer  posterior drawer  and pivot shift tests were negative in all knees  all knees were stable to varus and valgus stress at both 0 and 30 degrees of flexion  the external rotation recurvatum test also was negative in all knees  a positive reversed pivot shift sign was present in 35 per cent of the knees  suggesting that it may not signify abnormality  at least not without a negative test on the contralateral knee  the results of the posterolateral drawer test were variable  difficult to quantify  and did not always have a firm end point  the amount of maximum external rotation of the tibia  measured from the reference line of the medial border of the foot  was extremely variable at both 30 and 90 degrees of flexion of the knee  external rotation  as determined by this reference  was slightly greater  averaging 9 degrees  at 90 than at 30 degrees of flexion  the normal range of maximum external rotation of the foot was 10 to 45 degrees at 30 degrees of flexion of the knee and 15 to 70 degrees at 90 degrees of flexion  the presence of a large angle of external rotation and a positive reversed pivot shift sign correlated strongly with increased ligamentous laxity and mild varus alignment of the knee  
class5	skeletal involvement in children who have chronic granulomatous disease  chronic granulomatous disease is a rare disorder of the oxidative metabolism of the white blood cells that results in immunodeficiency  in a retrospective review of the records of forty two patients who had chronic granulomatous disease  we identified thirteen patients who had a total of twenty skeletal infections  two types of infection were noted  type 1  which resulted from a direct spread of the infection from an adjacent focus  usually of fungus or mycobacteria  and type 2  which resulted from hematogenous spread  usually of nocardia or more common bacteria  the thoracic vertebrae  ribs  and metatarsals were the most commonly involved bones  all four patients in whom the vertebrae were involved had a type 1 fungal infection  paresis developed in three of these patients  and two of them died  antibiotics alone effectively eradicated the infection in only one patient  wide operative debridement combined with administration of antibiotics was the most successful treatment  comprehensive preoperative imaging and several cultures are necessary to locate the infection in the bone and to identify the organism  
class5	posterior transfer of the adductors in children who have cerebral palsy  a long term study  seventy eight posterior transfers of the adductors of the hip in forty two children who has spastic cerebral palsy were reviewed an average of 5 7 years after the operation  range  two to 14 6 years   the results were assessed on the basis of the patient s ability to walk  the range of motion of the affected hip or hips  and the radiographic measurements  in 88 per cent of the patients  the transfer was successful in improving or maintaining abduction  extension  functional walking  and stability of the hip  the failures were all in patients who were unable to walk and who had spastic quadriplegia  tenotomy of the iliopsoas tendon at the time of the transfer procedure resulted in an improved range of motion of the hip  
class5	deformities of the hip in adults who have sickle cell disease and had avascular necrosis in childhood  a natural history of fifty two patients  we report the natural course of the hip in fifty two patients  ninety five hips  who had sickle cell disease and had had avascular necrosis in childhood  there were twenty one african  twenty one west indian  and ten mediterranean patients  at the most recent follow up examination  at an average duration of nineteen years after the onset of the disease   80 per cent of the hips that had been affected by avascular necrosis during childhood were painful and had permanent damage with regard to decreased mobility  limb length discrepancy  and an abnormal gait  when the patients were evaluated  at an average age of thirty one years  fifteen hips  16 per cent  had had an operation for progressive disability and sixty  63 per cent  had major problems because of pain  of the twenty hips  21 per cent  that were not painful  five were in patients who had an abnormal gait  with decreased agility  the mean iowa hip rating score at the most recent follow up examination was 73 points  range  30 to 100 points   correlations were found between the hip score and the patient s age at the onset of the disease and at the latest follow up  between the hip score and degenerative changes in the hip  and between degenerative changes and radiographic evidence of deformity of the hip  
class5	systemic mastocytosis presenting as osteoporosis  a clinical and histomorphometric study  ten patients with systemic mastocytosis  sm  were evaluated for their metabolic bone disease  4 men and 6 women  mean     sd  59     13 yr   all patients presented with generalized osteopenia and or atraumatic vertebral compression fractures  three patients had long standing urticaria pigmentosa  in these  the diagnosis of cutaneous mastocytosis had been established by skin biopsy  one of the 3 and 2 of the other 7 individuals had symptoms suggestive of sm  although six patients had previously undergone decalcified bone marrow trephine core biopsy  dbmb   findings were consistent with sm in only 2 of them  x ray survey revealed generalized osteopenia in all 10 patients and vertebral compression fractures in 9  no patient had sclerotic bone lesions  histological findings of undecalcified transiliac crest biopsy  utbb  specimens from 9 patients  5 patients underwent both dbmb and utbb  4 underwent only utbb  and 1 had only dbmb  disclosed bone marrow that contained nodules characteristic of mast cell granulomas and numerous scattered oval  and spindle shaped mast cells  the trabecular bone contained abundant newly synthesized bone matrix and a significant increase in osteoblastic  osteoclastic  and resorptive surfaces  dynamic histomorphometric parameters revealed a significantly increased mineral apposition rate  our study suggests that sm may be a more frequent cause of osteoporosis than previously recognized  generalized osteopenia with compression fractures may be the only presentation of sm  undecalcified bone biopsy is useful in the diagnosis of sm  accelerated bone remodeling is a characteristic histomorphometric feature of sm with diffuse osteopenia  
class5	effect of a single infusion of aminohydroxypropylidene on calcium and bone metabolism in healthy volunteers monitored during 2 months  recently  bisphosphonates have been used to prevent postmenopausal bone loss  as the effects of bisphosphonates on normal bone metabolism are unknown  3 amino 1 hydroxypropylidene 1 1 diphosphonate  apd  was studied in healthy subjects  the effects of a single 20 mg apd infusion on biochemical parameters of calcium and bone metabolism were investigated during 2 months in 10 healthy male volunteers  this single moderate dose of apd reduced biochemical parameters of bone resorption during the time of follow up  after 2 months  urinary hydroxyproline excretion was still below the basal level  the decreased serum calcium levels did not return to basal values  biochemical parameters of bone formation  serum alkaline phosphatase and osteocalcin  showed a slight increase during the first month after stimulation of the parathyroids and a corresponding increase in serum 1 25 dihydroxyvitamin d  these formation parameters decreased thereafter  probably representing coupling between bone resorption and bone formation  
class5	osteomalacia in hereditary hypophosphatemic rickets with hypercalciuria  a correlative clinical histomorphometric study  we characterized the bone disease of transilial biopsy specimens from children with hereditary hypophosphatemic rickets with hypercalciuria  hhrh  and genetically related asymptomatic hypercalciuric subjects  all hhrh patients showed irregular mineralization fronts  markedly elevated osteoid surface and seam width  increased number of osteoid lamellae  and prolonged mineralization lag time  these findings are consistent with a mineralization defect and indicate unambiguously that the bone disease in hhrh is osteomalacia  the only abnormality seen in the asymptomatic hypercalciuric subjects was slightly extended osteoid surface  parametric and nonparametric statistical analyses performed on a pooled sample of hhrh patients and asymptomatic hypercalciuric subjects revealed a very high inverse correlation and a tight linear relationship between serum phosphorus and osteoid parameters  serum 1 25 dihydroxyvitamin d  which is low in other forms of hereditary hypophosphatemia and osteomalacia  is elevated in hhrh and correlated positively with osteoid parameters and the mineralization lag time  serum alkaline phosphatase showed similar relationships  these results as well as the clinical  biochemical  and radiological remission of bone disease consequent to phosphate therapy strongly suggest that in hhrh 1  hypophosphatemia alone is sufficient to cause osteomalacia  and 2  the elevation of 1 25 dihydroxyvitamin d reflects the degree of the primary renal phosphate leak  but is not involved in the pathogenesis of the bone disease  
class5	spinal epidural abscess  an unusual complication of a duodenal ulcer  a 50 year old man had several months of progressively worse low back pain associated with constitutional symptoms and a history of retroperitoneal tumor and bleeding duodenal ulcer  initial evaluation suggested a lumbar spine tumor  but myelography confirmed the presence of an epidural abscess  further evaluation revealed a duodeno spinal fistula at the site of the previous duodenal ulcer  which proved to be the cause of the abscess  
class5	estrogen and progestin therapy to prevent osteoporosis  attitudes and practices of general internists and gynecologists  study objective  to assess combined hormone therapy  cht  prescribing patterns  possible impediments to cht prescribing  and use of endometrial biopsy to monitor therapy  design  mailed questionnaire survey  subjects  gynecologists and general internists at two boston teaching hospitals  measurements and main results  based on a 71  response rate  72  of internists and 100  of gynecologists reported ever having prescribed cht  almost 60  of internists  compared with 8  of gynecologists  reported that over half of their female patients were older than 50 years of age  by logistic regression analysis of the internists  data  female gender of physician  odds ratio 11 0   belief that cht decreases myocardial infarction risk  odds ratio 3 4   and knowledge of cht s benefits and risks  odds ratio 2 8  were associated with prescribing  endometrial biopsy was performed by a majority of physicians only when unexpected vaginal bleeding occurred and in cases of unclear menopausal transition  physicians who were concerned about litigation were seven times more likely to perform baseline endometrial biopsy  conclusions  in the authors  sample  as well as nationally  internists are more likely to provide care for menopausal women  among internists  gender and knowledge are strongly associated with cht prescribing  these findings have important educational implications if internists are to routinely provide information and counseling to women about osteoporosis and cht  
class5	impairment of specific host defense mechanisms in patients with chronic post traumatic osteomyelitis  we studied both in vivo and in vitro specific host defense mechanisms in patients suffering from chronic post traumatic osteomyelitis  n   26   the cell mediated immunity in vivo was impaired as indicated by the reduced reactivity in the delayed type hypersensitivity skin test  the concanavalin a or phytohemagglutinin induced t cell proliferation in vitro was markedly decreased in comparison to healthy donors  in contrast  b cell proliferation stimulated by staphylococcus aureus cowan i was not altered  while the absolute lymphocyte counts and the percentage of t  b  and o cells were within the normal range  nine out of the 26 patients showed a significantly diminished ratio of cd4  and cd8  t cells  humoral immunity in the patients was less affected as assessed by the unchanged serum levels of immunoglobulins  ig   however  the t cell dependent polyclonal ig synthesis after in vitro stimulation with pokeweed mitogen was suppressed  our results provide evidence that cell mediated immune functions are predominantly impaired in patients with post traumatic osteomyelitis which may contribute to the persistence of the localized bone infection  
class5	schwartz jampel syndrome with dominant inheritance  the schwartz jampel syndrome  sjs  is a rare congenital multisystem disorder of unknown pathogenesis which is characterized by distinct faces  skeletal deformities  joint contractures  short stature  muscle hypertrophy  clinical myotonia  and continuous muscle fiber activity  the inheritance pattern of sjs has been assumed to be autosomal recessive  we report the occurrence of the classic sjs syndrome in both a father and son in a non consanguineous family  suggesting that sjs has the potential for a dominant pattern of inheritance  
class5	polymyositis  pulmonary fibrosis and autoantibodies to aminoacyl trna synthetase enzymes  the clinical and laboratory features of 29 patients who had one of three anti aminoacyl trna synthetase autoantibodies  anti jo1  histidyl trna synthetase   anti pl12  alanyl trna synthetase  or anti pl7  threonyl trna synthetase  were analysed and compared with the findings of other published reports  these autoantibodies were found to be associated with a syndrome delineated by inflammatory myositis  24 patients  and pulmonary fibrosis  23 of 29   but also including inflammatory arthritis  26 29   keratoconjunctivitis sicca  17 29   sclerodactyly  21 29   raynaud s phenomenon  27 29   hepatitis  8 29  and subcutaneous calcinosis  7 29   the most important clinical determinant of outcome in this group of patients was the severity of the interstitial pulmonary disease  no patient fulfilled the classification criteria for systemic lupus erythematosus  although 10 had autoantibodies to extractable nuclear antigens including ro  la  rnp  and sm  and two patients had anti dsdna antibodies  although it seems unlikely that anti aminoacyl trna synthetase antibodies are directly responsible for causing disease  they may provide an important clue to the aetiology of this unusual syndrome  
class5	dialysis arthropathy  a clinical  biochemical  radiological and histological study of 36 patients  out of a population of 97 haemodialysis patients  36 patients with dialysis arthropathy were identified  dialysis arthropathy is a chronic symmetrical polyarthritis which affected 97 per cent of the patients who had been undergoing cuprophane haemodialysis for more than 10 years  it commonly affected the shoulders  hips  hands  knees and wrists  worsening with time and extending to other joints  fifty eight per cent of the patients complained of morning stiffness and 47 per cent complained of exacerbation of shoulder pain during or after haemodialysis  half of the patients also suffered from carpal tunnel syndrome  which recurred and was associated with a long lasting disability  the most common radiological abnormality was periarticular bone cysts  followed by articular erosions and a destructive spondyloarthropathy  but clinical symptoms were more common than radiological signs  patients with dialysis arthropathy had a higher c reactive protein level than patients without arthropathy  18 6 mg l versus 11 4 mg l   indicative of an inflammatory process  some of the clinical manifestations of the disease correlated with levels of c reactive protein and ferritin  serum ferritin levels correlated strongly with the units of blood transfused in the past five years  rs   0 83   and the logarithm of ferritin level correlated weakly with c reactive protein  r   0 32   haemarthroses were documented in 19 per cent of patients  mean serum beta 2 microglobulin was elevated in the patients with  57 3 mg l  and without arthropathy  50 7 mg l   and there was no difference in the parathormone or aluminium levels between these groups  articular tissue was obtained in 25 patients  beta 2 microglobulin amyloid was present in 24  larger deposits were present in the capsular tissue  and these appeared to replace collagen bundles in eight cases  amyloid deposits replaced the lining layer in six cases  it is likely therefore that amyloid disrupts normal joint function by replacing normal joint tissue  mild chronic synovitis with haemosiderin deposition were found in approximately 60 per cent of cases  these findings suggest that amyloid derived from beta 2 microglobulin has a primary role in the pathogenesis of dialysis arthropathy  but there was also evidence of inflammatory processes  it is suggested that iron overload or haemarthroses might contribute to the inflammation  but other factors  such as dialysis related bioincompatibility reactions  may also have a role  
class5	clinical value of magnetic resonance imaging for cervical myelopathy  the magnetic resonance imaging  mri  findings in 115 cases of cervical myelopathy  121 cases of cervical radiculopathy  and 64 cases of neck pain with no neurologic deficit were prospectively studied to investigate the clinical value of mri for cervical myelopathy  the mri findings in the t1 weighted sagittal projection were classified into four groups according to the degree of the compressed deformities of the cervical cord  the degree of compression of the cervical cord on mri findings showed a significant correlation with the severity of myelopathy  the anteroposterior diameter of the spinal column  and the degree of compression of the dural tube in the myelograms  p less than 0 01   fifty one patients of cervical myelopathy had undergone both preoperative and postoperative mri  of these  the spinal canal of 47 patients that was well decompressed was recognized according to plain computed tomography  ct   however  24  51   of these 47 patients showed on mri a deformity in the spinal cord amounting to cord atrophy  the correlation between the clinical function of the spinal cord and the recovery of the cord deformity on mri at the operative levels was accurately investigated in 34 patients who had no cord deformities in the adjacent intervertebral levels  twenty patients with cord atrophy had slightly poor clinical results  although no significant difference was found between these 20 and 14 patients with recovery in the cord deformities  from these results  it was evident that t1 weighted mri is useful in the accurate diagnosis of compression myelopathy  in accurately deciding the level of the disease focus  and in the accurate assessment of the surgical results  
class5	motion analysis of the cervical spine in athetoid cerebral palsy  extension flexion motion  frequently instability and premature onset of spondylosis of the cervical spine are found in athetoid cerebral palsy  cp  patients  these structural abnormalities appear to be related to athetoid motion of the neck in cp  through motion analysis  the authors aimed to clarify the abnormalities of cervical motion that could precipitate structural abnormalities  the gross characteristic feature of cervical motion in athetoid cp is  whip movement   both velocity and acceleration during extension flexion motion were greater than in normal subjects  especially at the upper cervical levels  also  a sudden increase in velocity and acceleration occurred during rapid motions at certain levels  followed by a larger range of motion of the cervical spine  such kinematic abnormalities were thought to generate a greater shearing force and bending moment exerted on the corresponding cervical articulations discs and facets  olisthetic instability often accompanied disc degeneration at the upper cervical levels  a large range of extension  flexion motion of the cervical spine  analogous to a cantilever  caused a repeated bending moment of extraordinary magnitude and was regarded as a precipitative factor for disc degeneration and osteophytosis common at the middle and lower levels of the disc  
class5	identification of alpha motor nerve fiber potentials in lumbar epidural space and its clinical significance  the alpha efferent component of spinal root potentials  srps  was recorded in the lumbar epidural space stimulating the tibial and peroneal nerves for clinical diagnosis and clinical treatment  five normal volunteers and 15 clinical cases with lumbar disc herniation  ldh  were examined  the srp by the tibial nerve stimulation in the normal control group consisted of two kinds of potentials with different latency  simultaneous electromyogram  emg  recording from the stimulated muscles indicated that the shortest latency potential  first potential  was the ascending volley  including orthodromic afferent and antidromic alpha efferent volleys  and that the long latency potential  second potential  was the descending volley of reflexively evoked alpha efferents by the group ia afferents  the component of alpha efferent fiber potential was recorded in the following two methods by changing the intensity of stimulation  1  identifying alpha efferent components in the first potential and 2  recording the second potential  conduction blockage of spinal roots in 15 clinical cases was demonstrated as abnormal positivity and prolonged duration of the potentials  new methods were introduced to estimate two parameters quantitatively  the present study showed either of these signs in all patients tested  the examination was helpful to determine the level s  of lumbar motor radiculopathies  and the extent of pathologic neuropathy  
class5	pathomechanism  pathogenesis  and results of treatment in cervical spondylotic myelopathy caused by dynamic canal stenosis  in this study  the pathomechanism and pathogenesis of dynamic canal stenosis caused by cervical instability in patients with cervical spondylotic myelopathy and the validity of the concept of instability are clarified by analyzing the results of treatment in 53 cases  in cases of cervical spondylotic myelopathy caused by dynamic canal stenosis  the authors found that the posterior slide of the vertebral body occurs as a result of degeneration in the cervical spine due to aging changes  and that the dynamic sagittal diameter of the spinal canal decreases with an increase of the degree of posterior slide  this is followed by gradual aggravation of the clinical symptoms  continuous cervical traction was found to be the first choice of treatment  surgical treatment is indicated in cases in which the traction was ineffective  or even when it was effective  in cases in which the japanese orthopaedic association  joa  score remained low or when there was a tendency toward rapid aggravation of symptoms  it was demonstrated that the shorter the duration of the myelopathy  the better the results of treatment obtained  a limit of the dynamic sagittal diameter of the spinal canal of 12 mm was considered as valid  
class5	problems and solutions of pedicle screw plate fixation of lumbar spine  fifty seven patients with low back pain and sciatica of various causes were reviewed with reference to problems associated with pedicle plate fixation of the lumbar spine  eleven percent of patients had neurologic problems postoperatively and 3 5   two patients  had severe sensory impairments  all patients had this complication in the early phases of the study  of 297 screws  17 broke  ie  5 7   these breakages occurred in 12 of 57 patients  21    in patients with spondylolisthesis  the degree of slip correction averaged 53  postoperatively  which decreased to 35  at the 1 year follow up  slip angle was maintained after correction  pedicle screw plate fixation is an effective form of immobilization of the lumbar spine used in achieving arthrodesis  the surgeon must be fully trained in methodology  it is recommended that screw and plate materials be improved to prevent screw breakage  
class5	magnetic resonance imaging of lumbar disc herniation  comparison with myelography  fifty three patients with surgically confirmed lumbar disc herniation at 55 levels were studied retrospectively to compare the diagnostic accuracy of high field strength surface coil magnetic resonance imaging  mri  with that of myelography  disc herniation was classified into three groups according to mri findings  namely  unilateral single disc herniation  central single disc herniation  and multilevel disc herniation  magnetic resonance imaging diagnosis of unilateral single disc herniation was extremely reliable  so myelography was considered to be unnecessary  conversely  mri findings of central single disc herniation and multilevel disc herniation were less definite  in that myelography was necessary in locating the disc causing symptoms  
class5	ultrasonic level diagnosis of lumbar disc herniation  although the use of diagnostic ultrasound to measure the spinal canal has been proposed  the value of ultrasound for lumbar disc herniation has not been yet fully assessed  the purpose of this investigation was to evaluate the effectiveness of ultrasound in the level diagnosis of herniated nucleus pulposus  prospective ultrasound examinations were performed on 80 consecutive patients with clinically suspected lumbar disc herniation  in 41 discs of those 40 patients with surgically confirmed lumbar disc herniation  there were 32 discs  78   with true positive ultrasound diagnoses  37 discs  90   with true positive myelographic diagnoses  and 20 patients  50   with true positive neurologic diagnoses  conversely  ultrasound diagnoses showed positive echogram in 24  60   of 40 nonoperative patients  these results suggest that ultrasound is of value as an aid for diagnosing the level of lumbar disc herniation  
class5	the system and procedures of percutaneous intradiscal laser nucleotomy  since 1986  percutaneous intradiscal laser nucleotomy  piln  has been studied in the authors  laser laboratory  the purpose of this report is to develop piln as an alternative to chemonucleolysis and percutaneous discectomy  which are currently applied  and to establish a safe  easy  accurate and short time therapy method for lumbar disc herniation  after laser irradiation  intradiscal pressures  idp  decreased and the nucleus pulposus was gradually replaced with cartilaginous fibrous tissue  the evaluation of heat distribution with thermocouples and thermography was done to determine safe optimum irradiating conditions and to develop a new double lumen needle and a bare quartz fiber  neodymium yttrium aluminum garnet  nd yag  laser devices have been improved for easy and safe use  and a new tip type pressure transducer has been made for improved therapeutic results using this new method  
class5	postoperative lumbar spinal instability occurring or progressing secondary to laminectomy  the manifestations and pathomechanism of postoperative lumbar spinal instability  occurring or progressing secondary to laminectomy  was clarified by means of functional radiographic analysis in a series of 46 patients over 40 years of age  the relation between instability and the clinical symptoms also is discussed  in patients under 60 years of age  instability at the operated level tended to appear in cases of wide laminectomy more often than in cases of partial laminectomy  occurrence or progress of instability seems to be promoted by resection of the posterior spinal elements rather than the disc  it is further considered that the postoperative aggravation of clinical symptoms may be influenced not only by instability  but also by the other factors  
class5	unstable lumbar spine without hypermobility in postlaminectomy cases  mechanism of symptoms and effect of spinal fusion with and without spinal instrumentation  the morbid conditions of unstable lumbar spine that are not associated with hypermobility in postlaminectomy cases were studied  the dura and the nerve roots with adhesion could be affected by minimal movement of the spine  which seemed to be the mechanism of symptoms of instability without hypermobility  the effects of spinal instrumentation on this particular instability were studied  the spinal instrumentation provides instantaneous rigid fixation  and maintains it until fusion is obtained  which might prevent adhesion  new bone formation  and re stenosis  spinal instrumentation seemed to be the effective treatment for this particular instability  
class5	lumbar trapezoid plate for lumbar spondylolisthesis  a clinical study on preoperative and postoperative instability  the authors studied the effects of a  lumbar trapezoid plate   spinal plate and pedicle screwing   performed for lumbar spondylolisthesis  observing the effect on the remaining adjacent discs with regard to preoperative and postoperative instability  the authors examined changes in preoperative and postoperative lumbar rom  range of motion   displacement of motor unit levels  and occurrence of instability in the remaining discs  such as horizontal and rotational displacement  in 26 patients who were followed up for a mean of 29 postoperative months  13 patients had spondylolytic spondylolisthesis and 13 patients degenerative spondylolisthesis  the authors studied the effects of the fused vertebral angle and reduction of spondylolisthesis on the remaining upper and lower adjacent discs and the preoperative and postoperative fused disc heights  intervertebral fusion must affect the remaining adjacent discs  but compensatory function of the remaining motor unit level was more influenced by the fused intervertebral angle than by repositioning of the spondylolisthesis  fusion at a physiologically lordotic position is quite necessary  for this purpose  it is considered important to prevent grafted bones of the posterior lumbar interbody fusion  plif  from collapse and to maintain the achieved alignment of the lumbar spine  
class5	natural history of degenerative spondylolisthesis  pathogenesis and natural course of the slippage  to clarify the natural course of degenerative spondylolisthesis  the mechanism and progression of disk slippage were studied clinically and radiographically in 40 patients  progressive slippage was observed in 12 patients  30    no progression of slippage was noted in patients who showed narrowing of the intervertebral disk  spur formation  subcartilaginous sclerosis  or ossification of ligaments  these suggest that the mechanisms of spinal restabilization prevent progression of the disease  general joint laxity was observed in many patients  65    and this was believed to be involved in the pathogenic mechanism of this disease  there was no correlation between the clinical symptoms and progression of slippage  these findings suggest that careful consideration of the natural mechanisms of spinal restabilization as well as the natural course of the disease is important  
class5	long term results of anterior interbody fusion for treatment of degenerative spondylolisthesis  thirty nine patients  34 women and five men  underwent anterior decompression and interbody fusion for degenerative spondylolisthesis between february 1958 and august 1988  their average age at surgery was 51 years  range  34 74 years   and their average follow up period was 12 years 7 months  range  6 months to 30 years   clinical evaluation was done by the score rating system of the japanese orthopaedic association  joa score   patients with joa scores of 25 points or more were rated as  satisfactory   survivorship was analyzed by the method of kaplan and meier to determine the cumulative percentage of patients with satisfactory results  the following results were obtained  seventy six percent of the patients had satisfactory results for 10 years after the anterior interbody fusion  60  for 20 years  and 52  for 30 years  irrespective of their age at surgery  the patients generally maintained satisfactory results up to 65 years of age  
class5	clinical study on stability of combined distraction and compression rod instrumentation with posterolateral fusion for unstable degenerative spondylolisthesis  the authors examined the stability of combined distraction and compression rod instrumentation with posterolateral fusion in 40 consecutive patients with unstable degenerative spondylolisthesis  all operations were performed by floating fusion of l3 4 or l4 5 after decompression procedures  mobility at the fused level was checked every 4 weeks after operation by the disc space angle on the functional radiographic films without brace  the average period of postoperative follow up was 26 months  in 30 patients  no mobility was found at any time  in six patients  any mobility disappeared within 24 weeks  and in three patients  within 1 year  pseudoarthrosis was found in one patient  the solid fusion rate was 97 5   the values of percent slippage and slip angle were slightly improved  lumbar lordosis was in the normal range at follow up  
class5	eosinophilic granuloma of bladder  eosinophilic granuloma of the bladder  a rare and certainly poorly known disease  simulates bladder neoplasms  clinical aspects  histology  and therapy in a young boy are described  
class5	congenital monomelic hypertrophy with progressive myopathy  we describe a patient with congenital monomelic hypertrophy who later developed progressive footdrop due to a degenerative myopathy  the clinical  electrophysiologic  and pathologic features of the case are described and compared with those of a previously reported case  
class5	the relationship of complement mediated microvasculopathy to the histologic features and clinical duration of disease in dermatomyositis accumulating evidence indicates that a complement mediated microvasculopathy may play a pathogenic role in dermatomyositis  in a previous study  we demonstrated neoantigens of the c5b 9 complement membrane attack complex in the muscle microvasculature of childhood and adult cases of dermatomyositis  to further characterize the relationship between the vascular complement deposits and histologic changes  quantitative histopathologic analyses were performed on 39 dermatomyositis biopsy specimens  26 adult  13 children   there was a significant correlation between the percentage of fascicles with fibers having focal myofibrillar loss  a change seen early in the evolution of ischemic muscle fiber damage  and the percentage of fascicles having capillary deposits of membrane attack complex  conversely  in biopsy specimens with a higher percentage of fascicles with perifascicular atrophy  membrane attack complex deposits were significantly less common  a fascicle by fascicle analysis supported these observations  patients whose biopsy specimens were negative for microvascular membrane attack complex had clinical weakness for a significantly longer time than those patients with vascular complement deposits  these data support the hypothesis that the complement mediated vasculopathy is a primary immunopathogenic event in the evolution of muscle lesions in dermatomyositis  
class5	focal myositis  a new cause for the pediatric neck mass  focal myositis is an inflammatory pseudotumor of skeletal muscle that may involve the head and neck  it can closely mimic either a neoplastic or infectious process  we present the case of a 7 year old boy with a 2 week history of a painful  unilateral neck swelling  fever  and torticollis  he failed to respond to antibiotic therapy and required an open neck exploration  an incisional biopsy of the indurated  inflammatory tissue adherent to his sternocleidomastoid muscle showed focal myositis  focal myositis is an unusual  but important possibility in the differential diagnosis of any neck mass and especially one in a child  although its cause is unknown  it is a self limited disease and neither excisional biopsy nor radical resection is justified  
class5	surgical treatment of internal derangements of the temporomandibular joint  a long term study  a long term surgical follow up study of 176 patients  211 joints  with documented internal derangements of the temporomandibular joint was carried out  arthrograms and tomograms were used in all cases  forty of the patients  49 joints  were nonsurgical control patients  diagnostic staging of the cases was accomplished as previously published  a clinical radiologic assessment index was derived  which included seven measured parameters  surgical patients  grouped by diagnostic stages and selected operations  were compared with each other and with control patients over the follow up period  average  8 1 years  range  5 to 14 years   the surgical procedures included meniscectomy  reconstructive arthroplasty  and arthroplasty with temporary silastic  dow corning wright  arlington  tenn  implant  the overall success rate for surgical cases with all stages and procedures was 93 8   in contrast  the control group demonstrated significant clinical and radiographic progression  the surgical results were stage dependent for the same operative procedure  significantly better success rates were obtained in early stage cases  96 9   than in late stage cases  89 4    with respect to comparison of operative procedures  it was found that reconstructive arthroplasty provided results superior to those of meniscectomy  there was no significant difference between results obtained by meniscectomy and those by arthroplasty with a temporary silastic implant  long term stability was excellent in most cases  follow up radiographic changes for the surgical group were less than expected  on the other hand  radiographic analysis of the control group demonstrated progressive degenerative changes in 73 5  of cases  complications over the entire study were rare  it was concluded that surgery can provide successful long term results in the treatment of internal derangements  
class5	computed tomographic assessment of old calcaneal fractures  prolonged pain and disability are common complications of calcaneal fractures  a prospective study was conducted on the value of computed tomography  ct  in 63 patients with 73 calcaneal fractures sustained more than 6 months before  the fractures were classified from the initial plain radiographs  and the patients  current clinical condition assessed in terms of a  disability score   the mean disability scores  mds  associated with the different types of fracture were correlated with the ct findings  the highest mds was found in the intra articular fracture group which comprised 71  of the series  in this group the mds was increased in the presence of post traumatic osteoarthrosis of the subtalar joint  61  of cases   involvement of the calcaneocuboid joint  39  of cases  and subluxation dislocation of the peroneal tendons  47  of cases   structural abnormalities of the peroneal tendons were associated with a higher mds including chronic tenosynovitis  eight cases   chronic partial tendon rupture  eight cases   complete peroneus brevis tendon rupture  two cases  and scarring indicating stenosing tenosynovitis  14 cases   a similar spectrum of appearances affecting the medial tendons of the hindfoot was identified in eight cases  direct ct measurements of the degree of comminution did not correlate well with the patients  mds  in the patient with persistent symptoms  ct is of value in the later assessment of long term complications by revealing abnormalities of the subtalar joints and adjacent tendons  
class5	magnetic resonance imaging of primary skeletal muscle diseases  patterns of distribution and severity of involvement  magnetic resonance imaging of the lower extremities was performed with a low field system in 51 patients representing three different categories of biopsy proven primary skeletal muscle disease  muscular dystrophies  congenital myopathies and polymyositis  the intermuscular distribution of abnormal signal intensity and the grade of involvement of individual muscles were assessed  large differences in the degree of pathological signal intensity between individual muscles were found in all categories  in the muscular dystrophy and polymyositis patients  the overall involvement was significantly more severe than in patients with congenital myopathy  definite patterns of selective involvement were seen  statistical evidence of selective muscle sparing was found  the gracilis muscle was significantly less affected than the other muscles in all three disease groups  other muscles with significant sparing include the rectus femoris and sartorius muscles of the thigh and the tibialis posterior muscle of the leg  common anatomical and functional characteristics of muscles may be related to the distribution of muscular disease  
class5	identification of osteoclast precursors in multilineage hemopoietic colonies  the osteoclast is known to be derived from the hemopoietic stem cell  but its lineage and the mechanisms by which its differentiation is regulated are largely unknown  there is evidence that osteoclastic differentiation is induced through a contact dependent interaction between bone marrow stromal cells and hemopoietic precursors  to analyze osteoclastic lineage  colonies were generated in semi solid medium from mouse spleen cells in the presence of erythropoietin with either wehi 3b conditioned medium or interleukin 3  il3   after 7 days  individual colonies were picked  half of each colony was phenotyped by the morphology of cells in cytospin preparations  the second half of each was incubated for 7 days with a bone marrow derived cell line  ts8  that induces osteoclastic differentiation from hemopoietic cells  on bone slices in the presence of 1 25 dihydroxyvitamin d3  after incubation  bone resorption was assessed by scanning electron microscopy  no resorption was induced in cells derived from single lineage colonies  but resorptive cells differentiated in 17  of granulocyte macrophage  gm  colonies and 38  of multilineage colonies  since only a minority of gm colonies contained osteoclastic precursors  this suggests that the gm colonies that contained osteoclasts were not typical gm colonies but may have been a form of multilineage colony analagous to other multilineage colonies that contain granulocytes  macrophages  and a third cell type  no resorptive cells were formed when il3 derived colonies were incubated on bone slices without ts8 cells  the results suggest that osteoclasts are derived from a multilineage precursor  upon which il3 acts to generate cells capable of osteoclastic differentiation  which form resorptive cells upon incubation with bone marrow stromal cells in the presence of 1 25 dihydroxyvitamin d3  
class5	high concentrations of 17 beta estradiol stimulate trabecular bone formation in adult female rats  although the effects of low concentrations of 17 beta estradiol  e2  on bone formation and resorption are well described  little is known of the effects of e2 on bone at concentrations that circulate during pregnancy  we  therefore  investigated the effects of administration of high dose e2 to 3 month old female wistar rats on biochemical and histomorphometric indices of bone formation and resorption  animals receiving exogenous e2  4 mg kg day for 17 days  n   9  showed a mean serum e2 concentration of 17 5     2 9 nm  compared with 0 6     0 2 nm in those receiving vehicle alone  n   10   the bone formation rate  measured at the proximal tibial metaphysis after the administration of double fluorochrome labels  was greatly increased in the e2 group  13 6     2 0 x 10  2  microns3 microns2 day  compared to controls  3 9     0 9   as was serum alkaline phosphatase  e2  133 6     10 1 iu  controls  87 5     5 5   this increase in the rate of bone formation was associated with a significant increase in trabecular bone volume  e2 treatment did not affect urinary hydroxyproline excretion or histomorphometric indices of bone resorption  these findings suggest that high concentrations of e2 strongly stimulate the formation of trabecular bone  this may represent an important mechanism by which calcium stores are accumulated during pregnancy in rats  in anticipation of the mineral requirements of lactation  
class5	elevated expression of the genes for transforming growth factor beta 1 and type vi collagen in diffuse fasciitis associated with the eosinophilia myalgia syndrome  full thickness skin biopsies obtained from four patients with rapidly progressive diffuse fasciitis associated with the eosinophilia myalgia syndrome  ems  were examined for the expression of transforming growth factor beta 1  tgf beta 1   type vi collagen  and fibronectin genes employing immunohistochemistry and in situ hybridizations  the immunohistochemical studies demonstrated increased deposition of tgf beta  type vi collagen  and fibronectin epitopes in the extracellular matrix of the fascia in comparison to the adjacent dermis in the same specimens  increased levels of type vi collagen mrna  as evidenced by positive in situ hybridization signals with an alpha 2 vi  collagen cdna  were also found in the fascia in comparison with the dermis  in situ hybridizations of affected fascia with a human sequence specific tgf beta 1 cdna demonstrated numerous fibroblasts displaying positive hybridization signals indicative of high levels of transcripts for this cytokine  in contrast  no hybridization signal for tgf beta 1 was detected in fibroblasts in the adjacent dermis  these findings suggest that tgf beta 1 may play an important role in the development of the connective tissue alterations present in ems associated diffuse fasciitis  
class5	diagnostic utility of lower extremity radiographs of young children with gait disturbance  the diagnostic utility of lower extremity radiographs was evaluated using 84 outpatients 1 to 5 years of age with gait disturbance whose lower extremities appeared physically normal  chief complaints included limp  65 children  77     refusal to walk or stand  37 children  44     and frequent falling  6 children  7     a total of 43 children  51   had more than one complaint  the mean age of patients was 26 months and the median duration of symptoms was 1 day  trauma was reported in 43  51   cases and fever in 14  17    results of radiographical studies appeared normal in 81 children  96    demonstrated soft tissue swelling in 2 children  and revealed a bony island in 1 child  in 1 patient admitted to the hospital for failure to thrive and irritability  and whose radiographic results appeared normal  findings consistent with osteomyelitis later developed  of the remaining children  68  81   were available for follow up observation 4 to 28 months after the initial visit and all reported spontaneous resolution of the initial complaint  it was concluded that in a well appearing child with an otherwise normal physical examination results  an acute gait disturbance is likely to be a self limiting condition and radiographs are unlikely to contribute to the diagnosis  
class5	psychological characteristics of children with shwachman syndrome  twelve children and young adults with shwachman syndrome were compared with their unaffected siblings and with controls suffering from cystic fibrosis in terms of intellectual ability  motor skills  and behaviour  there were highly significant differences in intelligence quotient between those with shwachman syndrome and the other two groups  four of the index subjects but none of the control subjects were below the normal range  the differences between groups on other tests of cognitive and motor skills were not significant  though those with shwachman syndrome tended to have the lowest scores  there was no evidence that those with shwachman syndrome had more behavioural difficulties than the control subjects  we suggest that the intellectual difficulties of patients with shwachman syndrome may be of neurological rather than social origin and that they may originate before birth  
class5	early antibiotic treatment of reactive arthritis associated with enteric infections  clinical and serological study  objective  to find out whether a 10 14 days  course of antibiotics early in the course of reactive arthritis associated with enteric infections could reduce the severity and duration of the disease and whether the antibody response in patients with reactive arthritis associated with yersinia infection differed between those treated and those not treated with the antibiotics  design  prospective multicentre trial in which patients were randomised to treatment or no treatment with antibiotics  patients were seen at three and six weeks and three  six  nine  12  and 18 months after their first visit  setting  departments of infectious diseases in three hospitals in linkoping  malmo  and stockholm  sweden  patients  40 consecutive patients who had had symptoms of reactive arthritis associated with enteric infection for less than four weeks  interventions  20 patients were allocated to treatment with antibiotics and 20 patients did not receive antibiotics  all patients received non steroidal anti inflammatory drugs  and four also received intra articular steroid injections after at least six weeks  observation  main outcome measures  arthritic symptoms assessed clinically and by using ritchies  index  blood measurements reflecting inflammatory activity  serum igg  igm  and iga antibody titres  hla tissue type  results  no difference was observed concerning duration of arthritis  grade of inflammation  and number of joints affected between patients treated and those not treated with antibiotics  furthermore  there was no significant difference between the two groups in erythrocyte sedimentation rate and haptoglobin  igg  and iga concentrations  all values had returned to normal within three months  no patient developed chronic arthritis  but sustained slight arthralgia occurred in three patients  the hla b27 antigen was found in 23  58   of the patients  and its presence did not affect clinical outcome  the igg  igm  and iga antibody responses were similar in patients treated with antibiotics and those not treated  conclusion  short term antibiotic treatment has no beneficial effect on the clinical outcome of reactive arthritis associated with enteric infection  
class5	effect of thiazide on rates of bone mineral loss  a longitudinal study  published erratum appears in bmj 1991 jan 26 302 6770  18  objective  to determine the effect of thiazide diuretic drugs on rates of bone mineral loss  design  longitudinal  observational study with a mean follow up of five years  setting  hawaii osteoporosis center  honolulu  subjects  1017 japanese american men born between 1900 and 1920  of whom 378 were treated for hypertension  study group  and 639 did not have hypertension  control group   intervention  thiazide diuretics were taken by 325 men for a mean of 11 9 years  53 men took antihypertensive drugs other than thiazides  main outcome measure  rate of bone loss estimated from serial photon absorptiometric scanning at three skeletal sites  calcaneus  distal radius  and proximal radius   results  rates of bone loss at all three sites were significantly reduced among thiazide users when compared with controls  the reductions in loss rate ranged from 28 8   p   0 02   distal radius  to 49 2   p   0 0005   calcaneus  relative to the controls  at all three sites the men taking other antihypertensive drugs had faster loss rates  22 6 43 1   than those of the controls but the difference was significant only for the distal radius  conclusion  thiazide diuretics slow the rate of bone loss in elderly men  
class5	cutaneous manifestations of the l tryptophan associated eosinophilia myalgia syndrome  a spectrum of sclerodermatous skin disease  the natural history of the clinical and pathologic features of skin disease was reviewed prospectively in 30 patients with the l tryptophan associated eosinophilia myalgia syndrome  overall  cutaneous manifestations developed in 26 patients  87    early lesions were nonspecific and characterized predominantly by an erythematous macular eruption on the trunk and extremities  the most characteristic abnormality noted was the spectrum of sclerodermatous disease in 15 patients  50   often after a subacute stage of peripheral or truncal edema  clinical and or biopsy evidence of eosinophilic fasciitis was seen in nine patients  30    findings consistent with diffuse  limited  or localized scleroderma were subsequently observed in nine patients  33    small mucinous papules  similar to those seen in scleromyxedema  were found in five patients  17    alopecia  frequently a late sequela  developed in 11  37    common histologic features included papillary dermal fibrosis  dermal and fascial infiltrates consisting of mononuclear cells and eosinophils  deposition of glycosaminoglycans in the dermis  and  in some patients  numerous mast cells  
class5	central corpectomy for cervical spondylotic myelopathy  a consecutive series with long term follow up evaluation  since 1984  a consecutive series of patients with cervical spondylotic myelopathy has been treated by central corpectomy and strut grafting  this report focuses on 40 cases operated on between 1984 and 1987 and followed from 2 to 5 years  the perioperative complication rate was 47 5   with a 7 5  incidence of persistent sequelae  severe c 5 radiculopathy in one patient  swallowing dysfunction in one  and hypoglossal nerve palsy in one  no single factor  age  duration of symptoms  or severity of myelopathy  was absolutely predictive of outcome  however  syndromes of short duration had the best likelihood of cure  similar outcomes were associated  individually  with long duration of symptoms  age over 70 years  and severe myelopathy  after factoring a 5  regression of improvement  the long term cure rate was 57 5  and the failure rate was 15   myelopathy worsening was not documented  
class5	the interspinous method of posterior atlantoaxial arthrodesis  thirty six patients underwent c1 2 posterior wiring and fusion procedures over a 5 year period for unstable c 2 fractures  eight cases   unstable atlas axis combination fractures  six cases   rheumatoid c1 2 instability  14 cases   os odontoideum  four cases   traumatic c1 2 ligamentous instability  three cases   or instability secondary to a c 2 tumor  one case   in each case  the atlantoaxial arthrodesis utilized sublaminar wire at c 1 and incorporated an iliac crest strut graft positioned between the posterior arches of c 1 and c 2  held in place by securing wire around the base of the spinous process of the axis  follow up examination was performed in all patients after a mean postoperative duration of 33 7 months  the technical aspects and clinical merits of this fusion procedure  which led to a 97  union rate  one nonunion  and minimal morbidity and mortality rates  are presented  
class5	orbital rim and malar advancement for unilateral coronal synostosis in the older pediatric age group  the authors describe a technique for lateral orbital rim and malar advancement in patients in the older pediatric age group  the technique makes use of a strip craniotomy containing the supraorbital margin  greater sphenoid wing  and temporal bone  with en bloc inclusion of the lateral orbital rim  zygoma  and malar prominence  the method allows a contoured yet stable construction secured in a tongue in groove fashion with plate and screw fixation  it creates a symmetrical reconstruction of both frontal and lateral orbital aspects in the untreated or inadequately treated older plagiocephalic child with orbital dystopia  the accompanying malar recession is likewise corrected  
class5	indium 111 chloride and three phase bone scintigraphy  a comparison for imaging experimental osteomyelitis  to investigate the utility of indium 111 chloride  111in cl  imaging in detecting osteomyelitis complicating surgical or fracture sites  the proximal tibia of 11 dogs were experimentally infected with staphylococcus aureus after creation of a cortical defect  the contralateral limb served as a sham operated control  animals were serially imaged by radiography  three phase technetium 99m methylene diphosphonate  99mtc mdp  scintigraphy  and 111in cl scintigraphy  there was a significant difference between infected  1 93  and noninfected  1 32  limb s tibia femur count density ratios on 24 hr  p   0 0001  and 72 hr  p   0 0001  111in cl images  a smaller difference was found for 99mtc mdp bone phase tibia femur ratios  p   0 0199   using receiver operator characteristic analysis of tibia femur ratios  a sensitivity of 61   specificity of 88   and positive  75   and negative  79   predictive values were determined for the 24 hr 111in cl images  indium 111 chloride was superior to 99mtc mdp in differentiating infected and noninfected operative sites  
class5	methotrexate nonsteroidal antiinflammatory drug interaction in children with arthritis  in order to assess the interaction between methotrexate  mtx  and nonsteroidal antiinflammatory drugs  nsaid   we studied the pharmacokinetics of oral mtx alone and in the presence of the usually prescribed nsaid in 7 children with chronic arthritis  the nsaid studied included tolmetin  indomethacin  naproxen  and aspirin  six patients were treated with multiple nsaid  the mean mtx elimination half life was prolonged when nsaid were coadministered  1 7     0 5 vs 1 2     0 1 h  p   0 03   however  neither the apparent mtx clearance  ci   10 6     5 5 vs 13 1     3 5 l h  p   0 19   the area under the serum mtx concentration time curve  auc   2 1     1 0 vs 1 5     0 6 mumol l h  p   0 08  or the apparent volume of distribution  vd   23 0     6 2 vs 21 9     6 4 l  p   0 53  was significantly altered by the administration of nsaid  although the differences between the mean cl and auc were not statistically significant  a wide variation in the impact of nsaid on mtx cl was observed  in 6 of 7 patients  the auc increased during nsaid administration from 19 to 140   this degree of increase may be clinically significant in some individuals  it is consequently recommended to closely monitor patients who are receiving mtx and nsaid for mtx toxicity until these results can be verified in a larger population  
class5	some osseous and soft tissue causes of human intervertebral canal  foramen  stenosis  much attention has been paid to the causes of vertebral canal stenosis in humans but relatively little has been documented with regard to intervertebral canal  intervertebral  foramen   lateral spinal canal  nerve root canal  stenosis  as the dural sleeve ends at the outer opening of the intervertebral canal  a false  normal  myelogram is possible when a space occupying lesion occurs beyond the subarachnoid space  also  if stenosis affects only vascular structures  compression of these structures cannot be noted during myelography  so venous stasis may be overlooked  our cadaveric study investigates some causes of intervertebral canal stenosis due to encroachment by bony and soft tissue structures  and low magnification photomicrographs are used to illustrate some causes of stenosis  
class5	hla class ii and t cell receptor gene polymorphisms in psoriatic arthritis and psoriasis  hla drb  dqa and dqb genes as well as the t cell receptor  tcr  alpha  beta  and gamma genes were studied by southern blot analysis of genomic dna from patients with psoriatic arthritis  psa  and psoriasis alone  ps   a subtype of dr7  dr7a  was found in 38 8  of patients with psa  41 5  of patients with ps  and in 8  of healthy individuals  n   psa vs n  pc   0 0002  rr   7 1  ps vs n  pc   0 0002  rr   7 9   no association with tcr genes was found  our findings suggest either that the dr7a allele may be in linkage disequilibrium with hla cw6 or that it may be an important susceptibility factor for psa and ps  
class5	macroscopic and microscopic gut lesions in seronegative spondyloarthropathies  a retrospective study by ileocolonoscopy and multiple biopsies was performed on 96 patients with seronegative spondylarthropathy  17 patients with osteoarthritis  oa  and 19 patients with chronic abdominal discomfort  under these conditions  inflammatory gut lesions were detected in 66 7  of the patients with spondyloarthropathy  12 5  with oa and 15 8  with chronic abdominal discomfort  in 10 patients treated by sulfasalazine  salazopyrine   pathologic lesions disappeared simultaneously with an improvement of the rheumatic conditions  comparison between patients treated and untreated with nonsteroidal inflammatory drugs  nsaid  demonstrated that nsaid did not enter into the etiopathology of the intestinal lesions  our study therefore confirms the high incidence of inflammatory gut lesions among patients with spondylarthropathy which seems not to be related to nsaid therapy  
class5	differential diagnosis between osteitis condensans ilii and sacroiliitis  published erratum appears in j rheumatol 1991 may 18 5  790  sacroiliitis of seronegative spondyloarthropathy may sometimes show on pelvis plain films findings indistinguishable from those of osteitis condensans ilii  computed tomography  ct  can differentiate earlier than plain radiography between the 2 conditions  furthermore  it should also be possible to make this differentiation clinically  the aim of our study was to verify whether the criteria recently proposed by the european spondylarthropathy study group  eesg  for the classification of spondyloarthropathy are useful  ct scans through the synovial part of the sacroiliac joints of 7 consecutive patients meeting the essg criteria and showing typical findings of osteitis condensans ilii on plain films were mixed with those of 15 consecutive patients with osteitis condensans ilii not meeting the essg criteria  scans were examined for joint space and surface abnormalities blindly and independently by 2 observers  six patients in the spondyloarthropathy group and one in the osteiitis condensans ilii group showed clear erosions and or joint space narrowing of less than 2 mm in at least one joint  the difference was statistically significant  p less than 0 001   our results suggest that by using criteria valid for the whole group of seronegative spondyloarthropathies  it is possible to differentiate clinically between seronegative spondyloarthropathies with sacroiliitis mimicking osteitis condensans ilii and  true  osteitis condensans ilii  
class5	relapsing polychondritis in pregnancy  a 25 year old patient presented at 14 weeks of her 3rd pregnancy with chondritis affecting the cartilaginous portion of her right ear  the clinical syndrome of recurrent chondritis  scleritis  iritis and arthritis supported a diagnosis of relapsing polychondritis  fetal and maternal outcomes were favorable despite steroid dependent active disease during the period of fetal organogenesis  chondritis was limited to the 3rd pregnancy  ocular inflammation occurring in the 2nd and 3rd pregnancies  a 4th pregnancy was uneventful  this may represent the first case of relapsing polychondritis in pregnancy  
class5	l tryptophan induced eosinophilia myalgia syndrome  we describe the spectrum of clinical and histologic abnormalities of 11 women with l tryptophan induced eosinophilia myalgia syndrome  the illness is characterized by musculoskeletal symptoms including myalgias  arthralgias and paresthesias  the physical findings consist of muscle tenderness  neuropathies  rash  peripheral and periorbital edema  electroneurography performed in 10 patients demonstrated a neuropathy in 5 and myopathic changes in 3  skin and muscle biopsies showed fascial edema  inflammation and perivascular infiltrates in the skin  whereas perineural infiltrates and venulitis were identified in muscle  seven patients were treated with prednisone  eosinophilia disappeared promptly although myalgias and neuropathy persisted  
class5	eosinophilia myalgia syndrome associated with l tryptophan use  the eosinophilia myalgia syndrome associated with the use of oral preparations of the amino acid l tryptophan was recognized in late 1989  we describe the clinical and laboratory manifestations  pathological findings and early clinical course of 20 patients with the eosinophilia myalgia syndrome  prominent clinical findings included severe myalgias limiting function  fatigue  rashes  edema and weight gain  weight loss  muscle weakness and shortness of breath  laboratory findings included eosinophilia  often marked   normal erythrocyte sedimentation rate  and elevated aldolase with normal or low creatine kinase values  on biopsy fascial inflammation was always seen consisting of lymphocytes  histiocytes and eosinophils in a perivascular distribution  invasion of the vascular wall by lymphocytes was seen in 20   capillary and arteriolar endothelial cell thickening was found in most cases on electron microscopy and endothelial cell necrosis or mural invasion by lymphocytes was seen in 25  of cases  two patients improved with no therapy  ten patients responded to therapy with prednisone alone  three patients have had progressive disease and one of these died  the relationship of this syndrome to previously described disease entities associated with eosinophilia is discussed  
class5	microangiopathy in the eosinophilia myalgia syndrome  the eosinophilia myalgia syndrome associated with the ingestion of l tryptophan was recognized in late 1989  we describe our pathologic study of skin  fascial  and muscle biopsies from 21 patients evaluated by light microscopy  histochemistry  and electron microscopy  a perivascular  lymphocytic infiltrate with eosinophils was present in the dermis  fascia  and skeletal muscle  lymphocytic infiltration of arteries and arterioles was seen  ultrastructurally  capillary and arteriolar endothelial cell thickening and necrosis was present  this microangiopathy suggests that ischemia may be a contributing factor to the findings in this syndrome  
class5	an eosinophilia myalgia syndrome associated with an l tryptophan containing product  a syndrome of eosinophilia and myalgias associated with the usage of l tryptophan containing products has been recently described by the centers for disease control  we report a case of this new clinical entity  highlighted by severe myositis  and compare this illness with similar reported syndromes  
class5	eosinophilic myositis an expression of l tryptophan toxicity  eosinophilia myalgia syndrome possibly due to l tryptophan is a new clinical entity that has been recently reported  we describe the clinical presentation of eosinophilia  eosinophilic pustular folliculitis  myalgia  and eosinophilic myositis  that led to respiratory failure in a young man taking an l tryptophan containing compound  
class5	eosinophilia myalgia syndrome in association with l tryptophan ingestion  the association between the recently described eosinophilia myalgia syndrome and l tryptophan is now well established  we describe a patient with eosinophilia myalgia syndrome who developed incapacitating myalgias and peripheral eosinophilia responsive only to high dose corticosteroids  when massive upper gastrointestinal hemorrhage developed while receiving corticosteroid therapy  surgery was complicated by striking abdominal wall rigidness  a discussion of this case and of eosinophilia myalgia syndrome is presented  
class5	l tryptophan associated eosinophilia myalgia syndrome  environmental chemicals are increasingly incriminated in the pathogenesis of several disease states  the eosinophilia myalgia syndrome is a recently described entity attributed to the ingestion of the normal dietary amino acid l tryptophan  we describe a patient who fulfills criteria for the eosinophilia myalgia syndrome and who was ingesting supplemental l tryptophan  exhaustive investigations failed to reveal other causes for her eosinophilia or her myalgic neuropathic complaints  and she improved dramatically when she discontinued the l tryptophan supplements  the mechanisms whereby this chemical may induce this syndrome are discussed  
class5	a useful technique for measurement of back strength in osteoporotic and elderly patients  improvement of back extensor strength  bes  can be used as a therapeutic method for patients with chronic back pain and osteoporosis  the method of evaluation must be reliable and accurate without compromising the condition of the patient  we report the development of a back isometric dynamometer  bid 2000  designed specifically by two of us to address these concerns in elderly patients with osteopenia or osteoporosis  as the demographics of the general population change  increasing numbers of patients will need the type of monitoring that the bid 2000 provides  aging has been shown to cause a reduction in the number of functional muscle motor units  to examine this effect on bes  we tested 50 normal  healthy women who were 30 to 79 years old  proper testing of bes in patients with fragile vertebrae should include isometric measurement in the prone position  maneuverability of the device to allow comfortable positioning of the patient  and simplicity of technique to minimize repetitious performance of maximal contraction  the bid 2000 incorporates each of these features and also provides meaningful results inexpensively  the device offers a safe  reliable  coefficient of variation   2 33    and valid  p   0 001  method of evaluation  the results of our study demonstrated moderate  steady reduction of bes with increasing age and with each successive decade  
class5	giant intradiploic epidermoid tumor of the occipital bone  case report  the authors describe a case of a giant intradiploic epidermoid cyst of the occipital bone with an intracranial extension in the posterior fossa and no signs of neurological involvement  the lesion started as a painless lump under the scalp  roentgenographic and computed tomographic findings led to a correct diagnosis  and the complete removal of the cyst was accomplished  despite its large size  the total removal of these cysts is associated with a good prognosis  
class5	occult  bilateral anterior sacral and intrasacral meningeal and perineurial cysts  case report and review of the literature  none of the more than 180 cases of anterior sacral meningocele reported in the past 150 years has been bilateral  and only two have been associated with occult intrasacral meningocele  we report a unique case of bilateral anterior sacral cysts  communicating with the subarachnoid space  associated with occult intrasacral meningeal and perineurial  tarlov s  cysts  in an asymptomatic woman  the pertinent clinical and diagnostic imaging literature is reviewed  
class5	methods of treating plantar ulcers  the purpose of this article is to describe the indications  precautions  and fabrication techniques for orthotic devices the authors use to facilitate the healing of plantar ulcers  the methods of fabricating and applying three types of orthotic devices developed by the staff at the gillis w long hansen s disease center  walking casts  walking splints  and cutout sandals  are described  patient examples are given for each of the methods  these techniques  in conjunction with patient education and the use of special footwear  provide clinicians with procedures they can use to aid in the healing of plantar ulcers secondary to leprosy  diabetes  or other neuropathic conditions  
class5	restoration of the anterior neck surface in the burned patient by free groin flap  in treating extensive burn contractures of the anterior neck  we obtained good results using free flaps  ninety nine patients with neck contractures were treated with free flaps  the ages of the patients range from 2 to 64 years  we used 84 free groin flaps  10 free latissimus dorsi musculocutaneous flaps  2 free deltopectoral flaps  2 free scapular flaps  and 1 free anterolateral thigh flap  in all patients  contractures were sufficiently released and no recurrences followed after a mean follow up of 8 7 years  after defatting procedures  natural profiles and good appearances were restored  especially in patients in whom groin flaps were used  
class5	trigger finger secondary to anomalous lumbrical insertion  a case report and review of the literature  trigger finger is a relatively common clinical entity  most frequently caused by stenosing tenosynovitis  several other conditions not related to tenosynovitis also have been described as a cause of triggering  and these have been reviewed  we present a rare anomaly of the fourth lumbrical muscle insertion as a cause of triggering of the right little finger  this was completely relieved following excision of the anomalous muscle  this rare anatomic variant should be added to the list of potential causes of trigger finger  
class5	pulmonary involvement in the eosinophilia myalgia syndrome  we describe the cases of three women with pulmonary involvement in the eosinophilia myalgia syndrome  the illness was characterized by elevated peripheral blood eosinophil counts  myalgias  fatigue  and dyspnea  two of three patients had bilateral infiltrates on chest roentgenograms  all three had markedly decreased carbon monoxide diffusing capacities and pulmonary hypertension  high dose prednisone therapy provided only partial resolution of the pulmonary symptoms  open lung biopsy specimens showed chronic interstitial and perivascular infiltrates in two of the patients and moderate fibrointimal hyperplasia of pulmonary vasculature in the third  high dose prednisone therapy prior to the biopsies may have modified the original histologic features  
class5	reviewing the unicystic ameloblastoma  report of two cases  classification of ameloblastoma into solid  multicystic  unicystic  and peripheral types based on clinical appearance and effects has gained recent recognition  the unicystic ameloblastoma is a less encountered variant of the ameloblastoma  it appears more frequently in the second or third decade with no sexual or racial predilection  it is almost exclusively encountered asymptomatically in the posterior mandible  the following report of two cases discusses the pathophysiology  demographics  histology  and prognosis of the unicystic ameloblastoma  
class5	infectious mononucleosis  epstein barr virus  and chronic fatigue syndrome  a prospective case series epstein barr viral infection  specifically infectious mononucleosis  typically has a more protracted course than other acute viral illnesses  some recent observers have additionally suggested the possibility that epstein barr virus  ebv  is the etiologic infectious agent in chronic fatigue syndrome  based on the finding of higher proportions of elevated antibodies to the ebv early antigen in some patients complaining of chronic fatigue  straus et al reported on 23 patients with chronic fatigue  83  of whom exhibited persistently elevated antibodies in modest titer to the early antigen  ten of these patients had never fully recovered from an episode of acute infectious mononucleosis  other studies had noted similar associations between persistently elevated antibodies to ebv specific antigens and chronic symptoms in patients who presented with chronic symptoms after mononucleosis  three important antigen complexes  demonstrable by immunofluorescence procedures  are expressed in ebv infected cells  the early antigen is thought to function perhaps in early replication of viral dna  a late antigenic complex  the viral capsid antigen  may represent  in addition to structural capsid proteins  components of the viral enzymatic machinery for late phases of replication or transformation  the epstein barr nuclear antigen is felt to function in viral transformation of host cells  
class5	evaluation of ultrasound in the diagnosis of pathologic processes in the parotid gland  the values of ultrasound in differentiation of pathologic processes in the parotid gland were studied in 61 patients  the ultrasound findings were compared with operative and histologic findings  in 28 patients with chronic inflammatory processes  the ultrasound findings were in complete correlation with the histologic findings  showing enlarged parotid glands  homogenous glandular epithelium  and small  multiple cysts  in 31 patients with a tumor of the parotid gland  ultrasound scanning detected the presence of the tumor  in determining the location of the tumor  the method is highly specific when it is localized in the superficial lobe  100    and it is less specific when it is localized in the deep lobe of the parotid gland  also  it is highly specific in determination of tumor size  96    in two cases with retention cysts  the ultrasound findings also correlated with the histologic and operative findings  the results obtained show that ultrasound is a reliable diagnostic method for detection of pathologic changes in the parotid gland  
class5	arthroscopic treatment of temporomandibular joint locking resulting from disc derangement  two year results  this article reports 2 year postarthroscopic surgical treatment data for 18 subjects  17 female and 1 male  who had a diagnosis of restricted mandibular movement due to an internal derangement of the temporomandibular joint  tmj   these subjects had been treated by an average of 2 1     1 1 doctors for their tmj problem before seeing the surgeon for arthroscopic treatment  the subjects  mean pain score at the final time point  21 to 30 months after surgery  was decreased by 57  in usual pain intensity  jaw function showed an average improvement of 67   these subjects also showed a 13 mm mean increase in their maximum active opening ability at the 2 year postsurgical time point  slight to definite clicking noises were present presurgically in 11 of 18 patients  and similar joint noises were reported in 14 of 18 patients postsurgically  the mean overall improvement was rated as 8 18     2 4  with 10 the highest possible rating  one subject rated her improvement as 0  two subjects rated their improvement as 6 out of 10  no significant morbidity was reported by the subjects as a result of their surgery  
class5	extracranial and mandibular augmentation with hydroxyapatite collagen in induced diabetic and nondiabetic rats  published erratum appears in j oral maxillofac surg 1991 jun 49 6  669  this study evaluated three hydroxyapatite  ha  preparations placed subperiosteally in rats given streptozotocin  70 mg kg  to induce diabetes  id   n   24  and in nondiabetic  nd  rats  n   24  used as controls  implants of 1  nonporous ha granules  hag   2  ha granules hand mixed with bovine collagen  hacm   and 3  ha granules and purified fibrillar collagen in a preprocessed block  pfc ha  were randomly placed in subperiosteal pockets created on the cranium and adjacent to the left right mandibles of each rat  six rats from each group were killed at 3  6  12  and 24 weeks postimplantation  animals killed after 3 weeks showed sporadic bone proliferation and bone resorption  whereas those killed after 6  12  and 24 weeks showed formation of new bone at the implant bone interface  contact of the implant with bone was a requirement for osteogenesis  but bone formed only into the basilar layers of the implants  the id group showed the greatest inflammatory response as well as the greatest degree of osteogenesis at all intervals of time  the addition of collagen to ha appeared to reduce the inflammatory response  specimens implanted with hacm showed the least inflammation of the three implanted materials in both id and nd groups  
class5	internal derangement of the temporomandibular joint  a histochemical study  the purpose of this study was to correlate histologic findings in temporomandibular joint  tmj  condyles and discs with their macroscopic appearance at surgery  the 24 patients with internal derangement of the joint included 20 women and 4 men  mean age  37 years  range  18 to 61 years   the tissue lesions varied in degree from mild soft tissue fraying and bone remodeling to extensive resorption and new cartilage and bone formation with high phosphatase enzyme activities  and even to loss of articular soft tissue and breakdown of cortical bone  reactions may arise in the hard tissues before they occur in the articular surface layers  
class5	drugs to lower uric acid levels  how to avoid misuse in gouty arthritis  several points regarding the use of drugs to lower uric acid levels deserve emphasis  first  these agents are not useful in the management of acute gout  second  all forms of the drugs should be initiated at low dose with gradual increments to achieve a serum uric acid level between 5 and 6 mg dl  there are no data to support the widely presumed notion that dropping the uric acid level to a very low range  1 to 3 mg dl  hastens resorption of tophi or improves joint function  third  the uricosuric agents probenecid  benemid  and sulfinpyrazone  anturane  interact with a number of drugs  and both the patient and physician should be aware of this  finally  and most important  careful and frequent monitoring is needed during the first several months of therapy with these drugs  
class5	chronic fatigue syndrome  is it real  epstein barr virus is no longer considered an important cause of chronic fatigue syndrome  instead  the disease is probably related to an underlying psychiatric disorder  subtle immunologic dysfunction  or an interaction between these two factors  a carefully taken history  physical examination  and simple laboratory testing are usually sufficient to establish the diagnosis  therapy with antidepressants or nonsteroidal anti inflammatory drugs may be effective in selected patients  thorough follow up conducted with empathy and optimism is important in all cases  
class5	musculoskeletal abnormalities in a patient with juvenile hypothyroidism  abnormalities in growth and development are the most striking clinical features of juvenile acquired hypothyroidism  therefore  physicians should consider the diagnosis of hypothyroidism in any child with musculoskeletal growth dysfunction  drs kilpatrick and fincher describe a case demonstrating the severe and potentially irreversible effects of prolonged  untreated hypothyroidism  
class5	laboratory tests for rheumatic diseases  a carefully taken history and thorough physical examination remain the most crucial aspects of diagnosing rheumatic disorders  non rheumatologic conditions also need to be kept in mind  laboratory tests should be looked on as mostly supportive or confirmatory  because many of the tests are relatively nonspecific and may lack sensitivity  if their limitations are recognized  however  the tests can be invaluable tools when the clinician confronts the task of differentiating an array of rheumatologic disorders  
class5	recurrent rhabdomyolysis in association with cocaine use  as the popularity of cocaine increases in our society  so does the frequency and variety of medical complications associated with its use  a growing number of cases have implicated cocaine use in the development of rhabdomyolysis and its complication  acute renal failure  we have reported the first case of recurrent rhabdomyolysis and acute renal failure directly associated with cocaine use  although adulterants might cause muscle damage  we believe cocaine should be added to the list of drugs that are capable of producing rhabdomyolysis  
class5	deep venous thrombosis in intravenous cocaine abuse mimicking septic arthritis of the shoulder  we describe two patients with deep venous thrombosis of the upper extremity who initially were thought to have septic arthritis of the shoulder  these patients had a history of recent intravenous cocaine abuse  the diagnosis of deep venous thrombosis should be considered when a patient with a swollen shoulder has an appropriate history  
class5	spinal cord compression due to pagetic spinal stenosis with involvement of extradural soft tissues  a case report  although paget s disease of the spine may cause neurological dysfunction by bone hypertrophy or collapse  it is very rare for the disease process to extend into the soft tissues of the spinal canal  we report a case of paget s disease causing ossification of the ligamentum flavum and extradural fat  thus causing spinal cord compression  decompressive laminectomy was carried out  resulting in neurological improvement  in such cases surgical decompression should be followed by therapy with calcitonin  
class5	the painful shoulder  part ii  intrinsic disorders and impingement syndrome  intrinsic disorders that can cause shoulder pain include arthritis  gout  pseudogout and osteonecrosis  in its mildest form  impingement syndrome may cause only minimal discomfort  at its worst  impingement syndrome may lead to rotator cuff tear  bicipital tendinitis and rupture of the biceps tendon may also be associated with impingement  early rehabilitative intervention is important  physical therapy is directed toward restoring range of motion and muscle strength  
class5	association of treacher collins syndrome and translocation 6p21 31 16p13 11  exclusion of the locus from these candidate regions  treacher collins syndrome  tcs  is an autosomal dominant defect of craniofacial development which has not been chromosomally localized  we have identified a mother and two children who have tcs and also a balanced translocation t 6 16  p21 31 p13 11   which suggested the possibility that the tcs locus might be located at one of the translocation breakpoints  these were defined by in situ hybridization as 6p21 31  by using loci in the hla complex defined by the probes p45 1dp beta 003 hla dpb2 and prs5 10 hla class i chain  and 16p13 11  by using probes pachf1 3 2 d16s8 and vk45 d16s131   pairwise and multipoint linkage analysis using localized chromosome 6 probes and chromosome 16 probes in 12 unrelated tcs families with multiple affected siblings excluded the tcs locus from proximity to both translocation breakpoints  these data were confirmed when a third affected child  who did not exhibit the translocation  was born to the mother  
class5	predictability of difficult laryngoscopy in patients with long term diabetes mellitus  the laryngoscopic conditions of 62 diabetic patients who underwent renal transplantation or vitrectomy were studied  anaesthesia was induced with fentanyl and a sleep dose of thiopentone  conditions for direct laryngoscopy after 0 1 mg kg vecuronium were scored from 0 to 3  easy very difficult   all patients gave their palm prints after operation which were scored  0  phalangeal areas completely visible  1  phalangeal areas partly visible  2  phalangeal areas hardly visible  3  only fingertips printed  the incidence of difficult laryngoscopy was 31   the higher the scores in the palm test  the more difficult was the laryngoscopy  the correlation coefficient between these two factors was r   0 6  p less than 0 001   our study shows that joint rigidity possibly caused by tissue glycosylation may also involve laryngeal and cervical areas resulting in a strenuous laryngoscopy  a defective palm print is a warning sign for difficult laryngoscopy  
class5	eosinophilic fasciitis associated with tryptophan ingestion  a manifestation of eosinophilia myalgia syndrome  recently  the ingestion of tryptophan has been associated with eosinophilia myalgia syndrome  which is characterized by eosinophilia  myalgias  and several less consistently reported findings  we treated 13 patients who exhibited clinical features of eosinophilic fasciitis who were taking high dose tryptophan before the onset of clinical symptoms  twelve patients exhibited eosinophilia  with eosinophil counts ranging from 0 13 to 0 88  the remaining patient was taking oral corticosteroids when her eosinophil count was determined  eight patients complained of myalgias  other symptoms included arthralgias  pruritus  cutaneous burning  weakness  fever  rashes  malaise  edema  muscle spasms  and alopecia  5 hydroxyindoleacetic acid levels were elevated in four of the eight urine specimens that were tested  our findings suggest that previously diagnosed cases of eosinophilic fasciitis may represent variants of tryptophan associated eosinophilia myalgia syndrome  derangements in the metabolism of tryptophan may play a role in sclerotic diseases  
class5	ichthyosis  exocrine pancreatic insufficiency  impaired neutrophil chemotaxis  growth retardation  and metaphyseal dysplasia  shwachman syndrome   report of a case with extensive skin lesions  clinical  histological  and ultrastructural findings   the shwachman syndrome comprises exocrine pancreatic insufficiency  growth retardation  and bone marrow hypoplasia resulting in neutropenia  clinical  morphological  and ultrastructural studies  as well as hair analysis  were performed in a patient with shwachman s syndrome and severe ichthyosis  clinical findings were lamellar ichthyosiform desquamation on the extremities  the hair was scanty and short on the scalp  in the eyelashes  and in the eyebrows  the nails were hyperkeratotic  morphologic findings were slight  regular acanthosis and severe diffuse hyperkeratosis with variable parakeratosis  the granular layer was thickened  the papillary dermis showed very slight perivascular lymphocyte infiltration  the most prominent ultrastructural finding was the presence of solitary or multiple droplets of varying size in the cytoplasm of the keratinocytes  hair analysis revealed no abnormalities  the cystine concentration in hair specimens was normal  
class5	corticosteroid induced juxta articular adiposis dolorosa  long term treatment with high doses of corticosteroids leads to the development of truncal obesity and focal fatty deposition  these deposits characteristically are located on the face  the nuchal and truncal areas  and episternally  as well as in the mediastinum and epicardium  we studied a patient with juxta articular adiposis dolorosa who had l tryptophan associated eosinophilia myalgia syndrome and was treated with high doses of prednisone  this is the first reported case of adiposis dolorosa occurring as a complication of corticosteroid treatment  alterations of fat metabolism induced by corticosteroid excess may have played a role in the development of this unusual painful syndrome  
class5	fatigue in postpolio syndrome  a survey was conducted to better understand complaints of fatigue in patients previously diagnosed as having polio  eighty six individuals with postpolio syndrome and 20 healthy controls completed a questionnaire about their fatigue  the beck depression inventory  and the cage questionnaire  the results showed that fatigue in postpolio syndrome usually occurred on a daily basis and increased in severity as the day progressed  both the study group and controls described their fatigue as tiredness and a lack of energy  however  physical weakness was reported only in the postpolio group  minimal physical exercise exacerbated fatigue in 48  of the postpolio group  whereas it diminished fatigue in 70  of the controls and in 15  of the postpolio group  twenty seven percent of the postpolio group and none of the controls reported mild to moderate depressive symptoms  however  depression  age  alcohol abuse  and employment status did not significantly affect the differences between groups in reported prevalence or description of chronic fatigue  criteria to separate psychologic from organic causes of fatigue and treatment interventions are discussed  
class5	psychosocial  functional  and quality of life assessment of patients with posttraumatic fracture nonunion  chronic refractory osteomyelitis  and lower extremity amputation  one hundred nine patients with long bone fracture nonunion  chronic refractory osteomyelitis  or posttraumatic amputation were evaluated for the impact of chronic disability on quality of life  as measured by the arthritis impact measurement scale  aims  and the psychosocial adjustment to illness scale  pais   a self administered pais for spouses assessed psychosocial adjustment of spouses or significant others  a final questionnaire ranked the reasons for either continuing medical therapy or accepting amputation  the pais scores differed significantly between osteomyelitis patients and both nonunion and amputation patients  p less than  05   the presence or absence of pain produced significant differences in aims and pais scores of nonunion and osteomyelitis patients  p less than  05   subscale analysis of aims scores revealed significant differences among the three groups in health perception and scale of orthopedic problem  osteomyelitis patients were more severely affected than nonunion or amputation patients  the pais detected no statistically significant difference in psychosocial adjustment of spouses of patients in the three population groups  the most common reason for continuing medical and surgical management of nonunion and osteomyelitis was expectation for cure  the amputee group chose ablation to avoid further treatment  differences in psychosocial and functional ability were related to disease diagnosis  pain  status of fracture healing  and timing of amputation  
class5	histopathology of metastatic temporal bone tumors  temporal bone metastasis is now being reported with increasing frequency  to understand the process of temporal bone metastasis  complete histologic evaluation of the temporal bones is essential  in this study  60 temporal bones from 33 patients were evaluated  different patterns of temporal bone involvement were noted depending on the mode of spread to the temporal bone  involvement of the temporal bone usually occurs late in the disease process and is often asymptomatic  
class5	familial chondrocalcinosis due to calcium pyrophosphate dihydrate crystal deposition in english families  familial predisposition to chondrocalcinosis  cc  due to calcium pyrophosphate dihydrate  cppd  crystal deposition is described in five english kindreds  two families were characterized by premature onset polyarticular cc with little associated structural arthropathy  in one of these families  recurrent childhood fits were strongly associated with subsequent development of cc  affected members of the other three families resembled sporadic disease in showing predominantly late onset  oligoarticular cc with mild arthritis and destructive change in only one case  knee synovial fluid levels of inorganic pyrophosphate  ppi  and nucleoside triphosphate pyrophosphate  ntpp  did not differ from those of 59 sporadic cases of cc due to cppd  although ppi and ntpp levels in both groups were higher than in normal knee synovial fluid  p less than 0 0001   urinary ppi levels were not different from normal controls  screening for other metabolic abnormality was negative in all cases  this is the first report of familial cc in the uk  and the first to associate this condition with childhood fits  absence of overt primary abnormality of ppi metabolism suggests that other factors relating to crystal nucleation growth may be more relevant to predisposition in these cases  
class5	septic arthritis as a non surgical complication in rheumatoid arthritis  relation to disease severity and therapy  more aggressive therapy including cytotoxic drugs is increasingly used in the treatment of rheumatoid arthritis  ra   and may confer increased susceptibility to infections  septic arthritis is one infectious complication known to be overrepresented in ra  we studied the impact of disease severity and medication in a group of nine ra patients with proven septic arthritis  excluding those occurring as a complication of orthopaedic surgery  two control groups were used for comparison  the septic arthritis patients were functionally more incapacitated and more often treated with cytotoxic drugs  six of the nine septic arthritis patients had received an intra articular injection into the infected joint within 3 months prior to the onset of the septic arthritis  only one of these occurred immediately after arthrocentesis  the annual frequency of septic arthritis was approximately 0 2   during the 4 year period studied the frequency was 0 5   when related to the number of glucocorticosteroid injections  a frequency of 1 per 2000 injections was found when late septic arthritis was included  the high frequency of delayed septic arthritis after intra articular glucocorticosteroid administration should alert physicians to this complication  
class5	immunogenetic heterogeneity in rheumatoid disease as illustrated by different mhc associations  dq  dw and c4  in articular and extra articular subsets  genetic variants at drb1  dw subtypes   dqb  and c4 loci were compared in rheumatoid disease subjects with or without the extra articular feature of felty s syndrome or major vasculitis  dr4 positive subjects with rheumatoid arthritis alone showed no preferential associations with dqb or dw variants or with c4 null alleles  felty s subjects showed associations with the dqb encoded dqw7 allele and with the c4b null allele but no preferential associations with any dw subtype of dr4  by contrast dr4  ve rheumatoid vasculitic subjects showed associations with the dw14 as well as with dqw7 and the c4a null allele  these different mhc associations in different clinical disease subsets show that rheumatoid disease is immunogenetically heterogeneous and suggest that mhc genes outside the drb1 locus may also influence susceptibility or modify expression of the rheumatoid disease process  
class5	ultrasound guided hepatic cryosurgery in the treatment of metastatic colon carcinoma  preliminary results  cryosurgery  the in situ freezing of cancer  has been proposed in the past as a possible treatment for unresectable hepatic tumors  its advantage lies in the fact that it is a very focal treatment sacrificing less normal tissue than surgical resection  allowing treatment of multiple lobes  because cryosurgery does not affect large vessels  tumors in difficult locations  such as adjacent to the inferior vena cava  ivc   can be treated  with the use of intraoperative ultrasound to place the cryoprobes and monitor the freezing process  18 patients with unresectable metastatic colon carcinoma confined to the liver were treated  of the 18 patients treated  4  22   are in complete remission as determined by computed tomography  ct  scans and carcinoembryonic antigen  cea  levels  with a mean follow up of 28 8 months  four patients  22   were not adequately treated at the time of cryosurgery  the number of lesions frozen in each patient ranged from 1 to 12  with a mean of 6 lesions  fourteen patients had bilobar disease  three patients had previous right lobectomies with recurrences in their remaining left lobes prior to cryosurgery  and one patient had unilobar disease  mean survival of the 14 cases with recurrence was 21 4 months  with 2 of the 14 still alive  ultrasound guided hepatic cryosurgery appears to be an effective treatment for metastatic colon carcinoma to the liver that is unresectable  including patients with bilobar and multiple lesions   these preliminary results indicate that the procedure warrants further study  
class5	effects of inosine on glycolysis and contracture during myocardial ischemia  the effects of inosine  ino  on substrate metabolism and rigor formation in ischemic myocardium were examined in isolated rabbit hearts  metabolite content was assessed in tissue extracts by chemical analysis and in the whole heart by 13c and 31p nuclear magnetic resonance spectroscopy  in ischemic hearts metabolizing either  3 13c pyruvate or  1 13c glucose  1 mm ino increased both total and 13c labeled alanine content  lactate content was unaffected  at 3 minutes of ischemia  tissue alanine was 1 81     0 11 microm g wet wt  mean     sem  in hearts perfused with pyruvate ino versus 1 23     0 15 microm g wet wt in hearts perfused with pyruvate alone  p less than 0 05   ino reduced tissue glycogen during ischemia in pyruvate perfused hearts  tissue alanine content in ischemic hearts that were supplied glucose ino  1 29     0 13 microm g wet wt  was greater than in ischemic hearts supplied glucose alone  0 65     0 14 microm g wet wt   alanine was found to originate from pyruvate and was a glycolytic end product in glucose perfused hearts  ino raised the  3 13c alanine  3 13c lactate ratio in ischemic  intact hearts  glucose   0 24     0 07 versus glucose ino   0 60     0 09  pyruvate   0 49     0 08 versus pyruvate ino   0 89     0 08   at 7 minutes of ischemia  atp content fell to 70     3  with glucose ino versus 58     5  with glucose alone  rigor  stone heart  was delayed from 14 7     1 3 to 23 2     1 6 minutes with ino  ino did not change atp content in ischemic hearts that were supplied pyruvate but delayed rigor  pyruvate   9 9     1 2 minutes  pyruvate ino   15 6     1 0 minutes   possibly at the expense of glycogen  supplemental glucose improved the effectiveness of ino with pyruvate to preserve atp  pyruvate glucose   42     6   pyruvate glucose ino   72     6   and further delayed rigor  pyruvate glucose   13 3     1 5 minutes  pyruvate glucose ino   20 3     1 8 minutes   glucose metabolism supported improved energetic and contractile states in ischemic hearts treated with ino  thus  cardioprotection of the ischemic heart by ino was associated with preservation of functional integrity and improved energy production due to increased glycolytic activity  activation of glycolysis in the presence of ino was accommodated by augmented alanine production without the additional accumulation of lactate  
class5	relationship of limited joint mobility to abnormal foot pressures and diabetic foot ulceration  objective  to investigate the role of limited joint mobility  ljm  in causing abnormal foot pressures and foot ulceration  research design and methods  the subjects were recruited from a general diabetes clinic where patients were screened for neuropathy  retinopathy  and elevated plantar foot pressure  sixty four patients in five groups were matched by age and sex in the following groups  group 1  patients with ljm and neuropathy  group 2  nonneuropathic diabetic patients with ljm  group 3  patients with neuropathy and no ljm  group 4  diabetic control subjects  and group 5  nondiabetic control subjects  joint mobility was assessed in the foot at subtalar and metatarsophalangeal joints  plantar foot pressures were assessed by optical pedobarography and neuropathic status by a biothesiometer and electrophysiology  results  joint mobility was reduced at both sites in groups 1 and 2 compared with groups 3  4  and 5  p less than 0 001   plantar foot pressures were significantly higher in groups 1 and 2 compared with groups 3  4  and 5  p less than 0 001   no differences in plantar foot pressures were observed between groups 1 and 2  there were strong correlations between plantar foot pressures and joint mobility in the foot  r    0 7  p less than 0 001   previous foot ulceration was present in 65  of patients in group 1  none in group 2  and 5  in group 3  conclusions  1  ljm may be a major factor in causing abnormally high plantar foot pressures  2  abnormal plantar foot pressures alone do not lead to foot ulceration  and 3  ljm contributes to foot ulceration in the susceptible neuropathic foot  
class5	brucellar and tuberculous spondylitis  a comparative study of their clinical features  the clinical data from 19 patients with brucellar spondylitis and 15 with tuberculous spondylitis were compared  the former disease affects males whose occupations expose them to brucella  the lumbar spine is usually involved and there are other symptoms of brucellosis  tuberculous spondylitis is not usually accompanied by general symptoms  the dorsal spine is more frequently affected and may exhibit vertebral collapse and paraspinal abscesses  these differences permit a presumptive aetiological diagnosis  but the definitive diagnosis depends upon bacteriological tests  
class5	spinal instability secondary to metastatic cancer  fifty five patients with severe pain from spinal instability secondary to metastatic cancer were referred to hope hospital  none being judged to be in a terminal condition  one patient had too extensive disease for surgery so 54 were treated by 55 spinal stabilisations  49 obtained complete relief of pain and two had partial relief  there were three failures  twenty eight of the patients had clinical evidence of spinal cord or cauda equina compression and were decompressed at the time of stabilisation  of these  20 had major recovery of neurological function  patients with pre operative evidence of extradural tumour had  prophylactic  decompression at the time of stabilisation  none of these patients later developed signs of cord or cauda equina compression  the results suggest that alleviation of pain and restoration of mobility are best achieved by segmental spinal stabilisation  a few patients require a combined anterior and posterior stabilisation  postoperative radiotherapy should be given whenever possible  and the causative tumour should be treated by endocrine or chemotherapy  as indicated  
class5	dislocation after primary arthroplasty for subcapital fracture of the hip  wide range of movement is a risk factor  dislocation is the most frequent serious complication following total hip replacement for subcapital femoral fracture  we report a prospective study  using matched groups  which compared the range of hip movement following hip replacement for arthritis and for fracture  the range of movement was significantly greater in the fracture group  we suggest that this is a predisposing factor for dislocation  
class5	ten year results of operations for rheumatoid cervical spine disorders  the outcome of operations performed on 38 patients for rheumatoid disorders of the cervical spine were analysed 10 or more years later  the mean age of the patients at the time of operation was 56 years  35 to 77   32 had seropositive disease  the mean duration of the disease was 17 years  four to 36   twenty seven patients had painful anterior atlanto axial subluxation  aas   nine had subaxial subluxation alone and two had severe cranial subluxation of the odontoid  one also with subaxial subluxation  one patient died from postoperative staphylococcal septicaemia and another 18 died during the follow up period  patients with coincident cardiac or other diseases  and those with cranial subluxation of the odontoid of more than 3 mm had an increased mortality  neither the patients  age nor the magnitude of aas correlated with mortality  of the 37 patients with occipitocervical pain  30 were relieved and all the six patients with tetraparesis were improved  of the 24 gallie fusions only 12 were solidly united  patients with long term cortisone treatment were more likely to develop pseudarthrosis  there was no correlation between clinical outcome and radiological result  four patients had further operations to treat subluxation which developed below the fused segments  
class5	surgical treatment of double major scoliosis  improvement of the lumbar curve after fusion of the thoracic curve  we have evaluated two methods of surgical treatment of adolescent idiopathic double major scoliosis in 59 patients  in group 1  31 patients were treated by fusion of the upper curve only  in group 2  28 patients had lumbar fusions also including most of the lower curve  the magnitude of the lower curve and the correction obtained in traction were good indicators of the correction achieved postoperatively  forty four patients were reviewed at a minimum of 10 years after operation  those in group 1 showed sustained improvement of the lower curve with minimal stiffness and pain  group 2 patients had lumbar curves of similar severity at review  but had significantly more low back pain and stiffness  the number of lumbar segments which remained mobile appeared to be a critical factor in determining the outcome  selective fusion of the upper curve in double major scoliosis produces satisfactory results if the lumbar curve is less than 50 degrees  it may also be appropriate for flexible lumbar curves of larger angle  
class5	tarsal tunnel syndrome  causes and results of operative treatment  from 1975 to 1988  operative treatment was performed on 50 feet in 45 patients with tarsal tunnel syndrome  the causes of this syndrome were correlated with operative findings and included ganglia in 18  and a bony prominence from talocalcaneal coalition in 15  five feet had sustained an injury  tumours were found in three and there was no obvious cause in nine  in most cases in need of operative treatment  there was a space occupying lesion  classifying the results according to causes  those with coalition or a tumour fared better  and idiopathic and traumatic cases had a worse outcome  in cases with a definite lesion  an excellent result can be expected from surgical treatment carried out soon after onset of the condition  
class5	treatment of freiberg s disease  a new operative technique  a method of treating freiberg s disease of the metatarsal head by shortening the metatarsal bone is described  this operation has been performed in 15 patients  16 feet   excellent relief of pain was obtained  although most patients had persistent stiffness of the metatarsophalangeal joint  
class5	transarticular fixation for severely displaced supracondylar fractures in children  we have reviewed 34 children who had been treated by open reduction through a medial incision and transarticular pinning for a severely displaced supracondylar fracture of the humerus  follow up ranging from nine months to 20 years showed that 27 of 34 elbows  79   had excellent or good results  with satisfactory resolution of neurovascular problems and no complications due to the method of treatment  
class5	bone lesions secondary to benign phaeochromocytoma  four cases in childhood  metaphyseal sclerotic bone changes associated with benign phaeochromocytoma are very rare in childhood  we report four cases  in each of which the radiographic changes returned to normal after removal of the tumour  
class5	pseudo abscess of the psoas bursa in failed double cup arthroplasty of the hip  seven psoas bursae filled with purulent fluid and inspissated debris were revealed at revision operations for failed resurfacing hip arthroplasties  an incidence of 5 8  in such revisions  histological and microbiological investigations demonstrated that the psoas bursa collections resulted from the tissue response to polyethylene wear debris  none was due to infection  
class5	correction of coxa vara in childhood  the use of pauwels  y shaped osteotomy  the long term results following the correction of coxa vara by pauwels  y shaped intertrochanteric osteotomy have been evaluated in 14 children  ten of the children had unilateral hip disease and were otherwise normal while four had bilateral hip disease due to generalised skeletal dysplasias  in each case  the growth plate was vertical  the femoral head was displaced inferiorly and there were abnormalities in the metaphysis of the femoral neck  the results indicate that this osteotomy provides lasting correction of the deformity  regardless of the cause  as long as the inclination of the growth plate is corrected to 40 degrees or less and adequate support is provided for the metaphyseal defect and the displaced femoral head  
class5	joint proprioception in normal  osteoarthritic and replaced knees  we measured joint position sense in the knee by a new method which tests the proprioceptive contribution of the joint capsule and ligaments  the leg was supported on a splint  and held in several positions of flexion  the subjects  perception of the position was recorded on a visual analogue model and compared with the actual angle of flexion  eighty one normal and 45 osteoarthritic knees were examined  as were 10 knees with semi constrained and 11 with hinged joint replacements  all were assessed with and without an elastic bandage around the knee  there was a steady decline in joint position sense with age in subjects with normal knees  those with osteoarthritic knees had impaired joint position sense at all ages  p less than 0 001   knee replacement improved the joint position sense slightly  p less than 0 02   semi constrained replacement had a greater effect than hinged replacement  the effect of an elastic bandage in subjects with poor position sense was dramatic  improving accuracy by 40   p less than 0 001   it is proposed that reduced proprioception in elderly and osteoarthritic subjects may be responsible for initiation or advancement of degeneration of the knee  
class5	natural history of nontraumatic avascular necrosis of the femoral head  we studied the natural history of nontraumatic avascular necrosis of the femoral head  anfh  in 115 hips in 87 patients  69 steroid induced  21 related to misuse of alcohol and 25 idiopathic  the average length of follow up was over five years  collapse occurred most often when the focus of bone necrosis occupied the weight bearing surface of the femoral head  flatness of the head due to subchondral fracture was an early manifestation of collapse  classification into six types based upon the radiographic findings provided an accurate prognosis for individual cases of anfh which is useful in planning treatment and in assessing its outcome  
class5	long term results of the evans procedure for lateral instability of the ankle  we studied the late outcome of 40 ankles  from a consecutive series of 42  treated by a modified evans procedure  the peroneus brevis tendon was used to fashion a static tenodesis  all the patients had suffered from persistent lateral instability following an ankle sprain  the follow up period was between nine and 12 years  excellent or good results were achieved in 33 ankles  82 5    three had a fair result  and four were poor  the clinical results were matched by the radiographic results which showed significant talar tilt or anterior talar translation in only three ankles  the functional result showed no positive correlation with the stress radiographic analysis  we concluded that this modification of the evans operation gives satisfactory long term results  which show little change from the good results at 24 to 35 months reported in an earlier paper from our department  
class5	effect of menopause and hormone replacement therapy on the urinary excretion of pyridinium cross links  pyridinoline  pyr  and deoxypyridinoline  d pyr  are two cross links of collagen molecules that are present in the extracellular matrix and released during its degradation  in contrast to the wide distribution of collagen  pyr is present in bone and cartilage  but not in significant amounts in other connective tissues  and d pyr appears to be specific for bone tissue  therefore  the urinary excretion of pyr and d pyr might be a sensitive marker of bone matrix degradation  using a specific high pressure liquid chromatography assay we have measured pyr and d pyr cross links in a 24 h and a fasting urine sample in 60 early postmenopausal women and 19 premenopausal women matched for age  menopause induced a 62  increase in fu pyr  49 8     18 7 vs  30 8     8 0 pmol mumol creatinine  p less than 0 001  and an 82  increase in fu d pyr  8 2     3 4 vs  4 5     1 4 pmol mumol creatinine  p less than 0 001   in 20 postmenopausal women on hormone replacement therapy  urinary pyr and d pyr returned to premenopausal levels within 6 months  contrasting with unchanged levels during placebo treatment  the 24 h excretion of pyr and d pyr was significantly lower than the fasting excretion  but was similarly decreased after hormone replacement therapy  pyr and d pyr excretion measured in the same urinary sample were highly correlated  r   0 85 for fasting and 0 83 for 24 h sampling   but correlations between fasting and 24 h values were weak  d pyr  r   0 30  pyr  r   0 29  p less than 0 05 for both   correlations between urinary cross links and other markers of bone turnover  fu hydroxyproline creatinine and plasma osteocalcin  were significant but low  pyr vs  osteocalcin  r   0 29  p less than 0 05  pyr vs  hydroxyproline  r   0  34  p less than 0 01  d pyr vs  osteocalcin  r   0 39  p less than 0 01   except for d pyr vs  hydroxyproline  r   0 24  p   0 07   suggesting that these markers reflect different events of bone metabolism  finally  a single measurement of the fasting excretion  but not of the 24 h excretion  of cross links was significantly correlated  pyr  r   0 34  p less than 0 05  d pyr  r    0 46  p less than 0 01   with the subsequent spontaneous rate of bone loss assessed by repeated measurements of the radial bone mineral content in 37 postmenopausal women  abstract truncated at 400 words   
class5	the course of biochemical parameters of bone turnover during treatment with corticosteroids  the mechanisms by which glucocorticoids cause osteopenia are incompletely understood  it is generally accepted that bone formation is depressed during corticosteroid treatment  but the cause of the ongoing bone resorption is less clear  secondary hyperparathyroidism and changes in vitamin d metabolism are thought to play a role  this is based mostly on data from cross sectional studies in heterogeneous patient groups  we  therefore  studied longitudinally the course of biochemical parameters and the hormones influencing bone turnover in a homogeneous group of 10 euthyroid patients with graves  ophthalmopathy  all euthyroid for at least 1 yr before  during  and after a 12 week course of prednisone  bone formation was depressed as reflected by a fall in serum osteocalcin  3 0     2 1  1 7     1 1  and 2 4     1 9 micrograms l at weeks 0  4  and 12  respectively  p   0 02  and in total alkaline phosphatase  1 15     0 33  0 83     0 22  and 0 88     0 40 mukat l  p   0 001   parameters of bone resorption  urinary hydroxyproline creatinine ratio  serum acid phosphatase  and the levels of vitamin d metabolites remained unchanged  serum intact pth seemed to decrease slightly  our findings suggest that glucocorticoid induced osteopenia is caused by a depressed bone formation in the presence of an unaltered but ongoing bone resorption  secondary hyperparathyroidism and changes in vitamin d metabolism are apparently not involved  
class5	correlation between serum osteocalcin and 24 25 dihydroxyvitamin d levels in paget s disease of bone  we have studied the possible correlation between serum 24 25 dihydroxyvitamin d  24 25  oh 2d  and osteocalcin levels  sbgp  in paget s disease of bone  we measured serum calcium  phosphate  pth  25 hydroxyvitamin d  1 25  oh 2d  24 25  oh 2d  alkaline phosphatase  sap   and the urinary hydroxyproline creatinine ratio  uoh prol creat  in 19 patients with paget s disease of bone and 16 age  and sex matched controls  as expected  sap  uoh prol creat  and sbgp levels were significantly elevated  and there was a tendency to a decrease in serum levels of 24 25  oh 2d in pagetic patients with respect to the control group  there was no significant difference between patients and controls in serum calcium  phosphate  pth  25 hydroxyvitamin d  and 1 25  oh 2d  the pagetic patients were subdivided into two subgroups  subgroup a had normal sbgp levels  less than 5 ng ml   and subgroup b had increased sbgp levels  greater than 5 ng ml   serum 24 25  oh 2d levels in subgroup b were significantly lower than those in controls  while subgroup a showed levels similar to those in the control group  we also found a positive linear correlation between sap and sbgp and between sap and uoh prol creat as well as a negative linear correlation between sbgp and 24 25  oh 2d and between 24 25  oh 2d and uoh prol creat in pagetic patients  these results point to a possible role of 24 25  oh 2d in disease activity  
class5	ureaplasma urealyticum chronic osteomyelitis in a patient with hypogammaglobulinemia  mycoplasma species are recognized as important pathogens in patients with hypogammaglobulinemia  in this article we describe  for the first time  a patient with hypogammaglobulinemia who developed osteomyelitis of the hip caused by ureaplasma urealyticum  this article emphasizes the need for considering infection with mycoplasma species in patients with antibody deficiency  
class5	hyposomatomedinemia in men with post poliomyelitis syndrome  the age of onset of the post poliomyelitis syndrome  pps  coincides with the tendency for declining activity of the growth hormone somatomedin c  gh smc  axis  the normal plasma smc range in men before the age of 40 is 0 50 to 1 50 units ml  after age 40 about 30  of men have a plasma smc level below 0 35 units ml  signifying no detectable spontaneous gh secretory pulses  because the gh smc axis stimulates dna  rna  and protein synthesis in muscle cells and increases their size and number  a deficiency of the gh smc axis could theoretically contribute as a secondary factor to the occurrence or severity of the pps  accordingly  the authors measured the plasma smc level in 10 men with pps  ages 35 to 63  and in 94 healthy men of similar age  in the pps men  100  of the values were less than or equal to 0 40 units ml  and 90  were less than or equal to 0 35 units ml  the corresponding proportions in the healthy men were 40  and 27   analysis of variance including age as a factor showed smc to be significantly lower in the pps men than in the healthy men  in an additional comparison  totally immobile nursing home men did not have lowered smc values  in fact their smc values were slightly higher than those of healthy men of similar age  the data revealed a new biochemical feature of pps  hyposomatomedinemia  which might play a contributory role in the pathogenesis of the syndrome  
class5	haemangiopericytoma of the temporal bone  haemangiopericytoma is an uncommon vascular tumour with a widespread distribution  although meningeal involvement is well recognized  only a few sporadic cases of temporal bone lesions have been documented  all with doubtful sites of origin  late presentation together with the restrictive anatomy of this region often precludes its effective removal and even minimal residual disease may progress rapidly  a series of three such patients are presented in order to discuss the natural history  histological features and treatment of this disease  
class5	effect of aortic sclerosis on bone mineral measurements by dual photon absorptiometry  measurements of the bone mineral content  bmc  of lumbar spine by dual photon absorptiometry  dpa  are performed mainly in the anteroposterior  ap  projection  due to superimposition of the abdominal aorta  the bmc measured for patients with aortic calcification usually is too high  to determine the influence of aortic calcifications  dpa scans were performed in the ap projection on 100 dissected abdominal aortae with different degrees of atherosclerosis placed on a human lumbar spine cast in lucite  the measured values were compared with those obtained in the same projection without the aortae  the average increase of the bmc values relative to the mean for the vertebrae l2 to l4 for aortae with severe complicated lesions  i e   those containing larger amounts of calcium  was 0 03 g cm2  with a maximum deviation of 0 09 g cm2  aortae with fatty streaks or fibrous plaques did not cause significant increases of the bmc  the mean deviation for aortae with mild complicated lesions  i e   those containing smaller amounts of calcium  was within the range of instrument precision  
class5	isolated muscular sarcoidosis causing fever of unknown origin  the value of gallium 67 imaging  an unusual case of a patient with a long standing fever of unknown origin  fuo  is presented whose gallium 67  67ga  images revealed increased activity only in the calf muscles bilaterally  other imaging modalities also failed to show chest or other abnormal findings  subsequent biopsy of the right gastrocnemius muscle revealed noncaseating granulomas consistent with the diagnosis of sarcoidosis  when using 67ga to evaluate a patient with a fuo  imaging of the extremities should always be included  also  when abnormal ga 67 uptake is present in the extremities  sarcoidosis should be included in the differential diagnosis  
class5	gallium uptake in tryptophan related pulmonary disease  we describe a patient who developed fever  fatigue  muscle weakness  dyspnea  skin rash  and eosinophilia after taking  high doses  of tryptophan for insomnia for two years  a gallium 67 scan revealed diffuse increased uptake in the lung and no abnormal uptake in the muscular distribution  bronchoscopy and biopsy confirmed inflammatory reactions with infiltration by eosinophils  mast cells  and lymphocytes  ct scan showed an interstitial alveolar pattern without fibrosis  emg demonstrated diffuse myopathy  muscle biopsy from the right thigh showed an inflammatory myositis with eosinophilic and lymphocytic infiltrations  
class5	aluminum accumulation during treatment with aluminum hydroxide and dialysis in children and young adults with chronic renal disease background  the control of hyperphosphatemia is a major clinical problem in patients with chronic renal failure receiving regular dialysis treatment  despite continuing concern about aluminum toxicity  aluminum containing antacids are still used in many of these patients as phosphate binding agents  although maximal acceptable doses of aluminum hydroxide have been recommended  the safety and efficacy of these guidelines have not been evaluated  methods  seventeen children and young adults  mean      sd  age  14 1     3 7 years  undergoing regular peritoneal dialysis were randomly assigned to treatment with either aluminum hydroxide  n   7  maximal dose  30 mg per kilogram of body weight per day  or calcium carbonate  n   10  dose range  2 5 to 12 g per day  according to serum phosphorus levels   aluminum retention was assessed by serial measurements of plasma aluminum  deferoxamine infusion tests  and measurements of bone aluminum content during a mean      sd  follow up of 13     2 months  the evolution of bone disease was also evaluated  results  plasma aluminum levels and the increment in plasma aluminum after infusion of deferoxamine increased from base line values in the patients treated with aluminum hydroxide  and aluminum related bone disease developed in one patient  serum phosphorus levels remained higher and serum calcium levels lower in the patients receiving aluminum hydroxide than in those receiving calcium carbonate  the skeletal lesions of secondary hyperparathyroidism improved in 7 of 10 patients receiving calcium carbonate but persisted or progressed in 6 of 7 patients given aluminum hydroxide  p less than 0 025   conclusions  aluminum hydroxide is less effective than calcium carbonate as a phosphate binding agent for the control of hyperphosphatemia and is associated with aluminum retention in children and young adults with chronic renal failure who are receiving dialysis therapy  
class5	eosinophilia myalgia syndrome associated with ingestion of l tryptophan  muscle biopsy findings in 4 patients  muscle biopsies of 4 patients with the eosinophilia myalgia syndrome associated with ingestion of l tryptophan showed lymphocytic infiltrates with occasional eosinophils largely restricted to interstitial fibrous tissue and perivascular areas  there was inflammation and fibrosis of muscle spindle capsules in 3 patients  in the 2 sickest patients  there was profound muscle atrophy  affecting both muscle fiber types  
class5	the  numb cheek limp lower lid  syndrome  a patient developed isolated numbness  1st confined to the lateral nose and upper lip  but later involving the cheek  lower lip  upper gingiva  and the palate  this numbness was later associated with paresis of the muscles of the upper lip and angle of the mouth and with ipsilateral lower lid droop  the  numb cheek limp lower lid  syndrome   squamous cell carcinoma was discovered infiltrating the infraorbital nerve and distal branches of the facial nerve  cheek numbness associated with lower eyelid or upper lip weakness may herald a neoplasm affecting the infraorbital nerve and distal facial nerve branches  
class5	stimulation of dorsal root ganglia and degradation of rabbit annulus fibrosus  the authors sought to determine whether narrowing of the intervertebral neural foramen  by itself and in association with vibration  would stimulate the mechanosensitive dorsal root ganglia and result in degradation of proteoglycan and collagen of the annulus fibrosus  as proposed in their working model of dorsal root ganglia neuropeptide mediated degeneration of the spinal motion segment  degradation of proteoglycan and collagen of rabbit annulus was observed when there was narrowing of the neural foremen and the degradation process was accelerated by vibration  vibration alone  in the absence of structural abnormalities of the spinal motion segment  did not induce matrix degradation probably because of a less pronounced stimulation of the dorsal root ganglia  biological events similar to those postulated here  fomented by a combination of structural abnormalities and environmental factors  could be involved in human disc degeneration  
class5	coexistence of cervical and lumbar disc disease  a retrospective analysis of 200 patients requiring cervical disc surgery was performed to determine the frequency of coexistent lumbar disc or spine abnormalities  the duration of follow up ranged from 5 to 25 years  averaging 14 years  sixty percent were women and 40  were men  their ages ranging from 25 73 years  antecedent motor vehicle injury had occurred in 49 cases and work injury to the spine in 23  sixty four percent had no history of prior back injury  it was found that over 31  had undergone lumbar disc surgery  and a high number of patients demonstrated abnormal lumbar radiographs or myelograms  including 78 with bulging discs  100 with major root defects  78 with minor root defects  8 with spinal stenosis  and 7 with spondylolisthesis  myelograms were normal in 22 cases  the sites of lumbar abnormalities included l4 5  110   l5 s1  90   and multilevel  8   there was a higher incidence of lumbar disc abnormalities associated with multilevel cervical spondylosis  there also was a relationship between residual symptoms and myelographic abnormalities  two studies in the authors  institution suggest an autoimmune basis for the frequent coexistence of cervical and lumbar disc disease  namely the demonstration of antigenic properties in the nucleus pulposus and high serum immunoglobulins  
class5	pyogenic spinal sepsis in adults  twenty adult patients presented with bacteriologically and histologically proven nontuberculous spinal sepsis  thirteen patients presented with varying degrees of neurologic impairment  all patients underwent spinal decompression  in 11 this was combined with an anterior fusion using autogenous tricortical iliac grafts  all patients have recovered and are ambulatory  and no patient s disorder was made worse by surgery  twenty three separate organisms were cultured  only five of which were staphylococcus  the antibiotic courses were shorter and pain relief more rapid with anterior fusion  all anterior bone grafts incorporated rapidly  and there was no progression of kyphosis or sequestration of grafts  regardless of organisms or level  the rational treatment of adult spinal sepsis necessitates the securing of tissue from the spine for histologic and bacteriologic examination  pain relief  stabilization  and neural decompression can best be achieved with anterior decompression and fusion  autogenous iliac crest grafts incorporate in the presence of sepsis  
class5	scoliosis in trisomy 18  patients with trisomy 18 typically present with multiple congenital anomalies and most die within the first year  however  long term survivors are not uncommon  seventeen patients with trisomy 18 were evaluated to study the development of scoliosis associated with this disorder  there were 13 females and 4 males with ages ranging from birth to 22 years  twelve patients died by age 2  none developed scoliosis or had vertebral anomalies  the five patients who survived beyond age 2 developed scoliosis  curve progression was demonstrated in the patients who returned for follow up  bracing was not well tolerated in two patients with curves of 48 degrees and 58 degrees  both had poor motor control and sitting ability  one patient with a 30 degree curve was successfully managed by bracing  another patient with a severe scoliosis was successfully fused with anterior and posterior instrumentation  patients with trisomy 18 should be carefully evaluated for scoliosis  scoliosis in the older child  surviving beyond age 2  may be progressive and difficult to manage  
class5	nighttime bracing for adolescent idiopathic scoliosis with the charleston bending brace  preliminary report  the authors report their preliminary experience with the charleston bending brace for the treatment of adolescent idiopathic scoliosis  this brace holds the patient in the position of maximum side bend correction and is worn only at night  patients in this prospective multicentered study met all the following criteria  skeletal immaturity  risser 0  1   or 2    curvature greater than 25 degrees before bracing  no prior treatment  and greater than 1 year follow up since initiation of treatment  there were 191 structural curves in the 139 patients  one hundred fifteen patients  83   showed improvement or less than 5 degree change in curvature  twenty four patients  17   demonstrated an increase in curvature greater than 5 degrees  based on these preliminary results  continued use of bending brace treatment at nighttime only is justified for adolescent idiopathic scoliosis  patients with double curves should be observed closely for increase in compensatory curves  
class5	analysis of sagittal plane instability of the lumbar spine in vivo  segmental instability secondary to degenerative disc disease may result in chronic low back pain  in the sagittal plane  segmental instability can be characterized during lumbar motion from full extension to full flexion  the authors studied this movement using a translational method for the kinematic analysis  implementing a new concept known as the instability factor  both translational and angular components of motion are evaluated  by computing the incremental motion parameters at different stages of spinal bending  the total amount of translation and angulation is obtained and combined in a ratio termed the instability factor  this factor increases with linear instability and decreases with rotational instability  the authors reviewed 12 control subjects and 36 patients with chronic low back pain  the diagnoses of patients were categorized into three groups  idiopathic low back pain  lumbar disc prolapse  and degenerative disc disease  lateral radiographs of each subject s spine at the l4 5 level were obtained using low dose radiography and were performed serially as the subjects moved from full extension to full flexion  it was found that the group of patients with degenerative disc disease had an average age corrected instability factor of 37 3  mm radian   which was significantly larger than that of normal subjects 25 5  mm radian    p   0 0065   no significant difference was seen in the instability factor of patients with idiopathic low back pain or lumbar disc prolapse  
class5	spinal rehabilitation by work tolerance based on objective physical capacity assessment of dysfunction  a prospective study with control subjects and twelve month review  a work tolerance program was used for rehabilitation treatment of 45 patients with spinal dysfunction  patients entering the treatment group were prospectively evaluated by objective physical capacity assessment  pca   treatment patients averaged 4 weeks of three  one half day sessions per week  these patients were compared with a control group of 33 patients who did not participate in the rehabilitation program but were evaluated by pca  a telephone review of all patients in each group was carried out at 6  and 12 month follow up  results demonstrated that 78  of the rehabilitation treatment group were discharged with an improved functional work capacity  most importantly  at 6 month follow up  73 0  of patients in the treatment group were productively working while only 38  of control group patients were actively employed  in addition  84 4  showed an improvement in spinal range of motion  the subjective pain scale ratings of these treatment patients demonstrated only 44 4  decreased pain  while 51 1  stayed the same  and two patients increased discomfort  further medical diagnostics or intervention was required in 24 4  of treatment patients  these findings definitely show that a spinal rehabilitation work tolerance program based on objective measurement will enhance an increased rate of return to productive employment activity  there is poor correlation of subjective pain assessment when compared to objective pcas  therefore  recommendations of patients for return to productive work should be based pain ratings  when adjusted for nonselection patients  the authors community based hospital program showed similar results to other programs  the work tolerance and rehabilitation program in concord  new hampshire  demonstrated a significant cost effective approach  being less expensive  less time consuming  and less psychologically oriented  
class5	analysis of spinal and muscular activity during flexion extension and free lifts  detailed measurements of the relative contributions of spine motion and pelvic motion during flexion extension and free lifts  squat type  are examined  the results are consistent with the conclusion that passive stretching of the ligamentous tissues transmits significant extensor moment in these activities  the power being supplied by the hip extensor complex acting on the pelvis  in addition  certain injuries result in measurable changes in the kinematic parameters that determine the ligamentous involvement  and these changes can be used to help evaluate spinal condition  
class5	lumbar isthmic spondylolisthesis in children and adolescents  radiologic evaluation and results of operative treatment  a clinical and radiologic follow up study of a group of 75 children and adolescents  comprised of both boys and girls  who underwent spondylodesis for spondylolisthesis between the years 1979 and 1984 is reported  sagittal rotation  lumbosacral joint angle  lumbar lordosis  wedging of olisthetic vertebrae  and the rounding of the upper sacrum showed considerable statistical correlation to the amount of slipping and accordingly should be noted when estimating the risk of progression of the spondylolisthesis  when the spondylolisthesis was accompanied by scoliosis  it was noted that seriousness of the former was closely correlated to that of the latter  most patients profited by the operation  and solid fusion was achieved in almost all cases  the posterolateral spondylolysis performed using graft from the iliac crest  the interbody fusion technique  or their combination turned out to be the most reliable surgical methods  the combined technique was especially required in cases with a high degree of slipping  
class5	knodt rod distraction instrumentation in lumbosacral arthrodesis  review of 40 patients undergoing lumbosacral fusions over a 4 year period was done to determine the value  efficiency  and safety of knodt rod distraction instrumentation  the age range was 30 80 years  mean age was 51 years  follow up was 1 4 years  twenty patients underwent decompression and fusion for spinal stenosis  nine underwent spinal arthrodesis for instability  six underwent the same for spondylolisthesis  and five underwent fusions for other diagnoses  a posterior midline approach was used  laminal hook sites were prepared  and care was taken to prevent dural compression or tenting  balanced distraction was done to restore soft tissue tension and stability  no attempt was made to reduce deformity  a posterior and lateral mass fusion augmented with allograft bone was performed on all but three patients  in whom autogenous bone was used  the majority of patients were placed in a custom molded lumbosacral orthosis for 3 6 months after operation  there were no neurologic complications  dural tears  or pseudomeningoceles  the first sacral laminas were instrumented in 22 patients  nine of the 40 patients underwent rod removal  reasons for removal were pain due to loosening in five patients and failure of fusion in two  on rod removal in two patients  no abnormality was found  insertion within the sacral laminas did not lead to neurologic complications  the major problem appeared to be loosening  which necessitated rod removal in 12  of the patients  knodt rod distraction instrumentation is a safe and effective method of internal fixation for lumbosacral fusions  
class5	vascular and nonvascular expression of incam 110  a target for mononuclear leukocyte adhesion in normal and inflamed human tissues  inducible cell adhesion molecule 110  incam 110   is a 110 kd adhesion receptor for lymphocytes and monocytes identified on cytokine activated endothelium  using immunoperoxidase techniques  little or no incam 110 was detected on endothelium in normal human tissues  in contrast  incam 110 was expressed in postcapillary venules in a variety of active inflammatory processes  in acute appendicitis  incam 110 was found coincident with strong expression of endothelial leukocyte adhesion molecule 1  elam 1   a cytokine inducible molecule that functions in neutrophil adhesion  however  in certain chronic inflammatory processes  eg  sarcoidosis   incam 110 was observed without simultaneous elam 1 expression  anti incam 110 antibody e1 6 also marked several extravascular cell types  including lymphoid dendritic cells  some tissue macrophages  synovial lining cells  and reactive mesothelial cells  these data suggest a role for endothelial incam 110 in the pathophysiology of both acute and chronic inflammatory reactions  furthermore incam 110 may function as an adhesion molecule for mononuclear leukocytes in a variety of extravascular sites  
class5	stapes surgery in osteogenesis imperfecta  analysis of postoperative hearing loss  the disappointing results in 12 of 58 stapedectomies  including 4 revision operations  performed on osteogenesis imperfecta patients were analyzed and compared with reports in the literature  it is concluded that the results described as disappointing were not always the product of the stapes operation  a progressive sensorineural hearing loss arising independently of the operation as a result of progression in the disease process of osteogenesis imperfecta appears to have a severe influence on the final hearing threshold  
class5	skull base malignancy following long term sinus mucocele and osteomyelitis  a case of skull base malignancy following long term sinus mucocele is presented  while the similarity in clinical signs between sinus mucocele and malignancy has recently been emphasized in the literature  no previous case of skull base malignancy following frontoethmoid mucocele has been reported  the literature is reviewed and the association between inflammatory conditions and sinus malignancy is outlined  
class5	serum levels of bone gla protein in inhabitants exposed to environmental cadmium  serum levels of bone gla protein  bgp   the vitamin k dependent ca2    binding protein  were evaluated in 76 cadmium  cd  exposed subjects with renal tubular dysfunction  32 men  44 women  and 133 nonexposed subjects  53 men  80 women   serum bgp levels were higher in the cd exposed subjects than in nonexposed subjects  significant correlations between bgp and each index measured by bone microdensitometry  md   serum alkaline phosphatase activity  and cd in blood and urine were found  for all of the cd exposed and nonexposed men and women  bgp showed a significant standard partial regression coefficient  multiple regression analysis  with the metacarpal index  mci   which was one of the md indicators  bone gla protein also correlated significantly with urinary beta 2 microglobulin in the men and with serum creatinine in the women  serum bgp values strongly reflect the degree of bone damage and also reflect  although less strongly  the degree of renal damage induced by exposure to cd  
class5	lipomatous hamartoma of the orbit  proliferations of mature adipose tissue  while common in retroperitoneal and subcutaneous sites  rarely occur in the orbit  we describe the clinical  radiographic  and histopathologic findings of a nonencapsulated lipomatous tissue overgrowth of the right orbit in a 35 year old man  the mass had caused proptosis since childhood and was apparently present since birth  due to the age at onset  the histologic similarity to normal orbital fat  and the lack of encapsulation or choristomatous elements  we propose the term lipomatous hamartoma for this entity  
class5	microscopically assisted posterior lumbar interbody fusion  microscopically assisted posterior lumbar interbody fusion was performed on 27 patients who had either spondylolisthesis or chronic lower back pain after previous lower back surgery  overall improved satisfactory results occurred in 22 of 27 patients  roentgenographic  stable  interbody fusion occurred in 22 of 27 patients  the poorest results and highest rate of pseudarthrosis occurred in patients with double level fusions  pseudarthrosis occurred in four of six patients with double level fusions and unsatisfactory clinical results occurred in five of six patients with double level fusions  advantages of the microscopic technique are better examination of the surgical site  less blood loss  and less surgical dissection than other surgical salvage techniques  this procedure should be reserved for single level pathology in the lumbosacral spine  
class5	the role of the supraspinatus and infraspinatus muscles in glenohumeral kinematics of anterior should instability  to investigate a socket mechanism responsible for controlling the kinematics in the statically positioned glenohumeral joint  a suprascapular nerve block was performed in 13 selected patients  with recurrent anterior instability and defects of the labrum  kinematics were then documented by roentgenograms in four positions within the horizontal motion plane  combined paralysis of the supraspinatus and infraspinatus muscles resulted in abnormal anterior translation in only two of 47 roentgenograms  normal ball and socket kinematics were retained in the remaining 45 roentgenograms  the consistent arthroscopic findings were an undamaged glenoid articular surface with a detached or absent labrum  the injury to the labrum reduced the depth of the socket by one half  the other one half of the socket provided by the contour of the glenoid remained intact  a balanced muscle envelope was not required to maintain normal kinematics in selected  actively positioned  unstable shoulders  the retained glenoid depth was sufficient to produce the observed ball and socket kinematics  further in vivo study of shoulder kinematics will be needed to clarify the interactive roles of the socket and muscle envelope in maintaining glenohumeral stability during the more demanding stresses during active shoulder motion  
class5	local antibiotic delivery in the treatment of bone and joint infections  antibiotics can be delivered locally via an implantable pump to treat bone and joint infections  this is a completely closed system  and the pump is refilled percutaneously at intervals based on its flow rate  the use of this method is described in three specific clinical situations   1  resistant osteomyelitis  patients with persistent infections despite previous therapy    2  acutely infected arthroplasties  symptomatic for less than six weeks   and  3  chronically infected arthroplasties  patients infected more than six weeks   in all three clinical situations  hospitalization time was shortened  and high local and low systemic levels of antibiotic were obtained  there was only one incident of side effects to the antibiotic used  this method has been successful in obtaining long term suppression of infection in 30 of 42 patients with resistant osteomyelitis  30 of 37 patients with acutely infected arthroplasties  and seven of ten patients with chronically infected arthroplasties  the complication unique to this method of therapy is pump site and catheter site infections  this occurred in three patients with recalcitrant osteomyelitis and three patients with acutely infected arthroplasties  
class5	periprosthetic chronic inflammation characterized through the measurement of superoxide anion production by synovial derived macrophages  periprosthetic macrophages were isolated from the synovium of primary and revision arthroplasty patients  inflammatory activity was determined by the level of superoxide  o2   production de novo and in response to phorbol myristate acetate  pma  stimulation  nonstimulated primary arthroplasty derived macrophages produced 2 54     2 04 pmoles of o2  minute 10 5  cells  when identical reaction tubes were stimulated with pma  o2  levels increased to 5 76     3 77 pmol of o2  minute 10 5  cells  nonstimulated revision arthroplasty derived macrophages produced 3 26     2 02 pmol of o2  minute 10 5  cells during this ten minute time period  when identical reaction tubes were stimulated with pma  o2  levels increased to 3 98     2 52 pmol of o2  minute 10 5  cells  the difference in the ratio of o2  production in response to stimulation between primary and revision groups was statistically significant  the observation of a chronic moderate level of activation and the lack of responsiveness to a potent stimulator suggests that macrophage inflammatory activity is down regulated in periprosthetic synovium  
class5	a histologic and immunohistochemical study of calcium pyrophosphate dihydrate crystal deposition disease  the articular cartilage  synovial membrane  and meniscus from ten patients who had calcium pyrophosphate dihydrate  cppd  crystal deposition disease showed strong immunoreactivity for dermatan sulfate proteoglycan  type i collagen  and s 100 protein in hypertrophic chondrocytes around the crystals  their pericellular matrix  and deposits of the crystals  electron microscopy revealed that small crystals were formed around the hypertrophic chondrocytes  especially in the degenerated matrix containing electron dense granular materials and cellular debris  chondrocytes of this kind were never observed in the articular tissue from ten patients who had osteoarthrosis  these hypertrophic chondrocytes with several unique immunohistochemical characteristics may initiate the formation of cppd crystals  
class5	hereditary internal anal sphincter myopathy causing proctalgia fugax and constipation  a newly identified condition  a newly identified myopathy of the internal anal sphincter is described  in the affected family  at least one member from each of five generations had severe proctalgia fugax  onset was usually in the third to fifth decades of life  three members of the family have been studied in detail  each had severe pain intermittently during the day and hourly during the night  constipation was an associated symptom  in particular difficulty with rectal evacuation  clinically the internal anal sphincter was thickened and of decreased compliance  the maximum anal canal pressure was usually increased with marked ultraslow wave activity  anal endosonography confirmed a grossly thickened internal anal sphincter  two patients were treated by internal anal sphincter strip myectomy  one showed marked improvement and one was relieved of the constipation but had only slight improvement of the pain  the hypertrophied muscle in two of the patients showed unique myopathic changes  consisting of vacuolar changes with periodic acid schiff positive polyglycosan bodies in the smooth muscle fibers and increased endomysial fibrosis  in vitro organ bath studies showed insensitivity of the muscle to noradrenaline  isoprenaline  carbachol  dimethylpiperazinium  and electrical field stimulation  immunohistochemical studies for substance p  calcitonin gene related peptide  galanin  neuropeptide y  and vasoactive intestinal peptide showed staining in a similar distribution to that in control tissue  a specific autosomal dominant inherited myopathy of the internal anal sphincter that causes anal pain and constipation has been identified and characterized  
class5	familial cervical dysplasia  nine of twelve family members from three generations were affected by an inherited form of cervical vertebral dysplasia  all of the affected people had an abnormality of the first cervical vertebra  some also had defects of the axis and caudad to it  the mode of transmission of the disorder is autosomal dominant  with apparently complete penetrance and variable expressivity  two patients had symptoms  one had a passively correctable tilt of the head  with an associated audible clunk and hypoplasia of the left superior facet of the second cervical vertebra  this patient had no local symptoms  neurological involvement  or muscle spasm  in the other patient  suboccipital pain developed  radiographs revealed an anterior atlanto occipital dislocation  the symptoms resolved after reduction and arthrodesis  because of the apparently complete penetrance of this disorder  physicians caring for patients who have this type of congenital malformation of the cervical spine should consider examination of closely related members of the family  clinical findings such as tilting of the head  torticollis  or limitation of cervical motion suggest that additional evaluation should be done  the examination should include lateral radiographs of the cervical spine in flexion and extension  three dimensional computed tomography reformatting was helpful in demonstrating the complex cervical anatomy in our patients  patients who have recognized abnormalities should be followed and should be re examined whenever local or neurological symptoms develop  a magnetic resonance image of the spine in flexion and extension was valuable for identification of the potentially disastrous situation of impending damage to the cord in patients who had instability and evolving symptoms  
class5	the role of venous hypertension in the pathogenesis of legg perthes disease  a clinical and experimental study  thirty two patients in whom legg perthes disease apparently involved only one hip were examined with venography  measurement of intraosseous and intra articular pressures  arthrography  and dynamic triphasic bone imaging with 99mtc methylene diphosphonate  the arterial flow of blood in the affected femoral head was slightly decreased  but the difference from that on the normal side was not statistically significant  however  there was marked disturbance of the venous drainage in the diseased hip  elevated intraosseous pressure in the affected femoral neck  and increased intra articular pressure in the involved hip compared with the normal side  an animal model was then created in twenty immature dogs  venous drainage was obstructed  and intraosseous pressure of the femoral head and neck was elevated by injection of four milliliters of semiliquid silicone into the femoral neck  in eleven of the dogs  areas of avascular necrosis resembling those associated with legg perthes disease developed in the femoral head  
class5	treatment of de quervain tenosynovitis  a prospective study of the results of injection of steroids and immobilization in a splint  in a prospective study of non operative treatment of de quervain tenosynovitis  ninety nine wrists of ninety five consecutively seen patients who had this diagnosis had an injection of one milliliter of a 1 per cent lidocaine solution and one milliliter of a suspension containing forty milligrams of methylprednisolone acetate  twelve patients  twelve wrists  were lost to follow up  of the remaining eighty seven wrists  fifty four  62 per cent  had a satisfactory outcome at a mean of eighteen months  minimum follow up  twelve months   the duration of symptoms before treatment did not affect the outcome  the result in thirty three wrists  38 per cent  was considered unsatisfactory  thirty of these wrists were subsequently treated with operative release of the first dorsal compartment  and twenty two  73 per cent  of the thirty were found to have a separate compartment for the extensor pollicis brevis  the prevalence of a separate compartment is significantly higher than that in the general population  as shown in anatomical studies of cadavera  
class5	management of pseudarthrosis after arthrodesis of the spine for idiopathic scoliosis  sixty three first  second  or third time repairs of one or more pseudarthroses were done in fifty one patients who had had an arthrodesis for idiopathic scoliosis  forty five of the patients were female and six were male  the average age was 30 2 years  the indications for the sixty three repairs were pain  twenty five repairs   progression of the curve  sixteen   both pain and progression of the curve  twelve   and radiographic changes only  ten   failure of the implant was identified before 27 per cent of the sixty three procedures  the pseudarthroses were diagnosed an average of 2 8 years after the initial arthrodeses  sixty eight per cent of the defects were visible on plain radiographs preoperatively and 32 per cent were identified at operation  during the time between the original arthrodeses and the repairs of the pseudarthroses  the scolioses increased by a mean of 7 degrees and the kyphoses  by a mean of 10 degrees  harrington distraction was the most commonly used instrumentation  twenty six  41 per cent  of the sixty three procedures   and autogenous iliac bone was the most commonly used material for the graft  thirty three  52 per cent  of the procedures   
class5	valgus deformities of the feet and characteristics of gait in patients who have rheumatoid arthritis  to investigate the cause of valgus deformity of the hindfoot in patients who have rheumatoid arthritis and to characterize the effects of the deformity on gait  two groups of patients were evaluated clinically  radiographically  and with gait analysis in the laboratory  group 1 consisted of seven patients who had seropositive rheumatoid arthritis and normal alignment of the feet and group 2  of ten patients who had rheumatoid arthritis and valgus deformity of the hindfoot  in group 2  the disease was of longer duration and the feet were more painful than in group 1  there was no evidence of muscular imbalance  equinus contracture  valgus deformity of the tibiotalar joint  or isolated deficiency of the tibialis posterior  such as weakness  tenosynovitis  or rupture of the tendon  that could have contributed to the development of the valgus deformity  in the patients who had valgus deformity  quantitated electromyography demonstrated that the intensity and duration of activity of the tibialis posterior was significantly increased  apparently in an effort to support the collapsing longitudinal arch of the foot  gait studies revealed decreases in velocity  stride length  and single limb support time  as well as delayed heel rise in both groups  but the decreases were more marked in the patients who had valgus deformity  the results of this study suggest that valgus deformity of the hindfoot in rheumatoid patients results from exaggerated pronation forces on the weakened and inflamed subtalar joint  these forces are caused by alterations in gait secondary to symmetrical muscular weakness and the effort of the patient to minimize pain in the feet  radiographs also suggested an association between the valgus deformity of the feet and valgus deformity of the knees in patients who have rheumatoid arthritis  
class5	cardiac arrest during hip arthroplasty with a cemented long stem component  a report of seven cases  seven patients had a cardiac arrest during hip arthroplasty with a cemented long stem femoral component  four patients died in the operating room  and three patients were successfully resuscitated  when the three survivors were eventually discharged from the hospital  they had no known permanent cardiac  pulmonary  or neurological sequelae  factors that were common to all of the patients were advanced age  osteoporotic bone  a previously undisturbed intramedullary canal  and use of a long stem femoral component and several batches of methylmethacrylate  hip arthroplasty with a long stem femoral component is associated with substantial risk in these patients  excessive pressurization of cement should be avoided  and invasive hemodynamic monitoring should be used when the described conditions are present  
class5	reconstruction of the chronically insufficient anterior cruciate ligament with the central third of the patellar ligament  the results of reconstruction of the anterior cruciate ligament with the central third of the patellar ligament as a free  autogenous  non vascularized graft were retrospectively reviewed at our institution  eighty reconstructions in seventy nine patients were evaluated after a minimum of two years  in forty eight  60 per cent  of the knees  the reconstruction was augmented with an extra articular lateral sling of iliotibial band  the patients were evaluated with a physical examination  a kt 1000 arthrometer  radiographs  a subjective questionnaire  and a revision of the scale of the hospital for special surgery for rating ligaments  postoperatively  seventy six  95 per cent  of the eighty knees no longer gave way  and the pivot shift test was negative in sixty seven  84 per cent  of the knees  the average score on the ligament rating scale was 93 points  all of the patients who had clinical instability at the time of the most recent follow up had associated ligamentous instability that had not been appreciated or addressed at the time of reconstruction  arthrometric evaluation revealed that the laxity differed by three millimeters or less from that of the untreated knee in sixty  76 per cent  of the treated knees  in the patient who had bilateral reconstruction  the laxity was the same in both knees  seventeen patients  who had more than three millimeters of translation  also had additional related ligamentous instability  most commonly posterolateral instability and insufficiency of the medial collateral ligament  we think that major associated ligamentous instability predisposes the reconstruction to failure and should be corrected in conjunction with the reconstruction  
class5	contracturing granulomatous myositis  a separate entity  granulomatous muscle disease is most commonly seen in sarcoidosis  but may be seen in association with a wide variety of other disorders or in isolation  patients with granulomatous myositis usually present with slowly progressive muscle pain and weakness affecting mainly proximal muscles  there are  however  a few reports of granulomatous muscle disease presenting with flexion contractures of the limbs  two further patients with granulomatous muscle disease and flexion contractures of the limbs  but with no evidence of systemic granulomatous disease  is presented  it is suggested that such patients represent a separate clinical entity that is distinct from idiopathic granulomatous myositis presenting with muscle pain and weakness  the association of contracturing granulomatous myositis with a long standing vasculitis in one patient suggests that the two conditions may be related  
class5	juvenile intervertebral disc calcification  recognition  management  and pathogenesis  juvenile intervertebral disc calcification is an uncommon disorder of childhood  characterized by calcification of the nucleus pulposus of one or more intervertebral discs  calcification may remain dormant or subsequently become symptomatic  the symptoms include fever  malaise  and neck pain and are associated with an elevated erythrocyte sedimentation rate and  occasionally  leukocytosis  although disc protrusion occurs in 38  of patients  neurological signs are distinctly uncommon  we report the case of a patient with a herniated t2 t3 calcified intervertebral disc and compressive myelopathy  juvenile intervertebral disc calcification is generally a self limiting disease that seldom requires an operation  the symptoms are transient  and resorption of the disc calcification is the rule once symptoms occur  neither the cause of the disc calcification nor the trigger for the onset of symptoms is known  an inflammatory response within the disc appears to give rise to clinical symptoms and is associated with eventual resorption of the disc calcification  
class5	the caspar microsurgical discectomy and comparison with a conventional standard lumbar disc procedure  the outcome in 119 patients who were operated on with a conventional standard lumbar discectomy procedure was retrospectively compared with that in 299 patients who were operated on with a microsurgical discectomy technique developed in homburg saar  federal republic of germany by the senior author  w c    all patients in this consecutive series had  virgin  lumbar radiculopathy evaluated and operated upon by two experienced surgeons at one institution  determination of the final outcome was made objectively by an impartial third party using identical criteria for both groups  and with a patient self evaluation form  the study looked at various pertinent aspects of the treatment course and at final outcome  the results in the microsurgical group were significantly favorable  fewer levels were explored  there was less operative blood loss and a decreased incidence of deep venous thrombosis  urinary tract infections  pulmonary emboli  and bladder catheterization  the time to full ambulation  discharge  and return to work was faster  and there was a decrease in change of occupation and a greater percentage of satisfactory final outcomes  as measured both objectively and subjectively  a description of the microsurgical technique used in this study  which differs significantly from existing microdisectomy techniques  is presented  the authors conclude that the microsurgical disectomy technique presented in this study is a safe and effective approach to the treatment of lumbar radiculopathy  
class5	tibial collateral ligament bursa  mr imaging  the bursa of the tibial collateral ligament  tcl  may be visualized at magnetic resonance  mr  imaging when it becomes distended with fluid  in the authors  experience  this finding signifies a pathologic condition either in the medial capsuloligamentous complex or in the bursa itself  such a finding may indicate tcl bursitis  tcl bursitis can be suspected in the setting of isolated pain in the medial joint line in the absence of mechanical symptoms  prolonged relief of symptoms after injection of steroid into the bursa is supportive of the diagnosis  seven cases are presented in which a fluid filled tcl bursa was identified at mr imaging  in five cases  tcl bursitis was suspected  the differential diagnosis for the mr findings is discussed  
class5	mycetoma  comparison of mr imaging with ct  magnetic resonance  mr  images obtained in 18 patients with pathologically confirmed mycetoma in the body  n   4  or lower extremity  n   14  were retrospectively reviewed and compared with computed tomographic  ct  scans in 15 patients and surgical findings in 10  t1 weighted images showed an infiltrating mass  same signal intensity as muscle  involving skin  subcutaneous fat  muscles  tendons  and other tissues  on t2 weighted images  the mass and affected structures showed moderately increased signal intensity  bone marrow involvement was detected in seven patients and was best visualized on t1 weighted images  ct showed moderate enhancement of the infiltrative process in all patients  bone changes  seen in nine  included coarse trabeculation  periosteal reaction  endosteal proliferation  and patchy destruction  mr imaging and ct were comparable and correlated well with surgery in showing the extent of soft tissue involvement  early bone changes  important for therapy planning for pedal mycetoma  were seen only at ct  the study showed that mr imaging is sensitive for assessing the extent of mycetoma in the soft tissues  ct should be the method of choice for staging pedal lesions because it can be used to detect early bone involvement  
class5	deposition of calcium pyrophosphate dihydrate crystals in the ligamentum flavum  evaluation with mr imaging and ct  four patients had spinal canal stenosis associated with deposition of calcium pyrophosphate dihydrate within the ligamentum flavum  radiologic evaluation was performed with magnetic resonance imaging or computed tomography  and surgery was performed on all four patients  pathologic examination of the surgical specimens demonstrated deposits of calcium pyrophosphate crystals within the ligamentum flavum  focal enlargement of the ligamentum flavum was present in the cervical spine  n   1   while a more diffuse  bilateral enlargement was identified in the lumbar spine  n   3   enlargement of the ligament either caused or was a component of spinal stenosis that caused neurologic signs or symptoms  three of the patients had evidence of calcium pyrophosphate deposition elsewhere  deposition of calcium pyrophosphate dihydrate within the ligamentum flavum causing either focal or diffuse enlargement can be associated with significant spinal stenosis  
class5	anterior tibial translation during a maximum quadriceps contraction  is it clinically significant  quadriceps exercises are used sparingly in the early rehabilitation of acl reconstructions because of concern about prematurely stretching the acl graft  the aim of this study was to determine if a maximum isometric quadriceps contraction significantly translates the tibia anteriorly at 15 degrees  30 degrees  45 degrees  60 degrees  and 75 degrees of flexion  secondly  the role of the acl in knee stability was analyzed by comparing the amount of tibial translation in normal  acl deficient  and reconstructed knees  thirdly  the location in the motion arc where a quadriceps contraction produces anterior tibial translation was determined  anterior tibial translation was measured using an arthrometer  kt 1000  during an 89 n and manual maximum translation applied to the knee at rest  the manual maximum translation test determines the magnitude of anterior tibial translation produced by a high anterior force applied directly to the proximal calf  these translations were compared to the tibial translation intrinsically induced by a quadriceps contraction  testing was performed in normal  n   22   acl deficient  n   10   and reconstructed  n   10  knees  anterior tibial translation produced by a maximum quadriceps contraction was measured at 15 degrees  30 degrees  45 degrees  60 degrees  and 75 degrees of flexion  the extension exercise resulted in less anterior tibial displacement than an 89 n drawer and half the translation produced by a manual maximum translation  p less than 0 001   instrumented laxity testing produced greater anterior translation of the tibia than a maximum isometric quadriceps contraction  anterior tibial translation was the same during maximum isometric knee extension in all tested knees  
class5	the contribution of the glenohumeral ligaments to anterior stability of the shoulder joint  the purpose of this study was to investigate the ligamentous stabilizing mechanisms preventing anterior instability in the glenohumeral joint  six freshly thawed  unembalmed cadaveric shoulders were dissected  preserving the joint capsule and glenohumeral ligaments  the coracohumeral ligament  and the subscapularis tendon  hall effect strain transducers were placed on the superior  middle  and inferior glenohumeral ligaments  the humerus and scapula were fixed in a specifically designed mounting apparatus that allowed the glenohumeral joint to be placed in 0 degree  45 degrees  or 90 degrees of abduction  the mounting apparatus was placed in a model ttc instron universal testing instrument  which applied an external rotation torque to the humerus  strain produced in the three glenohumeral ligaments was recorded on a three channel x y chart recorder  at 0 degree of abduction  the superior and middle glenohumeral ligaments developed the most strain  at 45 degrees of abduction  the inferior and middle glenohumeral ligaments developed the most strain  with considerable strain also being developed in the superior glenohumeral ligament  at 90 degrees of abduction  the inferior glenohumeral ligament developed the most strain  with strain also seen in the middle glenohumeral ligament  
class5	a prospective  randomized study of three surgical techniques for treatment of acute ruptures of the anterior cruciate ligament  treatment of acl tears is controversial  recent reports on nonoperative treatment have shown poor results  results after primary repair have deteriorated with time  leading to augmentation procedures that seem to have improved the results  however  there have been few prospective  randomized studies in this field  our goal was to compare primary repair with a bone patellar tendon bone augmentation method and with a new method using the kennedy ligament augmentation device  one hundred fifty patients aged 16 to 50  all of whom had acute acl tears  were randomized with the closed envelope method to one of three groups treated with open surgical methods  fifty patients were treated with primary repair  50 patients with patellar tendon augmentation  and 50 patients were augmented with the kennedy ligament augmentation device  all patients were operated on within 10 days of injury  the rehabilitation protocol was identical  consisting of a long leg cast for 2 weeks  followed by a brace with no weight bearing and limited motion for 6 weeks  the patients were followed prospectively by one surgeon  le  using the lysholm functional score  tegner activity level score  clinical evaluation and kt 1000 arthrometer at 6 months  1  and 2 years  three patients were lost to followup  there was no age or activity level difference between the groups  sport activities led to 85  of the injuries  with skiing  soccer  and european handball representing 80  of injuries  all three groups reduced their activity level the 1st year  the repair group remained at the same level after 2 years  
class5	postarthroscopy analgesia with bupivacaine  a prospective  randomized  blinded evaluation  the analgesic effect of intraarticular bupivacaine injected at the conclusion of knee arthroscopy done under general anesthesia was investigated in a prospective  randomized  and blinded fashion  pain scores  the use of analgesic medications  crutch use  weight bearing  activity level  and difficulty sleeping the night after surgery were all unaffected by the use of bupivacaine  the apparent lack of effect is most likely due to rapid clearance from the knee  leaving only a transient  1 to 2 hours of potential benefit  in this study  the patients were already quite comfortable during this time period due to the routine use of intraoperative narcotics  the preoperative level of knee discomfort was found to be a major determinant of postoperative discomfort  other much less important factors were synovial and chondral shaving  sex of the patient  and experience of the surgeon  
class5	intestinal permeability in patients with chronic urticaria angioedema with and without arthralgia  we evaluated the clinical response to oligoallergenic dietary treatment and the intestinal absorption of a protein antigen  cow milk beta lactoglobulin  blg  in 24 patients with chronic urticaria angioedema syndrome 13 of whom also suffered from joint symptoms  sixteen patients  77  of those with arthralgia  responded to diet  rd  with marked reduction of symptoms  the others did not respond  nr   ten  all but one rd with arthralgia  had increased permeability to blg after oral administration of cow milk  four with high titers of igg to blg showed the highest absorption of blg and the groups with arthralgia showed higher blg levels than those without arthralgia  in all cases  specific ige to cow milk was absent  these data suggest that the symptoms of a subgroup of patients with chronic urticaria  and especially patients with joint complaints that subside with diet  are related to excess intestinal permeability  the measurement of gut permeability to food proteins may be useful to define those who may benefit from dietary restriction  
class5	lyme disease  recommendations for diagnosis and treatment the incidence and the endemic range of lyme disease in the united states have increased steadily since the disease was originally recognized in lyme  connecticut  in 1975  because of the varied clinical manifestations of this illness and the use of unstandardized serologic testing methods  diagnosis is often uncertain and treatment outcomes are often difficult to evaluate  the antibiotic regimens that are commonly used in clinical practice have changed rapidly  they show much regional variation with little critical comparison of treatment results  the clinical diagnosis and the literature on the treatment of the various stages of lyme disease are reviewed  the reported data are supplemented with recommendations based on 15 years of clinical experience with this illness  
class5	mineral balance in infantile cortical hyperostosis  effects of corticosteroids  the effects on mineral metabolism of therapeutic doses of corticosteroids were investigated in infantile cortical hyperostosis  in four untreated cases the calcium  phosphorus  and magnesium balances were strongly positive  in one severe case  treatment with prednisolone was associated with an alteration to negative calcium and magnesium balance  and faecal losses of calcium were particularly high  this effect persisted for at least three months after the steroids had been discontinued  and during this period there was pronounced retardation of linear growth  six months after the treatment had been stopped mineral balance was again positive and there was rapid  catch up  in growth  in infancy  the negative effect of corticosteroids on calcium  phosphorus  and magnesium metabolism may contribute to inhibition of bone growth and steroid stunting  
class5	persistence of monosodium urate crystals and low grade inflammation in the synovial fluid of patients with untreated gout  synovial fluid  sf  from 74 asymptomatic knees of patients with gout was analyzed  these patients had never been treated with serum uric acid lowering agents  sf samples were analyzed for the presence of crystals and for cell counts  using undiluted sf directly in a niebauer cell counting chamber  thirty seven of the aspirated knees had previously been inflamed  and monosodium urate  msu  crystals were seen in sf aspirates from 36 of them  97    of the 37 knees that had never been inflamed  only 8 contained msu crystals  p less than 0 00001   after reaching the joint  msu crystals will persist in the sf as long as the serum uric acid level has not been lowered by appropriate treatment  in this situation  analysis of sf is an excellent diagnostic test for the intercritical gout  the mean cell count in the 44 sf samples that contained msu crystals was 449 mm3  95  confidence interval 310 589   the mean cell count in the 30 sf without msu crystals was 64 mm3  95  confidence interval 34 95   p less than 0 00002   the sf samples that contained msu crystals also had a higher percentage of polymorphonuclear leukocytes than those without msu crystals  p less than 0 002   these data suggest that there is a low grade inflammation present in the knees of patients with msu crystals  the consequences of which should be investigated  
class5	synovial membrane histology and immunopathology in rheumatoid arthritis and osteoarthritis  in vivo effects of antirheumatic drugs  we examined the histologic and immunopathologic features of the synovial membrane of 18 patients with rheumatoid arthritis  ra  and 12 patients with osteoarthritis  oa  who had undergone total knee arthroplasty  patients were classified into 5 groups according to therapeutic regimen and disease  ra treated with nonsteroidal antiinflammatory drugs  nsaids   ra treated with nsaids and prednisone  ra treated with nsaids and methotrexate  mtx   oa treated with analgesics  and oa treated with nsaids  there were no significant between group differences in the percentages or the distribution pattern of the infiltrating t cell subsets  cd4  cd8   hla dr  or interleukin 2 receptor bearing cells  however  inflammatory indices  which included the thickness of the lining cell layer and the density of the mononuclear cell infiltrate  were significantly higher in the ra patients treated with prednisone and those treated with mtx  p less than 0 05   similarly  fibrosis was markedly reduced in these 2 groups  the ra patients treated with nsaids alone and the 2 groups of patients with oa demonstrated similar profiles  these data suggest that prednisone and mtx may inhibit the development of fibrosis without altering the subsets of the inflammatory cell population  this observation raises the possibility that the action of these 2 drugs may be partly mediated by the suppression of inflammatory mediators that are responsible for fibroblast activation  
class5	spontaneous degenerative polyarthritis in male new zealand black kn mice  histopathologic studies and radiographic analysis revealed that male new zealand black kn  nzb kn  mice develop degenerative polyarthritis in the joints of the forepaw and hindpaw beginning at age 2 months  deposits of autoantibodies were observed on proliferating collagen fibers  nuclei of chondrocytes  and epidermal cells  increases in the frequency of positivity for rheumatoid factor and anti type ii collagen antibodies and in the level of serum oxidation activity were noted in these mice  the joint disease in male nzb kn mice was transferable to female nzb kn mice and male balb c mice by intraperitoneal injection of spleen cells from the male nzb kn mice  this animal model of arthritis will be extremely useful for analyzing not only the pathogenesis of rheumatoid arthritis  but also new strategies for its treatment  since nzb kn mice  unlike mrl lpr mice  do not develop severe lupus nephritis or lymph adenopathy  and therefore have a longer survival period  
class5	down regulation of adoptive adjuvant induced arthritis by suppressor factor s   we recently described a method for inducing immunologic tolerance to trinitrochlorobenzene  tncb   a hapten that generates suppressor cells capable of down regulating the efferent phase of tnp specific contact hypersensitivity in rats  peritoneal exudate cells  pec  of such tolerized rats  upon being triggered by specific hapten  suppressed contact hypersensitivity to another hapten elicited at the same time  this implied that cells that mediate delayed type hypersensitivity of any specificity might be down regulated  provided that the suppressor cells are activated with specific antigen and that the unrelated delayed type hypersensitivity is elicited in parallel  to rigorously test this possibility  we examined the ability of tnp specific suppressor lymphoid cell factors to affect cells that mediate adoptively transferable adjuvant induced arthritis  aia  in rats  to induce arthritis  spleen cells from freund s complete adjuvant injected rats were stimulated with concanavalin a and administered to naive recipients  prior to adoptive transfer  the cells were exposed for brief intervals to supernatants of lymphoid cells from control and hapten tolerized rats  supernatants of pec and lymph node cells from hapten tolerized rats were found to markedly reduce the effectiveness of cells that mediate aia  the hapten tolerized cells required reexposure to hapten prior to preparation of the supernatants  supernatants of spleen cells from hapten tolerized rats that had been hapten painted as well as hapten triggered and supernatants of lymph node cells and of pec from only hapten painted or hapten triggered rats were ineffective in altering the aia  thus  factors from suppressor cells induced toward hapten coupled self antigens have been found to adversely affect the function of lymphoid cells that mediate a totally unrelated inflammatory response  namely  aia  the clinical implications of these findings are discussed  
class5	prevalence of angioid streaks and other ocular complications of paget s disease of bone  seventy randomly selected patients with paget s disease of bone were examined for ocular complications  the prevalence of macular degeneration and cataract was 24 3   only one patient was found to have angioid streaks  eight patients had peripapillary chorioretinal atrophy  these findings suggest that the prevalence of serious ocular complications of paget s disease is not as high as previously thought  the significance of peripapillary chorioretinal atrophy requires further evaluation  
class5	magnetic resonance imaging of the head and spine  effective for the clinician or the patient  objectives  to test how the results of magnetic resonance imaging influence clinicians  diagnoses and management plans for patients with cranial and spinal problems and to assess changes in the quality of life of these patients  design  survey of patients undergoing cranial and spinal magnetic resonance imaging with questionnaires about diagnoses and intended management plans before and after imaging and quality of life questionnaires at the time of imaging and again four months later  setting  regional magnetic resonance imaging and spectroscopy unit  subjects  100 consecutive patients referred for cranial imaging in early 1989  100 similar patients referred for spinal imaging  main outcome measures  changes in clinicians  leading diagnoses after magnetic resonance imaging and their confidence in these diagnoses  changes in intended management plans  assessment of the contribution to the future management of the patient  changes in patients  quality of life  results  magnetic resonance imaging altered the clinicians  leading diagnoses in 35 of 169  21   cases  the clinicians became more confident about their leading diagnoses in 90 of 167  54    there was a change in management plan in 113 of 182  62    the clinicians considered that magnetic resonance imaging made an important contribution to management in 119 of 162  73   patients  overall  the patients  quality of life was unchanged at the four month assessment  conclusions  magnetic resonance imaging of patients with cranial and spinal problems influences clinicians  diagnoses and management plans  but the quality of life of these patients remains unchanged  
class5	antibody to coxsackie b virus in diagnosing postviral fatigue syndrome objective  to study the association between coxsackie b virus infection and the postviral fatigue syndrome and to assess the immunological abnormalities associated with the syndrome  design  case control study of patients with the postviral fatigue syndrome referred by local general practitioners over one year  setting  general practitioner referrals in dunbartonshire  scotland  patients  254 patients referred with the postviral fatigue syndrome  exhaustion  myalgia  and other symptoms referable to postviral fatigue syndrome of fairly recent onset  that is  several months  and age and sex matched controls obtained from same general practitioner  11 patients were rejected because of wrong diagnoses  resolution of symptoms  and refusal to participate  leaving 243 patients and matched controls  main outcome measures  detailed questionnaire  patients and controls  and clinical examination  patients  and blind analysis of blood sample at entry and after six months for determination of coxsackie b virus igm and igg antibodies and other variables  including lymphocyte protein synthesis  lymphocyte subsets  and immune complexes   results  percentage positive rates for coxsackie b virus igm at entry were 24 4  for patients and 22 6  for controls and for coxsackie b virus igg 56 2  and 55 3  respectively  there were no significant differences between different categories of patients according to clinical likelihood of the syndrome nor any predictive value in a fourfold rise or fall in the coxsackie b virus igg titre in patients between entry and review at six months  the rates of positive antibody test results in patients and controls showed a strong seasonal variation  of the numerous immunological tests performed  only a few detected significant abnormalities  in particular the mean value for immune complex concentration was much higher in 35 patients and 35 controls compared with the normal range and mean value for total igm was also raised in 227 patients and 35 controls compared with the normal range  conclusions  serological tests available for detecting coxsackie b virus antibodies do not help diagnose the postviral fatigue syndrome  percentage positive rates of the antibodies in patients simply reflect the background in the population as probably do the raised concentrations of total igm and immune complexes  
class5	clinical screening for collagen defects in connective tissue diseases  the defects in type i collagen structure or synthesis that produce all four types of osteogenesis imperfecta  oi  and ehlers danlos syndrome  eds  type vii and the defects in type iii collagen structure in eds type iv can be detected by analysis of collagens produced by fibroblastic cells cultured from affected individuals  quantitative defects in synthesis of type i collagen are seen in oi type i and qualitative defects of type i collagen characterize oi type ii  oi type iii  and oi type iv and eds type vii  eds type iv results from qualitative type iii collagen defects  all of the disorders are inherited typically in an autosomal dominant fashion so that recurrence among offspring of normal parents usually results from germline mosaicism for the mutation in one parent  analysis of type i and type iii collagen synthesized by cultured chorionic villus cells is used for prenatal diagnosis of these disorders  
class5	impaired exercise capacity in adults with moderate scoliosis  we measured lung function and exercise tolerance in 15 adults with moderate kyphoscoliosis  thoracic curvatures between 25 degrees and 70 degrees  mean     sd   46 93 degrees     14 02 degrees   forced vital capacity showed a slight reduction from values predicted from age and sex matched control subjects  3 39     1 06 vs 4 06     0 82 l  p less than 0 05   however  exercise tolerance was significantly lower than previously reported in healthy adults  vo2max   31 60     9 12 vs 37 07     4 91 ml kg min  p less than 0 05   despite the reduced exercise tolerance  the ratio of maximum tidal volume to vital capacity  vtmax vc  was similar to that observed in healthy adults  the mean dyspnea index  vemax mvv  was also normal at 69 4     19 0  hypoxic and hypercapnic ventilatory responses were within predicted normal limits at 0 67     0 37 l min 1 fall in sao2 1 and 1 67     0 92 l min 1 mm hg pco2  1   we conclude that the impairment of exercise performance found in adults with moderate scoliosis cannot be attributed to any important ventilatory limitation  abnormality in lung volume  or impaired chemoreceptor sensitivity  we suggest that the reduced vo2max likely arises from deconditioning and lack of regular aerobic exercise  
class5	hypercapnic respiratory failure due to l tryptophan induced eosinophilic polymyositis  a 24 year old man presenting with fever  rash  and myalgias subsequently developed hypercapnic respiratory failure and severe limb muscle weakness  muscle biopsy revealed eosinophilic myositis  due to the ingestion of large quantities of l tryptophan as a dietary supplement  complete recovery occurred with corticosteroid administration  significant involvement of the respiratory muscles can be a predominant feature of this newly described disease entity  
class5	hypertrophic osteoarthropathy in association with pulmonary tuberculosis  three white male patients with advanced cavitary pulmonary tuberculosis presented with hoa  no other pathology to explain the osteoarthropathy was detected  the osteoarthropathy responded symptomatically to nsai drugs and treatment of tuberculosis but resolved radiologically in only one patient  
class5	risk factors for disability among u s  adults with arthritis  this article studies risk factors for physical and social disability among u s  adults ages 55  who have arthritis  compared to non arthritis persons of those ages  the dependent variables refer to difficulties in walking  physical functioning  motions and strength   personal care  and household care  the data set is the supplement on aging  soa   n   16 148  that accompanied the 1984 national health interview survey  the soa data are cross sectional  relationships of risk factors to disability suggest causation but do not directly demonstrate it  logistic regressions show that risk factors are similar for arthritis and non arthritis people  with one important exception   1  the similarities are  for both groups  odds of disability rise with age  diminish with education  and are higher for non whites and non married persons  disability rises with number of chronic diseases and impairments  and it is elevated for underweight persons  body mass index  bmi  less than 20  further analysis indicates this reflects incomplete control of their severe illness status   long duration of arthritis and recent medical care for it are associated with disability   2  the exception is  severe overweight  bmi greater than or equal to 30  is a disability risk factor for arthritis people  but not for non arthritis people  previous research has shown that obesity overweight is a risk factor for etiology of osteoarthritis  our analysis now shows its continued importance for disability when the disease is present  
class5	reconstruction of the severely atrophic edentulous mandible by means of autogenous bone grafts and simultaneous placement of osseointegrated implants  a method of reconstructing the severely atrophic mandible that simultaneously provides additional strength and the ability to house osseointegrated implants is presented  the performance of the procedure from an external approach minimizes the possibility of oral contamination and  therefore  infection  the procedure has been performed on 10 patients  with a longest follow up of 3 years  a 93  success rate has been achieved  and bone resorption at the implant sites has thus far been negligible  prosthetic rehabilitation has been done in 9 of the 10 cases  3 have been tissue supported prostheses  and 6 have been completely implant supported prostheses  
class5	bone resorption  stability  and soft tissue changes following large chin advancements  large advancement genioplasties were performed in 10 patients  mean advancement  11 7 mm  by horizontal osteotomy of the inferior border of the mandible  with preservation of a musculoperiosteal pedicle to the advanced genial segment  preoperative  immediate postoperative  and long term follow up lateral cephalometric radiographs were retrospectively analyzed to evaluate the osseous and soft tissue changes of the chin  after a mean follow up period of 15 months  76  of the initial advancement was preserved  representing 24  osseous resorption  the enveloping soft tissues of the chin followed the bony movement in a ratio of 1 0 88  horizontal osteotomy of the inferior border of the mandible was a relatively stable procedure when used for large chin advancements  the broadcast possible musculoperiosteal pedicle should remain attached to the advanced genial segment to minimize osseous resorption and to achieve more predictable soft tissue changes  
class5	long term follow up of the use of nonporous hydroxyapatite for augmentation of the alveolar ridge  particulate hydroxyapatite  ha  was used in the augmentation of 18 mandibular and four maxillary ridges in 21 patients whose cases were followed postoperatively for 5 to 7 years  patients were evaluated clinically  radiographically  and through questionnaires  prosthodontic assessment of retention and stability of dentures showed improvement 5 years postoperatively  patients receiving ha rated their dentures favorably using parameters of the cornell medical index  the results of this study show that particulate ha alone can be used as a satisfactory material for augmentation of the alveolar ridge  
class5	nasopalatine duct cyst  an analysis of 334 cases  the nasopalatine duct cyst  npdc  is the most common cyst of nonodontogenic origin in the maxilla  however  the information reported about this lesion consists primarily of small surveys and isolated case reports  the purpose of this retrospective investigation was to gather demographic  clinical  and histologic data on a large series of npdcs  and to compare the findings with those of previous studies  in this study  the overall mean age at diagnosis was 42 5 years  and there was a slight male predilection  the mean radiographic diameter was 17 1 mm  but 75  of the lesions were 20 mm or less in diameter  symptoms were present in at least 70  of the cases  only 28  of the specimens contained respiratory epithelium  there was no correlation between radiographic size  patient s age  presenting symptoms  or type of epithelium  recurrence was noted in only 2  of the cases  
class5	the clinical course of osteoporosis in anorexia nervosa  a longitudinal study of cortical bone mass  women with anorexia nervosa have reduced bone mass and may develop fractures  neither the pathophysiology of this osteoporosis nor its natural history is known  to study the clinical course of osteoporosis  we followed up 27 women with anorexia nervosa for a median of 25 months  range  9 to 53 months   at study entry  cortical bone density  measured by single photon absorptiometry of the radial shaft  was low  mean     sd  0 63     0 07 g cm2  and inversely related to the duration of amenorrhea  r    0 49   during follow up  most patients gained weight  n   19   took calcium supplements  n   16   and exercised regularly  n   22   but fewer than half reached 80  or more of ideal body weight  n   11   resumed menses  n   6   or received estrogen  n   4   cortical bone density was stable during follow up for the group as a whole  the mean annual change      sd  was  0 005       015  g cm2  95  confidence interval   0 0009 to  0 0109   there was no significant difference in the mean change in bone density between women who attained 80  of ideal weight and those who did not or between groups who did or did not regain menses  take estrogen or calcium  or exercise vigorously  four fractures were clinically observed in three women during follow up  the rate of 0 05 nonspine fractures per person year  95  confidence interval  0 02 to 0 13  exceeds that of normal women in this age range  relative risk  7 1  95  confidence interval  3 2 to 18 5   we conclude that reductions in cortical bone density appear not to be rapidly reversed by recovery from anorexia nervosa and that anorectic women may have an increased risk of fracture  
class5	hydrocephalus  overdrainage by ventricular shunts  a review and recommendations  selected literature review of the clinical course of patients with ventricular shunts for hydrocephalus shows that the effects of cerebrospinal fluid overdrainage are subdural hematoma  craniosynostosis  slit ventricle syndrome  and low intracranial pressure syndrome  these occur sequentially at different age groups  but approximate averages of incidence and time of occurrence after first shunt reveal an overall incidence of 10  12  for at least one of these appearing at 6 5 years after shunting  the basic etiology  diagnosis  and variety of treatment modalities available are reviewed  including the need for shunt closing intracranial pressure control  included is a hydrocephalus program designed to minimize the need for long term extracranial shunts and to maximize therapeutic intracranial procedures for hydrocephalus  
class5	papillary carcinoma of thyroid with exuberant nodular fasciitis like stroma  report of three cases  three examples of an unusual morphologic variant of papillary thyroid carcinoma  ptc  are reported  the presence of a prominent stromal component resulted in low power microscopic appearances resembling fibroadenoma  phyllodes tumor  or fibrocystic disease of the breast in two cases  the carcinomatous component grew in the form of anastomosing narrow tubules  clustered glands  solid sheets with or without squamous differentiation  and or papillae  and exhibited the typical nuclear features of ptc  the abundant stroma had a nodular fasciitis like quality and was composed of short fascicles of spindle cells separated by varying amounts of mucoid matrix  collagen  and extravasated red blood cells  this was interpreted as an exuberant mesenchymal reaction to the carcinoma  the importance of recognizing this variant of ptc is that  when one encounters a fibroproliferative lesion of the thyroid  a diligent search should be made for papillary carcinoma  this variant also must be distinguished from the vastly more aggressive papillary carcinomas with anaplastic transformation and the so called carcinosarcomas  
class5	serum enzyme alterations in chronic muscle disease  a biopsy based diagnostic assessment  the results of interpretation of muscle biopsies were compared retrospectively to activities of serum enzymes and isoenzymes  a total of 137 patients seen at the cleveland clinic foundation in 1986 and 1987 were included in this study  serum enzymes evaluated were ck  ast  ld  and aldolase  als   as well as the percentage ck mb isoenzyme  the units of ck mb and the ratios of ck to ast  ld  and als were calculated  descriptive statistics  kruskal wallis one way analysis of variance  and stepwise logistic regression were performed  a diagnostic algorithm was constructed using a computer assisted rule generation program  myopathic diseases yielded a greater mean increase in serum enzyme activity than atrophic diseases  by multivariate stepwise logistic regression  increases in serum ast and ck activity were independently associated with the presence of inflammation in a muscle biopsy specimen  the diagnostic algorithm allowed for the separation of myopathies from atrophies and could identify cases of duchenne s muscular dystrophy and polymyositis  
class5	hypercalciuria in parathyroid disorders  effect of dietary sodium control  moderate dietary na restriction  80 mmol d for 7 days  during constant ca intake can reduce high urinary ca excretion to normal levels in idiopathic hypercalciuria  ih   a similar protocol was used to test its effect in primary hyperparathyroidism  phpt  and also in hypoparathyroid subjects  hopt  during treatment with dihydrotachysterol  dht   nine subjects with phpt  10 with hopt  and one with pseudo hopt were evaluated after na restricted  80 mmol d  and na supplemented  200 mmol d  diets for 7 days each with dietary ca constant  na restriction resulted in a decrease in mean urinary 24 hour ca excretion in phpt subjects  10 6 v 7 6 mmol d  424 v 304 mg   p less than 0 0001  and in one pseudo hopt subject  similar to the pattern seen previously in ih subjects  in contrast  na restriction was not accompanied by significant change in ca excretion in hopt  there was no change in serum immunoreactive pth  ipth  or 1 25 oh 2 vitamin d levels in either group when na intake was altered  thus  the presence of parathyroid hormone  pth  is necessary for sodium related alterations in urinary ca to occur  the effect of pth appears to be  permissive  rather than  active   dietary na restriction may have a role in the management of hypercalciuria in mild phpt cases when parathyroidectomy is contraindicated  
class5	flexion extension views in the evaluation of cervical spine injuries  study objective  to determine the efficacy of flexion extension  f e  cervical spine radiographs in detecting acute cervical spine instability in emergency patients  design  we retrospectively reviewed the charts of 141 consecutive trauma patients who had f e views performed after a routine cervical spine series  three views  was obtained in the emergency department  interpretations of the routine series were compared with those of the f e views to determine if additional useful information was provided by the latter  the charts also were reviewed to determine if any variables were associated with an increased use of f e views  an increased likelihood of these views demonstrating instability  or any neurologic sequelae resulted from these studies  setting  an urban level i adult trauma center  measurements  the interpretations of the routine series were noted to be either normal  abnormal but without demonstrable fracture dislocation  or demonstrating a fracture dislocation  the f e views were categorized as stable  unstable  or uninterpretable  results  cervical spine instability was demonstrated by f e views in 11 of the 141 patients  8    four of whom had normal routine cervical spine films  three of these four patients required surgical stabilization  prolonged neck pain  more than 24 hours   an initially abnormal spine series  and a neurosurgical consult were all associated with an increased use of f e views  ten of 11 patients with radiographic instability had significant neck pain by history  the remaining patient was intoxicated  no neurologic sequelae resulted from performing f e studies  there was one false negative f e study  which raises concern about the reliability of this procedure in the ed  conclusion  we believe that a large prospective study is required to determine which patients warrant f e views  
class5	incidence of cocaine associated rhabdomyolysis  study hypothesis  rhabdomyolysis is a common complication of cocaine use  and muscle symptoms fail to predict its development  study population  a prospective  convenience sample of patients presenting to the emergency department of a large inner city hospital with complaints related to cocaine use were eligible for inclusion  patients were excluded if they had other potential causes of elevated creatine kinase  ck  levels or rhabdomyolysis  a control group comprised patients who were not cocaine users and satisfied the exclusion criteria  sixty eight patients were studied  methods  initial evaluation included determination of the presence of muscle pain or swelling and total ck levels  patients with a ck level of more than 800 u l had additional tests  including a urine myoglobin  urine drug screen  and serum phosphorus  rhabdomyolysis was defined by a serum ck level of more than 1 000 u l  more than fivefold that of normal   ck levels were compared by two tailed student s t test  muscle symptoms were compared with the development of rhabdomyolysis by fisher s exact test  results  the ck level in the cocaine group was 931     1 785 u l  mean     1 sd   the ck level in the control group was 242     168 u l  p    028   of the cocaine users  24   eight of 34  had rhabdomyolysis  one developed multiorgan failure and died  no patient in the control group had a ck level of more than 1 000 u l  only one cocaine user who developed rhabdomyolysis had muscle symptoms  three cocaine users had muscle symptoms but did not develop rhabdomyolysis  no patient in the control group had muscle symptoms or developed rhabdomyolysis  muscle symptoms did not predict the ck level  p    55   conclusion  this study revealed that 24  of the cocaine users had rhabdomyolysis  many of the cases of rhabdomyolysis were not predictable from history or physical examination  making laboratory evaluation essential  
class5	application technique of cotrel dubousset instrumentation for scoliosis deformities  used in over 600 cases  the posterior cotrel dubousset spinal instrumentation device has become the device of choice  this technique allows the most effective correction for all kinds of spinal deformities  it requires lengthy preoperative planning and is a technically demanding surgical procedure  however  because of its versatility it can be adapted to most spinal deformities  the cotrel  dubousset technique is a rigid system of immobilization  and  because it does not require any postoperative immobilization  patients are able to resume their normal lives and activities very quickly  
class5	minor anatomic abnormalities of the hip joint persisting from childhood and their possible relationship to idiopathic osteoarthrosis  a retrospective review was made of roentgenograms from 30 patients with idiopathic osteoarthrosis of the hip  the roentgenograms were taken before the onset or very early in the course of the disease  nine measurements were made on the anteroposterior and cross table lateral roentgenograms  these were compared to 54 hips from normal patients  twenty nine of 30 patients had abnormal measurements  with as many as seven in a single individual  when compared to normal patients  there were no abnormalities in the control group  the availability of lateral views allowed an additional dimension to be added to previous studies in the literature  this study lends further support to the biomechanical theory of the etiology of idiopathic osteoarthrosis of the hip  
class5	radiocolloids in the management of hemophilic arthropathy in children and adolescents  radiocolloids have been used in the treatment of hemophilic arthropathy  fifty eight joints of 35 patients were injected with 2 5 mci of yttrium 90 silicate under local anesthesia  a preinjection arthrogram was performed to ensure correct placement of the needle  plaster of paris cast immobilization of the joint was used for three days  after a mean follow up period of seven years  range  two to 12 years   47 joints were pain free  and 13 joints had not experienced another hemorrhagic episode  the mean hemorrhagic frequency had decreased from four per month to two per year  the radiation risk was far outweighed by the benefits of the procedure  forty seven of the 58 joints were rated as improved by the patients  the roentgenographic appearance of the joints had changed little  only five complications occurred  three needle track necroses because of extravasation of the radiocolloid  two severely painful joints immediately after injection  and one massive hemorrhagic episode  this form of treatment is suggested for hemophiliacs who have failed to respond to intensive physical and hematologic therapy  and for those patients who have inhibitors  
class5	congenital anomalies of the cervical spine  congenital anomalies of the cervical spine are uncommon  the majority of afflicted individuals are asymptomatic or have only mild restriction of neck motion  if symptoms develop  they are usually due to cervical instability or degenerative osteoarthrosis  recent information indicates that patients with upper cervical anomalies such as atlantooccipital fusion  anomalies of the odontoid  or the transverse atlantal ligament have a great propensity to develop early instability and neurologic problems secondary to minor traumatic events  if symptoms occurs in the lower cervical spine  it is usually in adult life and due to degenerative arthritis in the hypermobile articulations adjacent to the area of synostosis  the relatively good prognosis of cervical lesions is overshadowed by the  hidden  or unrecognized associated anomalies  there is a high incidence of significant scoliosis  sprengel s deformity  renal anomalies  deafness  and neurologic malformations  early recognition and treatment of these problems may be of substantial benefit  sparing the patient further deformity or serious illness  
class5	osteoarthrosis retards the development of osteoporosis  observation of the coexistence of osteoarthrosis and osteoporosis  the clinical  roentgenographic  and biochemical features of the dorsal and lumbar spine were reviewed in 72 postmenopausal women  nineteen women had both osteoporosis  vertebral collapse  and osteoarthrosis  these patients were compared with 26 patients who had only osteoarthrosis of the spine and 27 who had only vertebral collapse  the patients who had both spinal osteoporosis and osteoarthrosis were older  more advanced in menopause  and physically smaller in stature and body weight than the other groups  they also had higher serum parathyroid hormone level  used nonthiazide diuretics more frequently  and had more nulliparity than the other two groups  these patients had osteoarthrosis of the hip to a lesser degree than patients affected by osteoarthrosis alone  and they had fewer fractures of the forearm and other sites than patients with osteoporosis alone  the incidence of femoral neck fractures in both groups  however  was comparable  these results suggest that osteoarthrosis or a related factor might have a protective effect on the progression of osteoporosis  these results confirm earlier observations that postmenopausal osteoporosis and osteoarthrosis are two distinct diseases and not the result of normal aging  
class5	analysis of 61 cases of vertebral osteomyelitis  sixty one cases of bacterial vertebral osteomyelitis from july 1969 to july 1979 were analyzed  the ages of the 49 men and 12 women ranged from 21 to 66 years  the portal of entry was hematogenous in 58 cases  gunshot wounds in two cases  and and adjacent retroperitoneal abscess in one case  biopsy was performed in 60 patients  there were 15 complications related to the disease  gram negative rods were the predominant bacteria isolated  blood culture was positive in 13 of the 26  50   patients tested  eleven of the 13  85   organisms isolated from the blood cultures correlated with organisms recovered from biopsy specimens  eleven of the patients had more than one disk level involved  of the 61 patients  29 went on to spontaneous fusion  17 were lost to follow up study  11 failed to fuse  three had surgical fusion  and one patient died  recommendations for diagnosis included the collection of blood cultures and radionuclide bone scans  management recommendations included systemic antibiotics for at least three weeks and immobilization with either bed rest or spinal orthoses  surgery was indicated if an abscess was present  neurologic complications occurred  instability became a factor  or the medical treatment failed  
class5	a test for knee posterolateral rotatory instability  a test for knee posterolateral instability  which is a modification of the standard posterolateral rotatory instability test  is described  in this test  the patient lies supine on the examination table with hips and knees flexed to 90 degrees  the examiner grasps both feet and attempts to maximally externally rotate them  a positive test is indicated by  1  excessive external rotation of the affected tibia  which is easily recognized since the feet act as pointers and amplify the external rotation  and  2  a slight posterior sag of the affected tibial tubercle  which is more subtle but still a very recognizable sign  
class5	knee function after surgical or nonsurgical treatment of acute rupture of the anterior cruciate ligament  a randomized study with a long term follow up period  one hundred fifty six patients with a total rupture of the anterior cruciate ligament  acl  were reexamined 41 to 80 months after injury  they were randomized to three treatment groups   1  repair and augmentation of the acl with an iliotibial strip   2  repair without augmentation  and  3  nonsurgical acl treatment  associated injuries of menisci and other ligaments were treated in the same way for the three groups  two thirds of the patients in the nonsurgically treated group complained of instability and 17  had had a subsequent reconstruction of the acl at the follow up examination  the group treated with an augmented repair had a less abnormal laxity measured by a laxity testing device  sixty three percent returned to competitive sports  as compared with 27  in the nonsurgical group and 32  in the only repair group  relative strength of the quadriceps and hamstrings muscles were similar for all groups  the augmented repair group had better hop tests  reflecting a superior stability  whereas running was not affected by treatment but was correlated with the activity level  
class5	fractional lengthening of the flexor tendons in clubfoot surgery  massive scarring of the z lengthened flexor digitorum and flexor hallucis longus is a constant finding in clubfoot surgery  a method of fractional lengthening of the tendons is described  this method has been proven effective in preventing this complication  
class5	experimental diabetes  insulin treatment  and femoral neck morphology and biomechanics in rats  to investigate the effects of diabetes and insulin treatment on trabecular bone  the morphologic and biomechanical characteristics of the femoral neck in rats with streptozotocin induced diabetes were studied  young sprague dawley rats were divided into three groups  control  diabetic  dm   and diabetic with insulin  di   and maintained for ten weeks  cantilever bending tests to failure were conducted on the proximal femur  and fracture surface cross sections were analyzed  morphologically  the femoral necks in diabetic rats decreased in the relative size of their cortical shell and increased their trabecular core  structurally  the load and the energy at the proportional limit and the total energy in diabetic femoral necks were significantly less than controls  in material properties  the diabetic femoral necks had significantly less stress at the proportional limit  compared to the dm group  the di femoral necks had significantly greater load and energy at the proportional limit and significantly greater total energy  femoral neck mechanical and morphologic properties in diabetic rats were significantly lower than controls  but insulin treatment ameliorated diabetic osteopathy in the rat femoral neck  
class5	histochemical localization of calcium with potassium pyroantimonate in the articular tissues in calcium pyrophosphate dihydrate crystal deposition disease  the ultrastructural localization of calcium in the articular cartilage  meniscus  and synovium of patients with calcium pyrophosphate dihydrate  cppd  crystal deposition disease was examined by using potassium pyroantimonate  focal areas with deposition of cppd crystals in each tissue showed electron dense precipitates of the antimony calcium complex   1  in the cytoplasm of hypertrophic chondrocytes around cppd crystals  especially on the margins of intracellular lipid droplets or within electron dense amorphous material or both  and  2  on the margins of lipid droplets and within electron dense amorphous material in the degenerated matrix surrounding the hypertrophic chondrocytes  the slender rodlike structures consisting of electron dense precipitates of the antimony calcium complex  suggestive of the precursor to rodlike cppd crystals  were also observed in the degenerated matrix  these findings suggest that the hypertrophic chondrocytes may contribute to the formation of cppd crystals by intracellular accumulation of calcium and subsequent release of high concentration of calcium into their surrounding matrix  
class5	a method of assessment of the clubfoot deformity  the literature on clubfeet is inadequate because a common method language for assessing the deformity is lacking  different severities of clubfoot deformity will give different results for a standard procedure  a less severe deformity can be corrected by limited releases  whereas a severe deformity requires radical procedures  this paper presents a language of assessment that has been used for a number of years  the importance of developing a language of assessment to be able to identify the various types of clubfoot deformity is important if the treatment of this condition is to develop within the field of pediatric orthopedics  
class5	the management of chronic osteomyelitis  chronic osteomyelitis of childhood is heterogeneous but it can be broadly classified into nonspecific or specific groups  children with chronic osteomyelitis because of mycobacteria or mycoses are included within the specific group  the nonspecific group is the larger  it includes chronic osteomyelitis as a sequel to late acute osteomyelitis as well as chronic unifocal and chronic multifocal osteomyelitis  whereas staphylococcus aureus and other pyogenic organisms are commonly cultured from chronic lesions following late acute osteomyelitis  they are less frequently cultured from those with chronic unifocal osteomyelitis and rarely cultured from those with chronic multifocal osteomyelitis  the methods of treatment and the results also differ between these subgroups of nonspecific osteomyelitis  lesions following late acute osteomyelitis are usually cured following surgery and antibiotics  chronic unifocal osteomyelitis is usually cured with antibiotics only or with surgery and antibiotics  in contrast  surgery and antibiotics are largely ineffective in children with chronic multifocal osteomyelitis  but the disease appears to be self limiting  
class5	a perspective on recent trends for scoliosis correction  the basic principles for scoliosis surgery learned during the harrington era are still valid today  experience has confirmed the need for careful selection of the vertebrae to be instrumented  the value of anterior release for rigid curves in imparting convertibility of the deformity  and the importance of careful fusion techniques  during the last decade  further development has occurred because of an increased knowledge of the biomechanical needs for the internally instrumented spine and a three dimensional appreciation of the scoliotic curve  biomechanical advances have centered on an understanding of the load sharing properties afforded by the multiple spinal purchase sites  segmental spinal instrumentation  and the value of two rod systems linked by couplers  these advances have provided an increased stiffness of the instrumental spine  a reduction in correction loss  improved fatigue properties of the implant  and fewer pseudarthroses  the most important advance of the last decade is an improved awareness of the three dimensional approach to the scoliotic deformity with the need to preserve or improve sagittal contours  in particular  the importance of the loss of normal thoracic kyphosis or lumbar lordosis has been emphasized  these conceptual gains have led to the development of many new instrument systems to correct deformity  each is associated with advantages  problems  and risks that must be understood to make intelligent choices for treatment  
class5	recovery from osteopenia in adolescent girls with anorexia nervosa  osteopenia is a frequent complication of anorexia nervosa  an   to determine whether the deficit in bone mineral changes during the course of this illness  we studied 15 adolescent patients prospectively for 12 16 months using dual photon absorptiometry of the spine and whole body  at follow up  mean weight  height  and body mass index  bmi  had increased significantly  although 6 girls had further weight loss or minimal gain  less than 1 2 kg   spontaneous menses occurred in 2 girls  and 3 others were given estrogen replacement  bone mineral density of the lumbar spine did not change significantly  mean     sd  0 836     0 137 vs  0 855     0 096 g cm2   while whole body bone mineral density increased  0 710     0 118 vs  0 773     0 105  p less than 0 05   despite gains in bone mineral  8 patients had osteopenia of the spine and or whole body  changes in weight  height  and bmi were significant predictors of change in bone mineral density  increased bone mass occurred with weight gain before return of menses  conversely  weight loss was associated with further decreases in bone density  in 1 patient who failed to gain weight  estrogen therapy resulted in increased spinal  but not whole body  bone mineral  we also studied a second group of 9 women who had recovered from an during adolescence  all 9 had normal whole body bone mineral for age  but 3 had osteopenia of the lumbar spine  we conclude that osteopenia in adolescents with an reflects bone loss  perhaps combined with decreased bone accretion  weight rehabilitation results in increased bone mineral before the return of menses  estrogen may have an independent effect on bone mass  the persistence of osteopenia after recovery indicates that deficits in bone mineral acquired during adolescence may not be completely reversible  
class5	levels of disability among u s  adults with arthritis  this article studies the excess levels of disability experienced by persons with arthritis  compared to persons without the disease  the data set is the supplement on aging  1984 national health interview survey   it has information for a national probability sample of community dwelling persons ages 55    n   16 148    1  arthritis people have more difficulty in physical functions  personal care  and household care than do nonarthritis persons  the excess disability is greatest for physical functions  walking  reaching  stooping  etc    disabled arthritis people have especially high degrees of difficulty in physical activities that require endurance and strength   2  various models are tested for walking  grasping  shopping  and light housework to show how comorbidity propels disability for arthritis people and to show arthritis  own contribution to disability in the presence of other chronic conditions  difficulties escalate for arthritis people when they have other concurrent conditions  these models affirm that arthritis has a pronounced effect on physical dysfunctions  but these are not readily translated into personal and household care problems  apparently  arthritis people often make successful accommodations so their roles and daily activities are not seriously affected by the disease  
class5	microheterogeneity of acute phase proteins in the differentiation of polymyalgia rheumatica from polymyositis  we studied an alpha 1 acid glycoprotein  agp  and an alpha 1 antichymotrypsin  acht  microheterogeneity in sera of patients with polymyalgia rheumatica  pmr   giant cell arteritis  gca pmr   polymyositis dermatomyositis  pm dm  and healthy individuals by affinity electrophoresis with concanavalin a  con a  as the ligand  our results are expressed as reactivity coefficients  the mean of agp reactivity coefficients  ag rc     sd  in pmr  0 92     0 17  and gca pmr  0 91     0 12  were significantly lower compared with the mean ag rc in patients with pm dm  1 48     0 52  as well as in healthy individuals  1 34     0 9   moreover  an additional microheterogeneous form of agp was noted in patients with pm dm  in parallel  we also found that the mean of acht reactivity coefficients  ac rc     sd  were lower in patients with pmr  2 94     1 24  and gca pmr  1 66     0 16  compared with healthy individuals  3 92     1 17   the mean of ac rc in patients with pm dm  6 74     4 35  was significantly higher than in patients with pmr and gca pmr as well as in healthy individuals  our results show that the changes in reactivity of agp and acht with con a are useful diagnostic markers for the differentiation of pmr and gca pmr from pm dm  
class5	hiv associated arthropathy  hiv antigen demonstration in the synovial membrane  light and electron microscopic studies were performed on the synovial membranes of 5 patients with hiv associated arthropathy  an immunoperoxidase technique with the use of monoclonal antibodies against cd4  cd8  b and dr lymphocytes  and hiv p24 antigen was also used  mild to moderate nonspecific proliferative changes and increased vascularity of the subsynovial space were seen  electron dense deposits and viral like particles were not observed  immunohistochemical staining revealed hiv p24 positive staining in cells of the synovial lining layer and in the mononuclear cells of the subsynovial space  cd4  cd8  with predominance of cd8  and b and dr cells were also present  the presence of hiv p24 antigen may be indicative of a role  yet to be defined  in the pathogenesis of hiv associated rheumatic disorders  
class5	fibromyalgia in human immunodeficiency virus infection  tenderness was assessed by point count and by scored palpation in 51 patients with human immunodeficiency virus  hiv  infection as well as 51 patients with rheumatoid arthritis  ra  and 50 patients with psoriatic arthritis  psa   fifteen of 51  29   patients with hiv infection met criteria for fibromyalgia  based on the presence of 10 tender  of 14   fibrositic  points  similar results were observed among patients with psa  24    the prevalence of fibromyalgia was higher among patients with ra  57    patients with hiv and psa were less tender than patients with ra  fibromyalgia in patients with hiv was significantly associated with myalgia and arthralgia  but not with age  duration of hiv infection  stage of hiv disease  or zidovudine therapy  
class5	a prospective double blind dummy placebo controlled study comparing triamcinolone hexacetonide injection with oral diclofenac 50 mg tds in patients with rotator cuff tendinitis  a prospective double blind placebo controlled study was carried out to compare the effects of subacromial injection of triamcinolone and oral diclofenac in patients with rotator cuff tendinitis over a 4 week period  both forms of treatment were superior to placebo in reducing pain  improving active abduction and reducing functional limitation  triamcinolone showed the greatest effect in these respects  and was significantly superior to diclofenac when patients showing improvements in all 3 variables together  responders  were considered  
class5	growth promoting peptides in osteoarthritis  insulin  insulin like growth factor 1  growth hormone  alterations of cartilage and bone  as seen radiographically  are fundamental features of osteoarthritis  oa   endogenous compounds that regulate bone and cartilage metabolism were quantified by radioimmunoassay in patients with oa and in suitable normotensive controls matched for age  sex  race  height  and weight  levels of 3 growth promoting compounds were abnormal in oa as demonstrated by low levels of insulin like growth factor 1  igf 1  and elevated levels of insulin and growth hormone  gh  compared to controls  our findings support a role for these peptides in the pathophysiology of oa  
class5	septic arthritis due to group c streptococcus  report and review of the literature  a case of polyarticular septic arthritis due to lancefield group c streptococcus is described and the clinical details of 9 reported cases of septic arthritis due to group c streptococcus reviewed  several features of the presentation and course of these patients  including polyarticular involvement  4 10   bacteremia  5 10   clinically important dysfunction in other systems  4 10 patients  cardiac  3  cns  2  pneumonia  1  gastrointestinal  1   fatal outcome  3 10 patients  2 during the course of active infection  and poor functional outcome in affected joints  4 7 surviving patients   serve to place group c streptococcus septic arthritis as a syndrome distinct from that usually expected with streptococcal septic arthritis  specific features of the bacteriology of group c streptococcus are reviewed  including confusion with group a streptococcus when analyzed using nonserologic methods  occasional zoonotic source  and frequency of tolerance to penicillin  in order to emphasize the importance of both the specific identification of this particular streptococcal strain and the initiation of aggressive antibiotic therapy when group c streptococcus is identified as the causative agent in a case of septic arthritis  
class5	septic olecranon bursitis caused by neisseria sicca  a man with rheumatoid arthritis developed a septic olecranon bursitis due to neisseria sicca  this case confirms the potential pathogenicity of neisseria sicca and emphasizes that positive cultures for this organism should not be readily dismissed  
class5	recurrent calcific periarthritis  erosive osteoarthritis and hypophosphatasia  a family study  we describe a mother and 2 daughters with familial recurrent calcific periarthritis in a family with an inherited tendency to develop generalized osteoarthritis  oa   low levels of serum alkaline phosphatase were found in 1 of the daughters while the mother developed erosive oa in later life  hla typing was noncontributory  however  the 3 individuals with periarthritis possessed blood group a   while the 6 unaffected family members were o   the experience of this family adds weight to the case that recurrent calcific periarthritis may be due to an inherited abnormality of alkaline phosphatase production and suggest that this may also be responsible for the recently observed association of calcific periarthritis and erosive oa  
class5	magnetic resonance imaging in the preoperative evaluation of cervical radiculopathy  forty patients with cervical radiculopathy were examined preoperatively with magnetic resonance imaging  mri   mri was used alone in 27  68   of the 40 patients  the remainder also had computed tomography in conjunction with myelography  the primary criterion on mri for a clinically significant lesion was asymmetrical narrowing of the subarachnoid space in the region of the nerve root  surgical confirmation of the abnormality was obtained in all 40 cases  the operative findings were a herniated nucleus pulposus  32 of 40 patients   spondylosis  2 of 40 patients   or a combination of the two  6 of 40 patients   mri identified a surgical lesion  herniated nucleus pulposus  spondylosis  or both  in 37 of the 40  92   patients  we think mri is the only preoperative imaging examination necessary in most cases of cervical radiculopathy  
class5	asymptomatic versus symptomatic herniated thoracic discs  their frequency and characteristics as detected by computed tomography after myelography  we retrospectively reviewed the myelograms of 433 patients and identified those who had no symptoms or signs referable to the thoracic cord  roots  or nerves  by post myelography computed tomographic scan criteria  our frequency of asymptomatic thoracic herniated discs  athds  was calculated  post myelography computed tomographic scans of 68 athds were analyzed  their imaging characteristics were compared with our own series of 5 symptomatic thoracic herniated discs and symptomatic thoracic herniated discs in the literature  we were unable to identify any imaging features that could reliably classify a disc as an athd or a symptomatic thoracic herniated disc  our results call into question the propriety of prophylactic surgery for athds  even when the lesions are radiographically impressive  
class5	spinal charcot arthropathy  charcot joints of the spine are well documented clinical entities most commonly associated with tabes dorsalis  spinal neuropathic joints  however  may be produced by other disease processes including syringomyelia  in this review  the authors discuss the cause and treatment of spinal charcot arthropathy with emphasis on surgical therapy and results  
class5	pott s puffy tumor  a complication of frontal sinusitis  in children sinusitis is a frequent complication of upper respiratory infections but an infrequently considered diagnosis  although most sinus infections are resolved without complications  when complications do occur they can be serious or life threatening  the most common ones occur in the orbit  but cns extension is not infrequent  osteomyelitis and resulting subperiosteal abscess of the frontal bone  the so called pott s puffy tumor  is a less common  and perhaps less frequently recognized  serious complication of frontal sinusitis  this paper describes two patients with subperiosteal abscess resulting from frontal sinusitis  one with cns and orbital extension  a brief literature review is presented  and presentation  diagnosis  and treatment are discussed  
class5	free tissue transfers for limb salvage utilizing in situ saphenous vein bypass conduit as the inflow  using vein grafts to bypass sclerotic and occluded arterial segments is a well established technique in vascular surgery  for infrapopliteal bypass  autogenous veins have better patency rates than synthetic grafts  although not resolved  in situ bypasses seem to be better than reversed bypasses  especially for  far away  segments  although the etiology is not understood  it is a well known clinical finding that sclerosis affects arteries more than the veins and  as a whole  is more advanced in lower extremities compared with the trunk and upper extremities  our experience with eight patients in whom critical soft tissue defects were covered with free tissue transfers in severely compromised lower extremities utilizing the in situ saphenous vein bypass as the inflow is presented  simultaneous bypass and free tissue transfers were performed in seven and delayed free tissue transfer was done in one  follow up ranged from 6 months to 3 years  to date  two patients underwent amputations  five patients are able to maintain bipedal ambulation  one patient is wheelchair bound with intact lower extremities  in well selected patients  this procedure may offer an alternative treatment to amputation  however  because of the complexity of these combined procedures  we strongly urge careful patient selection  
class5	composite reconstruction for chest wall and scalp using multiple ribs latissimus dorsi osteomyocutaneous flaps as pedicled and free flaps  a composite flap is presented based on the latissimus dorsi myocutaneous unit together with the underlying ninth to eleventh ribs  three patients are presented  in two  a full thickness chest wall defect was present  in one  a full thickness scalp and cranial defect was present  use of the composite osteomyocutaneous latissimus dorsi free flap as a pedicled flap in two patients and as a free flap in one patient resulted in successful definitive reconstruction in all with no complications  this procedure necessitates no transplantation of soft tissue prior to bone grafting to maintain local vascularity  so the simultaneous one stage reconstruction of an osseous soft tissue defect becomes possible easily  
class5	radiographic manifestations of congenital anomalies of the skull  congenital anomalies of the pediatric skull are caused by a diverse group of disorders  for the purposes of this discussion  these entities can be classified according to the radiographic appearance of the skull  which may be similar in a variety of different diseases  enlarged parietal foramina  sinus pericranii  aplasia cutis congenita  anterior fontanelle dermoid  cephaloceles  and craniolacunia are all examples of loceles  and craniolacunia are all examples of calvarial defects  although there are numerous causes for wormian bones  table 1   oi  cleidocranial dysplasia  congenital hypothyroidism  and hypophosphatasia are disorders that are commonly associated with defective ossification and the appearance of wormian bones  osteopetrosis is an important example of rare bony dysplasias that cause sclerosis and hyperostosis of the skull  a partial list of other disorders causing similar radiographic findings is found in table 2  craniosynostosis results in an abnormality of skull shape  the suture s  involved may be predicted by the deformed calvarial configuration  knowledge of the growth and development of the skull and an understanding of the varied causes of congenital skull anomalies can enable the radiologist to provide the diagnosis or an informed differential diagnosis when confronted with a specific radiographic finding  
class5	radiographic manifestations of anomalies of the limbs  limb anomalies and their commonly associated organ malformations are increasingly recognized in fetal life because of the use of high resolution real time sonography  in most instances plain radiography establishes the diagnosis of limb anomalies shortly after birth  in some neonates the diagnosis is tentative until full skeletal maturity is attained  when evaluation of the soft tissues and unmineralized cartilage or ossification center is a prerequisite to early definitive therapy  computed tomography and magnetic resonance imaging are the procedures of choice  
class5	mild spondyloepiphyseal dysplasia  namaqualand type   genetic linkage to the type ii collagen gene col2a1  namaqualand spondyloepiphyseal dysplasia  nsed  is a mild autosomal dominant form of spondyloepiphyseal dysplasia in which changes are maximal in the femoral capital epiphyses and the vertebral bodies  the condition is present in a large multigeneration south african family  and it is clinically important by virtue of severe progressive degenerative osteoarthropathy of the hip joint  which frequently necessitates prosthetic joint replacement in adulthood  linkage studies using molecular markers have shown that the loci for the nsed and type ii collagen genes are linked  lod score 7 98 at a recombination fraction of  00   
class5	carcinosarcoma of the lung with hypertrophic pulmonary osteoarthropathy  carcinosarcoma of the lung is a rare malignancy  endobronchial and parenchymal variants are classically described  clinicopathological features are often related to anatomical location  as is the case for most lung neoplasms  this case report details the surgical management of a carcinosarcoma in a patient seen with pulmonary osteoarthropathy  
class5	quantitative gait analysis in unilateral and bilateral total hip replacements  by qualitative and quantitative analysis of gait we evaluated the outcomes in 41 patients after total hip arthroplasty for degenerative arthritis  patients with unilateral and bilateral degenerative hip disease were evaluated in an effort to characterize preoperative and postoperative gait characteristics  patients were evaluated using a subjective hip rating scale and a gait evaluation mat  data were compared with those obtained from a control group of 91 patients  all patients showed a marked improvement in both subjective ratings and measured quantitative gait parameters  patients with unilateral hip disease improved to a greater extent than those with bilateral disease after arthroplasty  we have concluded that total hip arthroplasty can greatly improve the gait characteristics of patients with degenerative arthritis  and that this improvement can be quantified  documented  and followed by using a system of gait evaluation  
class5	indomethacin inhibition of middle ear bone resorption  localized osteoclastic bone resorption is responsible for the pathological changes within the middle and inner ear  which result in hearing loss and vertigo in chronic otitis media and otosclerosis  the local control of osteoclastic bone resorption is incompletely understood  various small  locally active molecules  cytokines  have been shown to affect resorptive processes  additionally  prostaglandins and their inhibitors have been shown to modulate the resorptive process in a number of in vitro studies  in this study  indomethacin  a cyclooxygenase inhibitor  was tested in a model of localized bone resorption  the pressurized gerbil bulla  after the experimental period  indomethacin was found to inhibit the number of osteoclasts and the resorptive area on the inner surface of the bulla  therefore  it is likely that endogenous cyclooxygenase metabolites are intermediates in the sequence of cellular events  which results in localized bone resorption as in some systemic models  
class5	muscle performance  voluntary activation  twitch properties and perceived effort in normal subjects and patients with the chronic fatigue syndrome  the decrease in maximal force generating capacity  the degree of central activation of the muscle  and the subjective perception of effort were measured during prolonged submaximal isometric exercise in 12 male patients suffering from the  chronic fatigue syndrome  and 13 naive  healthy male subjects  maximal voluntary isometric torque generated by the elbow flexors was measured before  and at 5 min intervals during an endurance sequence of 45 min of repetitive isometric contractions  6 s duration  4 s rest interval  producing 30  of the initial maximal voluntary torque  electrical stimuli were also delivered to the elbow flexors to measure the contractile force in the intervals between voluntary contractions  the degree of central motor activation during maximal voluntary contractions was assessed using a sensitive method of twitch interpolation  in addition  the perceived effort required to achieve the target submaximal contractions was recorded using a standardized self report scale  a high degree of central activation was achieved in maximal contractions during the endurance sequence both in the patients  mean of maximal force 93 6   sd 7 8    and in the control subjects  mean 90 9   sd 9 5    the relative torque produced by either voluntary or electrically stimulated contractions was not significantly different between patients and control subjects throughout the test  there was no significant difference in the perceived exertion between the patients and control subjects  these findings support the concept that neither poor motivation  nor muscle contractile failure is important in the pathogenesis of  fatigue  in patients with the chronic fatigue syndrome  
class5	variable phosphate mediated regulation of vitamin d metabolism in the murine hypophosphatemic rachitic osteomalacic disorders  the familial hypophosphatemic  vitamin d resistant  disorders are a variety of genetic and acquired syndromes that exhibit unexpected biochemical heterogeneity  manifest as variably abnormal or apparently normal regulation of 1 25 dihydroxyvitamin d  1 25  oh 2d  production  recently  we observed that hyp and gy mice  murine homologs of x linked hypophosphatemic rickets  exhibit similarly disparate regulation of vitamin d metabolism  while gy mice under basal conditions maintain an appropriate elevation  relative to hypophosphatemia  of renal 25 hydroxyvitamin d  25ohd  1 alpha hydroxylase  hyp mice manifest only normal  not increased  enzyme activity  whether such diversity results from maintenance of phosphate  p  regulated 1 25  oh 2d production in gy mice and loss of this function in hyp mice or from other variations remains unknown  therefore  we examined the integrity of p regulated enzyme activity in the gy and hyp mice by testing the effects of enzyme inhibition and alteration of the serum phosphorus concentration on 1 25  oh 2d production  initially  we discovered that inhibition of renal 25ohd 1 alpha hydroxylase suppressed enzyme function in hyp mice  but did not prevent expression of p mediated activity in gy mice  in this regard  while administration of a high calcium diet or 1 25  oh 2d  0 4 ng h  sc  for 48 h  resulted in a comparable inhibition of enzyme activity in hyp  5 9     0 5 vs  2 8     0 7 fmol mg min  and normal mice  4 4     0 6 vs  2 0     0 2 fmol mg min   similar treatment did not effect complete inhibition of 25ohd 1 alpha hydroxylase in gy  10 3     0 6 vs  4 9     0 3 fmol mg min  or p depleted mice  10 2     0 5 vs  5 1     0 4 fmol mg min   in accord with the apparent persistence of p mediated stimulation of enzyme function in gy mice  dietary p repletion in this mutant resulted in a serum phosphorus concentration similar to that of normal mice and decreased enzyme activity  4 0     0 8 fmol mg min  to a level no different from that expressed in controls  3 4     0 3 fmol mg min   however  in the absence of apparent p mediated stimulation of enzyme activity  identical treatment of hyp mice increased the serum phosphorus level comparably  but paradoxically enhanced 25ohd 1 alpha hydroxylase  3 1     0 4 vs  11 7     2 0 fmol mg min   collectively  these data indicate that enhanced renal 25ohd 1 alpha hydroxylase expressed in gy mice and probably in related human diseases results from normally maintained p regulation of enzyme activity  an action absent or mutated in the genetically distinct hyp mouse  
class5	differential regulation of insulin like growth factor i  igf i  and igf ii release from cultured neonatal mouse calvaria by parathyroid hormone  transforming growth factor beta  and 1 25 dihydroxyvitamin d3  in a previous study we found that pth stimulated bone resorption and release of insulin like growth factor i  igf i  and igf ii from cultured neonatal mouse calvaria  since igf i and igf ii stimulate osteoblast proliferation and collagen synthesis  these results suggested that increased release of igfs during resorption could mediate in part coupling of bone formation to bone resorption  in the present study two other osteolytic agents  transforming growth factor beta  tgf beta  and 1 25 dihydroxyvitamin d3  1 25  oh 2d3 were examined for effects on igf release from neonatal mouse calvaria  like pth  tgf beta stimulated resorption and increased release of igf i and igf ii  1 25  oh 2d3  however  stimulated resorption and igf ii release comparable to pth  but inhibited release of igf i  1 25  oh 2d3  0 1 100 nm  inhibited basal release of igf i  and 10 nm 1 25  oh 2d3 inhibited release of igf i induced by pth or tgf beta  the effects of 1 25  oh 2d3 were specific to this vitamin d metabolite and did not occur with 25 hydroxyvitamin d3 or 24 25  oh 2d3 at the same concentration  calcitonin  50 mu ml  decreased 1 25  oh 2d3 stimulation of resorption  but did not affect 1 25  oh 2d3 stimulation of igf ii release and inhibition of igf i release  this evidence that effects of 1 25  oh 2d3 on release of the igfs were independent of bone resorption supports the conclusion that 1 25  oh 2d3 modulated the production and secretion of igf i and igf ii in calvarial cells  the results of this and the previous study suggest that pth  tgf beta  and 1 25  oh 2d3 differentially regulate mouse calvarial cell igf i and igf ii production  
class5	cyclosporin a in vitro decreases bone resorption  osteoclast formation  and the fusion of cells of the monocyte macrophage lineage  we studied the in vitro effect of cyclosporin a  cya  on bone resorption using a fetal rat long bone resorbing assay  cya inhibited both pth stimulated and unstimulated bone resorption  the inhibitory effect of cya on basal resorption was dose dependent  and it was more pronounced during the second period  less than or equal to 0 1 microgram ml  of culture  days 5 7  than during the first period  days 2 4   a cytotoxic effect was ruled out by the absence of decrease in  3h thymidine incorporation into bones up to a concentration of 5 micrograms ml cya  histomorphometry performed after 4 and 7 days of culture showed that cya  1 microgram ml  decreased the number of osteoclasts per bone section after 7 days of culture  23 5     4 0 vs  41 7     2 9 osteoclasts bone section  p less than 0 05   but not after 4 days  25 6     3 3 vs  23 0     2 5   these data suggested an effect of cya on osteoclastic differentiation rather than on the function of mature osteoclasts  we further assessed the mechanisms of the inhibitory effect of cya on osteoclastic differentiation in order to determine 1  the level of this action  proliferation and or fusion of osteoclast precursors   and 2  if this action is direct or indirect  autoradiographic studies were performed on bone sections after incubation of bones with  3h thymidine for the last 48 h of culture  cya decreased slightly but significantly the percentage of labeled nuclei per osteoclast and the number of osteoclasts containing at least one labeled nucleus  20 2     0 7 vs  33 2     3 5  p less than 0 02   moreover the number of nuclei per osteoclast was decreased after 7 days in cya treated bones  2 4     0 05 vs  3 0     0 1  p less than 0 02   taken together these results demonstrate that cya slightly decreased the proliferation of osteoclast precursors  but markedly decreased their fusion  similar effects were observed in cultures of rat marrow macrophages  cya  1 microgram ml  inhibited the fusion of macrophages into multinucleated cells elicited by 1 nm 1 25 dihydroxyvitamin d3  but had only a slight effect on the proliferation of these cells  as assessed by autoradiography  cya also inhibited the formation of multinucleated cells and the fusion index in long term cultures of human cord blood monocytes  a cellular model for osteoclastic differentiation  by contrast  cya had no effect on the formation of myotubes by fusion of cultured mononucleated rat myoblasts  abstract truncated at 400 words   
class5	recurrent nonsense mutations in the growth hormone receptor from patients with laron dwarfism  in addition to its classical effects on growth  growth hormone  gh  has been shown to have a number of other actions  all of which are initiated by an interaction with specific high affinity receptors present in a variety of tissues  purification of a rabbit liver protein via its ability to bind gh has allowed the isolation of a cdna encoding a putative human growth hormone receptor that belongs to a new class of transmembrane receptors  we have previously shown that this putative growth hormone receptor gene is genetically linked to laron dwarfism  a rare autosomal recessive syndrome caused by target resistance to gh  nevertheless  the inability to express the corresponding full length coding sequence and the lack of a test for growth promoting function have hampered a direct confirmation of its role in growth  we have now identified three nonsense mutations within this growth hormone receptor gene  lying at positions corresponding to the amino terminal extremity and causing a truncation of the molecule  thereby deleting a large portion of both the gh binding domain and the full transmembrane and intracellular domains  three independent patients with laron dwarfism born of consanguineous parents were homozygous for these defects  two defects were identical and consisted of a cg to tg transition  not only do these results confirm the growth promoting activity of this receptor but they also suggest that cpg doublets may represent hot spots for mutations in the growth hormone receptor gene that are responsible for hereditary dwarfism  
class5	transforming growth factor beta 1 suppresses acute and chronic arthritis in experimental animals  systemic administration of the cytokine  tgf beta 1  profoundly antagonized the development of polyarthritis in susceptible rats  tgf beta 1 administration  1 or 5 micrograms animal   initiated one day before an arthritogenic dose of streptococcal cell wall  scw  fragments  virtually eliminated the joint swelling and distortion typically observed during both the acute phase  articular index  ai   2 5 vs  11  p less than 0 025  and the chronic phase  ai   0 vs  12 5  of the disease  moreover  tgf beta 1 suppressed the evolution of arthritis even when administration was begun after the acute phase of the disease  histopathological examination of the joint revealed the systemic tgf beta 1 treatment greatly reduced inflammatory cell infiltration  pannus formation  and joint erosion  consistent with the inhibition of inflammatory cell recruitment into the synovium  tgf beta 1 reversed the leukocytosis associated with the chronic phase of the arthritis  control animals subjected to the same tgf beta 1 dosing regimen displayed no discernable immunosuppressive or toxic effects even after 4 wk of treatment  these observations not only provide insight into the immunoregulatory effects of tgf beta  but also implicate this cytokine as a potentially important therapeutic agent  
class5	unusual presentation of squamous cell carcinoma of the middle ear and mastoid  an unusual case of squamous cell carcinoma of the middle ear and mastoid in which syncope was a major presenting feature is reported  no such case has been reported in the literature  a possible explanation is offered  
class5	cauda equina syndrome associated with multiple lumbar arachnoid cysts in ankylosing spondylitis  improvement following surgical therapy  a case of cauda equina syndrome with multiple lumbar arachnoid cysts complicating ankylosing spondylitis  as  is described  the value of computerised tomography  ct  and magnetic resonance imaging  mri  as a non invasive means of establishing the diagnosis is emphasised  in contrast to previously reported cases the patient showed neurological improvement following surgical therapy  surgery may be indicated in some patients  particularly when there is nerve root compression by the arachnoid cysts and when the patient is seen early before irreversible damage to the cauda equina has occurred  
class5	characteristics of respondents and nonrespondents in a prospective study of osteoporosis  during 1981 1982  a cohort of elderly japanese americans living in hawaii was recruited for an epidemiologic study of osteoporosis  the male subjects were simultaneously being examined for an epidemiologic study of heart disease  baseline data collected from both the men and women at a previous heart disease examination were used to compare responders vs nonresponders  the target population for the osteoporosis study consisted of 1685 men and 1594 women  of these  1379 men  81 8   and 1105 women  72 0   participated in the initial osteoporosis examination  for each sex  nonrespondents were older and had higher systolic blood pressure levels than did the respondents  male nonresponders had a higher stroke prevalence and more frequent recent use of vasodilator medicine  female nonresponders had a less frequent history of having ever taken female hormones than did the responders  the responders and nonresponders were reasonably similar in other respects  as indicated by the comparison of more than 40 other variables  this suggests that nonresponse bias is probably not a major influence in exposure disease associations in this osteoporosis cohort  we believe this is the first published report dealing with nonresponse characteristics in a cohort study of osteoporosis  
class5	depletion of muscle mitochondrial dna in aids patients with zidovudine induced myopathy  long term zidovudine therapy in patients with human immunodeficiency virus  hiv  infection can cause a destructive mitochondrial myopathy with histological features of ragged red fibres  rrf  and proliferation of abnormal mitochondria  in 9 zidovudine treated patients with this myopathy we found severely reduced amounts  up to 78  reduction vs normal adult controls  of mitochondrial dna  mtdna  in muscle biopsy specimens by means of southern blotting  in 2 hiv positive patients who had not received zidovudine  muscle mtdna content did not differ from that in the 4 controls  depletion of mtdna seems to be reversible  since 1 patient showed a substantial reduction in rrf and a concomitant pronounced increase in muscle mtdna content after zidovudine therapy was discontinued  depletion of muscle mtdna is probably due to zidovudine induced inhibition of mtdna replication by dna polymerase gamma and is not a secondary effect of hiv infection  
class5	intracranial complications of paranasal sinusitis  a combined institutional review  intracranial complications of paranasal sinusitis constitute true surgical and medical emergencies  the charts of all patients  n   649  admitted for acute or chronic sinusitis to the university of minnesota hospital and to the university of michigan medical center during a 13 year period  1975 to 1988  were retrospectively reviewed to determine the incidence of complications  the clinical presentation  bacteriology  involved sinuses  influencing host factors  white blood cell count on presentation  length of hospitalization  and postinterventional complications are presented  twenty four patients with intracranial complications from paranasal sinusitis are studied for an incidence of 3 7   aggressive medical and semi emergent surgical intervention are required to prevent excessive morbidity and or mortality  intracranial complications included subdural empyema  frontal lobe abscesses  intrahemispheric abscesses  cavernous and superior sagittal sinus thrombosis  and osteomyelitis  
class5	chronic musculoskeletal pain and depressive symptoms in the general population  an analysis of the 1st national health and nutrition examination survey data  chronic pain and depression frequently occur together  a selection bias afflicts all hospital clinic and family practice populations in which this relationship has been examined  we report here some of the results from civilian populations outside institutions  examined in the united states in national surveys  the findings are based upon the recollection of individuals with respect to the period of 12 months prior to interview and upon the occurrence of depression in the previous week as indicated by the answers to the depression scale of the centre for epidemiologic studies  ces d   they indicate that 14 4  of the united states population between the ages of 25 74 suffer from definite chronic pain related to the joints and musculoskeletal system  another 7 4  have some pain of uncertain duration  eighty three percent of the definite pain group received treatment  chronic pain subjects scored significantly higher than normals on the ces d  10 68     s e m  0 76 vs  8 05     0 23  p less than 0 01  with subjects with pain of uncertain duration scoring similar to the definite chronic pain population  11 13     0 76   using a high cut off score for depression  18  of the population with chronic pain were found to have depression  this is in contrast to 8  of the population who did not have chronic pain  
class5	codeine plus paracetamol versus paracetamol in longer term treatment of chronic pain due to osteoarthritis of the hip  a randomised  double blind  multi centre study  this randomized  double blind  multi centre study was undertaken to evaluate the efficacy and safety of treatment for 4 weeks with codeine plus paracetamol versus paracetamol in relieving chronic pain due to osteoarthritis of the hip  a total of 158 outclinic patients entered the study  eighty three patients  mean age 66 years  were treated with codeine 60 mg plus paracetamol 1 g 3 times daily  and 75 patients  mean age 67 years  with paracetamol 1 g 3 times daily  ibuprofen 400 mg was prescribed as rescue medication  due to an unexpected high rate of adverse drug reactions  the study was closed before the planned 400 patients had entered  over weeks 1 4  87   64   61  and 52  of patients in the codeine plus paracetamol group  and 38   31   22  and 29  of patients in the paracetamol group had one or more adverse drug reactions  significantly more patients in the codeine plus paracetamol group had adverse drug reactions in each of the 4 weeks  nausea  dizziness  vomiting and constipation were predominant adverse reactions in the codeine plus paracetamol group  during the first week of treatment  30 patients  36   in the codeine plus paracetamol group and 9  12   in the paracetamol group dropped out  as evaluated from patients completing the first week of treatment  the pain intensity during that week compared to their baseline pain was significantly lower in the codeine plus paracetamol group than in the paracetamol group  moreover  during the first week the paracetamol group received rescue medicine significantly more frequently  in conclusion  when evaluated after 7 days of treatment  the daily addition of codeine 180 mg to paracetamol 3 g significantly reduced the intensity of chronic pain due to osteoarthritis of the hip joint  however  several adverse drug reactions  mainly of the gastrointestinal tract  and the larger number of patients withdrawing from treatment means that the addition of such doses of codeine cannot be recommended for longer term treatment of chronic pain in elderly patients  
class5	nursing management of the adolescent with idiopathic scoliosis  management of the adolescent idiopathic scoliosis patient has many intricate considerations  whether the patient is braced or surgery is recommended  there is a lot of teaching  assessing  and compassion when dealing with adolescents whose biggest concern is being like their peers  it is important to allow as much independence in decision making as possible  whether it be about bracing or surgical intervention  as long as they clearly understand the consequences  newer  better surgical instruments  anesthesia  nursing care  and postoperative mobility all have changed the management of the operative scoliosis patient significantly  nursing assessment of neurologic  respiratory  function  emotional  and developmental needs of the adolescent patient  however  have not changed  if we  as nurses  understand the rationale for assessments  treatments  and restrictions  we can teach our patients and their families  
class5	diagnosis and treatment of shoulder injuries in the athlete  the goal of the treatment team dealing with patients who have sports related shoulder injuries is to return them to their previous activity  there is no substitute for knowledge of anatomy  diagnosis modalities  or current treatments  realistically  some of the athletes are not able to return to the level of competition they performed originally  for those patients  recommendations and suggestions for alternatives based on a sound knowledge of arthroscopic principles need to be considered  one of the greatest roles for the nurse treating these patients may be the temporary loan of her shoulder for them to lean on  
class5	the foot and footwear  in the field of sports medicine we see increasing numbers of foot  and leg related injuries that could have been avoided  either totally or in part  had the individual chosen the proper footwear  there is no such thing as the ideal shoe for all types of feet and all terrains  however  when an athlete has a chronic problem that does not respond to properly fitted shoes  a physician consultation should be considered  
class5	that old hip  the osteoporosis process  osteoporosis is a major health concern that will contribute to an increasing number of hip fractures as the population ages  researchers are continuing to evaluate the role that decreased level of estrogen at menopause and prolonged calcium insufficiency play in the development of osteoporosis  in addition  many health care recommendations are aimed at maximizing peak bone mass and preventing bone loss to decrease the chance of hip fracture  new studies are evaluating the efficacy of experimental medications to rebuild bone mass once osteoporosis has developed  current prevention guidelines include adequate calcium and vitamin d intake and moderate exercise  at menopause  estrogen replacement therapy is recommended for those younger than 50 years or considered at high risk for developing osteoporosis  all people are encouraged to decrease the risk of fracture by evaluating their home environment for hazards that might contribute to falls  nursing needs to develop new strategies and interventions to educate the public about osteoporosis  improve the quality of life for persons with osteoporosis  and decrease the osteoporotic hip fracture mortality rate  will it rise to the challenge   
class5	spinal stenosis  when arthritis is more than arthritis  spinal stenosis is the result of disc degeneration and narrowing accompanied by facet joint changes culminating in nerve root entrapment  symptoms of back and leg pain appear gradually usually over a period of years and slowly worsen  patients are usually in their 50s or older  most patients are treated initially with nonoperative measures concentrating on pain relief and maintenance of activity  if the symptoms worsen  surgical intervention to relieve pain by decompressing the affected nerve roots is appropriate  some patients with instability require a fusion  most patients are satisfied with the results of surgery in relieving preoperative leg pain  pain relief is often dramatic  allowing most patients to return to normal activity  elderly patients tolerate this procedure surprisingly well  old age alone should not be a contra indication for this surgery  therefore  the elderly should not be denied the benefits of surgical decompression  nursing interventions can help these patients learn about spinal stenosis and assist them in pursuing appropriate treatment resulting in improved quality of living  
class5	charcot s disease in diabetic patients  correct diagnosis can prevent progressive deformity  although charcot s disease and its association with diabetes have been described many times in the literature  it is still often misdiagnosed and incorrectly treated as osteomyelitis  arthritis  or gout  the best safeguard is a high index of suspicion  a warm  swollen foot in a diabetic patient with long standing neuropathy without local or systemic signs of infection must be considered charcot s disease until proven otherwise  the principal treatment is total abstinence from putting weight on the foot until warmth  swelling  and redness subside  protective weight bearing methods may then be slowly instituted  
class5	scalp pilomatrix carcinoma as an extra axial mass  we report the ct  mri  and angiographic findings in a case of pilomatrix carcinoma that had invaded the temporal bone and presented itself as an extra axial mass  even though bone destruction was better shown with ct  the tumor mass with its meningeal and tentorial extension was seen more clearly with mri  the arteriogram demonstrated a unique vascular supply from the external carotid artery  
class5	postanginal sepsis with dysphagia  we have described a 10 year old girl who had dysphagia followed abruptly by arthritis  streptococcus pyogenes was identified as the pathogen by fasciotomy with bone biopsy  and a tonsillar fluid collection confirmed the diagnosis of postanginal sepsis  the patient was cured by a 6 week course of parenteral antibiotics  
class5	management of symptomatic lymphocele via percutaneous drainage and sclerotherapy with tetracycline  lymph collections following pelvic surgery are usually asymptomatic  but may occasionally produce symptoms requiring invasive therapy  we have successfully obliterated a large lymphocele by employing percutaneous drainage and instilling tetracycline  
class5	hypercalcemia in malignancy  the pathogenesis of hypercalcemia in malignancy has been enigmatic until recent years  since the realization in 1980 that bioassays for parathyroid hormone detected a cross reacting substance in malignancy  progress has been remarkably rapid  a parathyroid hormone related protein was purified and identified by molecular cloning as a 141 amino acid peptide with limited homology to parathyroid hormone itself  nonetheless  both peptides activate the parathyroid hormone receptor to produce hypercalcemia  it is now clear that the parathyroid hormone related protein is the cause of hypercalcemia in most solid tumors  particularly squamous and renal carcinomas  new assays for the hormone as well as the related peptide have greatly simplified the differential diagnosis of hypercalcemia  at the same time  new agents for the treatment of hypercalcemia are becoming available  most notably the bisphosphonate drugs  
class5	extremely low serum pyridoxal 5  phosphate in children with familial hypophosphatemic rickets  the apparent vitamin b 6 status of 31 children with familial hypophosphatemic rickets  fhr  was determined  all children had alkaline phosphatase activity that was high normal to elevated for their ages  a sensitive assay for pyridoxal 5  phosphate  plp  indicated that 15 of the 31 children had an undetectable  less than 0 2 nmol l  concentration of the vitamer  the lowest values yet reported in human serum  the 16 remaining children had concentrations of the vitamer so low that they indicated a potential severe vitamin b 6 deficiency  however  none of the children had ever presented with any of the classical vitamin b 6 deficiency symptoms  treatment of three additional fhr children with 100 mg pyridoxine hcl d resulted in a moderate and transient elevation of their serum plp concentrations  a dramatic elevation of their erythrocyte plp concentrations  and no improvement in clinical condition  serum or plasma plp concentrations are an inappropriate index for determining vitamin b 6 status in people with fhr and perhaps in others with elevated alkaline phosphatase activity  
class6	rectal examination in general practice objective  to investigate factors influencing a general practitioner s decision to do a rectal examination in patients with anorectal or urinary symptoms  design  postal questionnaire survey  setting  general practices in inner london and devon  subjects  859 general practitioners  609  71   of whom returned the questionnaire  main outcome measures  number of rectal examinations done each month  the indication score  derived from answers to a question asking whether the respondent would do a rectal examination for various symptoms  and the confidence score  which indicated the respondent s confidence in the diagnosis made on rectal examination  results  279 general practitioners did five or fewer rectal examinations each month and 96 did more than 10 each month  factors significantly associated with doing fewer rectal examinations were a small partnership and being a female general practitioner  and the expectation that the examination would be repeated  lack of time in the surgery  and a waiting time of less than two weeks for an urgent outpatient appointment were also important  general practitioners were deterred from doing rectal examinations by reluctance of the patient  278   the expectation that the examination would be repeated  141   and lack of time  123  or a chaperone  39   confidence in diagnosis was significantly associated with doing more rectal examinations  the perception of having been well taught to do a rectal examination at medical school  and being a male general practitioner  conclusions  factors other than clinical judgment influence the frequency of rectal examination in general practice  rectal examination may become commoner with the trend towards larger group practices and if diagnostic confidence is increased and greater emphasis put on rectal examination in undergraduate and postgraduate teaching  
class6	choice of emergency operative procedure for bleeding duodenal ulcer in a consecutive series of 201 emergency operations in patients with bleeding duodenal ulcer the size of the ulcer was the only factor that showed a significant correlation with the procedure chosen  vagotomy  pyloroplasty and underrunning of the bleeding point was performed in 101 cases with ten deaths  10 per cent   partial  billroth ii  gastrectomy in 81 cases with ten deaths  12 per cent   and vagotomy and antrectomy in 16 cases with one death  6 per cent   a patient was more likely to be treated by partial gastrectomy if a giant ulcer with an internal diameter of greater than or equal to 2 cm was found  the results suggest that while vagotomy and pyloroplasty  combined with a direct attack on the bleeding point or excision of an anterior ulcer is an acceptable standard emergency operation for bleeding duodenal ulcer  gastric resection proved to be a satisfactory alternative procedure and should be considered in the technically difficult case with a very large ulcer  a giant ulcer was present in 37 per cent of cases coming to surgery  
class6	anterior lesser curve seromyotomy and posterior truncal vagotomy versus truncal vagotomy and pyloroplasty in the treatment of chronic duodenal ulcer  in a prospective randomized controlled clinical trial  anterior lesser curve seromyotomy with posterior truncal vagotomy  ampt  n   77  has been compared with truncal vagotomy and pyloroplasty  tvp  n   69  in 146 patients with chronic duodenal ulcer with a mean duration of symptoms of 7 years  the mean follow up time was 4 5 years with a range of 2 7 years  one elderly patient died from a myocardial infarction in the tvp group  acid secretory inhibition in response to insulin and pentagastrin stimuli was equal in both groups  indicating a similar degree of vagal denervation  recurrent ulcers were more common after ampt  five  than tvp  two   p   0 29  n s    dumping and diarrhoea were significantly commoner  p less than 0 001  after tvp  with 31 instances as opposed to eight with ampt  the mean operating time was increased by 6 min when ampt was performed rather than tvp  the results of this study have shown that ampt is associated with a lower incidence of dumping and diarrhoea and achieves better overall visick grading  however  continued monitoring is required to assess the long term incidence of recurrent ulceration after this procedure  
class6	elective resection for diverticular disease of the sigmoid colon  from 1966 to 1987  177 consecutive patients were operated on electively for diverticular disease of the sigmoid colon  the indications for surgery were  colovesical fistula  n   12   suspicion of residual abscess  n   39   two or more previous attacks of acute inflammation  n   52   chronic symptoms  n   72  and suspicion of carcinoma  n   2   an abscess was found at operation in 76 patients  43 per cent  and this was extracolic with local peritonitis in 52 patients  29 per cent   an unsuspected abscess was found in 25 of the 72 patients operated on for chronic symptoms  colonic resection with primary anastomosis was performed in 95 per cent of the 177 patients and in 94 per cent of those 52 patients with an extracolic abscess  there were no postoperative deaths and no clinical anastomotic leakages  long term results were very good in 85 per cent of the 177 patients and in 82 per cent of the 72 patients operated on for chronic symptoms  the results of this series suggest that a one stage procedure can be safely performed with some technical precautions in most patients operated on electively for diverticular disease  even if an extracolic abscess is found  the good long term results in patients operated on for chronic symptoms suggest that such symptoms should be taken into account with respect to surgical indications  
class6	gracilis muscle transposition for faecal incontinence  transposition of the gracilis muscle for faecal incontinence was performed in 13 patients  six gained satisfactory continence  four were improved  two did not benefit from the operation and one patient died from intercurrent disease before closure of a pre existing colostomy  anal manometry compared with a control group showed no alteration in resting and pressure at a median of 35 mmhg  range 5 63 mmhg   whereas maximum squeeze pressure increased from a median of 38 mmhg  range 5 79 mmhg  to 59 mmhg  range 10 143 mmhg   p   0 041  which was  however  significantly lower than 130 mmhg  range 81 236 mmhg  in the control group  all patients who benefited from the operation had an increase in maximum squeeze pressure  the ability to retain a viscous fluid in the rectum was measured in seven patients  four of whom had gained satisfactory continence and three of whom had improved continence  they were able to retain a median volume of 200 ml  range 50 225 ml  without leakage compared with 325 ml  range 250 400 ml  in the control group  these patients could retain the maximum amount of viscous fluid for 5 8 min  whereas all control subjects could do so for more than 15 min  it is concluded that  although gracilis transposition never results in normal continence  acceptable continence may be achieved in selected patients provided careful attention is paid to the technical details of the procedure and provided that systematic postoperative exercises are performed  
class6	pylorus preserving pancreatoduodenectomy  an overview  pylorus preserving pancreatoduodenectomy  pppd  was reintroduced 12 years ago  since that time  over 400 patients have undergone pppd with approximately 41 per cent having chronic pancreatitis and 54 per cent having pancreatic and other periampullary malignancies  reported 5 year survivals in this latter group have been comparable to those achieved by the classic whipple procedure  the postoperative mortality rate in 339 reported patients has been 3 8 per cent  postoperative morbidity  including delayed gastric emptying  has been similar to that of the classic whipple operation  however  pppd has been associated with fewer late problems with dumping  diarrhoea  delayed gastric emptying  8 6 per cent   and marginal ulceration  3 6 per cent   moreover  most patients undergoing pppd have been able to return to their preoperative and preillness weight  the additional advantage of decreased operative time makes pppd an attractive alternative to the classic pancreatoduodenectomy  
class6	operative choledochoscopy  common bile duct exploration is incomplete without it  this paper reviews the reported experience of operative choledochoscopy  development of choledochoscopes to the currently available rigid and flexible instruments is described  the collected results of both rigid and flexible choledochoscopy are reported  retained stones occurred in 97 of 2712 stone positive explorations with the rigid choledochoscope  3 6 per cent  and in 35 of 1726 stone positive explorations with the flexible choledochoscope  2 0 per cent   choledochoscopy should now be a mandatory part of common bile duct exploration  
class6	primary hepatic malignancy  the role of liver transplantation  between january 1982 and april 1989  134 patients with a suspected liver neoplasm were referred to the liver unit  queen elizabeth hospital  birmingham  in 105  78 per cent   a primary hepatic neoplasm was histologically confirmed  and 47 patients  45 per cent  proved to have primary hepatocellular carcinoma  twenty nine orthotopic liver transplants were performed in 28 of these patients  27 per cent   twenty patients  71 per cent  survived 30 days or longer  median 11 5 months  range 2 87 months   of whom nine are currently alive  we retrospectively analysed our data to determine the influence of preoperative evaluation  histological type and staging on outcome  computed tomography proved to be superior to intraoperative assessment  86 versus 58 per cent  in diagnosing tumour positive nodes  patients with tumour negative lymphadenopathy had a better prognosis  postoperative stage i ii had a median survival of 16 months  range 3 87 months  compared with 7 5 months  range 2 20 months  for stage iii  non cirrhotic patients with hepatocellular carcinoma had the best prognosis  cholangiocellular carcinoma and cirrhotic patients with hepatocelluar carcinoma had the worst outcome with no survivors beyond 1 year  because of the advanced stage of disease at the time of presentation  the value of liver transplantation in primary liver cancer is limited  for those presenting with advanced disease confined to the liver  stage i ii  in whom conventional hepatic resection is not possible  significant benefit can be achieved in selected cases  
class6	mucosal intussusception to avoid ascending cholangitis  many methods have been devised to prevent ascending cholangitis following kasai s hepatic portoenterostomy for biliary atresia  to investigate the effectiveness of mucosal intussusception in preventing ascending cholangitis  20 mongrel dogs were randomized to undergo roux en y cholecystjejunostomy and common bile duct ligation with or without mucosal intussusception  aeromonas hydrophila was instilled into the gastrointestinal tract  bacterial cultures were grown from samples taken from the gallbladders and lower jejunum  and blood chemistry and barium studies were performed  the barium studies showed satisfactory lack of reflux in all ten dogs with mucosal intussusception  only two of them had positive cultures for aeromonas from the gallbladder 3 days after bacterial instillation into the jejunum  all ten dogs in the control group had positive cultures for aeromonas from the gallbladder  our results showed that the mucosal intussusception group had a significantly lower rate of recovery of organisms from the gallbladder compared with the control group when the organisms were instilled into distal intestine  p less than 0 05   the method is worthy of clinical trial as a means of preventing or treating ascending cholangitis  
class6	gastrointestinal function and structure in hiv positive patients  we examined 19 patients  17 men  with human immunodeficiency virus  hiv  infection and gastrointestinal symptoms to determine whether those symptoms were due to either a gastrointestinal tract infection or a defect in mucosal absorption because of an enteropathy  the erythrocyte folate and serum vitamin b12 levels were within normal limits in all of the patients  the serum ferritin level was elevated in 12  the xylose absorption test results were abnormal in 8 of the 13 patients able to complete the study  none of the duodenal aspirates yielded a pathogen  light microscopy revealed nonspecific lymphocytic inflammation without infection in the stomach  in seven patients   the esophagus  in five   the duodenum  in two  and the rectum  in two   however  biopsy specimens were positive for candida albicans in the esophagus  four patients   cytomegalovirus in the esophagus  one  and the rectum  two   helicobacter pylori in the antrum  two   treponema infection in the rectum  two  and mycobacterium avium intracellulare in the small intestine  one   only three patients had a normal series of biopsy specimens  all of the patients had similar ultrastructural changes at the epithelial stromal junction of the antral glands and in the intestinal crypts  we conclude that abnormal biochemical and endoscopic findings are common in hiv positive patients with gastrointestinal symptoms  defects in carbohydrate absorption and ultrastructural changes may be responsible for some aspects of hiv enteropathy  
class6	cancer chemotherapy after solid organ transplantation  to assess how well chemotherapy is tolerated after solid organ transplantation  we reviewed our experience at the children s hospital of pittsburgh with five patients aged 1 to 12 years  four patients had a liver transplant  indications for which were hepatoblastoma in two patients  hepatic failure secondary to wilms  tumor chemoradiotherapy in one patient  and familial intrahepatic cholestasis in one patient  a fifth patient received a cardiac transplant for unresectable angiosarcoma of the right atrium  after transplant  chemotherapy was given for the treatment of the primary malignancy in four of the patients  the patient with familial intrahepatic cholestasis received chemotherapy for secondary lymphoproliferative disease that had not responded to the cessation of immunosuppression  all patients other than this patient were on immunosuppression with prednisone  0 5 to 2 mg kg daily  and cyclosporine  to maintain serum levels at 800 to 1000 ng ml radioimmunoassay  throughout the duration of chemotherapy  courses of chemotherapy included one or more of the following agents  adriamycin  adr  20 mg m2 daily  three patients   cyclophosphamide  ctx  1 gm m2  one patient   cisplatin  cddp  90 mg m2  one patient   vincristine  vcr  greater than 0 75 to 1 5 mg m2  three patients   actinomycin d  act d  7 5 micrograms kg  one patient   ifosfamide  i  1800 mg m2  one patient  and etoposide  vp 16  100 mg m2  one patient   all patients received greater than or equal to 3 courses  range  3 to 9  mean  5  of chemotherapy every 3 to 4 weeks  dose reductions were made because of neutropenia in three patients but none were greater than 50   severe rejection was seen in one patient who had  however  manifested evidence of rejection prior to his first postoperative course of chemotherapy  no nephro or cardiac toxicity was seen  this preliminary experience suggests that chemotherapy is well tolerated after solid organ transplantation  
class6	colonic polyamine content and ornithine decarboxylase activity as markers for adenomas  polyamine content  putrescine  spermidine  and spermine  or ornithine decarboxylase  odc  activity was measured in normal appearing colonic mucosa from patients undergoing colonoscopy  comparisons were made between those with and those without adenomatous polyps  colonic mucosal polyamine content was measured in 44 persons  mean putrescine content was 1 25     0 26  se  nmol mg protein in 22 patients with adenomatous polyps compared with 0 53     0 12 nmol mg protein in patients without polyps  p less than 0 02   tissue content of spermidine and spermine did not differ between these two groups  ornithine decarboxylase activity was measured in tissue from 45 patients  mean odc activity was 2 84     0 73 pmol hr mg protein in 23 persons with adenomatous polyps compared with 1 15     0 18 pmol hr mg protein in persons without polyps  p less than 0 05   mucosal putrescine and odc activity are elevated in patients with adenomatous polyps compared with patients without polyps  these biochemical markers may prove helpful in improving surveillance methods for colorectal cancer and premalignant adenomatous polyps  
class6	brush cytology in the diagnosis of colonic neoplasms  during a three year period  1986 1988   234 colonic brush specimens were received in the authors  laboratory  nine samples  4   were deemed unsatisfactory for evaluation because of inadequate cellularity and or poor fixation  in 11 cases concomitant or follow up histologic specimens were not available  the remaining 214 specimens included 82 malignant neoplasms  88 neoplastic polyps  adenomas   and 44 nonneoplastic lesions  sixty seven  82   of malignant neoplasms were correctly diagnosed by brush cytology  three cases of adenoma with severe dysplasia or in situ carcinoma were diagnosed as adenocarcinoma by cytology  no false positive diagnoses were made of nonneoplastic lesions  brush cytology was found to be a more sensitive technique in the diagnosis of colon cancer than endoscopic biopsy  82  and 74  sensitivity  respectively   the combination of the two techniques increased the sensitivity to 90  and improved the overall accuracy of the test  seventy one  82   of the colonic adenomas were correctly diagnosed by cytology  brush cytology is a convenient  safe  and accurate technique which should be used concurrently with endoscopic biopsy or polypectomy  
class6	the relationship of headache symptoms with severity and duration of attacks  efforts to develop clinically useful headache classification schemes have generally focused on linking specific symptom groupings with specific headache subtypes  an alternative conceptual approach  the  severity model  of headache  considers a continuum of headache ranging from mild to severe forms with specific headache subtypes distinguished by level of severity rather than unique constellations of symptoms  a population based telephone interview was carried out among 10 169 subjects aged 12 29 to estimate the prevalence of serious headaches and better characterize symptoms that accompany headache attacks  in an analysis of frequency of occurrence  pain and duration of recent  within 4 weeks prior to interview  headache attacks  the data revealed that common symptoms  such as forehead pain and pain in the back of the head  neck and shoulders  were reported frequently  but headaches with these symptoms were generally characterized by low levels of pain and short duration  although not an original study objective  the data were analyzed to determine whether distinct symptom constellations could be identified or whether symptoms overlapped between headache types  symptoms of migraine were frequently experienced concomitant with tension type symptoms  the resultant headaches were usually characterized as moderate in intensity  in contrast  symptoms usually associated with migraine in the absence of concomitant tension type symptoms were infrequently experienced  but resulted in headaches causing the greatest disability  the data provide some support for the severity model of headache  
class6	intraperitoneal lymphokine activated killer cell and interleukin 2 therapy for malignancies limited to the peritoneal cavity  autologous lymphokine activated killer  lak  cells and recombinant human interleukin 2  ril 2  were administered intraperitoneally  ip  to 24 patients with malignancies limited to the peritoneal space  ten patients had ovarian cancer  12 had colorectal cancer  and one patient each had endometrial carcinoma and primary small bowel adenocarcinoma  all ovarian cancer patients  three of twelve colorectal cancer patients  and one patient with endometrial carcinoma had received prior therapy  patients received il 2 100 000 u kg every 8 hours intravenously  iv  for 3 days  and 2 days later underwent daily leukapheresis for 5 days  lak cells were generated in vitro by incubating the peripheral blood mononuclear cells in il 2 for 7 days and were then administered ip daily for 5 days through a tenckhoff catheter  davol  inc  cranston  ri  together with il 2 25 000 u kg ip every 8 hours  all but one patient completed at least one cycle of therapy  toxic side effects included minor to moderate hypotension  fever  chills  rash  nausea  vomiting  abdominal pain and distension  diarrhea  oliguria  fluid retention  thrombocytopenia  and minor elevations of liver function tests  all of these rapidly improved after discontinuation of il 2  one patient had a grand mal seizure  and one suffered a colonic perforation  these were felt to be treatment related  ip fibrosis developed in 14 patients and limited repeated cyclic administration of this therapy in five patients  two of 10  20   ovarian cancer patients and five of 12  42   colorectal cancer patients had laparoscopy  or laparotomy documented partial responses  we conclude that lak cells and ril 2 can be administered ip to cancer patients  resulting in moderate to severe short term toxicity and modest therapeutic efficacy  further investigation of this form of adoptive immunotherapy modified to address the problem of ip fibrosis and with lower ip il 2 doses is justified by these initial results  
class6	hepatic venoocclusive disease in autologous bone marrow transplantation of solid tumors and lymphomas  retrospective review of 291 solid tumor and lymphoma patients undergoing autologous bone marrow transplantation  bmt  was performed to determine the influence of pretransplant characteristics and preparative regimen to the development of hepatic venoocclusive disease  vod   twelve patients  4 1   developed a clinical syndrome of right upper quadrant  ruq  tenderness or hepatomegaly  jaundice  and ascites  with or without encephalopathy  within 40 days of marrow reinfusion  evidence of metastatic liver disease was the only pretransplant characteristic predictive for vod  p    0002   sex  age  histology  hepatitis b serology  and elevated liver function tests were not predictive  no individual preparative agent had a significant effect on the development of vod  however  a single 2 hour infusion of carmustine  bcnu   greater than or equal to 450 mg m2  led to an increased incidence of vod when compared with the same dose administered in a fractionated schedule  p    0258  when given with two other chemotherapeutic agents  seven of eight autopsy specimens confirmed the clinical diagnosis of vod  the four patients in whom clinical vod resolved had lower median peak bilirubins  7 3 v 15 9 mg dl   lower median peak creatinines  2 1 v 4 1 mg dl   and relatively quick engraftment of neutrophils  mean  18 7 days   one of the four patients in whom vod resolved had other grade 4  life threatening  toxicities in contrast to eight of eight who succumbed  in summary  vod is an uncommon complication in autotransplantation of solid tumors and lymphomas  our data suggest caution in selecting patients with known metastatic liver disease and consideration of a fractionated bcnu schedule especially in combination with other alkylating agents  
class6	antagonism of serotonin s3 receptors with ondansetron prevents nausea and emesis induced by cyclophosphamide containing chemotherapy regimens the control of nausea and emesis in cancer patients receiving chemotherapy poses a significant management problem  in this randomized  double blind  placebo controlled study  we evaluated the effect of serotonin s3 receptor blockade with ondansetron  gr 38032f  on the prevention of nausea and vomiting induced by cyclophosphamide containing chemotherapy  cyclophosphamide was given in doses of 500 to 600 mg m2 and ondansetron as three intravenous  iv  doses of 0 15 mg kg  most patients had breast cancer  cyclophosphamide was given in combination with doxorubicin  65  of patients  or with fluorouracil  85  of patients  50  with adriamycin  doxorubicin  adria laboratories  columbus  oh  and 35  with methotrexate   all placebo treated patients experienced vomiting  whereas 70  of patients treated with ondansetron did not vomit  p    008   median nausea scores were 8 mm on ondansetron and 65 mm on placebo  p less than  001   seventy percent of patients treated with ondansetron retained their normal appetite  compared with 10  of placebo patients  adverse events occurred in six placebo patients and one ondansetron patient  diarrhea and headache were the most common events  both occurring more frequently in the placebo group  there were no extrapyramidal reactions  and the only significant biochemical change occurred in a placebo treated patient  these results suggest that serotonin s3 receptor antagonists represent a novel  effective  and safe mode of therapy for nausea and emesis induced by cyclophosphamide containing chemotherapies  in addition  our observations are compatible with the view that serotonin  acting on s3 receptors  mediates the nausea and emesis occurring after cyclophosphamide chemotherapy  
class6	a study of htlv i and its associated risk factors in trinidad and tobago  seroprevalence of human t lymphotropic virus type 1  htlv i  among a sample of persons selected from a government register of businesses in trinidad was 3 2  in 1 025 persons of african descent compared to 0 2  among 487 persons of asian descent and 0  among 46 persons of european descent  in tobago  from a coastal village  among persons of african ancestry ascertained as part of a cardiovascular survey  the rate was 11 4   which was significantly higher when corrected for age and race than the rate in trinidad  the seroprevalence rate of antibodies to hepatitis a and b was also significantly elevated in tobago compared to trinidad  htlv i seroprevalence rates were higher in females than males while hepatitis a and b rates were not significantly different in the two sexes  for males  age was a significant determinant of htlv i seropositivity  while for females  age  markers of poor sanitation  and hepatitis b were each independently linked to htlv i seropositivity  the frequent occurrence of multiple infectious exposures in persons of lower socioeconomic circumstances in this tropical environment may result in immune activation that heightens susceptibility to htlv i infection  
class6	computed tomographic and ultrasonographic findings in women with acute fatty liver of pregnancy  acute fatty liver of pregnancy is associated with complications that can influence antepartum management and necessitate delivery  to date  liver biopsy has been regarded as the  gold standard  for diagnosis  radiologic evaluation of the liver has been suggested as a less invasive means of diagnosing this entity  five patients with acute fatty liver of pregnancy underwent ultrasonography  three underwent concomitant computed tomography  ct  of the liver  the liver appeared to be normal in all the patients undergoing ct evaluation and all undergoing ultrasonography except one  normal liver examinations are not unusual findings in patients with acute fatty liver of pregnancy  
class6	mayer rokitansky kuster hauser syndrome with splenosis  a case report  this is the first reported case of simultaneously occurring pelvic splenosis and mayer rokitansky kuster hauser syndrome  no other congenital or anatomic abnormalities were observed in the patient  and she had no history of abdominal trauma or surgery  endometriosis was suspected initially during laparoscopy for pelvic pain  after tissue removal at laparotomy  the histologic evaluation established the diagnosis of splenosis  biopsy at laparoscopy should be considered to confirm the diagnosis in the presence of a congenital anomaly and lesions suspected of being endometriotic  
class6	clinicopathological features of elevated lesions of the duodenal bulb  we present here our findings on patients with an elevated lesion of the duodenal bulb  all these patients were treated in our clinics between the years 1984 and 1988  these lesions were present in 36 of 8 802 patients who underwent upper gastrointestinal pan endoscopy  two patients had a duodenal carcinoma  2 an adenoma  and 1 a brunner s gland adenoma  there were 15 with a hyperplastic polyp  3 with a heterogenic gastric mucosa  3 with brunner s gland hyperplasia  6 with duodenitis  and 4 with regenerative mucosa  among these 36 lesions  only 69   25 lesions  were evident on the upper gastrointestinal x ray series  adenoma and brunner s gland adenoma were of a pedunculated form of the gross type and had an irregular surface mucosa  both duodenal carcinomas were detected by endoscopic biopsy and were resected  histologically  these lesions were limited to the submucosal layer and were of the non pedunculated polypoid form  but there were no other characteristic endoscopic features  in comparison with other elevated lesions  thus  upper gastrointestinal endoscopy with routine observations of the duodenal bulb plus endoscopic biopsy will lead to a definite diagnosis of these elevated lesions and to the early detection and treatment of this rare malignant lesion  
class6	long term results of the belsey mark iv antireflux operation in relation to the severity of esophagitis a retrospective analysis of the results of the belsey mark iv operation has been conducted  relating these to the degree of esophagitis present preoperatively  analysis of 89 patients showed a 91 7  success rate in patients without esophagitis  good results diminished steadily as the severity of esophagitis increased  giving 76 5   75   66 7   and 50  success rates for first   second   third   and fourth degree esophagitis  respectively  we believe that shortening of the esophagus is an important factor in this  shortening is obvious in third  and fourth degree esophagitis but subtle in first  and second degree esophagitis  we conclude that the belsey operation is adequate for patients without esophagitis  but for patients with any degree of esophagitis more effective reflux control is needed  
class6	long term versus short term treatment with recombinant interferon alfa 2a in patients with chronic hepatitis b  a prospective  randomized treatment trial  we conducted a prospective  randomized trial to study the efficacy and tolerance of long term versus short term treatment with recombinant interferon alfa 2a in patients with chronic hepatitis b  ten patients were randomly assigned to a 6 month interferon regimen  and 10 patients were assigned to a 3 week interferon trial  eleven patients  five assigned to long term treatment and six to short term treatment  did not complete interferon therapy  eight had either severe thrombocytopenia or neutropenia  one had pronounced fatigue in relationship to administration of interferon  one had spontaneous bacterial peritonitis and sepsis and died  and one had a massive fatal variceal hemorrhage during interferon therapy  most of the serious hematologic complications occurred in patients with cirrhosis and hypersplenism  in one patient  seroconversion to hepatitis b virus dna negativity occurred before the onset of treatment  four of the five patients able to complete the 6 month interferon regimen and only one of four patients able to complete the 3 week trial had seroconversion to hepatitis b virus dna negativity  thus  we conclude that the therapeutic response was better among patients who were able to complete a 6 month interferon trial  in patients with cirrhosis and hypersplenism  development of either severe thrombocytopenia or leukopenia associated with interferon therapy precluded completion of treatment  
class6	unsuspected syphilitic hepatitis in a patient with low grade proteinuria and abnormal liver function a 25 year old patient was found to have cholestatic liver enzyme abnormalities during assessment for asymptomatic low grade proteinuria at the us naval hospital in portsmouth  virginia  these abnormalities persisted for a 6 month period  and an extensive workup  including viral serologic studies  rapid plasma reagin test  iron studies  ceruloplasmin  antimitochondrial  antinuclear  and anti human immunodeficiency virus antibodies  endoscopic retrograde cholangiopancreatography  and liver biopsy  was unrevealing until serologic tests for syphilis were repeated to evaluate a new onset of urethral discharge  the patient had none of the more characteristic signs of secondary syphilis  the liver enzyme abnormalities rapidly resolved after treatment with penicillin  syphilis remains the great impostor and still must be considered in the differential diagnosis of unexplained liver enzyme abnormalities  even in a patient with no symptoms or signs of early syphilis  
class6	outbreak of diarrhoea due to escherichia coli o111 b4 in schoolchildren and adults  association of vi antigen like reactivity  during six days in november  1987  611 pupils  age range 7 19 years  and 39 adults  23 57  at a school complex in southern finland had diarrhoea due to escherichia coli o111 b4  diarrhoea developed in 137 other household members during the two weeks after the school outbreak  the source of the organism remains unknown  the outbreak strains  when incubated at 22 degrees c or exposed to ampicillin  lost the lipopolysaccharide o antigen and began to react with antisera against salmonella typhi vi antigen  the vi antigen like reactivity increased the adherence of the organisms to hep 2 cells  these results indicate that e coli o111 b4  and possibly other enteropathogenic e coli strains  should be considered in the diagnosis of all diarrhoea cases and not only in infantile diarrhoea  expression of vi antigen in e coli may play a part in virulence by enhancing adherence to the intestinal epithelium  
class6	conservation surgery for glomus jugulare tumors  the value of early diagnosis  the results of lateral cranial base surgery for glomus jugulare tumors are gratifying when normal anatomy and function can be preserved  the goal of conservation surgery is to preserve normal ear anatomy and cranial nerve function  in general  conservation surgery is tumor size dependent  thus  excellent states of functional recovery depend upon accurate early diagnosis  this paper reviews the technical aspects of transtemporal conservation skull base tumor surgery while also reviewing our experience with nearly 100 glomus jugulare patients  adjuvants to early diagnosis will be highlighted from a review of presenting symptoms  clinical signs  and related diagnosis  our objective is to provoke a high index of suspicion in physicians charged with the responsibility of diagnosing these tumors  diagnostic guidelines are proposed  
class6	ulcerative colitis and colorectal cancer  a population based study  background  the risk of colorectal cancer is increased among patients with ulcerative colitis  the magnitude of this increase in risk and the effects of the length of follow up  the extent of disease at diagnosis  and age at diagnosis vary substantially in different studies  methods  to provide accurate estimates of the risk of colorectal cancer among patients with ulcerative colitis  we studied a population based cohort of 3117 patients given a diagnosis of ulcerative colitis from 1922 through 1983 who were followed up through 1984  results  ninety two cases of colorectal cancer occurred in 91 patients  as compared with the expected incidence  the incidence of colorectal cancer in the cohort was increased  standardized incidence ratio  ratio of observed to expected cases    5 7  95 percent confidence interval  4 6 to 7 0   less extensive disease at diagnosis was associated with a lower risk  for patients with ulcerative proctitis  the standardized incidence ratio was 1 7  95 percent confidence interval  0 8 to 3 2   for those with left sided colitis  2 8  95 percent confidence interval  1 6 to 4 4   and for those with pancolitis  extensive colitis  or inflammation of the entire colon   14 8  95 percent confidence interval  11 4 to 18 9   age at diagnosis and the extent of disease at diagnosis were strong and independent risk factors for colorectal cancer  for each increase in age group at diagnosis  less than 15 years  15 to 29 years  30 to 39 years  40 to 49 years  50 to 59 years  and greater than or equal to 60 years   the relative risk of colorectal cancer  adjusted for the extent of disease at diagnosis  decreased by about half  adjusted standardized incidence ratio   0 51  95 percent confidence interval  0 46 to 0 56   the absolute risk of colorectal cancer 35 years after diagnosis was 30 percent for patients with pancolitis at diagnosis and 40 percent for those given this diagnosis at less than 15 years of age  conclusions  close surveillance and perhaps even prophylactic proctocolectomy should be recommended for patients given a diagnosis of pancolitis  especially those who are less than 15 years of age at diagnosis  
class6	the effect of ursodiol on the efficacy and safety of extracorporeal shock wave lithotripsy of gallstones  the dornier national biliary lithotripsy study background  in the treatment of gallstones with extracorporeal shock wave lithotripsy  the bile acid ursodiol is administered to dissolve the gallstone fragments  we designed our study to determine the value of administering this agent  methods  at 10 centers  600 symptomatic patients with three or fewer radiolucent gallstones 5 to 30 mm in diameter  as visualized by oral cholecystography  were randomly assigned to receive ursodiol or placebo for six months  starting one week before lithotripsy  results  the stones were fragmented in 97 percent of all patients  and the fragments were less than or equal to 5 mm in diameter in 46 8 percent  on the basis of an intention to treat analysis of all 600 patients  21 percent receiving ursodiol and 9 percent receiving placebo  p less than 0 0001  had gallbladders that were free of stones after six months  among those with completely radiolucent solitary stones less than 20 mm in diameter  35 percent of the patients receiving ursodiol and 18 percent of those receiving placebo  p less than 0 001  were free of stones after six months  biliary pain  usually mild  occurred in 73 percent of all patients but in only 13 percent of those who were free of stones after three and six months  p less than 0 01   there were few adverse events  only diarrhea occurred with a significantly different frequency in the two groups  32 6 percent were affected in the ursodiol group  as compared with 24 7 percent in the placebo group  p less than 0 04   severe biliary pain occurred in 1 5 percent of all patients  acute cholecystitis in 1 0 percent  and acute pancreatitis in 1 5 percent  endoscopic sphincterotomy was performed in 0 5 percent  and cholecystectomy in 2 5 percent  conclusions  extracorporeal shock wave lithotripsy with ursodiol was more effective than lithotripsy alone for the treatment of symptomatic gallstones  and equally safe  treatment was more effective for solitary than multiple stones  radiolucent than slightly calcified stones  and smaller than larger stones  
class6	anatomy of anal sphincters and related structures in continent women studied with magnetic resonance imaging  five anally continent nulliparas of reproductive age were studied with magnetic resonance imaging  the internal and external anal sphincters could be easily delineated  as could the intervening longitudinal musculature  puborectalis muscle  anococcygeal raphe  anorectal lumen  vagina  uterus  bladder  urethra  coccyx  and pubis  the shape of the sphincters was nearly cylindrical  with an anterior component averaging 18 3 mm thick and 28 0 mm long  fifty four percent of this anterior thickness was attributable to the internal sphincter  the anorectal angle varied considerably  with a mean of 86 8     19 1 degrees  range 60 112   the angle between the portion of the rectal lumen supported by the anococcygeal raphe  or levator plate  and the plane of the puborectalis muscle was consistent at 149 0     6 3 degrees  138 154   the finding of anterior anal sphincters with substantial thickness and length contrasts markedly with a view often pictured in the literature of a female anal sphincter that narrows anteriorly to half its posterior length and forms a small bundle of muscle rather than a broad band  knowledge of these relationships is important in primary repair of obstetric sphincter lacerations as well as in surgical correction of anal incontinence  
class6	methotrexate therapy for persistent ectopic pregnancy after conservative laparoscopic management  persistent ectopic pregnancy is a recognized complication of conservative laparoscopic surgery  three such cases were treated successfully with methotrexate and citrovorum factor rescue  all three patients experienced mild lower abdominal pain for a maximum of 36 hours  no other adverse effects were noted  more experience with this therapy will be necessary before subsequent fertility rates can be determined  
class6	congenital chyloperitoneum as a cause of isolated fetal ascites  isolated fetal ascites is an unusual prenatal finding and must be differentiated from immune and nonimmune hydrops  this entity is most commonly associated with gastrointestinal and genitourinary anomalies  fetal chyloperitoneum  however  should be considered as a possible cause  pulmonary hypoplasia and abdominal dystocia during attempted vaginal delivery are potential complications  we present a case of isolated fetal ascites due to congenital chyloperitoneum  
class6	rapid intravenous rehydration in the pediatric emergency department children suffering from mild to moderate  3 to 6   dehydration likely caused by viral gastroenteritis are often hospitalized because they are unable to tolerate oral fluids  we studied 17 such children  aged one to six years  who were otherwise healthy  all had isonatremic dehydration and were treated with 30 ml kg of 3 3  dextrose and 0 3  saline over a period of three hours in the emergency department before being discharged  no patient required admission to the hospital  only one patient required another course of rapid intravenous rehydration and subsequently improved without hospitalization  although all our patients experienced vomiting before treatment  65  had no vomiting after treatment  rapid intravenous rehydration is an effective treatment  for children with mild to moderate dehydration secondary to presumed viral gastroenteritis  that obviates the need for hospitalization  
class6	hemolytic uremic syndrome in children  a serious hazard of undercooked beef  hemolytic uremic syndrome is the leading cause of acute renal failure in childhood  its incidence in north america is increasing  escherichia coli o157 h7 is the most common infectious trigger and is spread by contaminated beef products as well as from person to person  antibiotics or antidiarrheal medications should not be used in the treatment of e coli hemorrhagic colitis or hemolytic uremic syndrome  mortality in children with the syndrome has fallen to less than 10  in north america  largely because of careful attention to nutrition  maintenance of a normal fluid and electrolyte balance  and careful monitoring  education and emotional support of the family are important aspects of the treatment program  
class6	chest pain in teenagers  when is it significant  chest pain in teenagers often has no obvious organic cause  onset of symptoms with an emotionally stressful situation may indicate psychogenic chest pain  the differential diagnosis also includes cardiac  musculoskeletal  gastrointestinal  and respiratory disorders  routine testing generally does not help to establish a diagnosis and may even do harm by reinforcing a patient s unspoken fear of serious illness  most teenagers with chest pain have no such illness  and symptoms usually resolve without therapy  an important role for primary care physicians is to provide support during evaluation and follow up  
class6	infectious diarrhea  managing a misery that is still worldwide  infectious diarrhea is the largest single cause of morbidity and mortality in the world  bacteria  viruses  and protozoan parasites are the most common causative agents  treatment in most cases of bacterial and viral diseases consists of correcting fluid loss and electrolyte imbalance by oral or parenteral rehydration  antimicrobial therapy is reserved for very ill patients only  with the exception of cryptosporidium  for which no effective agent is yet available  all protozoan infections are treatable with metronidazole  
class6	clinical recognition and evaluation of peptic ulcer disease  when a patient has epigastric pain that worsens 1 to 3 hours after meals  the possibility of peptic ulcer disease should be considered  completely typical clinical presentations in patients younger than age 50 justify empirical therapy when no physical or laboratory findings suggest a mimicking disorder  esophagogastroduodenoscopy should be undertaken when response to therapy is incomplete  symptoms recur quickly  or dyspeptic symptoms present for the first time in a patient older than age 50  when gastric ulcers are diagnosed radiographically  endoscopy and biopsy at multiple sites should be done to exclude malignant disease  intractable duodenal ulcers may necessitate endoscopic biopsy of antral and duodenal mucosa to rule out an associated helicobacter pylori infection  which may modify therapeutic approaches  zollinger ellison syndrome is rare but should be suspected when ulcer disease presents atypically or aggressively or in families  diagnosis is not difficult to confirm  
class6	medical treatment and prevention of peptic ulcer disease  many agents seem to be equally effective for the treatment of peptic ulcer disease  this is true despite the drugs  varied mechanisms of action  and this observation has caused investigators to shift their focus from aggressive to defensive factors when studying ulcer pathogenesis  patients with a healed ulcer are always at risk for recurrence  and guidelines are available for management of these patients  ulcer prevention becomes a crucial issue in intensive care units where critically ill patients have many known risk factors  maintaining a gastric ph above 4 0 appears to reduce the morbidity and mortality associated with such stress induced ulcers  use of nonsteroidal anti inflammatory drugs increases ulcer risk and complications in the elderly  in women with rheumatoid arthritis  and in smokers and abusers of alcohol  prophylaxis with the synthetic prostaglandin analogue misoprostol  cytotec  appears to reduce this risk  
class6	hyponatraemia in patients with cirrhosis  hyponatraemia occurs in nearly half of patients in hospital with cirrhosis and ascites  and is due to the excessive retention of free water which results from the kidney s inability to excrete it normally  the morbidity and mortality associated with hyponatraemia is largely attributable to central nervous system disturbances  the degree to which brain water content increases depends on the duration of hyponatraemia and on compensatory mechanisms  altered steroid and peptide hormones in cirrhotic patients may contribute to the development of hyponatraemic encephalopathy  symptoms of which overlap with hepatic encephalopathy and uraemia  the occurrence of central pontine myelinolysis is unrelated to the rate of correction of hyponatraemia  the appearance of hyponatraemia in cirrhotic patients  long regarded as a poor prognostic sign  may be a function of unrecognized underlying impaired renal function  therapy for hyponatraemia remains suboptimal  
class6	alpha 1 antitrypsin granules in the liver  always important  we have studied the clinical histories and liver biopsy findings in 1951 consecutive adult patients with suspected chronic liver disease  and in four known piz homozygous alpha 1 antitrypsin deficient patients with emphysema  candidates for lung transplant  and no known liver disease  in order to assess the importance of periportal alpha 1 antitrypsin granules in the liver and their possible causal role in liver disease  and to assess the value of possible screening tests  periportal granules were found in 30  1 5 per cent  of the 1951 liver biopsies and in all four known piz homozygous subjects  they were the sole putative aetiological agent in eight of 85 patients  9 4 per cent  with otherwise cryptogenic cirrhosis and present in 2 5 per cent of patients with cirrhosis of known aetiology  alcohol  autoimmune etc    all but one were z phenotype  seven homozygotes  22 heterozygotes   alpha 1 antitrypsin granules were seen in 12 patients  including three of four lung transplant candidates  with no histological chronic liver disease  determination of serum alpha 1 antitrypsin levels was quite unhelpful in identifying these patients  this study does not support the concept that periportal alpha 1 antitrypsin granules are necessarily pathogenic  but in some cases they may be causally related to otherwise cryptogenic liver disease  the presence of granules gave no important diagnostic  therapeutic or prognostic information  
class6	final outcome of ursodeoxycholic acid treatment in 126 patients with radiolucent gallstones  one hundred and twenty six patients with radiolucent gallstones in  functioning  gallbladders were treated with 8 10 mg ursodeoxycholic acid  udca  kg day and followed to a treatment conclusion  complete or partial gallstone dissolution was achieved in 74  59 per cent   however  only 22 achieved complete gallstone dissolution  as judged by two normal oral cholecystograms  ultrasonograms were performed in 16 of these patients  and all were normal  udca was stopped in 76 patients  because of cystic duct obstruction  n   12   severe biliary pain  n   13   non response  n   25  or partial stone dissolution with arrested progress  n   26   life table analysis showed that complete gallstone dissolution rates at four years were 25 30 per cent  two normal oral cholecystograms  and 17 19 per cent  two normal oral cholecystograms plus one ultrasonogram   all patients with complete gallstone dissolution had shown partial stone dissolution at 6 12 months  of those with partial stone dissolution at six months  only 25 per cent went on to complete gallstone dissolution  and then always within two years  efficacy correlated inversely with stone size but not with age  sex  obesity or on treatment saturation indices  acquired surface gallstone calcification developed in 13 patients  life table analysis 22     7 per cent at four years   none of these patients achieved complete gallstone dissolution and only five achieved partial stone dissolution  thus  despite relatively high partial gallstone dissolution rates  the ultimate efficacy of udca in achieving complete gallstone dissolution is low  
class6	reactivation of hepatitis b virus replication in patients receiving cytotoxic therapy  report of a prospective study  one hundred chinese patients who received induction cytotoxic therapy for malignant lymphoma were prospectively studied to determine the incidence  morbidity  mortality  and predisposing factors for reactivation of hepatitis b virus replication during cytotoxic therapy  in 18  67   hepatitis b surface antigen positive and 10  14   hepatitis b surface antigen negative patients  hepatitis developed during cytotoxic therapy  p less than 0 0001   hepatitis could be attributed to exacerbation or reactivation of chronic hepatitis b in 13  72   hepatitis b surface antigen positive patients but in only 2  20   hepatitis b surface antigen negative patients  p less than 0 0001   sudden increase or reactivation of hepatitis b virus replication gave rise to icteric hepatitis  nonfatal hepatic failure  and death in 22 3   3 7   and 3 7  of patients who were positive for hepatitis b surface antigen  in 2   2   and 0  of those positive for hepatitis b antibodies  and in none of those who were seronegative  among the hepatitis b surface antigen positive patients  male sex was the only factor that was associated with an increased risk of reactivation of hepatitis b virus replication  we recommend that hepatitis b surface antigen positive patients with malignancies receiving cytotoxic therapy be closely monitored  
class6	prophylaxis of uric acid stones with alternate day doses of alkaline potassium salts  uric acid stone formation ordinarily is prevented by increases in the urinary ph after meals  this postprandial alkaline tide is lost in patients who make such calculi  single dose  alternate day administration of an alkaline potassium salt will increase urinary ph and simulate this normal physiological mechanism  an important part of the regimen is patient self monitoring to verify that the urinary ph increases to greater than 6 8  1 1 2 to 2 hours after the medication is taken  in contrast to multiple dose daily regimens  this mode of base administration is tolerated better and easier to follow  in 17 patients  7 with the recurrent gravel colic syndrome and 10 with prior stones  this regimen abolished calculus formation during an average followup of 2 1 2 years  however  further studies are needed before this regimen can be recommended as standard therapy for uric acid stone prophylaxis  
class6	safety of same day sequential extracorporeal shock wave lithotripsy and dissolution of gallstones by methyl tert butyl ether in dogs  passage of stone fragments after extracorporeal shock wave lithotripsy  eswl  of gallstones has resulted in biliary colic  duct obstruction  and pancreatitis in some patients  rapid dissolution of these fragments with methyl tert butyl ether  mtbe  may prevent such side effects and achieve complete clearance of gallstones within hours rather than several months to a year or longer  this study examines the safety of same day eswl fragmentation and mtbe dissolution of surgically implanted human gallstones in 15 dogs  the animals were randomly assigned to one of four treatment groups to assess mtbe absorption from the gallbladder and to observe hematology and chemistry profiles after 0  400  and 1 200 shock waves from a lithotriptor followed by mtbe dissolution therapy  they were sacrificed either immediately after treatment  12 dogs  or 2 weeks later  3 dogs   the results demonstrated that although eswl causes moderate trauma to the gallbladder  this did not result in increased mtbe absorption or histologic evidence of mucosal disruption  blood profiles demonstrated an increase in only the level of aspartate aminotransferase  the three dogs that were sacrificed 2 weeks after the combined treatment had no residual evidence of gallbladder injury or remaining stone material  in all animals  severe injury occurred where shock waves passed through lung or air filled colon  this study suggests that same day sequential fragmentation of gallstones by eswl followed by dissolution of stone fragments with use of mtbe may be associated with only mild to moderate and reversible gallbladder trauma and can rapidly achieve clearance of gallstones  
class6	familial occurrence of inflammatory bowel disease  background and methods  we assessed the familial occurrence of inflammatory bowel disease in copenhagen county  where there has been a long term interest in the epidemiology of such disorders  in 1987 we interviewed 662 patients in whom inflammatory bowel disease had been diagnosed before 1979  asking whether their first  and second degree relatives had this disorder  ninety six percent of the patients  504 with ulcerative colitis and 133 with crohn s disease  provided adequate information  results  as compared with the general population  the first degree relatives of the 637 patients with ulcerative colitis or crohn s disease had a 10 fold increase in the risk of having the same disease as the patients  after standardization for age and sex  the risk of having the other of the two diseases was also increased  but less so  and the increase in the risk of having crohn s disease was not significant in the relatives of patients with ulcerative colitis  the risk of ulcerative colitis in first degree relatives of patients with ulcerative colitis appeared to be virtually independent of the generation to which the first degree relative belonged and of the sex of the patient and the relative  the risk of ulcerative colitis in first degree relatives tended to be higher if the disease had been diagnosed in the patient before the age of 50  but the risk seemed to be independent of the current age of the relatives  the prevalence of the same disease as that of the patient  either ulcerative colitis or crohn s disease  among second degree relatives was increased  the prevalence of the other disease was not increased  conclusions  the 10 fold increase in the familial risk of ulcerative colitis and crohn s disease strongly suggests that these disorders have a genetic cause  
class6	appendectomy in primary and secondary staging operations for ovarian malignancy  appendectomy was performed at primary or secondary staging operations in 100 patients with ovarian malignancies  of 80 patients who underwent appendectomy at the time of their primary surgery  25  31 2   had appendiceal metastases  among 47 patients who were believed to have disease limited to the pelvis at the time of surgery  stage i  n   34   ii  n   7   iiia  n   5   and those designated stage iiic solely on the basis of microscopic para aortic nodal metastasis  n   1   the appendix was involved with disease in only two patients  4 3    however  among 33 patients with advanced disease  stage iiib  n   6   iiic except those designated iiic solely on the basis of microscopic paraaortic nodal metastasis  n   19   and iv  n   8   the appendix was involved with disease in 23 patients  69 7    p less than  001   poorly differentiated tumors and serous histologic cell types more frequently metastasized to the appendix  64  15  6  and 8  for grades 3  2  and 1 and borderline histology  respectively  p less than  001  and 48  13  and 8  for serous  endometrioid  and mucinous  p less than  001   of 20 patients who underwent appendectomy at their secondary staging procedure  two had metastases  metastatic disease in the appendix was microscopic in nine of 27 patients  because the frequency of appendiceal metastasis is similar to that of other metastatic sites in stages i and ii ovarian cancer  it should be removed at primary staging procedures  appendectomy should also be performed in patients with advanced ovarian malignancies if it contributes to cytoreduction or at the time of secondary staging procedures  
class6	hepatocellular carcinoma within siderotic regenerative nodules  appearance as a nodule within a nodule on mr images  large regenerative nodules in cirrhotic livers may accumulate iron and develop internal iron poor foci of hyperplasia or malignancy  magnetic resonance examinations were performed on 23 patients with biopsy proved cirrhosis  a  nodule within nodule  appearance was noted in two patients  this appearance consisted of markedly low intensity of a large nodule on gradient echo images  with one or two internal foci that were isointense to the liver  each of the large nodules was 2 cm in diameter  and each of the internal foci was less than 1 cm  serum alpha fetoprotein levels were normal in both patients  aspiration biopsy performed in one patient failed to show malignancy  but histologic confirmation of hepatocellular carcinoma was obtained eventually in both cases  the nodule within nodule sign  which reflects the unique histopathology of hepatocellular carcinoma in large siderotic regenerative nodules  is strongly suggestive of early hepatocellular carcinoma  even if serologic markers and biopsy results do not support this diagnosis  
class6	retained intrahepatic stones  treatment with piezoelectric lithotripsy combined with stone extraction  extracorporeal shock wave lithotripsy  eswl  was performed in 11 patients with oriental cholangiohepatitis and intrahepatic stones associated with segmented strictures of intrahepatic ducts  all patients had previously undergone biliary surgery and basket extraction via a t tube tract at the time of lithotripsy  the indication for eswl was failure of  or anticipated difficulty with  basket extraction of the stones via a t tube tract  a piezoelectric lithotriptor was used in all procedures  the average total number of shock waves administered was 29 756  range  10 000 61 395   the average number of treatment sessions was 3 1  range  1 6   the number of shock waves used in a single session ranged from 10 000 to 15 000 with a frequency of five shots per second and 30  50  power  in six patients  the stones were successfully fragmented and completely removed  in three of the others of the stones were fragmented and removed  the overall success rate  including complete  54   and incomplete  27   success  was 82   difficulty in targeting stones  and severe strictures and deformities of intrahepatic ducts  were the factors responsible for failure  no significant complications were observed  
class6	esophageal inflammation and stricture  complication of chronic granulomatous disease of childhood  esophagitis in children with immunodeficiency is most commonly due to opportunistic infection  the authors describe three patients with chronic granulomatous disease  cgd  of childhood who developed esophageal strictures that were believed to be complications of the primary disease  at radiologic examination  all three patients initially had a focal narrowing of the upper thoracic esophagus  endoscopy showed no signs of opportunistic infection or barrett esophagus  biopsy of the strictures in two patients revealed findings consistent with cgd  in two of the three patients  inflammation extended to involve the middle and distal esophagus  long term response to balloon dilation was poor in the first two patients  the third patient was lost to follow up after a partial clinical and radiographic response to dilation  
class6	bleeding gastroesophageal varices  gastric vein embolization after partial portal decompression  shunts that decompress the portal vein are effective in the treatment of bleeding esophageal varices  use of large caliber portacaval shunts  however  results in the complete decompression of the portal system and the risk of subsequent development of hepatic encephalopathy  use of small caliber portacaval shunts results in mild portal hypertension and less frequent hepatic encephalopathy but may increase the risk of recurrent bleeding  thirty three patients underwent angiography after partial decompression portacaval shunting  median trans shunt pressures  8 mm hg   embolization of residual varices  noted in 13 patients  was performed  results included one complication with no sequelae and no bleeding a mean of 13 months after the procedure was performed  trans shunt embolization of esophageal varices effectively prevents bleeding varices after partial portal decompression  
class6	oral cholecystography in contemporary gallstone imaging  a review  the introduction of nonoperative alternatives to elective cholecystectomy in the management of gallstones has resurrected use of oral cholecystography  ocg   this article reviews basic principles involved in the proper performance of ocg and interpretation of the resulting images  the role of ocg in the current management of gallstones is discussed  
class6	pharynx  value of oblique projections for radiographic examination  the utility of oblique views for augmenting standard posteroanterior and lateral double contrast radiography of the pharynx was examined  over an 8 month period  two oblique views were added to the standard posteroanterior and lateral views of the pharynx during routine upper gastrointestinal studies in 102 patients divided into two groups  group 1 consisted of 81 patients without suspected pharyngeal or esophageal disease who demonstrated what was considered to be normal anatomy on all radiographic views  group 2 consisted of 21 patients who were known or suspected to have pathologic abnormality of the pharynx  the members of this latter group each demonstrated various abnormal pharyngeal anatomy on the standard views  in just over half of these cases the oblique projection contributed significant information not obtained with conventional views  therefore  the authors conclude that oblique images are a beneficial addition to the diagnostic evaluation of patients highly suspected of having pharyngeal disease  
class6	detection of gastric erosions  comparison of biphasic radiography with fiberoptic endoscopy  biphasic radiography was compared with fiberoptic endoscopy in detecting gastric erosions in a prospective  blinded study of 385 patients with dyspepsia  because no absolute standard was available for the comparison  since histologic confirmation of all erosions was not possible  the kappa statistic was used to compare results from both modalities  flat  incomplete  erosions were detected with endoscopy only and were considered to be present in 42 patients  11 2    varioliform  complete  erosions were identified with both radiography and endoscopy in 12 patients  3 2    for the detection of varioliform erosions  a substantial agreement beyond chance between both modalities was found  kappa   0 73  standard error  0 12   thus  flat erosions were detected with endoscopy only  whereas state of the art radiography and endoscopy were equally sensitive for detecting varioliform erosions  histologic confirmation of erosions was obtained in only 75  of the patients  it is unknown whether the demonstration of erosions with radiography and or endoscopy correlates with dyspepsia  
class6	liver and pancreas  improved spin echo t1 contrast by shorter echo time and fat suppression at 1 5 t  t1 weighted spin echo magnetic resonance  mr  images have had limited soft tissue contrast at 1 5 t  the authors investigated the effects of echo time  te  minimization and fat suppression on mr images of the liver and pancreas  two sets of mr images were obtained with identical repetition times and other parameters  in 10 subjects with seven liver lesions  images with tes of 20 and 12 msec were compared  in 18 additional subjects with seven liver lesions and five pancreatic carcinomas  images with identical tes but with and without fat suppression were compared  contrast to noise ratios  cnrs  were greater with a te of 12 msec than with a te of 20 msec for liver versus spleen  7 6 vs 4 9  p    014  and liver versus lesion  6 9 vs 3 9  p    031   in patients without fatty liver  cnr for six lesions versus liver was greater  9 5 vs 6 0  p    014  with fat suppression  cnr between glandular pancreas and cancer was most conspicuous with fat suppression  but fat planes were less distinct  minimization of te improves t1 weighted images significantly  fat suppression also improves cnr  but the disadvantages of fat suppression do not allow elimination of conventional t1 weighted images  
class6	pancreatic cancer versus chronic pancreatitis  diagnosis with ca 19 9 assessment  us  ct  and ct guided fine needle biopsy  the authors prospectively performed serum ca 19 9 assessment  ultrasound  us   computed tomography  ct   and ct guided fine needle aspiration biopsy  fnab  of the pancreas in 81 consecutive patients with suspected chronic pancreatitis or pancreatic neoplasm  the final diagnosis was pancreatic cancer in 54 patients and chronic pancreatitis in 27 patients  ca 19 9 assessment  us  ct  and fnab were considered nondiagnostic  respectively  in 0   25   19   and 6  of cases  when a definite diagnosis was rendered  the positive predictive value was 90  for ca 19 9 assessment  95  for us  98  for ct  and 100  for fnab  the negative predictive value was  respectively  69   95   86   and 100   the accuracy of all diagnostic and nondiagnostic studies was 81  for ca 19 9 assessment  72  for us  77  for ct  and 94  for fnab  it is concluded that ct guided pancreatic fnab is the most reliable examination for enabling differential diagnosis of pancreatic cancer and chronic pancreatitis  when the pancreas is well visualized at us  the negative predictive value for pancreatic cancer is more accurate than that of ca 19 9 assessment and ct  
class6	resting and total energy expenditure in patients with inflammatory bowel disease  patients with inflammatory bowel disease often present with weight loss  among possible causes  an elevated energy expenditure has frequently been suggested but is the least documented  in this study resting metabolic rate  rmr  and total daily energy expenditure  tdee  were measured in 15 outpatients with inflammatory bowel diseases and in eight healthy control subjects  measured rmr as a percentage of that predicted from fat free mass was not significantly different for control subjects  102     9 8   mean     sd  and patients  100     13 3    tdee  expressed as a multiple of rmr  was 1 70     0 31 for control subjects and 1 78     0 24 for patients  when patients were subgrouped as greater than or equal to 90  or less than 90  desirable body weight  a mean increase over rmr predicted from fat free mass was seen in the underweight patients  106     9 3   but not in normal weight patients  99 0     15 6    mean tdee rmr values for the patient subgroups were 1 70     0 30 and 1 88     0 08  respectively  we conclude that stable outpatients with inflammatory bowel disease have only a minimal increase in energy needs  
class6	factors affecting the enterohepatic circulation of oral contraceptive steroids  oral contraceptive steroids may undergo enterohepatic circulation  but it is relevant for only estrogens  because these compounds can be directly conjugated in the liver  animal studies show convincing evidence of the importance of the enterohepatic circulation  but studies in humans are much less convincing  the importance of the route and the rate of metabolism of ethinyl estradiol are reviewed  some antibiotics have been reported anecdotally to reduce the efficacy of oral contraceptive steroids  but controlled studies have not confirmed this observation  although gut flora are altered by oral antibiotics  the blood levels of ethinyl estradiol are not reduced  and one antibiotic at least  cotrimoxazole  enhances the activity of ethinyl estradiol  
class6	gastrointestinal disease and oral contraception  oral contraceptive steroids play a major role in modern family planning  with the present tendency to decrease the doses of both estrogens and progestogens  any factor that reduces the bioavailability of the lower dose preparations may have an impact on contraceptive protection  although ethinyl estradiol  the most commonly used oral estrogen  is liable to an enterohepatic circulation as unchanged drug  the commonly used progestogens are not  at present  no convincing evidence exists in the human subject that disruption of the enterohepatic circulation by antibiotics or antacids does reduce contraceptive efficacy of the pill  oral contraceptive steroids are mainly absorbed from the small bowel  and contraceptive efficacy depends on its absorptive capacity  enhanced passage of gastrointestinal contents or impaired absorption may thus contribute to contraceptive failures in patients who have chronic inflammatory disease  diarrhea  ileostomy  or jejunoileal bypass  
class6	oral contraception in disease states  oral contraceptives are clearly contraindicated in patients with a history of thromboembolic disease  ischemic heart attack  or cerebral stroke  patients requiring long term anticoagulant treatment can be treated with gonadotropin releasing hormone analogs to prevent ovulation  because ruptured follicles can cause massive intraperitoneal bleeding  patients with essential hypertension and severe liver diseases should also discontinue treatment 4 weeks before major elective surgery  migraine and diabetes mellitus are regarded as relative contraindications  depending on the individual situation  long term diseases  such as crohn s disease  epilepsy  and sickle cell anemia  also require individualized consultation  
class6	efficacy of ephedrine in the prevention of postoperative nausea and vomiting  although reported in the aerospace literature and anecdotally by anesthesiologists  the putative antiemetic effect of ephedrine remains unquantitated  we therefore prospectively studied ephedrine as an antiemetic agent in the perioperative setting in 97 patients undergoing general anesthesia for outpatient gynecologic laparoscopy  patients were assigned in a double blind randomized fashion to receive a standardized general anesthetic followed by an intramuscular dose of either ephedrine  0 5 mg kg   droperidol  0 04 mg kg   or saline before the conclusion of surgery  nausea  retching  or vomiting  as well as the degree of sedation and discharge times  were assessed in the recovery room and for 24 h postoperatively  ephedrine was found to have a significantly antiemetic effect  p less than 0 05  when compared with placebo and an antiemetic effect similar to that of droperidol  sedation scores were also significantly less in the ephedrine group than in both placebo and droperidol groups  finally  variations in mean arterial blood pressure among the three groups were not statistically significant  we conclude that ephedrine is an effective antiemetic agent with minimal sedative side effects in patients undergoing outpatient laparoscopy  
class6	which clinical variables predict an abnormal double contrast barium enema result  objective  to determine the relations among patient history  symptoms  objective indicators  and abnormal double contrast barium enema results in outpatients  patients and setting  seven hundred and ninety four patients receiving care in a large multispecialty medical group  design  physicians completed a form before ordering a double contrast barium enema  listing information about patient history  symptoms  and objective findings  including the results of a complete blood count  stool hemoccult  and sigmoidoscopy  measurements and main results  outcome measures were colon cancer and any abnormal finding  the results of 18 6  of the barium enemas were abnormal  the most frequent positive findings were of polyps  8 8   and colon cancer  2 9    over 50  of the barium enemas were ordered solely on the basis of symptoms  yet there was no statistical correlation between symptoms and colon cancer or any positive finding  using logistic regression  four variables were shown to be significant predictors of colon cancer  p less than 0 05   abnormal sigmoidoscopy  iron deficiency anemia  positive stool hemoccult results  and relevant history  the respective odds ratios of these variables were 3 76  95  ci  2 89 to 4 90   2 86  ci  2 13 to 3 74   1 87  ci  1 46 to 2 39   and 1 91  ci  1 44 to 2 52   respectively  in a patient without any of these indicators  the predicted probability of having colon cancer was only 0 7   in a patient with at least two objective indicators  the probability of having colon cancer was greater than 15   conclusions  symptoms without objective indicators or pertinent risk factors do not correlate with an abnormal double contrast barium enema result  objective indicators are useful predictors of an abnormal barium enema result  particularly when looking for colon cancer  
class6	the effect of ambulation on recovery from postoperative ileus  to determine whether ambulation hastens recovery from ileus following laparotomy  34 patients were studied  10 of whom followed an ambulatory regimen beginning on postoperative day 1  group a   the other 24 patients  group c  did not become ambulatory until postoperative day 4  all patients underwent placement of seromuscular bipolar recording electrodes on the roux limb  if present  stomach  jejunum  and colon at laparotomy  group a was recorded before and after ambulation so comparisons could be made to determine if ambulation had an acute effect on myoelectric activity  group a preambulation and group c recordings were compared to judge whether there was an over all effect of ambulation on myoelectric recovery  no effect on slow wave frequency or percentage of slow waves with associated spike potentials was noted acutely or overall in the stomach  colon  or jejunum in continuity with the duodenal pacemaker  transient increases in phase ii spike activity in patients having a roux limb and their jejunum distal to the enteroenterostomy were noted on postoperative days 1 to 2  but these differences resolved by postoperative days 3 or 4  the data suggest that ambulation as a means to help resolve postoperative ileus and its accompanying cramps and bloating may be more perceived than real  
class6	efficacy of octreotide acetate in treatment of severe postgastrectomy dumping syndrome  the present study evaluates the acute and chronic use of a long acting somatostatin analog  octreotide acetate  in the treatment of patients with severe postgastrectomy dumping syndrome  in the acute phase  10 patients with severe dumping were studied over 2 consecutive days before and for 3 hours after the ingestion of a  dumping breakfast  in a randomized double blind fashion  on one day octreotide  100 micrograms  was given subcutaneously 30 minutes before the test meal and on the other day an equal volume of vehicle was injected  an additional group of six postgastrectomy patients without dumping were studied in a similar fashion and these acted as controls  during placebo treatment the test meal resulted in an immediate increase  p less than 0 01  in the pulse rate and in plasma levels of glucose  glucagon  pancreatic polypeptide  neurotensin  and insulin  similar changes were seen in the control group with respect to placebo  however glucagon and neurotensin  p less than 0 05  did not show the same magnitude of increase as seen with placebo  treatment with octreotide acetate prevented the development of both vasomotor and gastrointestinal symptoms and completely ablated all of the above responses in plasma peptides  these changes were associated with complete ablation of diarrhea  p less than 0 001   pretreatment with octreotide acetate completely suppressed the rise in plasma insulin response to the meal and this ablated the late hypoglycemia of dumping  treatment with octreotide acetate resulted in delayed gastric emptying and transit time  578     244 minutes  versus 76     23 minutes with placebo and 125     36 minutes in controls  p less than 0 05   chronic daily treatment with octreotide acetate resulted in minimal side effects  these patients demonstrated a stable fasting plasma glucose  normal liver function tests  and an average weight gain of 11  during a 12 month period  in addition most patients were able to resume employment  the long acting somatostatin analog  octreotide acetate  is highly effective in preventing the development of symptoms of severe dumping syndrome  both vasomotor and gastrointestinal  
class6	the risk of large bowel cancer after partial gastrectomy for benign ulcer disease  the relative risk  standardized incidence ratio  sir  for colorectal cancer after partial gastrectomy for ulcer disease was examined in a population based cohort comprising 6459 patients operated during 1950 to 1958  follow up through 1983 revealed 131 cases of colorectal cancer versus 150 3 expected cases  sir   0 87  95  confidence limits 0 73  1 03   the relative risk was decreased during the first 19 years of follow up  sir   0 75  0 58  0 96  and close to equal thereafter  sir   1 02  0 79  1 29   sex  age at operation  type of operation  and diagnosis at operation  stomach or duodenal ulcer  did not affect the relative risk significantly  confounding by socioeconomic status is one conceivable explanation for the decreased relative risk during the first years of follow up  whereas the increasing risk with longer duration of follow up might be a consequence of the surgical procedure itself  
class6	involvement of thromboxane and neutrophils in multiple system organ edema with interleukin 2  interleukin 2  il 2  produces toxicity characterized by generalized edema within 24 hours  this study tests whether the rate of il 2 administration modulates the onset of edema and examines thromboxane  tx  and neutrophils as possible mediators of this event  recombinant human il 2  10 5  u  n   7   10 6  u  n   9   or vehicle  n   8  were given to anesthetized rats intravenously during a period of 1 hour  at 6 hours edema  as measured by increase in wet to dry weight  w d  ratio  was present in the heart  liver  and kidney  with 10 5  u il 2 and in the lung  heart  liver and kidney  with 10 6  u il 2  relative to values with vehicle infused controls  all p less than 0 05   with a 1 hour infusion of 10 6  u il 2  there was an increase in plasma thromboxane  tx b2 level to 1290     245 pg ml  higher than 481     93 pg ml in control rats  p less than 0 05   lung polymorphonuclear leukocyte  pmn  sequestration of 53     7 pmn 10 higher power fields  hpf  relative to 23     2 pmn 10 hpf in controls  p less than 0 05   and increased bronchoalveolar lavage  bal  fluid protein concentration of 1970     210 micrograms ml relative to 460 micrograms ml in controls  p less than 0 05   when 10 6  u il 2 was given as a 1 minute intravenous bolus  n   9   edema was not demonstrated  plasma txb2 levels were similar to controls  there was no leukosequestration  and bal protein levels were normal  these data indicate that a constant infusion but not the rapid bolus administration of il 2 produces in rats multiple system organ edema  increased plasma txb2  sequestration of pmns  and microvascular permeability  these findings may explain the early toxicity seen in patients given high dose il 2 in cancer treatment  
class6	autologous implant of peritoneal mesothelium in rabbits and man  with the purpose of studying peritoneal physiology  original biopsy methods were devised and human and rabbit peritoneal mesothelial cells cultured and characterized  it was then decided to verify whether these cells could be implanted autologously during peritoneal dialysis in cases of acute loss of mesothelial surface  staphylococcal peritonitis was induced in 12 rabbits and after 4 days of antibiotics  6 of them were autoimplanted with cultured mesothelial cells  previously marked in 3 cases with thymidine  h3tdr   implanted rabbits sacrificed after 3 and 6 days showed taking of the new mesothelial cells both by direct morphological observation and by autoradiography  four uremic capd patients recovering from severe peritonitis were implanted with 300 million of their own peritoneal mesothelial cells  previously cultured and frozen  morphological signs of taking were evident by laparoscopy and from peritoneal biopsies performed 3 and 6 days after implant  the fact that such implants are possible may have interesting applications in medicine and surgery  
class6	changes in interferon receptors on peripheral blood mononuclear cells from patients with chronic hepatitis b being treated with interferon  we studied the binding of 125i labeled human interferon alpha to peripheral blood mononuclear cells and the activity of 2  5  oligoadenylate synthetase in peripheral blood mononuclear cells obtained from 21 patients with chronic hepatitis b who were treated with human interferon alpha or interferon beta  fourteen patients were given interferon daily for 4 wk  interferon receptors per cell decreased to about 50  of baseline but increased to baseline by 2 wk after therapy ended  the activity of 2  5  oligoadenylate synthetase rose about fivefold during therapy  decreasing to baseline by 1 wk after the end of therapy  the seven other patients were given interferon daily for 2 wk  no interferon for 2 wk and then interferon daily for 2 wk more  during both periods of therapy on this schedule  interferon receptors decreased to about 50  but returned to baseline 1 wk after the interferon was stopped  the activity of 2  5  oligoadenylate synthetase increased about fivefold during both the first and second periods of therapy and decreased to baseline 1 wk after interferon was stopped  close negative correlation existed between the number of interferon receptors and the 2  5  oligoadenylate synthetase activity  the results of interferon therapy could not be predicted by either the numbers of interferon receptors before therapy or by the decrease in this number during therapy  
class6	interferon antibodies may negate the antiviral effects of recombinant alpha interferon treatment in patients with chronic hepatitis b virus infection  in a randomized controlled trial of recombinant alpha 2a interferon for chronic hepatitis b  interferon antibodies developed in 21  39   of 54 chinese adults who received ifn  no correlation was observed between sex  age  pretreatment serum alt level or liver histological findings and the development of interferon antibodies  antibodies were significantly more likely to develop in patients who received lower doses  2 5 or 5 mu m2  of alpha 2a interferon than in those who received a higher dose  10 mu m2   53  vs  11   p   0 006   the development of interferon antibodies appeared to reverse the initial antiviral response to treatment  with reappearance of hepatitis b virus dna in serum in 12 patients and hbeag in three patients  sustained clearance of hbeag was achieved in only one  5   patient but was achieved in seven  21   patients without interferon antibodies  the mere presence of interferon antibodies did not preclude an antiviral response to interferon therapy  but patients with high titer neutralizing antibodies were less likely to respond  these findings suggest that interferon antibodies may negate the antiviral effects of alpha 2a interferon  a higher incidence of interferon antibodies in chinese vs  white patients with chronic hepatitis b may contribute to the poorer antiviral response in chinese patients  
class6	a biphasic pattern of anti pre s responses in acute hepatitis b virus infection  the clinical relevance of the immune response to the translation products of the pre s1 and pre s2 regions of hepatitis b virus was examined by testing sequential serum samples from 17 patients with acute self limited hepatitis b and from two patients in whom chronic liver disease developed  anti pre s antibodies were determined by enzyme immunoassays based on the inhibition of binding of monoclonal antibodies to epitopes in the pre s1 and pre s2 sequence  in acute  self limited infection  anti pre s antibodies appeared in a biphasic pattern  the early antibodies were detected at the time of clinical signs of acute disease when hbsag and often hbeag were present  but hepatitis b virus dna was no longer detectable in serum  anti pre s levels then fell  but subsequently reappeared as the late antibody during the recovery phase  after development of anti hbe  but before anti hbs  anti pre s responses were detected in 15 of 17 patients who recovered  88 2   and in both patients with acute hepatitis b virus infection evolving to chronic liver disease  although the early antibodies to pre s1 and pre s2 proteins appeared at the time of decreasing levels of infectious virus in serum in cases of self limited infection  these antibodies also were transiently or continuously present with high levels of serum hepatitis b virus dna in patients in whom chronic hepatitis b infection developed  thus the anti pre s response in acute hepatitis is not a prognostic marker for clinical resolution  
class6	early and frequent detection of hbxag and or anti hbx in hepatitis b virus infection  to clarify the significance of the x gene of hepatitis b virus  we have tested for anti hbx in the serum and hbxag in the liver at different stages of the natural history of hepatitis b virus infection  sera were screened by enzyme linked immunosorbent assay and positive results confirmed by immunoblot  purified recombinant ms2 pol hbx fusion protein was used as target for both assays  among serial sera of patients with nonfulminant acute hepatitis  24 of 64 patients  37 5   were positive for anti hbx  in fulminant cases  15 of 36 patients  42   had anti hbx  in chronic hepatitis patients with high rates of hepatitis b virus replication  we found a significantly  p less than 0 01  higher prevalence of anti hbx  14 of 25 patients  56    than in those with low replication  14 of 66 patients  21    or among asymptomatic hbsag carrier blood donors  20 of 126   16   without detectable hepatitis b virus replication  p less than 0 0001   the highest prevalence of anti hbx was found in hbsag carriers with cirrhosis  41 of 54 patients   76   and or with hepatocellular carcinoma  18 of 33 patients   54    the findings suggest that anti hbx appears as a common and early marker of hepatitis b virus infection  transient in self limited hepatitis but persisting with progression to chronicity  in chronic hepatitis  the prevalence of anti hbx correlated with the intensity and duration of hepatitis b virus replication but neither with the severity of the liver disease nor with malignant transformation per se  
class6	defects in the precore region of the hbv genome in patients with chronic hepatitis b after sustained seroconversion from hbeag to anti hbe induced spontaneously or with interferon therapy  hepatitis b virus dna clones were propagated from sera of six patients with chronic hepatitis b who seroconverted from hbeag to antibody to hbeag either spontaneously or after administration of alpha interferon  defects in the precore region blocking synthesis and secretion of hbeag were detected in all 46 hepatitis b virus dna clones from three patients who remained positive for antibody to hbeag and in whom hepatitis resolved  defective clones had point mutations from guanine to adenine at nucleotide 83 in the precore region  converting codon 28 from tryptophan  tgg  to a stop codon  tag   in contrast  this defect was not found in any of 39 hepatitis b virus dna clones from three patients who seroconverted to antibody to hbeag but then redeveloped hbeag with reactivation of hepatitis  using these results  the g to a point mutation at nucleotide 83 in the precore region would predict sustained positivity for antibody to hbeag and remission of hepatitis in patients who have seroconverted either spontaneously or with interferon therapy  
class6	influence of hepatitis delta virus replication in the presence of hepatitis b virus dna in peripheral blood mononuclear cells  the presence of hepatitis b virus dna was studied in peripheral blood mononuclear cell samples from 259 hbsag carriers  229 anti hepatitis delta negative  30 anti hepatitis delta positive   16 anti hbc positive hbsag negative patients and 30 patients without hepatitis b virus markers  hepatitis b virus dna sequences were detected in peripheral blood mononuclear cell from 115  44 4   of the chronic hbsag carriers and from two  12   of the anti hbc positive  hbsag negative patients  in anti hepatitis delta negative patients  viral dna was positive in peripheral blood mononuclear cell from 74  46   and from 24  35 5   with and without serum hbv dna  respectively  with respect to anti hepatitis delta positive patients  viral dna was found in peripheral blood mononuclear cell in 8 of 13  61 5   of the patients with circulating hepatitis delta virus rna and in 9 of 17  53   of the hepatitis delta virus rna negative subjects  regarding hepatitis b virus dna in serum and peripheral blood mononuclear cell  71   5 of 7  of the patients with serum hepatitis b virus dna had this marker in peripheral blood mononuclear cell  whereas 52   12 of 23  of the patients without serum hepatitis b virus dna had hepatitis b virus dna in peripheral blood mononuclear cell  a southern blot analysis was also carried out on peripheral blood mononuclear cell samples from 30 patients  hepatitis b virus dna was detected in 16 patients as free forms  in 12 patients as dimers and free forms and as free circular together with free linear forms in the remaining two patients  
class6	association of autoimmune hepatitis with hla bw54 and dr4 in japanese patients  human leukocyte antigen d region related alleles  human leukocyte antigen dr and dq  and human leukocyte antigen class i alleles were typed serologically in 31 japanese patients with autoimmune hepatitis  these patients had increased serum levels of ast and igg  high titers of autoantibodies  no history of blood transfusion and were negative for hbsag and antibodies to hbc  three hundred eighty six healthy subjects and 30 patients with cryptogenic chronic hepatitis served as control groups  the frequency of dr4 was significantly higher in autoimmune hepatitis patients  90 3   than in healthy subjects  38 6   and in cryptogenic chronic hepatitis patients  30    the frequency of bw54 was significantly higher in autoimmune hepatitis patients  45 2   than in healthy subjects  10 9    the risk to dr4 positive subjects for autoimmune hepatitis was 14 8 relative to healthy subjects  two of 31 patients  6 5   with autoimmune hepatitis were positive for antibody to hepatitis c virus  both clearly satisfied criteria for autoimmune hepatitis and both had bw54 and dr4  this study revealed a highly significant association of autoimmune hepatitis with human leukocyte antigen bw54 and dr4 in japanese patients  among the dr4 positive patients with autoimmune hepatitis  no significant differences were seen between those positive or negative for bw54 with regard to clinical or laboratory data  relapse of disease or efficacy of prednisolone  thus human leukocyte antigen class ii alleles contribute to susceptibility and resistance to autoimmune hepatitis in japanese patients  with distinct racial differences from those in white patients  
class6	the human hepatic asialoglycoprotein receptor is a target antigen for liver infiltrating t cells in autoimmune chronic active hepatitis and primary biliary cirrhosis  autoantibodies to the human hepatic asialoglycoprotein receptor have been found in nearly 50  of the sera of patients with autoimmune chronic active hepatitis and in 15  of patients with primary biliary cirrhosis  in this study we demonstrate that the human hepatic asialoglycoprotein receptor is also a target antigen for t cell mediated immune responses  peripheral blood lymphocytes of 37   7 of 19  of patients with autoimmune chronic active hepatitis and 33   2 of 6  of patients with primary biliary cirrhosis showed a proliferative response to highly purified human hepatic asialoglycoprotein receptor  whereas no proliferation was found with peripheral blood lymphocytes of patients with chronic viral hepatitis  0 of 13  and healthy blood donors  0 of 4   moreover  we isolated t cell clones from liver biopsy samples of two patients with autoimmune chronic active hepatitis and two patients with peripheral blood lymphocytes  between 2 8  and 14 3  of these clones showed a specific proliferative response to purified human hepatic asialoglycoprotein receptor  the response was restricted to autologous antigen presenting cells and could be blocked by monoclonal antibodies against human leukocyte antigen dr molecules  the response of t cells to the human hepatic asialoglycoprotein receptor did not require the lectinlike activity of the asialoglycoprotein receptor  thus the human hepatic asialoglycoprotein receptor could be identified as a major target antigen of humoral and cellular immune reactions in autoimmune mediated liver diseases  
class6	decreased toxicity of polymorphonuclear neutrophils toward hepatocytes isolated from rats with acute inflammatory reaction  we have recently demonstrated that polymorphonuclear neutrophils were toxic to hepatocytes through a protease mediated mechanism  since synthesis of antiproteases is markedly increased during acute inflammatory reaction  the aim of this work was to investigate the toxicity of neutrophils against normal vs  inflammatory rat hepatocytes  acute inflammatory reaction was induced by subcutaneous injection of turpentine 24 hr before the experiments  hepatocytes from normal and turpentine treated rats were isolated by collagenase digestion  they were incubated with human neutrophils stimulated by 1 mg ml opsonized zymosan  cytotoxicity was quantified by the percentage of alanine aminotransferase activity released by hepatocytes in culture medium after an 18 hr incubation period  by comparison to normal hepatocytes  inflammatory hepatocytes were more resistant to the toxicity of neutrophils  at a neutrophil hepatocyte ratio of 20 1  the alanine aminotransferase activity releases were 53 7      5 4   mean     1 s e   and 27 4      4 8  for normal and inflammatory hepatocytes  respectively  similarly  inflammatory hepatocytes were found to be less sensitive than normal hepatocytes to the toxic effect of purified neutrophil cathepsin g  in contrast  both types of hepatocytes exhibited the same sensitivity to h2o2 generated by a system consisting of glucose and glucose oxidase  two arguments suggested that the resistance of inflammatory hepatocytes to protease toxicity was explained by an increased production of antiproteases by these cells   a  when tested against cathepsin g and porcine pancreatic elastase activities  the protease inhibitory capacity of conditioned medium from inflammatory hepatocytes was higher than that of conditioned medium from normal hepatocytes   b  conditioned medium from inflammatory hepatocytes markedly reduced the toxicity of stimulated neutrophils as that of cathepsin g  
class6	restoration of liver function in gunn rats without immunosuppression using transplanted microencapsulated hepatocytes  microencapsulation of cells within synthetic semipermeable membranes is a novel technique that enables the transplantation of cell cultures without the need for immunosuppression  we have previously shown that transplanted isolated encapsulated hepatocytes can provide sufficient short term metabolic support to improve the survival of animals with galactosamine induced fulminant hepatic failure  here we have demonstrated the feasibility of isolated encapsulated hepatocyte transplantation in providing long term metabolic liver support in gunn rats  gunn rats have a congenital inability to conjugate bilirubin and thus exhibit lifelong hyperbilirubinemia  we studied the feasibility of isolated encapsulated hepatocyte transplantation in restoring this specific liver function  free hepatocytes  isolated from male wistar rats  were microencapsulated with collagen within a trilayered sodium alginate poly l lysine sodium alginate membrane using techniques developed in our laboratory  a total of 45 gunn rats underwent intraperitoneal transplantation with free hepatocytes  5 x 10 7   isolated encapsulated hepatocytes  5 x 10 7   control  empty  microcapsules or no transplant  untreated controls   serum bilirubin levels were monitored daily for 10 days after transplantation  and subsequent weekly samples were obtained for up to 1 mo  microcapsules were studied by light and electron microscopy 1 mo after transplantation  during the first week after transplantation  the mean maximum reduction in serum bilirubin levels for the isolated encapsulated hepatocytes  free hepatocytes and control microcapsule transplanted groups was 45 7   18 6  and 14 3   respectively  for up to 1 mo thereafter the mean reduction in serum bilirubin levels in these respective groups was 34 8   13 5  and 3 3   
class6	normalization of ventilation perfusion relationships after liver transplantation in patients with decompensated cirrhosis  evidence for a hepatopulmonary syndrome  to examine the effect of liver transplantation on the respiratory and cardiovascular functions  ventilation perfusion relationships were determined by multiple inert gas elimination technique in six patients with end stage liver disease 1 to 19 mo before and 2 to 6 mo after liver transplantation  cardiac output and pulmonary vascular pressures were measured after catheterization of the pulmonary artery  all patients had normal spirometry and chest x ray films before transplantation  pao2 before transplantation was 78 8     7 4 mm hg  range   51 8 to 102 8 mm hg   all patients had perfusion of poorly ventilated lung regions  low ventilation perfusion relationships  varying from 3  to 19  of cardiac output  mean   8 5      2 4  of cardiac output  and two patients had intrapulmonary shunting  3  and 20  of cardiac output   measured and calculated pao2 agreed closely  indicating absence of pulmonary diffusion abnormality  as well as of extrapulmonary shunting  after transplantation  pao2 normalized in all patients  and both shunting and low ventilation perfusion relationships disappeared  cardiac output decreased from 9 1     1 4 to 6 6     0 5 l min  p less than 0 05   and the pulmonary vascular resistance increased from 0 69     0 14 to 1 64     0 43 mm hg l min  p less than 0 05   the systemic vascular resistance also increased  before   8 7     1 0  after   15 3     1 1 mm hg l min  p less than 0 001   normalization of respiratory and cardiovascular alterations  after liver transplantation  in patients with end stage liver disease indicates that these changes have a direct functional relationship to the diseased liver  it is hypothesized that this is part of a  hepatopulmonary syndrome   which in similarity to the hepatorenal syndrome disappears with improved liver function  
class6	differential regulation of liver p 450iii cytochromes in choline deficient rats  implications for the erythromycin breath test as a parameter of liver function  progressive liver fibrosis in rats develops when they are fed a diet deficient in choline  this diet also results in a pronounced and selective decrease in the liver microsomal content of a phase i drug metabolizing enzyme belonging to the cytochrome p 450iii gene family  because p 450iii cytochromes characteristically catalyze the n demethylation of erythromycin  we believed that the production of breath co2 from erythromycin would be dramatically reduced in choline deficient rats  however  when 12 choline deficient rats were compared with 9 control rats  the reduction in co2 production from erythromycin  mean decrease 71   was essentially identical to that from aminopyrine  mean decrease 69    a substrate believed to be metabolized normally by the hepatocyte in fibrotic liver disease  furthermore  we found that the relative erythromycin and aminopyrine demethylase activities were comparable when measured in vitro in liver microsomes prepared from the choline deficient rats  to determine the molecular basis for the erythromycin demethylase activity in the choline deficient rats  the liver microsomes were subjected to immunoblot analysis using a variety of polyclonal and monoclonal antibodies capable of distinguishing individual p 450iii related proteins  our studies confirm that a major erythromycin demethylase belonging to the p 450iii family  termed p 450p  was greatly reduced in the choline deficient rat liver  however  the specific concentration of a second p 450p related protein was essentially normal and that of a third p 450p related protein was actually increased in the choline deficient rat liver  
class6	attenuation of alcohol induced hepatic fibrosis by polyunsaturated lecithin  characteristic features of alcoholic liver injury include fibrosis and striking membrane alterations  with associated phospholipid changes  to offset some of these abnormalities  a 10 yr study was conducted in baboons  12 animals  eight females  four males  were fed a liquid diet supplemented with polyunsaturated lecithin  4 1 mg kcal  for up to 8 yr  with either ethanol  50  of total energy  or isocaloric carbohydrate  they were compared with another group of 18 baboons fed an equivalent amount of the same diet  with or without ethanol   but devoid of lecithin  in the two groups  comparable increases in lipids developed in the ethanol fed animals  but striking differences in the degree of fibrosis were seen  whereas at least septal fibrosis  with cirrhosis in two  and transformation of their lipocytes into transitional cells developed in seven of the nine baboons fed the regular diet with ethanol  septal fibrosis did not develop in any animals fed lecithin  p less than 0 005   they did not progress beyond the stage of perivenular fibrosis  sometimes associated with pericellular and perisinusoidal fibrosis  and had a significantly lesser activation of lipocytes to transitional cells  furthermore  when three of these animals were taken off lecithin  but continued on the same amount of the ethanol containing diet  they rapidly  within 18 to 21 mo  progressed to cirrhosis  accompanied by an increased transformation of their lipocytes to transitional cells  these results indicate that some component of lecithin exerts a protective action against the fibrogenic effects of ethanol  because we had previously found that choline  in amounts present in lecithin  has no comparable action  the polyunsaturated phospholipids themselves might be responsible for the protective effect  
class6	preventive therapy of first gastrointestinal bleeding in patients with cirrhosis  results of a controlled trial comparing propranolol  endoscopic sclerotherapy and placebo  propranolol and endoscopic sclerosis of esophageal varices are the two approaches currently used in prophylaxis of the first gastrointestinal hemorrhage in the cirrhotic patient  one hundred twenty six cirrhotic patients with esophageal varices and no histories of bleeding were included in the trial regardless of the gravity of the cirrhosis or the size of the esophageal varices  patients with hepatocarcinomas or other cancers  clearly impossible follow up  previous treatment for portal hypertension or contraindication to beta blockers were excluded  after randomization  43 patients received propranolol twice daily at a dose reducing the heart rate by 25   42 patients were treated with intravariceal and extravariceal injections of polidocanol  41 control patients received vitamin k orally as placebo  the patients were seen at 3 mo intervals for 2 yr  on entry to the trial the three groups were comparable in terms of clinical and biological parameters  including size of esophageal varices  grade i   51  grade ii   54  grade iii   17   child pugh classification  a   29  b   61  c   32  and the origin of cirrhosis  alcoholic in 79  of cases   twenty four patients bled  two bled in the propranolol group  nine bled in the endoscopic sclerosis of esophageal varices group and 13 bled in the placebo group   actuarial estimates  kaplan meier  of the time of onset of first bleeding showed that the differences were significant between propranolol and placebo  p less than 0 004  and between propranolol and sclerotherapy  p less than 0 03  but not between sclerotherapy and placebo  
class6	hepatitis b virus nucleocapsid pre s2 fusion proteins expressed in attenuated salmonella for oral vaccination  hybrid hbv nucleocapsid pre s 2  fusion proteins were stably expressed in several aromatic dependent attenuated salmonella typhimurium and salmonella dublin strains  when these live recombinant bacteria were administered i p  to balb c mice they induced high titer anti hepatitis b virus core ag  hbc  and detectable anti pre s2 serum antibodies  upon oral feeding of the recombinant salmonellae to mice  the rate of seroconversion to anti hbc was dependent on the salmonella strain used  with the best carrier strain high titer anti hbc antibodies and lower titer anti pre s2 serum igg antibodies were observed two weeks after a single oral immunization  the ig class and igg subclass distribution of anti hbc antibodies after i p  and oral immunization is consistent with the induction of functional t cell help  
class6	isolation and characterization of cdna encoding a human nuclear antigen predominantly recognized by autoantibodies from patients with primary biliary cirrhosis  autoantibodies to a novel nuclear ag  sp100  have recently been described that recognize a nuclear protein with an apparent molecular mass of 95 to 100 kda and a dot like distribution within cell nuclei  by immunoscreening of a lambda gt11 cdna expression library derived from hela cells with an anti sp100 autoimmune serum a 0 7 kb cdna  sp26  coding for a fragment of sp100 was isolated  expression of this cdna and use of the recombinant protein in elisa revealed that the fragment carries major sp100 autoepitopes and that anti sp100 autoantibodies predominantly occur in patients suffering from primary biliary cirrhosis  50 184   the sp26 cdna was used as hybridization probe for isolation of longer cdna from human liver  and placenta derived lambda gt10 cdna libraries  overlapping fragments were assembled to generate a full length cdna coding for a protein with a molecular mass of 53 kda and an isoelectric point of 4 7  the sp100 autoantigen expressed in vitro from this cdna and authenticated by a capture immunoblot assay  comigrated in sds page with the authentic hela autoantigen of 95 to 100 kda and thus showed an aberrant electrophoretic mobility  computer based protein sequence analysis of the sp100 autoantigen revealed regions of striking sequence similarities to the alpha 1 and alpha 2 domains of various human and non human mhc class i ag and to several transacting transcriptional regulatory proteins  
class6	cd8  t cell homing to the pancreas in the nonobese diabetic mouse is cd4  t cell dependent  the adoptive transfer of type i diabetes in nonobese diabetic mice requires the contribution of both cd4  and cd8  t cells  to further elucidate the cellular pathway s  of beta cell destruction and the responsibility of each subset  high doses of committed t cells from diabetic mice purified to single subsets  were injected into syngeneic nonobese diabetic neonates  the recipients of single or mixed subsets were followed for clinical manifestations of diabetes and examined at 30 days of age for in situ lesions  none of the animals injected with either cd4  or cd8  t cells became overtly diabetic during the 30 days of observation whereas 8 of 23 mice inoculated with a mixture of the two subsets developed glycosuria and hyperglycemia  however  insulitis was found in 6 of the 13 mice injected with cd4  t cells whereas only 1 of the 9 mice injected with cd8  t cells showed marginal infiltration of the pancreas  the lesions initiated by cd4  t cells alone were considerably less severe than those induced by the mixture of both subsets  corroborating the fact that overt disease did not occur in the former group  together  these results suggest a distinct function for each diabetogenic t cell subset  cd4  t cells  which have the capacity to home to the pancreas  promote in turn the influx of cd8  effector t cells that do not by themselves accumulate in this organ  these results illustrate a novel form of t t cell interactions leading to organ specific autoimmune lesions  
class6	evidence for the targeting by 2 oxo dehydrogenase enzymes in the t cell response of primary biliary cirrhosis  primary biliary cirrhosis  pbc  is a chronic autoimmune liver disease that includes the presence of lymphoid infiltrates in portal tracts  high titer autoantibodies against pyruvate dehydrogenase e2  pdh e2  and branched chain ketoacid dehydrogenase e2  bckd e2   and biliary tract destruction  the mechanism by which the autoimmune response is induced  the specificity of damage to the biliary epithelium  and the role of t cells in pbc are still unknown  to address these issues  we have taken advantage of a mouse mab  coined c355 1  and studied its reactivity against a panel of liver tissue from normal subjects as well as a panel of liver specimens from patients with pbc  progressive sclerosing cholangitis  and chronic active hepatitis  cah   c355 1  much like human autoantibodies to pdh e2  reacts exclusively by immunoblotting with pdh e2  binds to the inner lipoyl domain of the protein  and inhibits pdh e2 activity in vitro  in addition  we have also attempted to develop cloned t cell lines that react with pdh e2 and or bckd e2 using liver biopsies from patients with pbc  compared with cah  although monoclonal c355 1 produced typical mitochondrial fluorescence on sections of normal liver  pancreas  lung  heart  thyroid  and kidney  it produced a distinct and intense reactivity when used to stain the bile ducts of patients with pbc  nine of 13 pbc liver biopsies studied herein contained bile ducts on light microscopy  all of which reacted intensely at a 1 100 culture supernatant dilution of monoclonal c355 1  in contrast  although bile ducts of liver specimens from normals  cah  and progressive sclerosing cholangitis also reacted with c355 1  such reactivity was exclusively mitochondrial and readily detectable only at a dilution of 1 2  more importantly  we generated cd4   cd8   alpha beta tcr  cloned t cell lines from patients with pbc  but not from cah  that produced il 2 specifically in response to pdh e2 or bckd e2  
class6	pneumococcal pneumonia in a rat model of cirrhosis  effects of cirrhosis on pulmonary defense mechanisms against streptococcus pneumoniae  to study alterations in host defense mechanisms that enhance pneumococcal virulence  a model of streptococcus pneumoniae pneumonia was developed in cirrhotic rats  cirrhosis  with or without ascites  was produced in rats by intragastric administration of carbon tetrachloride  ccl4   histopathologic and laboratory studies demonstrated that ccl4 induced cirrhosis was similar to alcoholic cirrhosis in humans  cirrhotic rats were more susceptible to type 3 pneumococcal pneumonia induced by intratracheal challenge than controls  and the presence of ascites was associated with the lowest ld50  more cirrhotic rats with ascites had bacteremia and elevated levels of circulating capsular antigen after challenge compared with cirrhotic rats without ascites or controls  pulmonary clearance of pneumococci was markedly reduced in rats with cirrhosis and ascites and was associated with reduced serum complement levels  this model may be useful in further studies of the pathogenesis and therapy of pneumococcal infections in the compromised host  
class6	divergent efficacy of antibody to tumor necrosis factor alpha in intravascular and peritonitis models of sepsis  the role of tumor necrosis factor alpha  tnf alpha  in the lethal consequences of intravascular lipopolysaccharide  lps  or escherichia coli sepsis was compared with that in bacterial peritonitis  intravenous administration of e  coli lps or e  coli  live or dead  resulted in large transient increases in serum tnf alpha levels  peaking at 90 min at 10 000 30 000 units ml  in contrast  the serum tnf alpha response following the induction of bacterial peritonitis was substantially less  peaking at 200 500 units ml  sterile peritonitis  essentially nonlethal  and bacterial peritonitis  greater than 60  lethal  elevated tnf alpha levels to 1000 2000 units lavage within the peritoneal cavity 2 h after challenge  passive immunization with neutralizing goat anti tnf alpha igg improved survival from 8  to 75  in rats administered lps intravenously but was completely ineffective in protecting rats from lethal e  coli peritonitis  thus significant differences exist in the role tnf alpha plays in systemic intravascular models of sepsis and bacterial peritonitis  
class6	bismuth subsalicylate in the treatment of acute diarrhea in children  a clinical study  bismuth subsalicylate  bss  and placebo were evaluated in a double blind  placebo controlled study as adjunct to rehydration therapy in 123 children  aged 4 to 28 months  hospitalized with acute diarrhea  the dosing regimen was 20 mg kg five times daily for 5 days  significant benefits were noted in the bss group compared with placebo as manifested by decreases in stool frequency and stool weights and an improvement in stool consistency  significant improvement in clinical well being  and shortening of the disease duration  patients treated with bss had a significant reduction in duration of hospital stay  6 9 days  compared with placebo treated patients  8 5 days   also  intravenous fluid requirements decreased significantly more rapidly and to a greater degree in the bss treated group  bismuth subsalicylate was associated with clearance of pathogenic escherichia coli from the stools in 100  of cases but was not different from placebo in rotavirus elimination  bismuth subsalicylate was well tolerated with no reported adverse effects  blood bismuth and serum salicylate levels were well below levels considered toxic  in this study  bss provided effective adjunctive therapy for acute diarrhea  allowing children to get well sooner with less demand on the nursing and hospital staff  
class6	use and misuse of oral therapy for diarrhea  comparison of us practices with american academy of pediatrics recommendations  to determine how closely us pediatricians follow the 1985 american academy of pediatrics committee on nutrition s recommendations on oral therapy for acute diarrhea  a questionnaire was administered to four groups  new england private practitioners  pediatricians from 27 states attending a postgraduate course  representatives of departments of pediatrics at us schools of medicine  and housestaff at boston children s and massachusetts general hospitals  the responses from departments of pediatrics and housestaff were not significantly different from those of community practitioners in most categories  the reported rate of use of glucose electrolyte solutions recommended by the american academy of pediatrics was not different from the use of nonphysiologic  high osmolar  low salt solutions such as sodas and juices  the usage rate for glucose electrolyte solutions meeting the american academy of pediatrics recommended carbohydrate to sodium ratio of less than 2 1 was less than 30   other findings included the general lack of agreement on the use of a single type of therapy and the common use of oral therapy only for mild or no dehydration  although the american academy of pediatrics recommends that feeding be reintroduced in the first 24 hours of a diarrheal episode  the majority of respondents withhold feeding until the second day or later  these findings indicate that educational programs on oral therapy during acute diarrhea are needed in the united states  
class6	spontaneous aorto left renal vein fistula  the  abdominal pain  hematuria  silent left kidney  syndrome  spontaneous aorto left renal vein fistula  alrvf  is a rare occurrence  with this case  only 16 have been reported to date  common features in patients with alrvf include abdominal pain  81    hematuria  100    impaired renal function  85    and nonvisualization of the left kidney  100    less common but also present in the majority of cases are a left sided bruit  73    pulsatile abdominal mass  63    and proteinuria  50    also important  94  have a retroaortic left renal vein  unlike the six cases of traumatic alrvf that have been reported  this magnifies the diagnostic value of contrast abdominal computed tomographic scanning  which demonstrates not only the anomalous location of the left renal vein but also the abdominal aortic aneurysm and poor enhancement of the left kidney  these findings rule out the possibility of the  nutcracker syndrome   left renal vein compression between aorta and superior mesenteric artery   although confirming the presence of a fistula by early caval opacification  aortography does not always distinguish alrvf from the more common aortocaval fistula  this can be accomplished by duplex scanning with deep probes and even preferably color coding of velocity signals  with such precise preoperative localization  surgical repair is relatively easy and safe  
class6	adenomyomatosis of the gallbladder  a premalignant lesion  gallbladder cancer is the most common malignant tumor of the biliary tract  but its early diagnosis is uncommon  the use of ultrasonography has increased the detection of benign gallbladder tumors  and the premalignant potential of gallbladder adenomas is now undisputed  adenomyomatosis of the gallbladder has recently been suggested to have malignant potential  and we report a case of adenocarcinoma of the gallbladder occurring in localized adenomyomatosis that was successfully treated by radical curative surgery  the more rigorous use of ultrasonography and a more aggressive approach to  benign  polypoid lesions of the gallbladder may represent the best way of achieving early diagnosis and cure in gallbladder cancer  
class6	polyarteritis nodosa presenting as a biliary stricture  polyarteritis nodosa  a disease of the media of small and medium sized arteries  has protean manifestations and many presenting signs and symptoms  gastrointestinal involvement is common but involvement of the biliary tree is rare  we report a unique case of polyarteritis presenting as a biliary stricture  
class6	gastric duplication cyst communicating with the pancreatic duct  a rare cause of recurrent abdominal pain  a 41 year old woman with recurrent attacks of postprandial abdominal pain was found on endoscopic retrograde cholangiopancreatography and subsequent computed tomographic scan to have an enteric duplication within the substance of the pancreas with communication to the pancreatic duct  celiotomy demonstrated a noncontiguous gastric duplication cyst  internal drainage was curative  
class6	excipients in valproic acid syrup may cause diarrhea  a case report  a 5 year old child receiving valproic acid syrup for seizure control developed diarrhea probably from the excipient ingredients  each 5 ml of valproic acid syrup contains sucrose 3 g  glycerin 0 75 g  and sorbitol 0 75 g  providing daily amounts of 36  9  and 9 g of sucrose  glycerin  and sorbitol  respectively  the diarrhea resolved when the child was switched to another valproic acid product  clinicians should be aware of potential problems that may occur from excipient ingredients in pharmaceutical products when evaluating adverse effects of medications  
class6	the pharmacist as a health consultant  ten years later  pharmacists remain a readily accessible and trusted source of information about health  in order to assess the quality of counseling on health matters and the progress of the profession in this activity over the last decade  a study similar to one reported in 1978 was conducted  we visited 46 community pharmacies and requested advice from the pharmacists concerning the proper treatment of an infant with diarrhea  interviewers volunteered no additional information  but questions asked by the pharmacist were answered according to a predetermined hypothetical case involving an 18 month old infant with diarrhea and vomiting  findings include the following  approximately one third of the pharmacists recommended a product without caution and less than 20 percent inquired about fever  nausea  vomiting  diet  or the infant s condition  we believe pharmacists should approach health counseling with an increased awareness of the harmful potential in providing inappropriate medical information  
class6	warner lambert parke davis award lecture  pathobiology of the intestinal epithelial barrier  the major route of passive permeation across intestinal epithelia is paracellular  the intercellular tight junction lies in and serves as the rate limiting barrier in this paracellular pathway  once viewed as static  it is now clear that the structure and permeability of the tight junction is highly dynamic  not only may inflammatory events  cytokines  neutrophil transmigration  reversibly effect the tight junction but this key barrier also is regulated by physiologic events such as activation of absorptive cell na    nutrient cotransporters  such physiologic regulation of the junction is of major importance to the absorption of nutrients via parcellular solvent drag  
class6	reversibility of hepatic fibrosis in experimentally induced cholestasis in rat  the reversibility of hepatic fibrosis was investigated in an experimental model of extrahepatic cholestasis in the rat after common bile duct ligation for 2 weeks  followed by bilioduodenal anastomosis for 3 weeks  bile duct ligation resulted in a transitory marked elevation in the serum concentration of 5  nucleotidase  alkaline phosphatase  and bilirubin during the first 3 days  then these levels decreased to threefold  twofold  and 100 fold the normal values  respectively  during the following 4 weeks  histologic examination of the liver disclosed extensive bile duct proliferation and the formation of periportal fibrosis  with only slight inflammation and necrosis  the distribution of the major components of the hepatic extracellular matrix was analyzed 2 weeks after bile duct ligation  using the indirect immunoperoxidase method  fibrous septa were found to be strongly stained for collagens i  pro iii  iii and iv  fibronectin  and laminin  the most intense staining was found in enlarged periportal areas  collagen iv and laminin being particularly abundant around newly formed bile ducts  these changes paralleled high steady state levels of alpha 1 i  and alpha 1 iv  collagen and b2 chain laminin mrnas  relief of the obstruction for 2 weeks resulted in a shift in the serum concentration of 5  nucleotidase  alkaline phosphatase  and bilirubin toward normal values  a dramatic resorption of bile duct proliferations and periportal fibrosis were observed  three weeks after bile duct repermeabilization  immunohistochemical study showed that the pattern of distribution of extracellular matrix components was almost normal  except for collagen iv  which remained abundant in the sinusoids when compared with the normal liver  in parallel  the steady state b2 chain laminin mrna level became lower than in cholestatic livers  whereas alpha 1 i  and alpha 1 iv  mrnas were almost undetectable  these results show that hepatic fibrosis induced by experimental extrahepatic cholestasis in rat disappears in less than 3 weeks after relief of bile duct obstruction  suggesting that an active degradation of matrix protein occurs  except for collagen iv in the sinusoid  
class6	evidence for platelet activating factor as a late phase mediator of chronic pancreatitis in the rat  the role of platelet activating factor  paf  as a mediator of pancreatic inflammation was examined in the rat pancreatic duct ligation model of obstructive pancreatitis  pancreatic generation of paf  as measured by bioassay  ie  platelet  3h serotonin secretion   was determined at various times after induction of inflammation  tissue levels of paf in the normal pancreas averaged 600     49 pg g  but paf was not detectable during the initial 24 hours of pancreatitis  a time when the inflammatory reaction would be considered acute  that is  during the period of maximal serum amylase release and the development of interstitial edema  however a substantial increase in pancreatic paf levels  12 times control levels  was observed 7 to 14 days after duct ligation during the late phase response interval similar to the situation characteristic of chronic pancreatitis in which parenchymal atrophy  fibrosis  and pancreatic insufficiency evolve  one week after duct ligation when paf levels peaked  an evaluation was made of the effects of paf antagonists  bn52021 and web2170  on pancreatic lesions using evan s blue extravasation  pancreatic myeloperoxidase  mpo  activity  and acid phosphatase activity in peritoneal lavage fluid  bn52021 or web2170 treatment was shown to reduce pancreatic damage and inflammation significantly  long term in vivo administration of exogenous paf  20 micrograms kg hr for 7 days  exhibited a reduction of  3h thymidine uptake into and amylase release from pancreatic acini in vitro  our observations 1  that pancreatic paf levels increased significantly during the chronic phase of obstructive pancreatitis induced by duct ligation  2  that inhibition of the action of paf  through specific receptor antagonism  caused an attenuation of pancreatic lesions  and 3  that chronic administration of paf resulted in decreased pancreatic regeneration and exocrine function are consistent with a pivotal role for paf as a late phase inflammatory mediator in chronic pancreatitis in rats  
class6	clinical features of misdiagnosed appendicitis in children  study objective  to compare clinical features of children with misdiagnosed appendicitis with those of children with appendicitis initially diagnosed correctly  design  retrospective review of hospital  emergency department  and clinic records  setting  university medical center with annual ed census of 40 000 patients  participants  children less than 13 years old admitted between may 1  1979  and april 30  1989  with a discharge diagnosis of appendicitis  measurements  records were reviewed for historical  physical examination  laboratory  and pathologic features for all patients on their initial presentation to a physician and on final presentation during which the correct diagnosis was made  using chi 2 analysis and student s test  clinical features of misdiagnosed patients and patients diagnosed correctly were compared  results  one hundred eighty one cases were identified with 50 initially misdiagnosed  on initial presentation  misdiagnosed patients were younger and more likely to have vomiting before pain onset  constipation  diarrhea  dysuria  and signs and symptoms of upper respiratory infections  misdiagnosed cases were less likely to have right lower quadrant tenderness and documentation of bowel sounds  peritoneal signs  and rectal examinations  on final presentation  misdiagnosed patients were more likely to have pain duration of more than two days  temperature of more than 38 3 c  and to appear lethargic and irritable  p less than  05 for all measurements   conclusion  clinical features of children with misdiagnosed appendicitis differ from those of children with appendicitis initially diagnosed correctly  
class6	omeprazole enhances the efficacy of pancreatin  pancrease  in cystic fibrosis  we studied the effect of the addition of omeprazole  20 mg once a day  to treatment with pancreatin  pancrease  cilag  herentals  belgium   two or four capsules three times a day  on fecal fat excretion in a double blind  crossover fashion in nine patients with cystic fibrosis having persistent steatorrhea while taking pancrease  two capsules three times a day  mean fecal fat excretion  22 3   range  12  to 44    neither doubling of the dose of pancrease nor addition of omeprazole to the lower dose of pancrease significantly reduced fecal fat excretion  mean  19 6   range  10  to 34    mean  16 4   range  6  to 32    respectively   however  addition of omeprazole to the higher dose of pancrease  four capsules three times a day  significantly reduced fecal fat excretion when compared with the two doses of pancrease alone  mean  10 7   range  4  to 25   p less than 0 01   we conclude that adjunct therapy with omeprazole reduces fecal fat excretion in cystic fibrosis provided that a high dose of pancrease is supplied  
class6	seronegative juvenile rheumatoid arthritis and mast cell associated gastritis  we describe 4 children with seronegative inflammatory arthritis who had persistent  severe nausea and abdominal pain over several months  in spite of vigorous medical therapy  including antacids and histamine h2 receptor antagonists  endoscopy and biopsy of gastric and duodenal mucosa showed antral gastritis and an increased number of mast cells in 3 of the 4 patients  in the fourth patient  urinary histamine levels were elevated  these findings suggest an association between inflammatory arthritis and localized mast cell disease in some individuals  further studies are needed to determine whether this association represents an independent syndrome or whether mast cell related disease is secondary to long term treatment with nonsteroidal antiinflammatory drugs in children with mild arthritis  
class6	induction of arthritis in rats by aqueous suspensions of mycobacteria without the use of oil  we report for the first time the induction of arthritis by an aqueous  rather than an oil  suspension of killed tubercle bacilli  this was accomplished in the highly susceptible dark agouti strain of rats  by intraperitoneal injection during the healing phase of chemically induced peritonitis  the same procedure  injection after the induction of peritonitis  augmented the incidence of arthritis produced by bovine type ii collagen and freund s complete adjuvant  enhanced delivery of antigen from the peritoneal cavity to regional lymph nodes in the postinflammatory state was responsible for this increase in the induction of arthritis  
class6	risk factors for transmission of hepatitis b virus to gambian children  published erratum appears in lancet 1990 dec 22 29 336 8730  1596  risk factors for hepatitis b virus transmission were examined in 973 gambian children aged 6 months to 5 years  33  had evidence of infection with hepatitis b virus and a third of these were carriers  a significant association was found between infection and tropical ulcer scars  and between e antigenaemia and the presence of bedbugs in each child s bed  there was no association between infection and traditional scarring  circumcision  or injections  skin disease and arthropods are the two most likely modes of transmission of hepatitis b virus between children in west africa  
class6	effect of tetrahydroaminoacridine on cognition  function and behaviour in alzheimer s disease  objective  to determine the efficacy of tetrahydroaminoacridine  tha  in alzheimer s disease  design  randomized  double blind  multiple crossover trial with three treatment periods  each consisting of 3 weeks of active drug therapy and 3 weeks of placebo administration  setting  referral based geriatric practice in a community hospital  patients  thirty four patients with moderate to severe alzheimer s disease  subjects were included if they had stage 3 to 6 disease  as determined by the reisberg scale  and had not been taking psychotropic drugs for at least 1 month and if informed consent had been obtained from the patients and their next of kin  interventions  fifty to 100 mg of tha daily and matched placebo  results  of the initial 34 patients 14 experienced liver toxicity and 3 gastrointestinal side effects during the study  however  all 22 who completed the study were able to tolerate at least the minimum dose  for the 22 patients there was no clinically or statistically significant effect of tha on cognition  functional status or behaviour  the results for individual patients showed no subgroup of tha responsive patients  conclusion  tha has no clinically important benefits in alzheimer s disease and is associated with appreciable toxic effects  
class6	diagnosis of campylobacter pylori gastritis  campylobacter pylori is a bacterium that inhabits gastric mucosa  it causes chronic active gastritis and is highly associated with duodenal ulcer  campylobacter pylori has a urease enzyme  not present in man   which allows diagnosis by a  14c urea breath test  we compared two noninvasive tests  the breath test and serum elisa  to biopsy and histologic diagnosis  twenty two patients who underwent gastroduodenoscopy for evaluation of possible peptic ulcer disease entered the study  the breath test detected the organism in eight of eight patients biopsy positive for the organism  sensitivity 100    the breath test was negative in 12 of the 14 patients who were biopsy negative  specificity 86    the elisa was performed in 14 patients  it was positive in 5 of 5 patients biopsy positive for the organism  sensitivity 100   and negative in 7 of 9 patients who were biopsy negative  specificity 78    we conclude that both the elisa and the  14c urea breath test are excellent noninvasive methods to detect campylobacter pylori  however  only the breath test is suitable for following the response to treatment  as it detects the presence of the organism rather than an immune response to it  
class6	zollinger ellison syndrome  relation to helicobacter pylori associated chronic gastritis and gastric acid secretion  since helicobacter pylori infects the gastric mucosa in most patients with chronic duodenal ulcer  infection with this organism has been implicated in the pathogenesis of this common disease  we postulated that if h  pylori is pathogenic in the usual type of duodenal ulcer  it should be less common when duodenal ulcer has another  specific etiology  such as zollinger ellison syndrome  gastric mucosa was compared from 18 patients with proven zollinger ellison syndrome  17 of whom had had duodenal ulcer disease  and 18 controls with chronic duodenal ulcer without such a diagnosis  all subjects  who were matched for age and sex  had undergone elective gastric resections  gastric tissues were stained by hematoxylin eosin and giemsa and were reviewed by an experienced pathologist who was unaware of the diagnosis  the frequency of h  pylori in patients with zollinger ellison syndrome  8 18  was lower than in controls with duodenal ulcer  16 18  p less than 0 02   moreover  chronic antral gastritis scores were higher in patients with duodenal ulcer  p less than 0 01   in zollinger ellison syndrome  peak acid output was lower in patients positive  median 22 meq 30 min  compared to those negative for h  pylori  median 32 meq 30 min  p less than 0 02  but serum gastrin was correspondingly lower in patients positive for h  pylori  p less than 0 05   h  pylori infection appears to be more frequent when duodenal ulceration is not associated with another etiology  such as acid hypersecretion in zollinger ellison syndrome  h  pylori infection in zollinger ellison syndrome may also be associated with decreased gastric acid secretion  
class6	radiation induced proctosigmoiditis  prospective  randomized  double blind controlled trial of oral sulfasalazine plus rectal steroids versus rectal sucralfate  in a prospective study  37 consecutive patients with radiation induced proctosigmoiditis were randomized to receive a four week course of either 3 0 g oral sulfasalazine plus 20 mg twice daily rectal prednisolone enemas  group i  n   18  or 2 0 g twice daily rectal sucralfate enemas plus oral placebo  group ii  n   19   the two groups were comparable with respect to demographic features  duration of symptoms  and clinical and endoscopic staging of the disease  fifteen patients in group i and 17 in group ii completed the trial  at four weeks  both groups showed significant clinical improvement  p less than 0 01 for group i and p less than 0 001 for group ii  and endoscopic healing  p less than 0 01 for group i and p less than 0 001 for group ii   when the two groups were compared  sucralfate enemas showed a significantly better response as assessed clinically  p less than 0 05   although endoscopically the response was not statistically different  p greater than 0 05   we conclude that both treatment regimens are effective in the management of radiation proctitis  sucralfate enemas give a better clinical response  are tolerated better  and because of the lower cost should be the preferred mode of short term treatment  
class6	primary cytomegalovirus infection and gastric ulcers in normal host  a 42 year old woman presented with epigastric pain and vomiting  upper gastrointestinal endoscopy revealed three gastric ulcers  histologic examination of biopsies from the ulcers showed cytomegalovirus inclusion bodies  the appearance of igm antibodies to cytomegalovirus indicated a recent and primary infection  stored serum from her last pregnancy 17 months previously contained no cytomegalovirus antibodies  a thorough evaluation of her immune system revealed no abnormality  we are aware of only two other cases where seroconversion was documented in normal hosts  cytomegalovirus infections in the gastrointestinal tract of normal hosts are very unusual but a common cause of morbidity in immunocompromised hosts  we believe that cytomegalovirus may have a role in the pathogenesis of gastrointestinal lesions in nonimmunocompromised patients  
class6	helicobacter pylori and zollinger ellison syndrome  helicobacter pylori  previously campylobacter pylori  is almost invariably associated with chronic duodenal ulcer disease  the relationship between h  pylori infection and duodenal ulcer in zollinger ellison syndrome is unknown  we investigated the frequency of h  pylori infection in zollinger ellison syndrome and also what effect h  pylori infection had on gastric function in patients with zollinger ellison syndrome  h  pylori infection was diagnosed based on a specific serologic  elisa  assay based on high molecular weight cell associated proteins of h  pylori  we studied 20 patients with zollinger ellison syndrome  15 men and 5 women ranging in age from 24 to 71 years  median age 51  six zollinger ellison syndrome patients had h  pylori infection compared to 100 consecutive patients with chronic recurrent duodenal ulcer disease  p less than 0 05   pretreatment basal acid output in zollinger ellison syndrome patients ranged from 7 9 to 95 0 mmol hr  median 35 2  pentagastrin stimulated maximal acid output ranged from 8 5 to 132 mmol hr  median 52 7  acid secretion was lower in the h  pylori infected patients than the uninfected patients  bao 24 5     6 5 vs 45 4     6 6  and mao 44 3     11 8 vs 67 9     10 7  for h  pylori infected vs uninfected patients  respectively   the difference in bao was statistically significant  p less than 0 05   the present results indicate that h  pylori is not a major contributing factor in duodenal ulcer associated with zollinger ellison syndrome  the association of a reduced bao with h  pylori suggests that these findings may be related  
class6	peptic ulcer perforation as the presentation of zollinger ellison syndrome  we examined the characteristics of patients with zollinger ellison syndrome who developed a perforation prior to diagnosis to determine whether any clinical features were useful markers of the syndrome  of 160 patients with zollinger ellison syndrome  perforation occurred prior to the diagnosis being made in 11  7    at surgery  perforations were found in the duodenum in six cases and in the jejunum in five  in no case was tumor identified at emergency surgery  and the diagnosis of zollinger ellison syndrome was made only in the postoperative period when excessive gastric secretions were noted  neither acid output nor serum gastrin concentration were useful predictors for perforation  the patients  six men and five women  were 27 61 years old  median 48  and one had men 1  three patients had no symptoms prior to the perforation  the other eight had symptoms for 1 15 years  with diarrhea occurring in 45  of the cases  following the diagnosis of zollinger ellison syndrome  patients were given medication to control gastric acid hypersecretion  eight patients remained well  but the three patients who had had a partial gastrectomy had a complicated course despite medical therapy  although features of perforation in zollinger ellison syndrome are not specific  jejunal perforation or perforation associated with a history of diarrhea is suggestive of the diagnosis  serum gastrin should be measured in every case and a partial gastrectomy avoided  
class6	helicobacter pylori and gastric acid output in peptic ulcer disease  helicobacter pylori is associated with peptic ulcer  and a causal relationship has been postulated  we investigated the association between helicobacter pylori and gastric acid output  two hundred forty one patients were studied  173 with duodenal ulcer  51 with gastric ulcer  41 corpus  10 prepyloric   and 17 with combined gastric and duodenal ulcer  in 194 patients  80    helicobacter pylori could be demonstrated histologically from gastric antral biopsies  the presence or absence of helicobacter pylori was not influenced by age  sex  or use of tobacco or analgesics  patients with duodenal ulcer or combined gastric and duodenal ulcer had similar gastric acid outputs irrespective of the presence or absence of helicobacter pylori  however  gastric ulcer patients with helicobacter had higher basal and maximal acid outputs when compared to patients without helicobacter  mean basal output  4 1 mmol hr vs 2 4  p less than 0 05  mean maximal output 19 5 mmol hr vs  14 4  p less than 0 05   although helicobacter pylori is associated with both gastric ulcer and duodenal ulcer  its significance may be different in the two diseases  
class6	bowel dysfunction in fibromyalgia syndrome  fibromyalgia and irritable bowel syndrome frequently coexist  in this study  we utilized a previously validated self administered questionnaire to assess the prevalence of symptoms of bowel dysfunction and irritable bowel syndrome in 123 patients with fibromyalgia as compared to 54 patients with degenerative joint disease  djd  and 46 normal controls  ninety  73   of the fibromyalgia patients reported altered bowel function as compared to 20  37   djd patients and none of the normal controls  p less than 0 001   ninety nine patients  81   reported normal alternating with irregular bowel pattern  and 77  63   had alternating diarrhea and constipation  in contrast  only 24  44   of djd patients and six  13   of controls had regular alternating with irregular bowel pattern and only 12  22   of the djd patients and none of the healthy controls had alternating constipation and diarrhea  p less than 0 01   other bowel dysfunction complaints noted in the fibromyalgia group were abdominal gas  59    nausea  21    diarrhea  9    and constipation  12    seventy nine  64   fibromyalgia patients reported frequent abdominal pain that was stress related 47  of the time  laxative use was frequent in the fibromyalgia group  19   and absent in the other two groups  fifty percent of fibromyalgia patients  compared to 28  of djd patients  felt that their bowel complaints were worse during exacerbations of their joint disease  p less than 0 05   in conclusion  patients with fibromyalgia have a high prevalence of gastrointestinal complaints that should be carefully assessed  if the diagnosis of ibs is confirmed  appropriate treatment may improve patients  symptoms  although this approach requires further study  
class6	scintigraphic assessment of leukocyte infiltration in acute pancreatitis using technetium 99m hexamethyl propylene amine oxine as leukocyte label  the infiltration of leukocytes has been linked to the pathophysiology of complicated or severe pancreatitis  we have tested the ability of leukocyte scintigraphy using technetium 99m hexamethyl propylene amine oxine  hm pao  as label to demonstrate the localization of leukocytes in the pancreas during acute pancreatitis  twenty eight patients with acute pancreatitis  eight with biliary  13 with alcoholic  and seven with unknown origin  were studied with leukocyte scintigraphy using planar imaging and single photon emission computed tomography  spect   fourteen patients had a mild  group i   ii a severe  group ii   and three a lethal outcome  group iii  of pancreatitis  all patients of group iii  six of group ii  and two of group i had a positive leukocyte scan  thus  the sensitivity of leukocyte scintigraphy for the detection of a lethal course of acute pancreatitis was 100   of a severe course 54   and of a severe or lethal course 64   the specificity of a negative scan for a mild pancreatitis was 86   comparison of the results of leukocyte scintigraphy with those of contrast enhanced ct showed that six of eight patients with pancreatic necrosis in ct had a positive leukocyte scan  but only five of 20 patients without detectable pancreatic necrosis in ct  in summary  leukocyte infiltration into the pancreas during pancreatitis can be demonstrated by noninvasive leukocyte scintigraphy using technetium 99m hm pao as label  a correlation between the severity of the disease and leukocyte infiltration exists  
class6	pressure measurements from biliary and pancreatic segments of sphincter of oddi  comparison between patients with functional abdominal pain  biliary  or pancreatic disease  using a minimally compliant infusion system and a triple lumen pressure recording catheter  we obtained endoscopic manometric measurements from both the common bile duct and pancreatic duct segments of the sphincter of oddi  so  in 58 patients  fifteen patients  ages 27 69  had the diagnosis of functional abdominal pain  19 patients  ages 30 76  had partial biliary obstruction  and 24 patients  ages 15 80  had idiopathic acute recurrent pancreatitis  resting ductal pressure was similar in the common bile duct and pancreatic duct in all patient groups  in the group with functional pain  basal so pressure was similar  whether obtained from the common bile duct or pancreatic duct sphincteric segment  eight of 19 patients with partial biliary obstruction had elevated basal so pressure  five of these eight patients had elevated basal so pressure confined exclusively to the common bile duct segment of the sphincter  while three patients had elevated basal so in both segments  conversely seven of 24 patients with acute recurrent pancreatitis had an elevated basal so pressure  with five patients having pressure elevation only in the pancreatic duct segment while two patients had abnormal basal so pressure in both segments  we conclude that selective cannulation of the common bile duct and or the pancreatic duct during manometric study of the so is necessary in order to diagnose segmental so dysfunction responsible for partial biliary obstruction or episodes of acute recurrent pancreatitis  
class6	penetration of lanthanum through the main pancreatic duct epithelium in cats following exposure to infected human bile  the main pancreatic duct epithelium acts as a barrier to the diffusion of molecules from the duct lumen into pancreatic acinar and interstitial tissue  we studied sequential ultrastructural characteristics of the loss of epithelial barrier function in the cat using lanthanum  an electron opaque tracer  following perfusion of the duct from the tail to the duodenum with infected human bile  tight junctions between duct epithelial cells were found to become permeable to the tracer as early as after 15 min of exposure  later  there was progressive disintegration of intercellular junctions and epithelial loss  lanthanum penetrated the duct epithelium exclusively on an intercellular path  loss of barrier function of the pancreatic duct epithelium was consistently associated with subsequent development of acute interstitial edematous pancreatitis  there was no association between the degree of duct epithelial damage and the severity of acute pancreatitis  both bile and a suspension of bacteria alone were not harmful to the pancreas  sequential perfusion produced acute pancreatitis only when at first bile and then the bacterial suspension was perfused  a reversed succession of perfusates produced no morphologic alterations  we conclude   1  increased tight junction permeability is an early lesion in acute bile induced pancreatitis   2  loss of duct epithelial barrier function is important for the initiation but not for the severity of the inflammation  and  3  bile renders duct epithelial intercellular junctions vulnerable to escherichia coli bacteria  
class6	noninvasive measurement of portal venous blood flow in patients with cirrhosis  effects of physiological and pharmacological stimuli  the present study aims to evaluate the usefulness of combined pulse doppler real time ultrasonography as a noninvasive method for the measurement of portal blood flow in man  this measurement technique was performed on 12 healthy subjects and 20 patients with portal hypertension  ten patients  group 1  were evaluated prior to and after ingestion of a standard meal  ensure plus  or placebo  in the remaining 10 patients  group 2   the effects of isosorbide dinitrate  5 mg sl  administration or placebo were studied  in group 1  food intake caused a significant increase of portal blood flow  from 1038     539 to 1572     759 ml min  p less than 0 02   this effect was due to a significant rise in mean blood velocity  from 18 5     3 7 to 23 9     3 9 cm sec  p less than 0 02   in group 2  isosorbide dinitrate significantly reduced portal blood flow  from 985     491 to 625     355 ml min  p less than 0 05   a significant decline of mean blood velocity  from 18 8     4 5 to 14 5     2 5 cm sec  p less than 0 02  was observed  placebo administration had no significant hemodynamic effects in either group  our results suggest that doppler measurements gave accurate noninvasive estimations of portal blood flow and that this technique may be used to monitor physiological and pharmological stimuli in patients with portal hypertension  
class6	ulcerative proctitis in central sweden 1965 1983  a population based epidemiological study  ulcerative proctitis has by tradition been regarded as a subgroup of ulcerative colitis  population based epidemiological studies of ulcerative proctitis are  however  virtually nonexistent  in an epidemiological study of inflammatory bowel disease in the uppsala health care region  1065 cases of ulcerative proctitis were diagnosed from 1965 through 1983  males predominated  with the male to female ratio 1 4 1  annual incidence rates were higher in urban than in rural areas  the annual incidence rates increased threefold from 2 8 per 10 5  to 6 6 per 10 5  during the period  affecting all age groups over 14 years of age  in both urban and rural areas and in both sexes  differences in temporal trends and certain other epidemiological characteristics between ulcerative proctitis and extensive ulcerative colitis suggest that ulcerative proctitis is a specific disease whose etiology differs from that of extensive ulcerative colitis  
class6	metabolic and health complications of obesity  overnutrition manifested by obesity has emerged as a major health problem in affluent countries  in spite of increased interest in fitness  obesity is on the increase in the united states  this is particularly so among children and adolescents  although obesity is associated with many risk factors for diseases  the mechanisms whereby it enhances disease risk are not fully understood  such an understanding is needed to develop strategies for management of these conditions  in this report we suggest that overnutrition produces clinical diseases only in individuals who already possess a metabolic weakness or  defect  in a given system  in the absence of such underlying defects  overnutrition  or obesity  is well tolerated  one of the most common consequences of obesity is dyslipidemia  that is  elevations of very low density lipoprotein  vldl  triglycerides and low density lipoprotein  ldl  cholesterol and low concentrations of high density lipoprotein  hdl  cholesterol  the major effect of overnutrition on lipoprotein metabolism is to stimulate the production of vldl  for patients who have an underlying defect in lypolysis of vldl triglycerides  hypertriglyceridemia will develop in the obese state  for those who have defective clearance of ldl  obesity will accentuate hypercholesterolemia  both of these effects can be explained by overproduction of vldl  due to obesity  combined with a genetic defect in clearance of vldl or ldl  the mechanism whereby obesity causes a lowering of hdl cholesterol is uncertain  although it could enhance removal of hdl by an excess of adipose tissue  another disease associated with obesity is cholesterol gallstones  the presence of obesity more than doubles the risk for gallstones  two underlying factors increase the danger for gallstones  a deficiency of hepatic secretion of bile acids and a tendency for formation of cholesterol crystals in bile  overnutrition promotes the synthesis of whole body cholesterol  and the only route for excretion of this excess cholesterol is through the biliary tree  abstract truncated at 400 words   
class6	proximal esophageal ph metry in patients with  reflux laryngitis   fiberoptic laryngoscopic examinations were performed on 40 patients with gastroesophageal reflux disease  25 of whom had persistent laryngeal symptoms  dysphonia  cough  globus sensation  frequent throat clearing  or sore throat  and 15 without laryngeal symptoms who served as disease controls  ten patients with laryngeal symptoms but none of the controls had laryngoscopic findings consistent with reflux laryngitis  dual site ambulatory ph recordings were obtained with the ph electrodes spaced 15 cm apart and with the proximal sensor positioned just distal to the upper esophageal sphincter  patients in the three groups  disease controls  group 1  patients with symptoms but without laryngoscopic findings  group 2  and patients with both laryngeal symptoms and findings  group 3  were comparable in terms of age  smoking habit  the presence of esophagitis  and distal esophageal acid exposure  proximal esophageal acid exposure was  however  significantly increased in groups 2 and 3  and nocturnal proximal esophageal acidification occurred in over half of these patients but in none of the group 1 patients  we conclude that the subset of reflux patients who experience laryngeal symptoms show significantly more proximal esophageal acid exposure  especially nocturnally  and often have laryngoscopic findings of posterior laryngitis not observed in control reflux patients  
class6	helicobacter pylori infection in pernicious anemia  a prospective controlled study  although some authors believe that helicobacter pylori is the etiologic agent in chronic nonspecific gastritis  it has also been suggested that the bacterium colonizes inflamed mucosa as a secondary event  this study documents the prevalence of h  pylori in 28 patients with pernicious anemia and compares the findings with those of a group of 28 age   race   and sex matched asymptomatic control subjects  all subjects underwent endoscopy with biopsy of the gastric antrum and corpus  a sample of serum was obtained before endoscopy for determination of antibodies  immunoglobulin a and immunoglobulin g  to h  pylori  the prevalence of h  pylori  by biopsy  in patients with pernicious anemia was significantly less than that in controls  11  vs  71   p less than 0 0001   all patients with pernicious anemia had abnormalities of corpus histology  inflammation and or atrophy   in addition  50  of patients with pernicious anemia had a lymphocytic infiltration of the antrum  all controls with h  pylori had gastritis  50  having active chronic gastritis  atrophic changes of the corpus were more commonly found in patients with pernicious anemia  75  vs  7   p less than 0 0001   serology and biopsy results correlated poorly in the patients with pernicious anemia  all 5 patients with positive serology results had negative biopsy results  whereas all 3 patients with positive cultures on biopsy had negative serological studies  in conclusion  patients with pernicious anemia are protected from infection with h  pylori  and h  pylori does not passively colonize mucosa inflamed by an unrelated process  
class6	the epidemiology of inflammatory bowel disease  a large  population based study in sweden  previous population based incidence studies of inflammatory bowel disease are limited by small numbers  short duration  or inadequate case finding  to address these problems  we identified all persons with confirmed ulcerative colitis  n   2509  or crohn s disease  n   1469  in the uppsala health care region from 1965 to 1983  age specific incidence rates by sex were slightly greater for males with ulcerative colitis and females with crohn s disease  incidence rates for ulcerative colitis and crohn s disease were higher in urban than rural areas  the annual incidence rate of ulcerative colitis increased from less than 7 per 100 000 to more than 12 per 100 000 during the study period  while the rate for crohn s disease remained between 5 and 7 per 100 000  the increase in the incidence of ulcerative colitis was the result of a marked increase in the number of patients with ulcerative proctitis  analyses by 5 year birth cohorts suggest that those born from 1945 through 1954 were at higher risk for ulcerative colitis and crohn s disease  and that this effect was accounted for by those born in the first half of the year  the seasonality in the cohort effect  combined with the urban preponderance of disease  suggests that environmental causes may be involved in ulcerative colitis and crohn s disease  
class6	induction of ps2 and hsp genes as markers of mucosal ulceration of the digestive tract  the recently discovered ps2 protein is expressed under estrogen control in a subset of estrogen receptor positive breast cancers and in an estrogen independent manner in normal stomach mucosa  the ps2 gene belongs to a family of genes encoding peptides that contain a conserved 5 cysteine domain  the p domains  although the function of the ps2 protein is unknown  it has been suggested that it may have cell growth stimulatory activity  we report here that expression of the ps2 gene in the digestive tract  which is normally restricted to the stomach  is strongly induced by mucosal ulcerations elsewhere in the tract  most notably in crohn s disease  ps2 gene expression is restricted to the mucosal layers adjacent to the ulcerations  in a region where a novel epidermal growth factor secreting cell lineage was shown to be induced by mucosal ulceration  the human hsp gene  which contains a tandem duplication of the ps2 gene p domain and is coexpressed with the ps2 gene in normal stomach mucosa but not in breast cancers  is also expressed in crohn s disease  we suggest that ps2 gene expression may provide a useful marker for mucosal ulcerations of the digestive tract  
class6	colonic glycoproteins in monozygotic twins with inflammatory bowel disease  colonic glycoprotein composition was evaluated in monozygotic twins with inflammatory bowel disease using ion exchange chromatography  fifty three individuals  12 pairs and 1 single twin with ulcerative colitis and 14 pairs with crohn s disease  were evaluated  seven twin pairs were concordant for the presence of ulcerative colitis or crohn s disease  whereas twin siblings of 10 ulcerative colitis probands and 9 crohn s disease probands were not known to have inflammatory bowel disease  content of one chromatographically defined component of colonic mucin  designated hcm species iv  was reduced in both patients with ulcerative colitis  1040     300 cpm 10 000 cpm total hcm  and their apparently healthy twins  1340     540 cpm 10 000 cpm total hcm  compared with control subjects  4030     1 000 cpm 10 000 cpm total hcm   composition of mucin in crohn s disease patients and their nonaffected twins was not significantly different than in controls  these observations suggest that altered profiles of mucin glycoprotein may be present before the onset of ulcerative colitis and may be genetically defined  conversely  it appears that alterations in glycoproteins only are not sufficient to initiate mucosal inflammation  
class6	a controlled trial of psychological treatment for the irritable bowel syndrome  one hundred two patients with irritable bowel syndrome were studied in a controlled trial of psychological treatment involving psychotherapy  relaxation  and standard medical treatment compared with standard medical treatment alone  patients were only selected if their symptoms had not improved with standard medical treatment over the previous 6 months  at 3 months  the treatment group showed significantly greater improvement than the controls on both gastroenterologists  and patients  ratings of diarrhea and abdominal pain  but constipation changed little  good prognostic factors included overt psychiatric symptoms and intermittent pain exacerbated by stress  whereas those with constant abdominal pain were helped little by this treatment  this study has demonstrated that psychological treatment is feasible and effective in two thirds of those patients with irritable bowel syndrome who do not respond to standard medical treatment  
class6	multifocal colitis associated with an epidemic of chronic diarrhea  an outbreak of a chronic diarrheal syndrome was detected between may and august 1987 in rural henderson county  illinois  seventy two individuals were affected  epidemiological studies performed by the center for disease control implicated the water of a local restaurant as the source of the outbreak  five patients underwent a comprehensive evaluation  their mean age was 51 years  and they had a mean of 12 watery stools daily  range  6 40   detailed microbiological evaluations failed to identify a pathological organism  stool studies showed a mean stool weight of 392 g 24 h with a normal fat content  results of all biochemical studies of serum were normal  chemical analysis of stool water suggested a secretory diarrhea  colonoscopy revealed patchy erythema  and light microscopic examination of colonic biopsy specimens revealed multifocal areas of acute inflammation in the superficial mucosa in 4 of 5 patients  electron microscopy of the affected areas revealed no viral particles  after 2 years  all of our patients continued to experience chronic diarrhea  one patient agreed to a follow up colonoscopy  histological abnormalities of the colonic mucosa persisted after 2 years  we speculate that an infectious process arising from a contaminated water system induced a chronic  secretory diarrhea characterized by multifocal colitis  this histological abnormality may serve as a marker of an infectious  chronic diarrhea  
class6	anorectal sensory and motor function in neurogenic fecal incontinence  comparison between multiple sclerosis and diabetes mellitus  we measured anorectal sensory and motor function in 11 patients with multiple sclerosis and fecal incontinence  11 continent patients with multiple sclerosis  10 diabetics with fecal incontinence  and 12 healthy control subjects  the threshold volume at which patients with multiple sclerosis and fecal incontinence experienced rectal sensation was higher than that in healthy controls  42 7     6 2 ml vs  13 3     2 8 ml  p less than 0 01  and was similar to that in incontinent diabetics  36 5     5 7 ml   patients with multiple sclerosis and incontinent diabetics also showed increased thresholds of phasic external sphincter contraction compared with controls  p less than 0 05   diabetics with incontinence had reduced resting and maximal voluntary anal sphincter pressures compared with controls  p less than 0 05   whereas patients with multiple sclerosis and incontinence showed only decreased maximal voluntary anal sphincter pressures  p less than 0 01 vs  controls and diabetics   incontinent patients with multiple sclerosis also required smaller volumes of rectal distention to inhibit internal sphincter tone compared with diabetics and controls  p less than 0 01   decreased maximal voluntary squeeze pressures were less severe in continent patients with multiple sclerosis than in incontinent patients with multiple sclerosis  we conclude that impaired function of the external anal sphincter and decreased volumes of rectal distention to inhibit the internal anal sphincter or both may contribute to fecal incontinence in multiple sclerosis  in addition  increased thresholds of conscious rectal sensation in some incontinent patients with multiple sclerosis and diabetes mellitus may contribute to fecal incontinence by impairing the recognition of impending defecation  
class6	diarrhea in ciguatera fish poisoning  preliminary evaluation of pathophysiological mechanisms  ciguatera fish poisoning is a clinical syndrome consisting of a combination of gastrointestinal and neurological symptoms occurring after eating toxin containing tropical reef fish  it is a major cause of morbidity in hawaii  the south pacific  australia  and the caribbean  in an effort to define pathophysiological mechanisms responsible for the diarrheal component of the illness  we examined the effect of crude and fractionated toxin preparations on isolated rabbit ileal tissue in a ussing chamber model  both the crude toxin preparation  prepared from toxic ctenochaetus strigosus  and 10  and 50  methanol chloroform toxin fraction  prepared from a pool of toxic fish samples  gave a striking increase in transepithelial electrical potential difference and short circuit current  enterotoxic activity seemed to be mediated by calcium  when examined by light microscopy  the intestinal mucosa was not damaged by the toxin preparations used  our data demonstrate that toxins involved in ciguatera fish poisoning directly stimulate intestinal fluid secretion without accompanying tissue damage and suggest that calcium is the  second messenger  mediating the process  
class6	selective intestinal decontamination prevents spontaneous bacterial peritonitis  in a prospective randomized study  selective intestinal decontamination with norfloxacin was performed during hospitalization in 32 cirrhotic patients with low ascitic fluid total protein levels  the incidence of infections was compared with that in a control group of 31 nontreated cirrhotic patients of similar characteristics  we found a significantly lower incidence of infections  1 32  3 1   vs  13 31  41 9    p less than 0 005  and spontaneous bacterial peritonitis  0 32  0   vs  7 31  22 5    p less than 0 05  in patients receiving norfloxacin  the lower incidence of extraperitoneal infections  1 32  3 1   vs  7 31  22 5    p   0 052  in the treated group did not reach statistical significance  the incidence of infections  1 28  3 6   vs  9 22  40 9    p less than 0 01  and spontaneous bacterial peritonitis  0 28  0   vs  5 22  22 7    p less than 0 05  in cirrhotic patients admitted because of ascites was also significantly lower in the treated group  the decrease in the rate of mortality observed in the group undergoing selective intestinal decontamination did not reach statistical significance  these data show that selective intestinal decontamination is useful to prevent spontaneous bacterial peritonitis and extraperitoneal infections in hospitalized cirrhotic patients with low ascitic fluid total protein levels  
class6	a rodent model of cirrhosis  ascites  and bacterial peritonitis  we sought to develop a rodent model of spontaneous bacterial peritonitis and report here the preliminary results of carbon tetrachloride induced cirrhosis in which ascites and bacterial peritonitis predictably develop  of 41 rats that survived the initial carbon tetrachloride toxicity  38  92 7   developed cirrhosis with ascites  of these 38  21  55 3   developed 24 episodes of ascitic fluid infection without iatrogenic colonization  no surgically treatable source of infection was identified at autopsy in any rat  therefore  the infections were presumed to be  spontaneous   eight  50   of the 16 rats with culture positive ascitic fluid at postmortem examination also had spontaneous pleural fluid infection with the same organism  escherichia coli and proteus sp  were the organisms most commonly isolated  this rodent model of cirrhosis with ascites appears to be the first high yield animal model of spontaneous bacterial peritonitis  ascitic fluid infection in these rats resembles ascitic fluid infection in humans  this model will allow further investigation of the mechanisms of pathogenesis of ascitic fluid infection and provide insight into the prevention and treatment of spontaneous bacterial peritonitis and pleural fluid infection in patients with cirrhosis  
class6	effect of v1 vasopressin receptor blockade on arterial pressure in conscious rats with cirrhosis and ascites  angiotensin ii blockade with saralasin in human cirrhosis with ascites is associated with a significant reduction in arterial pressure  indicating that endogenous angiotensin ii plays an important role in the maintenance of systemic hemodynamics in this condition  the aim of the current study was to investigate whether vasopressin also contributes to the maintenance of arterial pressure in cirrhosis with ascites  the study was performed using three groups of cirrhotic rats with ascites and three groups of control animals  the administration of d ch2 5tyr me avp  a selective antagonist of the vascular effect of vasopressin  to 10 cirrhotic rats induced a significant reduction in mean arterial pressure  from 94     4 to 85     4 mm hg  p less than 0 001  and a significant increase in plasma renin activity  from 24 3     4 9 to 34 3     5 9 ng ml h  p less than 0 02  and plasma norepinephrine concentration  from 1474     133 to 2433     253 pg ml  p less than 0 01   similar results were observed following saralasin administration in a second group of 5 cirrhotic rats  mean arterial pressure decreased from 97     4 to 85     5 mm hg  p less than 0 0001   and plasma renin activity and norepinephrine concentration increased from 18 4     5 8 to 40 3     5 7 ng ml h  p less than 0 02  and from 1383     70 to 2312     334 pg ml  p less than 0 05   respectively   the simultaneous blockade of angiotensin ii and vasopressin in a third group of cirrhotic rats resulted in a significantly greater reduction of mean arterial pressure  from 97     6 to 74     6 mm hg  p less than 0 05   no changes in arterial pressure were observed in the three groups of control rats  these findings indicate that endogenous vasopressin is as important as angiotensin ii in the maintenance of arterial pressure in cirrhotic rats with ascites and support the contention that arterial hypotension is the initial event leading to the stimulation of the renin angiotensin system and vasopressin in this animal model of cirrhosis  
class6	hypophosphatemia and renal tubular dysfunction in alcoholics  are they related to liver function impairment  the study was designed to evaluate  a  the role of reduced renal phosphate reabsorptive capacity assessed as the ratio of maximum capacity for renal phosphate reabsorption  tmpo4  to glomerular filtration rate  gfr  in the pathogenesis of hypophosphatemia in alcoholics   b  possible mechanisms leading to reduced tmpo4 gfr  and  c  the effect of liver function impairment on tmpo4 gfr  the tmpo4 gfr  its major extrarenal determinants  ratios of urinary excretion gamma glutamyl transpeptidase and of alpha glucosidase to gfr  uggt gfr and uagl gfr   indices of structural damage of renal tubular cells  and fractional clearance of lysozyme  an index of proximal renal function  were evaluated in 31 alcoholics with alcohol related liver disease  24 alcoholics without alcohol related liver disease  14 patients with non alcohol related liver disease  and 25 control subjects  hypophosphatemia was found in 35  of alcoholics with alcohol related liver disease  29  of alcoholics without alcohol related liver disease  and no patients with non alcohol related liver disease  a reduced tmpo4 gfr was the major determinant of hypophosphatemia in both groups of alcoholics  no difference in extrarenal determinants of tmpo4 gfr was found between alcoholics with and without hypophosphatemia  alcoholics with and without alcohol related liver disease had increased uggt gfr and normal uagl gfr regardless of serum phosphate level  fractional clearance of lysozyme  instead  was increased only in hypophosphatemic alcoholics with and without alcohol related liver disease  the tmpo4 gfr correlated inversely with the fractional clearance of lysozyme in both groups of alcoholics  p less than 0 01   the tmpo4 gfr and urinary enzymes were normal in patients with non alcohol related liver disease  it was concluded that a reduced tmpo4 gfr is involved in the pathogenesis of hypophosphatemia in alcoholics  a proximal tubular dysfunction seems to be responsible for the reduced tmpo4 gfr  liver function impairment is not required for the expression of this tubular dysfunction  
class6	hepatic injury associated with small bowel bacterial overgrowth in rats is prevented by metronidazole and tetracycline  susceptible rat strains develop hepatobiliary injury following the surgical creation of self filling blind loops that cause small bowel bacterial overgrowth  luminal bacteria or their cell wall polymers were implicated in the pathogenesis of the lesions because sham operated rats and rats with self emptying blind loops  having only slightly increased bacterial counts  did not develop hepatic injury  in this study  antibiotics with different spectra of activities were continuously administered starting 1 day or 22 days after surgery to determine which intestinal flora may be responsible for the development of hepatic injury in rats with small bowel bacterial overgrowth  four weeks following surgery  lewis rats with self filling blind loops receiving no antibiotics had elevated liver histology scores  8 2     1 3 vs  0 7     0 4  and plasma aspartate aminotransferase levels  269     171 vs  84     24  compared with sham operated rats  p less than 0 001  oral gentamicin as well as oral and intraperitoneal polymyxin b  which binds endotoxin  did not prevent hepatic injury in rats with self filling blind loops  however  oral metronidazole and tetracycline therapy continuously administered beginning 1 day after surgery diminished hepatic injury  histology score 3 0     1 8  2 9     1 1  aspartate aminotransferase 87     25  98     34  respectively p less than 0 001 compared with self filling blind loops receiving no antibiotics   metronidazole also protected wistar rats that require 12 weeks to develop hepatic injury following experimentally induced small bowel bacterial overgrowth compared with rats with self filling blind loops that received no antibiotic treatment  histology score 10 4     1 3 vs  0 7     1 1  and aspartate aminotransferase 273     239 vs  76     20  p less than 0 001   when rats started metronidazole therapy 22 days after self filling blind loop surgery  elevated aspartate aminotransferase values decreased to normal during the next 77 days and final histology scores were normal  all rats with self filling blind loops had negative peritoneal  liver  spleen  and blood cultures but approximately 75  of mesenteric lymph node cultures were positive irrespective of antibiotic treatment  because bacteroides species have been implicated in causing vitamin b12 and disaccharidase deficiencies in rats with self filling blind loops  we documented the presence or absence of these organisms from blind loops using selective culture techniques  metronidazole and tetracycline eliminated bacteroides sp  from blind loops  but polymyxin b and gentamicin did not  abstract truncated at 400 words   
class6	pulmonary hypertension complicating portal hypertension  prevalence and relation to splanchnic hemodynamics  the prevalence of pulmonary hypertension in 507 patients hospitalized with portal hypertension but without known pulmonary hypertension who underwent cardiac catheterization was prospectively studied  ten  2   of these patients  6 of whom were clinically asymptomatic  had primary pulmonary hypertension  second  26 patients with symptomatic pulmonary hypertension complicating portal hypertension were reviewed  pulmonary hypertension occurred later after diagnosis of portal hypertension in patients with a surgical shunt  10 patients  than in those without a shunt  147     49 vs  44     27 months  p less than 0 0001   cardiac index correlated inversely with pulmonary arterial pressure  r    0 45  p less than 0 01  and was lower in the 5 patients who died of pulmonary hypertension than in the 5 who died of liver failure  1 52     0 14 vs  3 69     1 88 l min m2  p less than 0 05   third  systemic and splanchnic hemodynamics were compared in 285 patients with alcoholic cirrhosis and 29 controls  no significant relation was found between elevated pulmonary vascular resistance and increased portal pressure  zzygos blood flow  or cardiac index  pulmonary hypertension is considerably more frequent than was previously estimated in patients with portal hypertension  the risk of developing pulmonary hypertension could increase with the duration of portal hypertension without any clear relation to the degree of portal hypertension  hepatic failure  or amount of blood shunted  
class6	recurrent acute fatty liver of pregnancy associated with a fatty acid oxidation defect in the offspring  a case of a 29 year old woman who has had two episodes both clinically and biochemically consistent with acute fatty liver of pregnancy is described  these episodes occurred in two successive pregnancies  and liver biopsy confirmed the diagnosis in the second pregnancy  both pregnancies were managed by prompt fetal delivery  on both occasions this led to a complete biochemical resolution of the liver function abnormalities  two healthy babies were delivered by ceasarian sections  this case is of particular importance because a rapidly progressive and devastating illness developed in both infants  leading to death at 6 1 2 and 6 months  respectively  the illness in both babies was characterized by wide spread fatty infiltration of several vital organs and a failure of any treatment to influence the outcome of that illness  studies suggested that the illness in the children was caused by a still ill defined disorder of fatty acid oxidation  the biochemical disorder evidenced in this family is discussed  in an attempt to shed light on the etiology of acute fatty liver of pregnancy  
class6	neutrophil dysfunction in glycogen storage disease ib  association with crohn s like colitis  two cases of patients with crohn s like colitis and glycogen storage disease ib have been reported previously  in the current report  chronic inflammatory bowel disease that developed in another adolescent with this glycogenosis is described  thereby corroborating the association  the neutrophil dysfunction observed in glycogen storage disease ib is the most likely predisposing factor  neutrophil function was investigated in our patient in an attempt to shed light on the pathogenesis of his intestinal inflammation  the patient displayed reduced neutrophil chemotaxis to zymosan activated serum  n formyl methionine phenylalanine  and escherichia coli bacteria derived factor and reduced intracellular killing of staphylococcus aureus 502a  others have found this defective bacteriocidal activity to be caused by impaired oxidative metabolism  the recent recognition of chronic inflammatory bowel disease in glycogen storage disease ib  as well as in chronic granulomatous disease  suggests that further study of respiratory burst activity of neutrophils in crohn s disease is warranted  
class6	localization of calcitonin gene related peptide in human esophageal langerhans cells  previously undescribed calcitonin gene related peptide immunoreactive intraepithelial cells were seen in specimens of esophageal mucosa obtained by biopsy or surgical resection from 14 individuals  these calcitonin gene related peptide immunoreactive cells were sparsely seen in normal mucosa but increased markedly in esophagitis  they were inaccessible to routine histological stains  but osmication showed them as dendritic forms resembling langerhans cells of the skin  their cytological identity was determined with immunocytochemical tests for human antigenic markers such as ia  hla dr  and okt6 for langerhans cells  leu m5 and leu m3 for intraepithelial macrophages  cd3 and tcr 1 for t lymphocytes  leu 14 for b lymphocytes  s 100 for merkel cells  and chromogranin for amine precursor uptake and decarboxylation cells  double localization showed that calcitonin gene related peptide immunoreactivity colocalized with ia  hla dr  and okt6 but not with the other markers  these studies show that intraepithelial langerhans cells in the esophageal mucosa contain calcitonin gene related peptide  which may serve as an immunomodulator  
class6	hyperplastic polyps seen at sigmoidoscopy are markers for additional adenomas seen at colonoscopy  asymptomatic individuals undergoing screening flexible sigmoidoscopy were prospectively studied  polyps were found in 185 subjects  the endoscopist recorded an opinion on the polyps  histology based on endoscopic appearance  no polyps were removed at sigmoidoscopy  all subjects with rectosigmoid polyps then underwent colonoscopy and polypectomy  of them  99 subjects  54   had at least one rectosigmoid adenoma  69  37   had only hyperplastic polyps  and 17  9   had other findings  the endoscopists  opinion of the histopathology of polyps at sigmoidoscopy was correct for 61  of the lesions  of subjects with adenomatous rectosigmoid polyps  29  had additional adenomas at more proximal sites  proximal adenomas were found in 28  of patients with hyperplastic rectosigmoid polyps  patients with rectosigmoid hyperplastic polyps had the same risk for additional proximal adenomas as patients with rectosigmoid adenomatous polyps  
class6	cirrhosis and portal hypertension in a patient with adult niemann pick disease  a woman with known niemann pick disease  type b  presented at age 33 with upper gastrointestinal bleeding  ascites  and peripheral edema  evaluation showed massive hepatosplenomegaly  infiltration of the liver with niemann pick cells  cirrhosis  and evidence of portal hypertension  chronic gastrointestinal bleeding  thrombocyctopenia  and platelet dysfunction were treated successfully by splenectomy  cirrhosis and portal hypertension have not been reported previously in adult niemann pick disease in the absence of some other cause  
class6	mechanisms of gallstone formation in women  effects of exogenous estrogen  premarin  and dietary cholesterol on hepatic lipid metabolism  our aim was to define mechanisms whereby conjugated estrogens  premarin  exogenous estrogen  ayerst laboratories  new york  increase the risk of developing cholesterol gallstones and to determine the role  if any  of dietary cholesterol  we studied gallbladder motor function  biliary lipid composition and secretion  cholesterol absorption  cholesterol synthesis and esterification by peripheral blood mononuclear cells  the clearance of chylomicron remnants  and bile acid kinetics in 29 anovulatory women  13 were studied on both a low  443     119 mumol d  and high  2 021     262 mumol d  cholesterol diet  premarin increased the lithogenic index of bile  p less than 0 05   increased biliary cholesterol secretion  p less than 0 005   lowered chenodeoxycholate  cdca  pool  p less than 0 001  and synthesis  p less than 0 05   altered biliary bile acid composition    ca   dca  cdca increases  p less than 0 005   stimulated cholesterol esterification  p less than 0 03   and enhanced the clearance of chylomicron remnants  p   0 07   increases in dietary cholesterol stimulated the biliary secretion of cholesterol  p   0 07   bile acid  p less than 0 05   phospholipid  p   0 07   and as a result  did not alter lithogenic index  the reduction in cdca pool and synthesis by premarin was reversed by increasing dietary cholesterol  off premarin  only 24  of the increase in cholesterol entering the body in the diet was recovered as biliary cholesterol or newly synthesized bile acid  on premarin  68  of this increase in cholesterol was recovered as these biliary lipids  we conclude that premarin increases biliary cholesterol by enhancing hepatic lipoprotein uptake and inhibiting bile acid synthesis  these actions of premarin divert dietary cholesterol into bile  
class6	immunohistochemical demonstration of pancreatic secretory trypsin inhibitor in normal and neoplastic colonic mucosa  specimens of normal and neoplastic colonic mucosa from 52 patients were analysed by immunohistochemistry using a monospecific polyclonal antiserum against human pancreatic secretory trypsin inhibitor  psti   in normal colonic mucosa psti was found in the goblet cells in the basal parts of the crypts  in adenomas of tubular  villous  and tubulo villous types psti was also found in the upper parts of the polyps  usually occurring in the regeneration zone  there was a more intense staining reaction in polyps with increased atypia  carcinomas of different types and of various grades of differentiation and of in situ type did not contain psti  these findings indicate that psti could be a marker for adenomatous rather than carcinomatous epithelium in the colon  furthermore  the absence of the inhibitor in malignant cells might facilitate tissue invasion by malignant cells because of deficient protease inhibition  
class6	non specific reactions in enzyme linked immunosorbent assays for serum antibody to entamoeba histolytica and giardia lamblia in non endemic areas  serum samples from 20 indian children with diarrhoea were compared with those from 20 children resident in the united kingdom who had been diagnosed as having ulcerative colitis  or crohn s disease  or indeterminate colitis using enzyme linked immunosorbent assays specific for entamoeba histolytica and giardia lamblia  more than 50  of the united kingdom patients had high igg responses in elisas for e histolytica and g lamblia  a confirmatory elisa showed that the british sera reacted specifically to bovine serum proteins rather than to protozoal antigens  prior incubation of sera with 5  bovine serum prohibited this reaction  bovine serum is an integral part of the crude soluble antigen used in most elisas for e histolytica and g lamblia and needs to be replaced with purified antigen preparations  the british sera also reacted to other commonly used blocking agents such as bovine serum albumin  casein  and normal sheep serum  these reactions were attributed to uptake of dietary antigens or an enhanced immunological response to these antigens in patients with inflammatory bowel disease  
class6	biphasic modulation of acetaminophen bioactivation and hepatotoxicity by pretreatment with the interferon inducer polyinosinic polycytidylic acid  interferons and interferon induction can inhibit cytochromes p 450 and reduce the bioactivation and hepatotoxicity of acetaminophen  however  since p 450 inhibition often is followed by p 450 induction  which would enhance acetaminophen hepatotoxicity  the possibility of a biphasic modulation of acetaminophen hepatotoxicity by interferons was investigated  outbred male cd 1 mice of various ages  and young inbred male c57bl 6 mice were given the interferon inducer  polyinosinic polycytidylic acid  poly i c   10 mg kg intraperitoneally  followed 1 to 48 days later by a single dose of acetaminophen  300 to 450 mg kg intraperitoneally  hepatotoxicity was assessed by the peak plasma concentration of alanine aminotransferase  alt  occurring between 0 and 48 hr after acetaminophen treatment  poly i c inhibited the hepatotoxicity of acetaminophen given within 8 days  with maximal inhibition between 1 and 4 days  conversely  a maximal 7 fold enhancement of alt concentration was observed in cd 1 mice when 300 mg kg of acetaminophen was given 32 days after poly i c  p less than 0 05   in the c57bl 6 strain  poly i c inhibited the hepatotoxicity of acetaminophen when given within 16 days  whereas a maximal 20 fold enhancement of alt concentration was observed when 300 mg kg of acetaminophen was given 24 days after poly i c  p less than 0 05   the mechanism of toxicologic enhancement was examined in male c57bl 6 mice using the same treatment regimen  biochemical assessment of hepatotoxicity was confirmed by detailed histologic evaluation  plasma concentrations of acetaminophen and metabolites were determined by high performance liquid chromatography  acetaminophen bioactivation was quantified by production of the glutathione derived cysteine and mercapturic acid conjugates of acetaminophen  poly i c pretreatment produced a 5 fold increase in acetaminophen induced alt release  p less than 0 05   which correlated with histologic evidence of centrilobular necrosis  poly i c pretreatment produced respective 3 fold and 1 3 fold increases in the production of cysteine and mercapturic acid conjugates  p less than 0 05   which correlated with peak alt concentrations  cysteine  r   0 92  p less than 0 001  mercapturic acid  r   0 75  p   0 006   thus  the hepatotoxicity of acetaminophen can be inhibited when given within days after interferon induction  and conversely enhanced when given after several weeks  the toxicologic enhancement appears to be due to increased p 450 catalyzed bioactivation of acetaminophen  
class6	glutathione disulfide formation and oxidant stress during acetaminophen induced hepatotoxicity in mice in vivo  the protective effect of allopurinol  acetaminophen  500 mg kg i p   induced hepatotoxicity in fasted icr mice in vivo  acetaminophen also caused a long lasting 50  reduction of the hepatic atp content  an irreversible loss of hepatic xanthine dehydrogenase activity and a transient increase of the xanthine oxidase activity  all effects occurred before parenchymal cell damage  i e   the release of cellular enzymes  the hepatic content of gsh and gssg was initially depleted by acetaminophen without affecting the gssg gsh ratio  1 200   however  during the recovery phase of the hepatic gsh levels the gssg content increased faster than gsh  resulting in a gssg gsh ratio of 1 18 24 h after acetaminophen administration  the mitochondrial gssg content increased from 2  in controls to greater than 20  in acetaminophen treated mice  the extremely elevated tissue gssg levels were accompanied by a 4 fold increase of the plasma gssg concentrations but not by an enhanced biliary efflux  although hepatic gssg formation and biliary excretion were not affected by acetaminophen  allopurinol protected dose dependently against acetaminophen induced cell injury  the loss of atp and the increase of the gssg content in the total liver and in the mitochondrial compartment without inhibiting reactive metabolite formation  high  protective as well as low  nonprotective doses of allopurinol almost completely inhibited hepatic xanthine oxidase and dehydrogenase activity  but only high doses prevented the increase of the mitochondrial gssg content  the data indicate a long lasting  primarily intracellular oxidant stress during the progression phase of acetaminophen induced cell necrosis  the protective effect of allopurinol is unlikely to involve the inhibition of reactive oxygen formation by xanthine oxidase but could be the result of its antioxidant property  
class6	experimental reduction of portal hypertension by mechanical increase of liver portal flow studies on the isolated perfused rat liver demonstrated that an increase in portal pressure is associated with an increase in the portal blood flow in normal and in cirrhotic livers  in two pigs with portal hypertension mesenteric portal pressure was lowered by mechanically increasing the liver portal blood flow by means of a balloon pump around the portal vein  
class6	upper gastrointestinal bleeding in relation to previous use of analgesics and non steroidal anti inflammatory drugs  catalan countries study on upper gastrointestinal bleeding to assess the risk of upper gastrointestinal bleeding associated with the use of individual non narcotic analgesics and non steroidal anti inflammatory drugs  nsaids   a multicentre study of 875 cases of upper gastrointestinal bleeding and 2682 hospital controls was done  with control for confounding factors  the overall odds ratio estimate for aspirin taken at least once during the week before the first symptom was 7 2  95  confidence interval 5 4 9 6   non aspirin nsaids associated with upper gastrointestinal bleeding were diclofenac  7 9  4 3 14 6    indomethacin  4 9  2 0 12 2    naproxen  6 5  2 2 19 6    and piroxicam  19 1  8 2 44 3    paracetamol  propyphenazone  and dipyrone did not increase the risk  a previous history of gastrointestinal bleeding or peptic ulcer did not greatly affect odds ratio estimates  which differed according to sex and were higher for younger than for older patients  however  the incidence of upper gastrointestinal bleeding was higher among the elderly  
class6	gingival and cutaneous xanthomatosis associated with primary biliary cirrhosis  report of a case  the first comprehensive case report of intraoral xanthomatosis associated with primary biliary cirrhosis is detailed  the lesions were present along the free gingival margin and labial vestibule  crevicular fluid was noted to be tinged yellow  generalized cutaneous eruptions were also seen  the xanthomas were attributed to the underlying hyperlipoproteinemia  advanced progression of the hepatic disease necessitated a liver transplant  disappearance of both oral and skin lesions were subsequently observed  
class6	would you recognize celiac axis syndrome  since its original description  celiac axis syndrome has been a topic of debate  clinical findings include postprandial abdominal pain  weight loss  and an epigastric bruit  diagnosis is often made by exclusion and is confirmed by lateral aortography  the role of surgery in treating celiac axis syndrome is controversial  
class6	cholecystokinin enhanced hepatobiliary scanning with ejection fraction calculation as an indicator of disease of the gallbladder  chronic acalculous cholecystitis represents 5 to 20 per cent of electively treated diseases of the gallbladder  a 70 per cent success rate in relieving these patients of chronic pain was reported when surgical treatment was recommended based on symptoms alone  the cholecystokinin ejection fraction  which is a quantitative measure of emptying of the gallbladder  was 95 per cent accurate in predicting which patients would be relieved of symptoms by surgical treatment  in this study  we report our consecutive experience during a 20 month period with 83 patients  
class6	isoperistaltic intestinal lengthening for short bowel syndrome  because of improvements in supportive care  many infants now survive massive intestinal loss and have short bowel syndrome  unfortunately  some survivors are left with an insufficient amount of intestine and cannot be weaned from total parenteral nutrition  an isoperistaltic intestinal lengthening procedure was used to treat surgically two such infants with 25 centimeters of remaining small intestine and absent ileocecal valves  this surgical technique longitudinally divides the short  dilated small intestine into two smaller  parallel lumens that are anastomosed end to end  this procedure preserves all mucosa  prolongs transit time by doubling intestinal length and corrects the ineffective peristalsis by tapering the dilated intestine  the lengthening technique can be performed because of the anatomic division of the intestinal vasculature within two leaves of the mesentery  longitudinal division between the two leaves maintains vasculature to each side of the intestine  the isoperistaltic intestinal lengthening procedure  as it was successfully applied to two infants  is described in detail  
class6	differences in expression of cystic fibrosis in blacks and whites  the recent identification of the cystic fibrosis  cf  gene confirms that genetic heterogeneity occurs in cf  a three base pair deletion in exon 10 resulting in a loss of the phenylalanine residue at amino acid position 508 of the gene product  termed the cf conductance regulator protein  accounts for 70  of cases of cf in white subjects  however  this gene defect occurs in only 37  of affected blacks  analysis of cf genes from american blacks has revealed a number of mutations  most of which are unique to that population  we therefore searched for potential differences in expression of cf between 24 black and 48 white patients with cf matched for birth date and gender  black patients more frequently presented with only respiratory symptoms  38  vs 10    black patients had fewer hospitalizations for pulmonary exacerbations  2 vs 6 9   a better mean forced vital capacity  77  vs 62  of predicted   and higher chest roentgenogram scores  18 2 vs 14 4  than white patients  complication rates were similar except for a higher incidence of hyponatremic dehydration  21  vs 2   and peptic ulcer disease  13  vs 0   in blacks  survival time appeared to be longer in blacks  but the difference was not statistically significant  we conclude that phenotypic differences exist between black and white patients with cf  which may be due to the genetic heterogeneity between these two populations  
class6	pearson syndrome and mitochondrial encephalomyopathy in a patient with a deletion of mtdna  a patient is described who has features of pearson syndrome and who presented in the neonatal period with a hypoplastic anemia  he later developed hepatic  renal  and exocrine pancreatic dysfunction  at the age of 5 years he developed visual impairment  tremor  ataxia  proximal muscle weakness  external ophthalmoplegia  and a pigmentary retinopathy  kearns sayre syndrome   muscle biopsy confirmed the diagnosis of mitochondrial myopathy  analysis of mtdna from leukocytes and muscle showed mtdna heteroplasmy in both tissues  with one population of mtdna deleted by 4 9 kb  the deleted region was bridged by a 13 nucleotide sequence occurring as a direct repeat in normal mtdna  both pearson syndrome and kearns sayre syndrome have been noted to be associated with deletions of mtdna  they have not previously been described in the same patient  these observations indicate that the two disorders have the same molecular basis  the different phenotypes are probably determined by the initial proportion of deleted mtdnas and modified by selection against them in different tissues  
class6	immunochemical studies of ferrochelatase protein  characterization of the normal and mutant protein in bovine and human protoporphyria  protoporphyria is a hereditary disorder characterized by a marked decrease in the activity of ferrochelatase  the terminal enzyme in the heme biosynthetic pathway  we have prepared specific polyvalent antibodies against bovine ferrochelatase in rabbits  the specificity of the antibody preparation against ferrochelatase was demonstrated by western blot analysis and immunoprecipitation of ferrochelatase activity  the antibody also cross reacted weakly with ferrochelatase from human mitochondria  to quantify immunoreactive ferrochelatase in tissue samples  a kinetic based enzyme linked immunosorbent assay  k elisa  was developed  ferrochelatase activity and the level of immunoreactive protein were measured in hepatic mitochondria isolated from six normal and nine protoporphyric  homozygous  cattle  ferrochelatase activity was less than 10  of normal in mitochondria from protoporphyric animals  the amount of immunoreactive material was equivalent to that from normal animals  similar studies were performed with samples from three normal and two protoporphyric  heterozygous  humans  ferrochelatase activity was decreased in protoporphyric samples  about 17  of normal  but there was no concomitant decrease in immunoreactive material  these data demonstrate that a normal amount of ferrochelatase protein is present and suggest that bovine and human protoporphyria result from point mutations in the gene encoding ferrochelatase  
class6	pharmacokinetics and pharmacodynamics of doxacurium in normal patients and in those with hepatic or renal failure  we determined the pharmacokinetics and duration of action of a bolus dose of doxacurium  15 micrograms kg  in 27 patients anesthetized with isoflurane and nitrous oxide  nine patients had normal renal and liver functions and were undergoing a variety of surgical procedures  nine were undergoing cadaveric kidney transplantation because of end stage renal disease  and nine were undergoing cadaveric liver transplantation because of end stage hepatocellular disease  plasma concentrations of doxacurium were measured for 6 h after administration using a sensitive and specific capillary gas chromatographic assay  plasma concentration versus time data were analyzed by a noncompartmental method based on statistical moments  neuromuscular blockade was assessed by measuring the electromyographic evoked response of the adductor pollicis muscle to train of four stimulation of the ulnar nerve  the degree of neuromuscular blockade after doxacurium administration was described as the percent of control of the first train of four response  the pharmacokinetic variables were  normal vs hepatic failure vs renal failure  respectively   volume of distribution at steady state  220     110 vs 290     60 vs 270     130 ml kg  mean     sd    plasma clearance  2 7     1 6 vs 2 3     0 4 vs 1 2     0 7 ml kg 1 min 1   mean residence time  95 2     57 vs 129 4     30 vs 270     210 min   and elimination half life  99     54 vs 115     31 vs 221     156 min   plasma clearance and mean residence time differed significantly between patients with renal failure and control patients  
class6	computerized identification of pathologic duodenogastric reflux using 24 hour gastric ph monitoring  duodenogastric reflux is a naturally occurring sporadic event  the incidence  occurrence  and detrimental effects of which have been difficult to assess  the reliability of 24 hour gastric ph monitoring to detect duodenogastric reflux was studied  central to the use of ph monitoring for this purpose is confidence in its ability to measure and display ph data in a way that reflects changes in the gastric ph environment with sufficient sensitivity  to test this the gastric ph of 10 dogs was measured in the fasting state  after feeding  and after pentagastrin stimulation  the antrum was more alkaline in the fasting state  p less than 0 01  and the display of data by frequency distribution graph was sensitive enough to reflect induced ph changes  to test the consistency of gastric ph at a given position  simultaneous 24 hour gastric monitoring was performed in 12 normal subjects with two probes placed at either 5 or 10 cm below the lower esophageal sphincter  only at the 5 cm position did the two probes read within 1 ph unit of each other more than 90  of the time  based on these principles  gastric ph monitoring was performed 5 cm below the lower esophageal sphincter in 30 normal subjects and 11 patients  fulfilling ritchie s clinical criteria for pathologic duodenogastric reflux  the data obtained was arranged into 71 variables and subjected to discriminant analysis  sixteen variables were identified  each with a corresponding coefficient to be used as a multiplier to derive a score  a score of more than  2 2 indicated a high probability of pathologic duodenogastric reflux  the test was applied to a validation population consisting of 10 additional normal subjects and 10 patients meeting ritchie s criteria  all normal subjects had a normal score and all but one  90   of the patients had an abnormal score  when compared to o diisopropyl iminodiacetic acid  disida  scintigraphy in another group of 22 normal subjects and 60 patients  24 hour gastric ph monitoring was superior in the detection of pathologic duodenogastric reflux  the study shows how the application of computer technology can be used to diagnose pathologic duodenogastric reflux in patients with complex foregut complaints  
class6	cholangiocarcinoma complicating primary sclerosing cholangitis  cholangiocarcinoma is more likely to develop in patients with primary sclerosing cholangitis  our aims were to describe the clinical presentation  course  and management of patients afflicted with both cholangiocarcinoma and primary sclerosing cholangitis and to estimate the prevalence of cholangiocarcinoma in patients with primary sclerosing cholangitis  a retrospective analysis was conducted of 30 patients with both primary sclerosing cholangitis and cholangiocarcinoma managed at our institution during an 8 year period  development of cholangiocarcinoma was heralded by rapid clinical deterioration with jaundice  weight loss  and abdominal discomfort  cholangiocarcinoma complicating primary sclerosing cholangitis often was detected at an advanced tumor stage  which precluded effective therapy  and overall median survival was 5 months  earlier recognition and treatment of cholangiocarcinoma in such patients will be necessary to increase survival rates  seventy patients with primary sclerosing cholangitis were followed prospectively in a clinical trial of medical therapy for an average of 30 months  twelve patients died and five were found at autopsy to have cholangiocarcinoma  the potential for cholangiocarcinoma to develop in patients with primary sclerosing cholangitis may indicate that liver transplantation should be considered earlier in the course of the disease  
class6	safety and efficacy of laparoscopic cholecystectomy  a prospective analysis of 100 initial patients laparoscopic cholecystectomy quickly emerged as an alternative to open cholecystectomy  however its safety  efficacy  and morbidity have yet to be fully evaluated  during the first 6 months of 1990  we performed 100 consecutive laparoscopic cholecystectomies with no deaths and a morbidity rate of 8   8 of 100 patients  4 major  4 minor   there were 81 women and 19 men  with a mean age of 46 1 years  range  17 to 84 years   all patients had a preoperative history consistent with symptomatic biliary tract disease  and most had proved gallstones by sonography  this included four patients with acute cholecystitis  mean operating time improved significantly from month 1 to month 6  122     45 4 minutes versus 78 5     30 minutes  respectively   indicating a rapid learning curve  mean hospital stay was 27 6 hours  reflecting a policy of overnight stay  postoperative narcotic requirements were limited to oral or no medications in more than 70  of patients  a regular diet was tolerated by 83  of the patients by the morning following the procedure  median time of return to full activity was 12 8     6 8 days after operation  in addition analysis of the hospital costs of these 100 cases demonstrates a modest cost advantage over standard open cholecystectomy  n   58   mean   3620 25      1005 00 versus  4251 76      988 00   there was one minor bile duct injury requiring laparotomy and t tube insertion  two postoperative bile collections  and one clinical diagnosis of a retained stone that passed spontaneously  four patients required conversion to open cholecystectomy because of technical difficulties with the dissection  although there is a significant learning curve  laparoscopic cholecystectomy is a safe and effective procedure that can be performed with minimal risk  laparoscopic cholecystectomy should be performed by surgeons who are trained in biliary surgery and knowledgeable in biliary anatomy  and  as with all operations  it should be performed with meticulous attention to technique  
class6	intra abdominal abscess in regional enteritis  intra abdominal abscess  iaa  developed in 129 of 610 patients  21 2   with crohn s disease confined to the small bowel  the location of the abscess was intraperitoneal  ipa  in 109  17 9   and retroperitoneal  rpa  in 20  3 3    there was a marked preponderance of male patients in the retroperitoneal group  ratio  18 2   p less than 0 0001   all 129 patients were operated on  thirteen of one hundred nine patients  12   with ipa were reoperated on for recurrent abscess  and nine  8 2   for other reasons  external fistula developed in 24 patients  22   after simple incision and drainage  four  3 7   died  one from hepatitis  and three from sepsis 5  14  and 90 days after surgery  of the 20 patients with rpa  two  10   were reoperated on for recurrent abscess and four  20   for other reasons  external fistula developed in two patients  10    there were no deaths in this group  a small number of patients with iaa complicating regional enteritis had persistent sepsis causing postoperative death  which is  however  six times lower than in our comparable series of crohn s  ileo colitis  
class6	risks of intestinal anastomoses in crohn s disease  six hundred fifty eight intestinal anastomoses in 429 operations for crohn s disease were studied prospectively during an 8 year period to detect variables connected with perioperative morbidity  postoperative complications occurred in 9 7  of the patients  4  had to be reoperated on  and the overall mortality rate was 0 5   in multivariate analysis by stepwise logistic regression  the only variable significantly  p   0 03  associated with overall rate of complications was long term corticosteroid therapy  serious complications were more common in cases of intra abdominal abscesses  p   0 01  and preoperative steroid medication  p   0 03   the combination of both of these risk factors increased the rate of reoperations from 0 6   no steroids  no abscess  to 16   steroids and abscess   no significant association with postoperative complications could be found for age  sex  duration of disease  previous operations  nutritional status  emergency surgery  extent of disease  type  number  and localization of anastomoses  presence of proximal ileo  colostomy  or histologically inflamed margins of resection  
class6	liver transplantation in children  although liver transplantation is now accepted as the ideal therapy for end stage liver disease  relatively few centers have gained a large experience in children  and good results have been elusive  technical difficulty and a high incidence of graft failure are among the obstacles to success  at the university of california at los angeles  39  of our liver transplants are in the patients who are younger than 18 years  we have analyzed our experience with 103 patients to emphasize factors important to a favorable outcome with the procedure  one hundred twenty three transplants were performed in 103 children  mean age  5 2 years  48  younger than 3 years   no reduced size grafts were used  scrupulous attention to technical details of the vascular reconstruction  including frequent use of the supraceliac aorta of the recipient and interrupted suture techniques  ensured construction of sound hepatic artery and portal vein anastomoses at the first operation  preoperative exchange transfusions were used if the prothrombin time was prolonged beyond 7 seconds  resulting in an average blood loss of only 3 3 volumes  cyclosporine dosage was maintained in the high therapeutic range for the first 4 weeks  and anti t cell antibody  okt3  was used for rejection  38    amphotericin prophylaxis was used for biliary atresia patients with multiple previous operations  eighty two of one hundred three patients  80   are alive  there were no intraoperative deaths  actuarial survival rates at 6 months  1 year  and 5 years are 80   79   and 77   respectively  survival of patients who underwent transplantation at age less than 1 year is 65  versus 85  at age more than 1 year  p   0 08   retransplantation was performed in 19 patients  18    with a survival rate of 58   hepatic artery thrombosis  the most frequent technical complication  occurred in only 16 patients  13    survival rates of abo identical match versus nonidentical match grafts were 96  and 60   respectively  p   0 02   graft survival was only 47  if more than one steroid cycle was needed  compared to 75  survival with okt3 treatment  despite impairment of renal function  glomerular filtration rate  gfr  less than 80 cc kg min  in 54  of patients and hypertension requiring therapy in 27   90  of the children demonstrated enhancement of growth  development  and functional status  the following conclusions were made   1  pediatric liver transplantation is the treatment of choice for all types of end stage liver disease and should be considered early   2  factors that enhance survival include technical precision  aggressive retransplantation  antifungal chemoprophylaxis and therapy  and judicious immunosuppression with use of okt3 for rejection  abstract truncated at 400 words   
class6	new surgical approach to complicated gastroesophageal reflux disease  transthoracic parietal cell vagotomy  surgical treatment of peptic stricture of the esophagus associated with columnar  barrett  metaplasia can be a difficult problem  collis nissen fundoplication restores an intraabdominal antireflux barrier for most cases of peptic stricture  however  20  of patients may have persistence of pathological acid reflux  by reducing acidity of postoperative reflux  parietal cell vagotomy may complement nonresectional surgical results for barrett stricture  
class6	intrathoracic nissen fundoplication  long term clinical and ph monitoring evaluation  from 1976 until april 1989  31 intrathoracic total fundoplications were performed for reflux esophagitis and irreducible hiatus hernia  in the first 16 patients  group 1  the operation was complicated with acute perforation of the wrap in 4 cases  bronchogastric fistula in 1  and herniation of the wrap higher in the chest in 1  technical modifications were applied to 15 more recent patients  group 2   these are enlargement of the hiatus  looseness of the wrap and its appropriate anchorage  avoidance of forceps when handling the stomach  care with the vagi  and efficient gastric decompression in the postoperative period  the postoperative course was always uneventful in group 2  twenty six patients  who still have their initial wrap  were considered for clinical evaluation  11 from group 1  mean follow up  81 5 months  and 15 from group 2  mean follow up  32 8 months   all are free from any symptom of reflux  gas bloat syndrome is infrequent and dysphagia is relieved  twenty four hour ph monitoring  performed in 14 patients  3 from group 1 and 11 from group 2   mean follow up  42 months   was normal in 13  a pathological upright reflux  time ph less than 4  8 4   was demonstrated in one symptom free woman in whom endoscopy was unremarkable  mechanisms of complications experienced in group 1 are analyzed in the light of the technical evolution of the procedure  and the place of the intrathoracic total fundoplication in the management of short esophagus is defined  considering the other available surgical techniques  
class6	a tongue force measurement system for the assessment of oral phase swallowing disorders  a computer aided measuring system using a highly sensitive beam transducer has been developed to provide a quantitative  reliable measure of tongue strength  this tool has application in both the diagnosis and treatment of dysphagic patients with oral stage dysfunction  the device is customized to comfortably adapt to each individual  audiovisual feedback is used to enhance subject interest and motivation  the device has proven reliable in measurements of upward and side tongue thrust in six able bodied subjects measured during five separate sessions  it has also been used with two dysphagic patients  
class6	effect of aerosolized fibrin solution on intraperitoneal contamination  the potential deleterious effects of aerosolized fibrin on contaminated procedures were investigated in a rat model of peritonitis  one hundred forty rats were divided into two groups  in the control group  gelatin capsules containing feces  10 7  bacteria per milliliter  and barium sulfate at various dilutions were placed into the abdomen  in the second experimental group  a solution of cryoprecipitate  thrombin  and calcium was sprayed diffusely into the peritoneal cavity after similar fecal contamination  fecal inocula with low bacterial concentrations  0 01  0 1  and 0 15 ml  caused few deaths from peritonitis or abscess formation in either group  heavy peritoneal contamination  0 25  0 3  and 0 5 ml  caused early deaths from peritonitis in both groups  with 80  of the deaths due to sepsis in the first 48 hours  however  in the moderately contaminated rats  0 2 ml of fecal inoculate   fibrin aerosol reduced the 10 day mortality from 80  to 10   in all survivors in the fibrin treated group  intraperitoneal abscesses developed  with intraperitoneal bacterial concentrations of 2 x 10 6  organisms  early acute mortality from fibrinopurulent peritonitis is decreased at the expense of late  localized  nonlethal abscess formation  aerosolized fibrin solution must be used with caution in contaminated surgery  
class6	intussusception and the diagnostic value of testing stool for occult blood  a retrospective review was performed to determine the diagnostic value of testing for occult blood in stool of children suspect for intussusception  ninety six children had barium enema studies for suspected intussusception  of the 57 children who had barium enema confirmed intussusception  29 did not have history or physical findings of gross blood per rectum  stool was tested for occult blood in 16 of these 29 patients  and 12  75   were positive  in comparison  three  20   of the children who did not have intussusception had stool positive for occult blood  stool with occult blood was significantly associated with intussusception  p less than  002   the only other clinical factor significantly associated with intussusception was abdominal mass  p less than  02   vomiting  episodic irritability  poor feeding  abdominal pain and lethargy were not significantly different in the two groups  in conclusion  the authors suggest stool testing for occult blood when evaluating children who present with nonspecific signs and symptoms supportive of intussusception  
class6	oral indomethacin for acute renal colic  a number of studies have suggested that nonsteroidal antiinflammatory agents can relieve renal colic by a mechanism of action different from that of narcotics  offering the potential advantage of avoiding narcotic side effects such as alteration of mental status  the authors prospectively administered oral indomethacin  50 mg  to 25 nonvomiting patients with acute renal colic due to a documented stone  eleven patients group  i  received the drug in an unblinded  nonrandomized fashion after failure of oral or parenteral narcotics to provide satisfactory pain relief  either at home or in the emergency department  in 14 additional patients group  ii  indomethacin was given as the only initial treatment  pain intensity before and after treatment was reported using a 1 to 10 scale  in group i  pain decreased from 5 8     2 7 to 3 6     3 8  p less than  02   six of the 11 patients reported a decrease in pain intensity of 50  or more  which occurred within 25     11 minutes  and in 5 of these 6  pain decreased to a 0 or 1 level  in group ii  pain decreased from 7 6     1 5 to 4 6     4 0  p less than  008   eight of the 14 patients reported a decrease in pain intensity of 50  or more  which occurred within 40     14 minutes  and in 5 of these 8 pain decreased to a 0 or 1 level  among all 25 patients who received indomethacin  pain relief was not significantly associated with the duration of pain before treatment or with patient age or sex  there was a trend for pretreatment pain intensity to be higher among nonresponders  p    07   
class6	perianal streptococcal cellulitis with penile involvement  perianal streptococcal cellulitis is described occurring in a 5 year old boy  the condition also involved the penis and presented as a possible case of sexual abuse  the correct diagnosis was established by culturing beta haemolytic streptococci group a from the penile and perianal skin  
class6	treatment of renal colic by prostaglandin synthetase inhibitors and avafortan  analgesic antispasmodic   in a study of the pain relieving effect of 3 drugs commonly used to treat acute renal colic in this hospital  intravenous indomethacin and intramuscular diclofenac  prostaglandin synthetase inhibitors  were compared with intravenous avafortan  analgesic antispasmodic   as first line analgesics  prostaglandin synthetase inhibitors  if given intravenously  offer an effective alternative to avafortan  of 145 patients studied  32 required a second injection for complete relief of pain  administering a second dose of prostaglandin synthetase inhibitors resulted in equally significant pain relief rate even though the route was intramuscular  
class6	limitation of transcatheter arterial chemoembolization using iodized oil for small hepatocellular carcinoma  a study in resected cases  the radiologic and histologic findings are presented of the resection of 14 small hepatocellular carcinomas  hcc   less than 2 cm in maximum diameter  after transcatheter arterial chemoembolization  tce  using iodized oil  the effect of tce on small hcc depended on the morphologic type of the tumors  when no extracapsular invasion of tumor cells occurred  tce was extremely effective against encapsulated tumors  however  in nine of the 14 resected specimens  viable tumor cells remained in or around the tumor  the authors suggest that small hcc are not always curable with tce alone and that a multi disciplinary approach is necessary for patients with small hcc  
class6	differential alpha fetoprotein lectin binding in hepatocellular carcinoma  diagnostic utility at low serum levels  the reactivity of serum alpha fetoprotein  afp  from 20 patients with hepatocellular carcinoma  hcc  with immobilized lentil lectin was examined and found to be significantly greater  39      18   than that of the same protein from seven patients with chronic liver disease  cld  11 2      3 3    seven with fulminant hepatic failure  fhf  10      8 4    and eight normal pregnant women  4 1      2 7    the reactivity with concanavalin a  con a  was also significantly greater for afp from hcc patients  44 5      12 5   than that from fhf patients  7 7      4   and normal pregnant women  5 3      3 3    but not from patients with cld  the reactivity with lentil lectin permitted distinction between those with hcc  31 3      14 1   and those with uncomplicated cld  11 2      8 4   even when the absolute levels of serum afp were in the same range  80 400 ng ml   evaluation of the alterations by lectin binding methodology may be useful in overcoming problems associated with distinguishing between malignant and cld  particularly at moderate serum afp elevations  
class6	plasma thrombin antithrombin iii complexes in the diagnosis of primary hepatocellular carcinoma complicating liver cirrhosis  detection of hypercoagulable state might be helpful in the diagnosis of primary hepatocellular carcinoma  hcc  complicating liver cirrhosis  lc   plasma levels of thrombin antithrombin iii complex  tat  were determined in 50 patients of lc with or without hcc  the levels were above 2 ng ml in 80  of 25 hcc patients  but only in 12  of 25 non hcc patients  p less than 0 01   the levels over 2 ng ml occurred even in five of six hcc patients whose serum alpha fetoprotein levels were below 20 ng ml as well as in two of three patients with hcc less than 2 cm in diameter  those levels in hcc patients were significantly decreased within 8 days after treatment with transcatheter arterial embolization or infusion of antitumor agents  without affecting plasma antithrombin iii levels  these results suggest that plasma tat levels may be useful in the diagnosis of hcc complicating lc  
class6	a pilot study of intermediate dose methotrexate and cytosine arabinoside   spread out  or  up front   in continuation therapy for childhood non t  non b acute lymphoblastic leukemia  a pediatric oncology group study  one hundred six children with newly diagnosed non t   non b cell acute lymphoblastic leukemia  all  were treated in a pediatric oncology group  pog  pilot study in which six courses of intermediate dose methotrexate  mtx  and cytosine arabinoside  ara c   1 g m2 each  were added to a  backbone  of standard continuation therapy  the dose and sequence of mtx ara c administration were based on a preclinical model that demonstrated synergism between mtx and ara c  poor risk patients  n   49  were assigned to  up front  therapy  in which the mtx ara c courses were administered during the initial 15 weeks of remission  standard risk patients  n   57  were assigned to  spread out  therapy  in which the mtx ara c courses were interspersed at 12 week intervals within continuation treatment  toxicity after intermediate dose mtx ara c  principally neutropenia and fever  was judged significant but manageable  unexpectedly  the incidence of fever and neutropenia less than 500 mm3 was greater after  spread out  therapy  38   than after  up front  therapy  6    at 4 years  the kaplan meier estimate of event free survival  efs  is 71       7   for standard risk patients and 53       8   for poor risk patients  the results of this pilot study support the use of intermediate dose mtx ara c in additional studies  
class6	appraisal of gut lavage in the study of intestinal humoral immunity  direct investigation of intestinal humoral immunity requires collection of intestinal secretions or mucosal biopsy specimens  or both  a non invasive technique of gut lavage  with a polyethyleneglycol electrolyte lavage solution as a means of collecting intestinal secretions for immunoglobulin and antibody studies  was evaluated  fifty patients were studied  25 immunologically normal patients or volunteers  15 patients with untreated coeliac disease  and 10 patients with active crohn s disease  protease inhibitors were added promptly to samples to prevent proteolysis of immunoglobulin content  treated lavage samples were assayed by enzyme linked immunosorbent assay for immunoglobulin and antibody content  studies of serial lavage specimens showed that early  faecally contaminated specimens contained negligible quantities of immunoglobulin  but once the specimens became clear a steady state was reached  with little variation in immunoglobulin content between serial specimens and with a uniform dilution  around 20   of the ingested polyethyleneglycol  gut lavage fluid iga was predominantly secretory  comprising 92   81 6   and 76 7  respectively of the total iga gut lavage fluid content in the control  coeliac  and crohn s groups  high values of total igm and iga and igm antigliadin antibodies were detected in the coeliac group  and high values of igg in the crohn s disease group  this method of gut lavage is not only an effective bowel cleanser  but also a noninvasive means of obtaining intestinal secretions for the study of humoral immunity in gastrointestinal disease  
class6	jejunal immunoglobulin and antigliadin antibody secretion in adult coeliac disease  we compared the local intestinal immunoglobulin  ig  secretion in six adult patients with coeliac disease and nine control subjects by perfusion of a small bowel segment under an occluding balloon and analysis of the perfusion fluid for the content of ig and secretory component  the results were compared to the number of ig containing plasma cells in the test segment  there was  respectively  a two fold and a fivefold increase in jejunal secretion rates of iga  both monomeric and polymeric  and igm in patients with coeliac disease compared with control subjects  the high iga and igm secretion rates parallel the increase of ig containing plasma cells in the lamina propria  in contrast  the igg plasma cell density increase was barely significant in patients with coeliac disease and did not result in a high igg secretion rate  the jejunal secretion rate of secretory component was significantly increased in patients with coeliac disease and no free dimeric iga was present in the jejunal fluid  antigliadin iga was detected in the serum and jejunal fluid of the six patients with coeliac disease  antigliadin iga  however  was almost entirely polymeric iga linked to secretory component in jejunal fluid  whereas 61  was dimeric iga not linked to secretory component in serum  this result  combined with a raised secretory component secretion rate with no evidence of secretory component saturation  suggests that serum and intestinal antigliadin iga might be of different origins in coeliac disease  
class6	gastrointestinal intraluminal ph in normal subjects and those with colorectal adenoma or carcinoma  recent evidence suggests that the production of colorectal carcinogens is facilitated when the ph of the colonic contents is alkaline  it follows that the colonic intraluminal ph of patients with colorectal neoplasms should be higher than in normal subjects  gastrointestinal ph has been measured in 30 patients with colorectal cancer and 37 patients with benign colorectal adenomas  using a ph sensitive radiotelemetry capsule   these values have been compared with those recorded in 66 normal subjects  no differences in gastrointestinal ph were found and the results did not support the hypothesis that colonic ph plays a role in the aetiology of colorectal neoplasia  
class6	in vitro anticolon antibody production by mucosal or peripheral blood lymphocytes from patients with ulcerative colitis  published erratum appears in gut 1991 apr 32 4  460  serum anticolon antibody and in vitro anti colon antibody production by peripheral blood and mucosal lymphocytes was investigated in patients with ulcerative colitis  the frequency of serum anticolon antibody was 71  in 41 patients with ulcerative colitis  estimated by enzyme linked immunosorbent assay  elisa  using isolated rat colon epithelial cells  this finding confirms our previous report on the frequency of serum anticolon antibody detected by flow cytometry analysis  the estimated frequencies of igg anticolon antibody secreting cells were 1 5 12 5 10 6  cells in the colonic mucosa and 0 1 0 5 10 6  cells in peripheral blood  from patients with ulcerative colitis when epstein barr virus  ebv  was used as a b cell polyclonal activator  poisson analysis of limiting dilution culture showed that about one per 140 igg cells in the colonic mucosa synthesised anticolon antibody  two monoclonal igg antibodies were obtained from ebv transformed anticolon antibody secreting cells by limiting dilution method  one reacted with goblet cells in the intestine  and the other reacted mainly with colonic epithelial cells  these results suggest that heterogeneous anticolon antibodies are present in patients with ulcerative colitis and that colonic mucosa may be the main source of anticolon antibody  local autoimmune reaction might have an important role in causing the inflammation of colonic mucosa in this disease  
class6	inflammatory bowel disease and tobacco smoke  a case control study  a case control study was carried out in stockholm  sweden between 1984 and 1987 to evaluate the association of cigarette smoking and exposure to environmental tobacco smoke during childhood and the subsequent development of inflammatory bowel disease  information on smoking was obtained by a postal questionnaire  the relative risk of crohn s disease in current smokers compared with those who had never smoked was 1 33  95  confidence limits 0 7  2 6  in men and 4 99  2 7  9 2  in women  the corresponding results for ulcerative colitis were 0 96  0 5  1 8  and 0 72  0 4  1 4   the relative risk of ulcerative colitis in recent exsmokers compared with those who had never smoked was 2 18  0 9  5 0   furthermore  an increase in the risk of crohn s disease was found in those who were exposed to environmental tobacco smoke during childhood  the relative risk being 1 50  1 0  2 3   the corresponding relative risk of ulcerative colitis was 0 98  0 6  1 5   
class6	rectal mucosal dysplasia in crohn s disease  serial sections of 812 rectal biopsy specimens from 356 crohn s disease patients were analysed for mucosal epithelial dysplasia  dysplasia was found in 18 patients  5    with four showing dysplasia on repeat biopsy specimen  in these 22 biopsy specimens the dysplasia was mild in 13  moderate in nine  and severe in none  subsequently  three patients  17   developed neoplasms including carcinoma in two and an adenomatous polyp in one  in colectomy specimens which showed dysplasia  significantly more dysplastic changes were found in seven patients who underwent colonic resection than in 10 others who underwent operation but had no prior dysplasia  p less than 0 001   thirteen patients still have their rectum in situ and remain at risk of developing colonic cancer  four carcinomas developed in patients with crohn s disease who did not have dysplasia on rectal biopsy specimen  
class6	mortality and causes of death in crohn s disease  review of 50 years  experience in leiden university hospital  six hundred and seventy one patients  52 5  women  with crohn s disease seen at leiden university hospital between 1934 and 1984 were identified  follow up was 98 2  complete  sixty four  9 7   of the 659 patients died  the cause of death was related to crohn s disease in 34 patients  probably related to the disease in four  and unrelated  from incidental causes  in 25  the cause of death could not be identified in one patient  there was a significant decrease of deaths related to the disease after 1973  causes of death such as amyloidosis and malnutrition have disappeared and postoperative deaths have decreased  the standardised mortality ratio showed an excess mortality of 2 23 for all patients  it was higher for women  3 30  than for men  1 76   a comparison of two recent 10 year periods showed a significant decrease in standardised mortality ratio in men but not in women  patients whose disease started before the age of 20 years had an excess mortality compared with older patients  this study supports the view that the prognosis of crohn s disease has improved in general but high quality medical and surgical management is important particularly for younger patients  
class6	efficacy of biofeedback training in improving faecal incontinence and anorectal physiologic function  the efficacy of biofeedback treatment on faecal incontinence and anorectal function was evaluated in eight patients with faecal incontinence treated with biofeedback training and medical therapy  outcome and anorectal function were compared with nine faecal incontinent patients who received medical therapy alone  three month follow up showed that 50  of patients in the biofeedback plus conventional treatment group and 56  of those treated conventionally only had improved  one year follow up showed that 13  in the biofeedback group were free of soiling and an additional 25  had improved  the results were similar in the conventionally treated group  11  were free of soiling and an additional 44  improved  anal pressures at rest and squeeze  the rectal distension volume that induced sustained inhibition of both the external and internal anal sphincter  and continence to rectally infused saline were significantly reduced in both groups of patients compared with controls  p less than 0 05   biofeedback treatment had no effect on these abnormal anorectal functions in either patients who improved or those who did not  the improvement in faecal incontinence was probably due to medical intervention or regression of symptoms with time  or both  and not the result of biofeedback training  
class6	comparison of gall bladder bile and endoscopically obtained duodenal bile  in 10 patients with gall stone disease  eight women  two men  mean  sd  age 47 4  13  years   bile was obtained by endoscopic aspiration after stimulation of the gall bladder with ceruletid and also by fine needle puncture of the gall bladder under local anaesthetic  the total lipid concentration of the puncture bile samples was mean  sd  11 9  4 7  g dl  significantly higher than the endoscopic bile samples  3 9  3 3  g dl  p less than 0 001   total bile acids  phospholipids  and biliary cholesterol  expressed in mol   and cholesterol saturation index showed no significant differences between the two types of samples  the glycocholic acid concentration in the endoscopically obtained bile  27 7  6 6  mol  v 23 3  5 4  mol   p less than 0 01  was significantly higher than the puncture bile samples  puncture bile exhibited a significantly shorter nucleation time  3 5  3 3  days v 19 6  11 9  days  p less than 0 001   for determination of the nucleation time  endoscopic bile aspiration after gall bladder stimulation with ceruletid led to adequately concentrated samples in 50  of the study subjects  cholesterol monohydrate crystal formation in native bile was observed in six samples of puncture bile and in three samples of the endoscopically obtained bile  the presence of cholesterol crystals and the determination of nucleation time in the puncture bile were the best discriminants between cholesterol and pigment gall stones and correlated well with computed tomogram analysis  
class6	strongyloides stercoralis associated with a bleeding gastric ulcer  infection with the helminthic parasite  strongyloides stercoralis  is usually acquired by skin invasion  or occasionally via ingestion of larvae   after transformation to the adult form  the parasite preferentially localises in the small intestine  especially in the duodenal and jejunal part  a remarkable feature of strongyloides is its property of endogenous reinfection  in the case of an immunocompromised host a massive infection  called hyperinfections strongyloides  may occur  numerous gastrointestinal complications of strongyloides infections  sometimes with a lethal outcome  have been reported  the intestinal manifestations are usually limited to the small bowel  and rarely involve the stomach  we report a patient with complicated strongyloides infection of the stomach  
class6	isolated lipase and colipase deficiency in two brothers  two brothers of arab origin  aged 15 and 10 years  with isolated congenital lipase and colipase deficiency are described  both were normally developed with a history of passing greasy stools since early infancy  both have remarkable steatorrhoea and low serum carotene and vitamin e concentrations  after exocrine pancreatic stimulation  lipase and colipase activities in the duodenal fluid were almost completely absent  while amylase trypsin  bile salt  and ph values were normal  no other aetiology for exocrine pancreatic insufficiency was found  this is the first report of congenital combined lipase and colipase deficiency in two brothers  
class6	stimulation of glucagon secretion by gastric inhibitory polypeptide in patients with hepatic cirrhosis and hyperglucagonemia  porcine gastric inhibitory polypeptide  gip  was infused iv  120 micrograms in 60 min  in seven patients with biopsy proven hepatic cirrhosis who had surgical porta caval anastomoses and hyperglucagonemia in the postabsorptive state  the infusions resulted in elevation of blood levels of immunoreactive gip into the upper range of those observed after ingestion of large mixed meals  this was accompanied by significant increments in immunoreactive glucagon  irg  in the plasma  similar infusions in two cirrhotic patients with surgical porta caval anastomoses who had normal plasma irg levels in the postabsorptive state had no effect on the plasma irg level  ingestion of triglyceride  60 g  in hyperglucagonemic cirrhotic patients with porta caval anastomoses also resulted in elevation of plasma immunoreactive gip  and this was again associated with significant elevation of the plasma irg level  chromatography studies showed that the increments in plasma irg after the administration of gip or triglyceride were largely accounted for by increases in pancreatic type glucagon  there were no significant effects of administration of gip or triglyceride on the blood levels of glucose or immunoreactive insulin  it is concluded that porcine gip is glucagonotropic in patients with cirrhosis of the liver who show elevated levels of irg in the plasma in the postabsorptive state  this effect is not due to diversion of portal blood to the systemic circulation and may be attributable to hypersensitivity of the alpha cells to stimulation by gip  
class6	primary lymphoma of the liver  clinical and pathological features of 10 patients  nine out of 10 patients with primary lymphoma of the liver presented in a manner that did not suggest a tumour  the initial diagnoses were chronic active hepatitis in three cases and  granulomatous cholangitis   inflammatory pseudotumour  and anaplastic carcinoma in one case each  moreover  extensive haemorrhagic necrosis in three cases initially suggested the budd chiari syndrome  all the tumours were diffuse non hodgkin s lymphomas like the 50 cases reported previously  but they differed from most of these in that nine were of t cell phenotype  five were pleomorphic small t cell  two t zone  and two t lymphoblastic lymphomas  only one was centrocytic and of b cell lineage  this report extends the range of clinical manifestations  diffuse hepatomegaly without a tumour   histological appearances  resemblance to chronic inflammatory or vascular liver diseases  and phenotype  of t cell lineage  of primary lymphoma of the liver  these features seemed to be related in this series  recognition is important as prognosis remains favourable in appropriately treated cases  although the appearances of the liver biopsy specimens may be difficult to interpret  the destructiveness of the infiltrate is an important clue to the diagnosis  
class6	gastric epithelium in the duodenum  its association with helicobacter pylori and inflammation  duodenal biopsy specimens from 471 adults and 47 children were examined to determine the prevalence and distribution of gastric epithelium in the duodenal bulb in relation to age  gender  gastroduodenal inflammation  smoking  alcohol and consumption of nonsteroidal anti inflammatory drugs  nsaid   gastric metaplasia was present in the anterior wall duodenal biopsy specimen in 31   was significantly less common in patients under 17 than in adults  and was more common in males than females  in sixty two adults who underwent multiple radial duodenal biopsy gastric metaplasia was randomly distributed around the duodenal circumference  sixty three per cent of the patients with gastric metaplasia found on multiple biopsy were detected by just the anterior biopsy  gastric metaplasia was not obviously associated with alcohol  cigarette  or nsaid consumption  while the presence of gastric metaplasia was associated with adulthood  male sex  and low fasting gastric juice ph  its extent was associated with active duodenitis and helicobacter associated gastritis  on logistic regression  gastric metaplasia in the duodenum and gastric helicobacter pylori were independent predictors of active duodenitis  but were not significantly associated with inactive duodenal inflammation  h pylori was observed in duodenal biopsy specimens from 32 patients  all with active duodenitis  bacteria were present only on foci of gastric metaplasia  and were more likely to be seen when the metaplasia was extensive  it is proposed that inflammatory injury to the duodenal mucosa by h pylori may stimulate the development of further gastric metaplasia  and that the area of duodenum susceptible to colonisation with h pylori may therefore increase progressively until mucosal integrity is compromised and ulceration supervenes  
class6	helicobacter pylori in dyspeptic patients in kuwait  two hundred and four patients  mainly arabs  attending for upper gastrointestinal endoscopy at the gastroenterology clinic in mubarak al kabeer hospital  kuwait  were examined for evidence of infection with helicobacter pylori and associated inflammation  biopsy specimens of antrum  body  and duodenum  gastric juice  and antral mucosal brushings were investigated by microbiological  cytological  and histopathological methods  clinical conditions diagnosed at endoscopy included gastritis  gastric ulcer  duodenitis and duodenal ulcer  but half the patients had endoscopically normal gastric and duodenal mucosae  h pylori was detected by one or more of the procedures in at least one specimen from 197  96 6   of the patients  histological and cytological analysis showed equal sensitivity  but bacteriological culture was less reliable  the proportion of positive cases was high  compared with other reported series  which may have been accounted for by the variety of diagnostic techniques used in this study  the selected population  all with gastrointestinal symptoms  or genetic or environmental predisposing factors peculiar to the sample population  
class6	omeprazole in h2 receptor antagonist resistant reflux esophagitis  we conducted a retrospective review of 25 patients with severe reflux esophagitis treated with omeprazole because of failure of h2 receptor antagonists to heal their esophagitis  prior to beginning omeprazole  40 mg day   all patients were on h2 antagonists for at least 9 months and still had endoscopic evidence of longitudinal  grade ii  or circumferential  grade iii  distal esophageal ulceration  omeprazole therapy brought about complete endoscopic healing in 24 of 25 patients  96    twenty three of 24 healed patients were then restarted on h2 antagonists as maintenance therapy  repeat endoscopy was performed if symptoms recurred  fourteen of 24 patients  58   had recurrence of endoscopic esophagitis documented between 26 and 300 days from the time of starting maintenance therapy  two of these 14 patients opted for antireflux surgery  whereas the remaining 12 were once again given omeprazole  which again resulted in symptom resolution in all patients  these data suggest that most patients with h2 receptor antagonist resistant ulcerative esophagitis cannot be successfully maintained on h2 antagonists even after the ulcers have been healed with omeprazole  further studies are required to determine the role of omeprazole compared to other treatments in the long term maintenance therapy of these patients  
class6	the site of recurrent duodenal ulcer  the aim of this retrospective study was to determine the site of recurrent duodenal ulcer in relation to the site of the index ulcer  one hundred and thirty five patients who had recurrent duodenal ulcer after documented healing of an index ulcer were studied  the recurrent ulcer was more likely to occur in the anterior bulb if the index ulcer was anterior  35 of 58   60   than if the index ulcer was not anterior  29 of 77   38   p less than 0 01   however  the likelihood of a recurrent ulcer on the posterior wall of the bulb was not significantly different whether the index ulcer was posterior  11 of 36   31   or not  22 of 99   22   p less than 0 24   three of 20 patients  15   who initially presented with bleeding bled again with their recurrent ulcers  compared with eight of 115 patients  7   who first presented with dyspepsia only  p   0 39   thirteen patients were assessed independently by two endoscopists to determine ulcer site  their assessments concurred for 12  92    
class6	treatment of duodenitis with cimetidine  a clinical  endoscopic  and histologic study  we studied the effectiveness of cimetidine in the treatment of endoscopically diagnosed duodenitis  sixty nine patients with the solitary endoscopic finding of duodenitis  6  of 1 200 patients who underwent fiberoptic endoscopy of the upper gastrointestinal tract in our unit over 3 years  were studied retrospectively  a good clinical response was apparent in 45 of 69 patients treated with cimetidine  65    and a fair response in another four  6    in a controlled  randomized prospective study  we evaluated the effectiveness of cimetidine in duodenitis  statistically significant improvement for the clinical and endoscopic scores was found in 10 patients treated with cimetidine  p less than 0 01   improvement in the histologic score did not reach statistical significance  no such improvement was demonstrated in seven placebo treated patients  we believe that duodenitis is a  peptic syndrome   has a good response to cimetidine treatment  and behaves much like duodenal ulcer disease  
class6	colonic volvulus as a complication of celiac sprue  colonic volvulus has been a rarely reported complication of celiac sprue  we describe two patients with long standing celiac sprue  one in whom a recurrent sigmoid volvulus developed  and in the other  a cecal volvulus  following surgery  both are now asymptomatic on a gluten free diet  the association between celiac sprue and colonic volvulus was first reported in 1953  there have been only a few isolated cases documented  surprisingly so because the two major predisposing conditions for colonic volvulus are often seen in patients with celiac sprue  colonic bacterial fermentation of malabsorbed carbohydrate  in celiac sprue  leads to excess gas production  flaccid bowel loops with sigmoid redundancy  a long mesentery  or cecal hypermobility are not uncommon  a motility disorder in celiac sprue has also been proposed  thus these factors together would suggest that the likelihood of development of colonic volvulus in celiac sprue would be relatively great  the possibility of underlying celiac sprue should be considered in patients with colonic volvulus who have a background history of recurrent abdominal distention or malabsorptive symptoms  
class6	six physicians with inflammatory bowel disease  this essay tells the stories of six physicians with inflammatory bowel disease  ibd  to emphasize how important denial and control become when a physician is a patient  guilt at the supposed psychosomatic  origin  of ibd suggests that we as physicians should never blame our patients for getting sick  
class6	erythrocyte sedimentation as a measure of crohn s disease activity  opposite trends in ileitis versus colitis  to test our hypothesis that the erythrocytic sedimentation rate  esr  correlates well with clinical activity in inflammatory disease of the colon  but not of the small bowel  we stratified 49 crohn s disease patients according to their anatomic involvement and then measured the correlations between esr and clinical activity within each of these anatomical subgroups  for 18 patients with crohn s disease involving primarily the colon  there was a trend toward a direct correlation between clinical score and esr  p   0 15   in the 14 patients with crohn s disease limited to the colon  this direct correlation was even more pronounced and statistically significant  p less than 0 02   by contrast  an opposite trend was observed for patients with small bowel disease  for the 26 patients with disease involving predominantly the small bowel  as well as for the 22 with disease limited to small bowel  there were statistically significant inverse correlations between clinical score and esr  p less than 0 04   this difference between the directions of the correlations for crohn s colitis versus ileitis was statistically significant  p less than 0 05   this study provides further evidence for the importance of analyzing putative indications of disease activity separately for each of the protean forms in which crohn s disease occurs  
class6	bronchopulmonary involvement in ulcerative colitis  we report two cases of pulmonary involvement in ulcerative colitis  the first patient  a 37 year old woman  had bilateral basal bronchiectasis full of mucopurulent secretion  with a marked improvement of pulmonary function and roentgenographic appearance after a conservative approach  the second patient had severe pulmonary fibrosis of autoimmune nature and died owing to a pulmonary infection  in the second patient  a sulfasalazine reaction as an etiologic factor was excluded  while in the first this possibility seemed unlikely  therefore  we take these two cases as examples of the extraintestinal manifestations of ulcerative colitis  
class6	refractory parastomal ulcers  a multidisciplinary approach  chronic parastomal ulcers in patients with ileostomy or colostomy stomas are unusual  previous reports have implicated infections  fistulas  recurrent inflammatory bowel disease  ibd   pyoderma gangrenosum  and trauma  over the past 8 years we have evaluated 10 cases of such refractory parastomal ulcers that occurred at a mean of 11 years after stomal surgery  eight patients had had an ileostomy for ibd while two had undergone colostomy for colon cancer  five patients with ibd were diagnosed as having pyoderma gangrenosum ulcerations  they required systemic treatment for a mean of 25 weeks to effect ulcer healing  the other five patients had either parastomal ulcers on the basis of dermatoses  contact dermatitis  eczema  or bullous pemphigoid  or contact ulcers due to face plate pressure and parastomal dermatitis  these patients received topical treatment with healing of ulcers in a mean of 4 weeks  we conclude that parastomal ulcers occurring in patients without ibd or ibd patients without classic pyoderma gangrenosum require early dermatologic evaluation as they respond relatively quickly to appropriate local therapy  
class6	biliary sludge  a critical update  biliary sludge has been for many years a poorly defined entity  usually with low amplitude  nonshadowing echoes within the most dependent part of the gallbladder  which shift under the influence of postural changes  from a sonographic point of view  the detection of sludge implies the coexistence of small sized  solid components and of a gel like embedding material  the chemical nature of biliary sludge has recently been recognized to be predominantly composed of a coaggregate of cholesterol monohydrate crystals and liquid crystalline droplets  and in some cases  such as obstructive jaundice or symptomatic liver diseases  by bilirubin granules  all embedded in a gel matrix of mucous glycoproteins  from a pathogenic point of view  biliary sludge is often associated with biliary stasis  or with conditions characterized by impaired gallbladder contraction  such as prolonged total parenteral nutrition  fasting  and pregnancy  other causes include mucus hypersecretion  which may favor cholesterol nucleation and crystal growth  and bile infection  sludge may be an intermediate step in the formation of different types of stones  from an epidemiological point of view  sludge is quite rare in the asymptomatic  free living population  but may be common in selected series of symptomatic patients  from a clinical point of view  sludge often has a fluctuating course  including frequent disappearances and reappearances  suggesting that the early stages of gallstone formation are reversible  
class6	spontaneous bacterial peritonitis due to salmonella enteritidis in cirrhotic ascites  spontaneous bacterial peritonitis due to salmonella is uncommon  we report three patients with ascites infected by salmonella  all three patients had advanced chronic liver disease  typically cirrhosis with portal hypertension  salmonella enteritidis grew in the ascite fluid culture of the three patients  there was no clinical or microbiological evidence of salmonella infection other than in the ascitic fluid  one patient died before antibiotic treatment was started  but the other two were treated with different combinations of antimicrobial drugs  one of them died on the fourteenth day of hospitalization  and the other survived  
class6	thoracic succussion splash  a new symptom and sign of achalasia  a patient with a  thoracic succussion splash  due to achalasia is described  she noted a splashing or sloshing sensation in her chest related to jogging and bending  on examination a splashing sound could be heard over the mid sternum and the posterior chest when the patient was rocked vigorously back and forth  
class6	spinal epidural abscess  an unusual complication of a duodenal ulcer  a 50 year old man had several months of progressively worse low back pain associated with constitutional symptoms and a history of retroperitoneal tumor and bleeding duodenal ulcer  initial evaluation suggested a lumbar spine tumor  but myelography confirmed the presence of an epidural abscess  further evaluation revealed a duodeno spinal fistula at the site of the previous duodenal ulcer  which proved to be the cause of the abscess  
class6	hypergastrinemia  gastric endocrine cell hyperplasia  and intractable diarrhea  a patient with pernicious anemia developed severe intractable diarrhea night and day  investigation revealed chronic atrophic gastritis and a markedly elevated level of serum gastrin  no obvious explantation for the diarrhea was found  but after antrectomy  the gastrin level returned to normal and the diarrhea subsided  possible mechanisms for an association between diarrhea and hypergastrinemia include colonic hypermotility secondary to release of acetylcholine and inhibition of fluid and electrolyte reabsorption within the small bowel  
class6	small bowel obstruction associated with a leiomyomatous uterus  a case report and review of the literature  a 38 year old woman developed small bowel obstruction shortly after a cholecystectomy because of a massively enlarged leiomyomatous uterus  small bowel obstruction is a relatively rare complication from fibroid tumors and results from entrapment of the bowel between serosal pedunculated fibroids  as in this patient   adhesions to infarcted leiomyomas  or from compression of the small bowel by the large mass  large uterine leiomyomas clearly must be considered in the etiology of intestinal obstruction  
class6	the management of postoperative chylous ascites  a case report and literature review  chylous ascites remains rare as a complication of surgical intervention  although therapeutic manoeuvres to control chylous ascites have been developed over the past 20 years  its pathophysiology is poorly understood  conservative approaches involving dietary restriction of long chain triglycerides and salt  together with multiple paracenteses  are still the therapies of choice  persistent chylous ascites may be treated surgically by ligation of leaking lymphatics or implantation of a peritoneovenous shunt once the lymphatic anatomy has been defined by preoperative investigations  we report a case of chylous ascites developing after laparotomy and duodenotomy for obscure gastrointestinal bleeding  which did not respond adequately to medical therapy and was successfully managed by the insertion of a peritoneovenous shunt  
class6	idiopathic sclerosing peritonitis in a man  idiopathic sclerosing peritonitis is a rare disease described in young adolescent women  characterized by fibrosis and adhesions of the peritoneum to loops of the small bowel  here we describe a 35 year old man who underwent exploratory laparotomy for repeated small bowel obstruction  only partial resection of the terminal ileum was possible because of adhesions  recurrent abdominal infections and leakage from anastomosis required further resection  which ultimately resulted in short bowel syndrome and malabsorption  the clinical and pathological findings were characteristic for idiopathic sclerosing peritonitis  we review the relevant literature  to confirm  to the best of our knowledge  that this is the first report of a male patient who has developed this rare disease  
class6	cystic mesothelioma of peritoneum  occurrence in a man  we report a case of cystic mesothelioma of the peritoneum in a 54 year old man in whom cystic masses were removed twice by surgery at an interval of 2 years  the patient died of cardiac arrest shortly after the second operation for a concurrent unresectable colonic cancer  the pathogenesis of the disease is uncertain  but we consider it neoplastic of low grade malignancy  
class6	ulcerative colitis and giant cell arteritis associated with sensorineural deafness sensorineural deafness is rarely associated with both ulcerative colitis and giant cell arteritis  a patient is described in whom acute sensorineural deafness occurred in association with episcleritis  ulcerative colitis and clinical features suggesting giant cell arteritis  
class6	skeletal scintigraphy in coeliac disease  a patient with undiagnosed  long standing coeliac disease had multiple hot spots on skeletal scintigraphy  similar to those observed in malignant disease metastatic to the skeleton  a gluten free diet corrected the pathological laboratory values  and a repeat skeletal scintigram 15 months after the first one was normal  it is important to identify the secondary hyperparathyroidism of coeliac disease as a cause of multiple hot spots in skeletal scintigraphy  the finding resembles malignancy  but is due to a benign  curable condition  
class6	treatment of severe colitis in behcet s syndrome with thalidomide  cg 217   a 35 year old male patient  known in our department since 1979 on account of a severe and complete behcet s syndrome  was treated with thalidomide  cg 217  as a final pharmacological measure to avoid colectomy during a severe attack of behcet colitis  prior to the administration of thalidomide  the patient had been treated for 7 weeks with full parenteral nutrition and high doses of steroids intravenously without a satisfactory effect on the colitis  treatment with sulphasalazin was unsuccessful because of a decreasing number of platelets on this drug  after a few days on thalidomide  300 mg given once daily at bedtime  the patient s stools were normalized and without reaction for blood  his oral ulcers and pleural effusion disappeared  and his steroid doses could be reduced  gradually he was put on oral nutrition again  and his rectal mucosa became normalized  the dose of thalidomide was reduced to 200 mg  and then to 100 mg daily when the patient was discharged from hospital  less than 3 weeks after institution of the drug treatment  after 5 months as an out patient his condition is still satisfactory and without symptoms of his former disease  thalidomide has previously been reported to be of value in treatment of behcet s syndrome  but to my knowledge never with such a dramatic effect on a severe colitis as reported in this case  
class6	gall bladder perforation after long term dapsone therapy  a 65 year old man on maintenance dapsone therapy for dermatitis herpetiformis for 30 years was admitted to hospital with acute abdominal pain and vomiting  investigations revealed a heinz body haemolytic anaemia  worsening symptoms prompted an emergency laparotomy that revealed a perforated gall bladder with pigmented biliary calculi  in previous reviews of the haematological abnormalities associated with dapsone therapy  life threatening cholecystitis has not been described  
class6	changes in the basal dendrites of cortical pyramidal cells from alcoholic patients  a quantitative golgi study  although a variety of pathological changes have been described in the brains of chronic alcoholic patients  there have been no studies which have addressed the question of alterations in cortical neuronal dendritic arborisation  loss of neurons from the superior frontal gyrus and shrinkage of neurons from both the superior frontal gyrus and motor cortex has been documented in chronic alcoholic patients  these areas were chosen for this study  using a modified rapid golgi technique the basal dendritic arborisation of layer iii pyramidal neurons was compared in 15 male alcoholic patients and 15 age matched male controls  all parameters measuring basal dendritic arborisation were significantly less in the alcoholic cases for both the superior frontal and motor cortices  changes in the arbor are in the terminal branches  which is consistent with other models of dendritic plasticity  such changes may explain both permanent and reversible functional deficits in chronic alcoholic patients  
class6	gallbladder perforation  correlation of cholescintigraphic and sonographic findings with the niemeier classification  we retrospectively analyzed the cholescintigrams and sonograms of 36 consecutive patients with gallbladder perforation to  a  determine the sensitivity of each for the preoperative detection of gallbladder perforation and  b  correlate the findings with the modified niemeier classification  cholescintigraphic criteria of perforation  free spill  pericholecystic hepatic activity  and scintigraphic gallstone ileus sign  were detected in 14 of 28  50   cases  while sonographic criteria of perforation  pericholecystic fluid or pneumobilia with gallstones  were present in 18   4 of 22  of patients  p less than 0 05   cholescintigraphic patterns of perforation associated with the niemeier classification were  type i  acute free perforation   3 of 7 scans demonstrated free spill  type ii  subacute pericholecystic abscess   9 of 19 scans showed pericholecystic activity  and type iii  chronic cholecystoenteric fistula   1 of 3 scans showed a scintigraphic gallstone ileus  thus  although cholescintigraphy appears superior to sonography  both modalities are relatively insensitive for the detection of gallbladder perforation  
class6	supportive evidence for the validity of the epidemiologic necropsy for gallstones objective  the epidemiologic necropsy measures the occurrence of unsuspected disease through the examination of necropsy records of patients who died for other reasons  the estimates of unsuspected disease derived from the epidemiologic necropsy should approximate what actually occurs in the living population  design setting  to test this hypothesis  all necropsy records of adult patients at the university of kansas medical center from 1950 to 1984 were examined for the presence of gallstones  patients with previous cholecystectomy or whose gallstones were diagnosed during life were excluded  the data were stratified by age and race and compared with those of a screening survey from canada  a surgical series from new york  two screening surveys from italy  and one from denmark  the crude necropsy detection rates and the rates from the screening surveys were standardized to the 1970 federal census for kansas city  results conclusions  the standardized occurrence rates were similar and suggest that the epidemiologic necropsy accurately assesses the occurrence of asymptomatic gallstones in the living population  thus strengthening its validity as a research tool  
class6	emergency center ultrasonography in the evaluation of hemoperitoneum  a prospective study  the reliability of ultrasonographic detection  us  of hemoperitoneum in blunt abdominal trauma was evaluated in a prospective study of 72 patients  independent of the examiner  sensitivity  specificity  and accuracy were  respectively  86 7   100   and 97 2   laparotomy was indicated in 76 9  of us hemoperitoneum positive cases  no negative laparotomies were performed in this study group  if hemoperitoneum is revealed in us and vital signs are unstable  we think laparotomy is indicated  we believe that us in an emergency center is a quick  safe screening method in the evaluation of blunt abdominal trauma  us might take over a great part of the role of diagnostic peritoneal lavage  
class6	congenital hepatic fibrosis in autosomal dominant polycystic kidney disease  congenital hepatic fibrosis was found in four families with autosomal dominant polycystic kidney disease  congenital hepatic fibrosis is commonly though to be characteristic for autosomal recessive polycystic kidney disease  but the reported families  show that it can also complicate autosomal dominant polycystic kidney disease  in three families close linkage between the mutation causing the disease and dna markers on chromosome 16 was demonstrated  the clinical course of the congenital hepatic fibrosis differed considerably  in one family the children with congenital hepatic fibrosis died soon after birth  in the three other families an approximately 20 years follow up showed no detectable progression of the liver disease  
class6	persistent rectal ulcer associated with human papillomavirus type 33 in a patient with aids  successful treatment with isotretinoin  rectal dysplasia and carcinoma associated with human papillomavirus infection are increasing in prevalence among homosexual men  particularly those infected with the human immunodeficiency virus  we report a case involving a 39 year old homosexual man with aids who developed a persistent rectal ulcer  a biopsy of the ulcer revealed severe squamous dysplasia  and human papillomavirus type 33 was detected in rectal tissue with use of in situ dna hybridization  this genotype of virus has not been previously associated with anal or rectal dysplasia in homosexual men  including those infected with the human immunodeficiency virus  the rectal ulcer resolved after 2 months of oral therapy with 60 mg d of isotretinoin  a retinoid  
class6	typhlitis due to balantidium coli in captive lowland gorillas  typhlitis caused by balantidium coli and requiring surgical resection occurred in three captive lowland gorillas over a 30 month period  not one of the other gorillas in the colony or their keepers was ill  b  coli is distributed widely geographically and widely among mammals  asymptomatic commensalism predominates  but invasion of the colonic mucosa can produce diarrhea and dysentery and set the stage for local or systemic spread  
class6	collagenous colitis  report of nine cases and review of the literature  collagenous colitis is characterized clinically by chronic watery diarrhea and pathologically by a distinctive band of collagen deposited below the colonic epithelium and an inflammatory cell infiltrate of the lamina propria  since 1976  more than 100 cases have been described  we report an additional nine cases occurring in five women and four men ranging in age from 18 to 80 years  diarrhea was present before diagnosis for 2 to 4 months in four cases and for 1 to 25 years in another four cases  one patient did not have diarrhea  results of radiologic and stool studies were normal in all cases  all patients had flexible sigmoidoscopy or colonoscopy  microscopic examination of biopsy material was interpreted as characteristic of collagenous colitis  two cases resolved with psyllium mucilloid therapy alone  of the five patients treated with azulfidine  three had marked improvement  one had partial response  and one had no change  
class6	the efficacy of palliative and definitive percutaneous versus surgical drainage of pancreatic abscesses and pseudocysts  a prospective study of 85 patients  we compared the efficacy of percutaneous to surgical drainage in a prospective study in 85 patients with pancreatic abscesses and pseudocysts  percutaneous drainage of pancreatic abscesses in 18 patients cured three and palliated 12 who were eventually cured by elective surgical ablation  three patients died  this compares well to our 15 surgical patients  of whom four were cured by surgery alone and six were palliated  all were subsequently cured by additional computerized tomography guided or ultrasound guided percutaneous drainage and medical management or surgery  five of the 15 died  percutaneous drainage cured 11 of 14 infected pseudocysts and palliated two  which were subsequently cured by surgery  one was palliated but the patient was lost to follow up  surgical drainage cured six of 12 infected pseudocysts and palliated the other six  of which four were cured by further surgery and the other two were cured by secondary percutaneous drainage  nine of 12 noninfected pseudocysts were cured by percutaneous aspiration  and two were palliated and later cured  in one patient  disease progressed  and he was ultimately lost to follow up  thirteen of 14 noninfected pseudocysts were cured by surgical drainage  the other patient died of pulmonary embolus  in patients treated by percutaneous techniques  there were four major complications  our study established distinct advantages of percutaneous drainage under computerized tomographic and ultrasonic guidance   1  the procedures can be carried out under ultrasonic guidance in an intensive care unit on critically ill patients   2  the technique proved highly effective for initial palliation  with defervescence and stabilization occurring in most critically ill patients within 48 hours   3  findings from fine needle aspiration provided valuable information as to microorganisms and antibiotic sensitivities and differed in 29 of 85 patients from those of concomitant blood cultures  and  4  definitive eradication of the process  surgical ablation of residual necrotic material  can be elected after the patient s clinical condition stabilizes  
class6	flexible sigmoidoscopy as a screening procedure in rural patients  in this study of flexible sigmoidoscopy as a screening procedure for rural  impoverished patients  16  of asymptomatic patients who were screened by sigmoidoscopy and 23  of patients with a positive test for fecal occult blood were found to have a polyp or carcinoma  flexible sigmoidoscopy appears to be an important part of the physical examination of patients older than 50  it is a test that can readily be done by primary care physicians in a rural setting  
class6	hepatobiliary manifestations of the acquired immune deficiency syndrome  patients with the acquired immune deficiency syndrome  aids  frequently develop hepatic dysfunction  although hepatic injury may indirectly result from malnutrition  hypotension  administered medications  sepsis  or other conditions  the hepatic injury is frequently due to opportunistic hepatic infection  directly related to aids  infection with mycobacterium avium intracellulare typically occurs in patients with advanced immunocompromise and with systemic symptoms due to widely disseminated infection  in contrast  hepatic tuberculosis often occurs with less advanced immunocompromise  cytomegaloviral infection may produce a hepatitis  cytomegaloviral and cryptosporidial infections have been implicated as causes of acalculous cholecystitis and of a secondary sclerosing cholangitis  about 10 20  of patients with aids have chronic hepatitis b infection  these patients tend to develop minimal hepatic inflammation and necrosis  the clinical findings in patients with hepatic cryptococcal infection are usually due to concomitant extrahepatic infection  hepatic histoplasmosis usually develops as part of a widely disseminated infection with systemic symptoms  hepatic involvement by kaposi s sarcoma is rarely documented ante mortem because an unguided liver biopsy is an insensitive diagnostic procedure  patients with non hodgkin s lymphoma of the liver typically have lymphadenopathy  hepatomegaly  and systemic symptoms  as a pragmatic approach  patients with liver dysfunction and hiv related disease should have a sonographic or computerized tomographic examination of the liver  patients with dilated bile ducts should undergo endoscopic retrograde cholangiopancreatography because opportunistic infection may produce biliary obstruction  patients with a focal hepatic lesion should be considered for a guided liver biopsy  patients with a significantly elevated serum alkaline phosphatase level should be considered for a percutaneous liver biopsy  when performed for these indications  liver biopsy will demonstrate a significant disease involving the liver in about 50  of patients with aids and in about 25  of patients who are hiv seropositive but who are not known to have aids  the clinical impact of a diagnostic biopsy is blunted by a lack of efficacious therapy for many opportunistic infections  
class6	colonoscopic fine needle aspiration cytology in the diagnosis of ileocecal tuberculosis  two cases of ileocecal tuberculosis are presented  the diagnosis was achieved by endoscopic fine needle aspiration cytology  fnac   while endoscopic biopsies and brush cytology were negative  the usefulness of endoscopic fnac in the diagnosis of gastrointestinal tract tuberculosis is highlighted  
class6	bleeding ectatic vascular lesion involving the sigmoid colon  endoscopically indistinguishable from angiodysplasia  in an 8 yr old boy  an 8 yr old japanese boy was hospitalized  complaining of active hematochezia  he was shown to have a cherry red  blood oozing area of vascular dilation with mucosal prominence in the sigmoid colon by endoscopy  but had no other mucocutaneous vascular abnormalities  a family history was noncontributory  under the clinical diagnosis of angiodysplasia of the sigmoid colon  he underwent an elliptical resection of the part  based on the intraoperative endoscopic findings  however  histological examination of the surgical specimen revealed a totally different picture from that seen in angiodysplasia  the thin walled  markedly ectatic  nontortuous veins with hemorrhage were seen only just below the muscularis mucosae  around which the normal ones were shown to coexist  he has had no rebleeding for the past 3 yr  this lesion is considered to be an isolated congenital visceral telangiectasia involving veins  
class6	upper gastrointestinal bleeding in dengue fever  twenty six virologically and serologically confirmed dengue patients with signs of upper gastrointestinal tract bleeding  13 1   were studied during the 1987 outbreak in southern taiwan  within a 1 yr period from 1987 to 1988 in kaohsiung chang gung memorial hospital  there were 198 patients with dengue fever confirmed  viral isolation and serological studies indicated that type i dengue was the cause  there was no evidence of sequential secondary infection among them  the 26 patients were evaluated gastroduodenoscopically  most of the dengue patients who developed upper gastrointestinal bleeding had gastric ulcers or duodenal ulcers  superficial and hemorrhagic gastritis are the other relevant endoscopic findings  thirteen patients  50   had a past history of peptic ulcer symptoms  whereas the other 13 did not  dengue infection is a precipitating factor in inducing peptic ulcer bleeding because of hemostatic derangements  supportive therapy and blood transfusions alone were adequate treatment  except for one patient who required surgery due to massive bleeding of a duodenal ulcer  no mortality was observed in this study  
class6	sequential esophageal motility studies after endoscopic injection sclerotherapy  a prospective investigation  to assess prospectively the effects of endoscopic intravariceal sclerosis  eis  on esophageal function  we performed esophageal manometry on 13 cirrhotic patients before eis  24 h after the second session and 4 wk after the fourth session  eis had no impact on lower esophageal sphincter pressure  however  a significant decrease in the amplitude of peristaltic waves was observed immediately post eis in the lower two thirds of the esophagus  there was no modification of duration or velocity of progression of peristaltic waves  a four fold increase in simultaneous contractions was observed early after eis  these changes were reversible  as assessed by late esophageal testing after eis  no correlations were demonstrated between esophageal motor parameters and doses of sclerosant  we conclude that sclerosant injection into the esophageal wall acutely impairs esophageal motility  but motor function is partially restored 4 wk after completion of eis  suggesting that dysmotility is reversible  
class6	pharmacokinetics of famotidine after intravenous administration in liver disease  the pharmacokinetics of famotidine were studied after the administration of a single intravenous dose of 20 mg to seven normal volunteers  six patients with chronic hepatitis  14 patients with compensated cirrhosis  and seven patients with decompensated cirrhosis  the plasma terminal elimination half life of famotidine was significantly prolonged and famotidine total body clearance was significantly reduced in patients with decompensated cirrhosis  whose creatinine clearance was 57 2     6 7 ml min 1 48 m2  but these changes were not significant in patients with chronic hepatitis  creatinine clearance  109 2     10 5 ml min 1 48 m2  or in patients with compensated cirrhosis  creatinine clearance  72 2     26 5 ml min 1 48 m2 in comparison with normal volunteers  the total volume of distribution at steady state was not significantly different between the normal volunteers and the three groups of patients  famotidine total body clearance showed a weak but significant correlation with the creatinine clearance  r   0 66  p less than 0 001   serum albumin level  r   0 51  p less than 0 01   and serum total bilirubin level  r   0 36  p less than 0 05   which suggested that the reduction in clearance was due in part to the concomitant renal impairment  as well as hepatic dysfunction in these patients  in conclusion  famotidine total body clearance was reduced in decompensated cirrhosis  indicating that the dose schedule requires modification in patients with this condition  
class6	reduction in hepatic venous pressure gradient as a consequence of volume contraction due to chronic administration of spironolactone in patients with cirrhosis and no ascites  the effect of plasma volume contraction induced by a 4 wk administration of spironolactone or furosemide on the hepatic venous pressure gradient was evaluated in consecutively allocated patients with cirrhosis and no ascites  in the spironolactone group  n   15   the hepatic venous pressure gradient decreased significantly  p less than 0 005   by 21 8   with a significant contraction of circulating plasma volume  p less than 0 01   although there were no statistically significant correlations between the change in hepatic venous pressure gradient and changes in circulating plasma volume or in simultaneously determined systemic hemodynamics  a significant negative correlation  r    0 74  p less than 0 01  n   12  between the hepatic venous pressure gradient change and the post treatment plasma aldosterone levels was found  however  in the furosemide group  n   10   the hepatic venous pressure gradient and circulating plasma volume did not significantly decrease  our data demonstrated a significant reduction in the hepatic venous pressure gradient on a chronic administration of spironolactone  which may have been due to volume contractions in patients with cirrhosis and no ascites  
class6	short term course of corticosteroids in the treatment of resistant ascites complicating schistosomal liver disease  the aim of this work was to evaluate the effect of short term corticosteroids in resistant ascites complicating schistosomal liver disease after 4 wk or more on standard treatment  thirty seven patients were randomly allocated to two groups  group i  18 patients  was put on 40 mg furosemide and 200 mg spironolactone  in addition to a 15 day  tapering dose of prednisone  15  10  5 mg   group ii  19  patients received the same diuretics without steroids  and served as controls  at the end of a 2 wk course of therapy  the mean variations were as follows  body weight in patients in group i   cases   decreased by 9 8 kg  compared with 4 3 kg in controls  abdominal girth decreased by 7 4 cm in cases  compared with 3 6 cm in controls  urine output increased by 635 9 ml in cases  compared with 364 6 ml in controls  urinary sodium excretion increased by 16 5 meq day in cases  compared with 4 1 meq day in controls  these differences between cases and controls were found to be statistically significant  p less than 0 01   on the other hand  there were insignificant differences as regards decrease in blood urea  3 2 g dl for cases and 2 7 g dl for controls   decrease in serum creatinine  0 2 mg dl for both cases and controls   increase in serum albumin  0 3 g dl in cases and 0 2 g dl in controls   increase in serum sodium  3 2 meq l in cases and 2 7 meq l in controls   and increase in serum potassium  0 2 meq l in cases and 0 4 meq l in controls   we conclude that a short term course of corticosteroids in conjunction with standard diuretics has proved to be an effective  safe  and economical modality to relieve resistant hepatic ascites  it can be considered a temporary alternative to paracentesis with albumin infusion  
class6	the combination of prednisone and colchicine in patients with primary sclerosing cholangitis  primary sclerosing cholangitis is a cholestatic liver disease characterized by inflammation and fibrosis of the biliary tract  the cause of the disease is unknown  and no effective medical treatment exists  in this study  12 patients received a combination of low dose prednisone  10 mg day  and colchicine  0 6 mg bid   their course was compared with that of a group of concurrent historical controls  at 6 and 12 months  there was significantly more improvement in liver test results over baseline values in patients receiving prednisone and colchicine than in the untreated controls  at 24 months  however  no significant differences in biochemical tests were appreciated between treated and untreated patients  analysis of serial liver biopsies showed no differences in histologic change in the two groups  during the 2 yr of follow up  there were two deaths in the control group but none in the treated group  four untreated patients developed ascites  gastrointestinal bleeding developed in three untreated patients  one of whom developed ascites  in contrast  in the treated group  ascites and bleeding developed in only one patient  we conclude that the combination of colchicine and prednisone does not retard histologic progression or progression of standard liver tests after 2 yr of therapy  there is a trend toward less clinical deterioration and improved survival after 2 yr of treatment  on the basis of these findings  we would not advocate empiric use of these drugs for patients with primary sclerosing cholangitis  but suggest that  if they are to be used at all in psc  they be evaluated in a controlled clinical trial as treatment for this as yet incurable disease  
class6	clinical evaluation of plasma abnormal prothrombin  des gamma carboxy prothrombin  in hepatobiliary malignancies and other diseases  des gamma carboxy prothrombin  dcp   a protein induced by vitamin k absence or antagonist ii  pivka ii  was measured in the plasma of patients with primary hepatocellular carcinoma and those with various other hepatobiliary and pancreatic diseases  dcp levels were determined by enzyme immunoassay  e 1023   using an anti dcp monoclonal antibody  forty two of the 91 patients  46 2   with hepatocellular carcinoma had abnormally elevated levels of dcp  whereas only one of the 24 patients with hepatic cirrhosis showed a slight increase  an increase was also observed in some patients with obstructive jaundice  there was no correlation between plasma levels of dcp and those of serum alpha fetoprotein  afp   in most patients with hepatocellular carcinoma  plasma dcp levels normalized after curative surgical resection  plasma dcp levels were not related to the plasma concentration of vitamin k in the patients with hepatocellular carcinoma  plasma dcp determination may be useful in the diagnosis and postoperative monitoring of the response of hepatocellular carcinoma  
class6	spontaneous rupture of hepatocellular carcinoma  a review of 172 japanese cases  the spontaneous rupture of a primary hepatocellular carcinoma  hcc  accounts for 10  mortality of hcc patients in japan  because this problem occurs much less frequently in western countries  it is often difficult for clinicians practicing in such countries to decide upon the best course of action during the crisis accompanying the spontaneous rupture of a hcc  in an effort to advance the general knowledge of this disease and clarify a selection for its treatment  we review 172 cases of spontaneous rupture of a hcc reported in the japanese literature  the chief complaint of the patients was sudden epigastralgia or right hypochondriac pain  abdominal paracentesis was positive in 86  of the patients  liver failure was the cause of death in 42  of the patients  therefore  it is important to evaluate liver reserve quickly  in addition  emergency hemostatic procedures must be implemented to avoid hemorrhagic shock  although two stage hepatectomy was performed in only 12  of the cases  these had the highest survival rates  consequently  this is the procedure of choice for the treatment of spontaneous rupture of a hcc  
class6	modified kraske approach for disease of the mid rectum  a modification of dr  paul kraske s approach for removal of mid rectal lesions has been used in 11 patients from 1977 to 1988 by the senior authors  patients ranged in age from 56 to 89 yr  with an average of 67 yr  there were seven male and four female patients  indications for surgery were as follows  villous adenoma  seven   carcinoid  one   recurrent dysplasia in a previous endoscopic polypectomy site  one   positive distal margin for neoplasm following low anterior sigmoid resection  one   and adenocarcinoma in one elderly poor risk patient  all lesions were in the middle rectum  7 11 cm from the anal verge  average 9 cm   the postoperative stay ranged from 6 to 12 days with a mean of 8 days  the average follow up for the 11 patients is 3 1 2 yr  1 month to 7 yr   with only one patient having a local recurrent lesion  there was no morbidity or mortality  we conclude that this modification of the kraske approach offers a good alternative for excision of mid rectal lesions in terms of technical ease  efficacy  safety  and patient tolerance  the modified kraske approach is indicated in certain situations and should be a part of the surgeon s armamentarium  
class6	disseminated pneumocystis carinii infection with hepatic involvement in a patient with the acquired immune deficiency syndrome  extrapulmonary infection with pneumocystis carinii  p  carinii  in aids patients is uncommon  and is often described only at postmortem examination  although most antemortem cases involve spread to the bone marrow or spleen  p  carinii involvement of other organs has only recently been described  despite the frequency of liver enzyme abnormalities in aids patients with a history of p  carinii pneumonia  p  carinii has been observed only rarely in the liver  we present a well documented case of p  carinii involving the liver in an aids patient with p  carinii pneumonia and progressive liver enzyme abnormalities  we suggest that p  carinii infection should be considered in the differential diagnosis of aids related liver disease  
class6	nodular regenerative hyperplasia  a cause of ascites and hepatomegaly after chemotherapy for leukemia  tender hepatomegaly and ascites occurred in a young woman receiving cytosine arabinoside and daunorubicin for acute myelogenous leukemia  whereas veno occlusive disease was suspected clinically  liver biopsy showed nodular regenerative hyperplasia with no evidence of hepatic vein abnormalities  it is postulated that nodular regenerative hyperplasia can be initiated by hepatotoxicity of chemotherapy agents used to treat leukemia and or that these agents exacerbate clinical manifestations of this histological abnormality  nodular regenerative hyperplasia should be added to the list of liver problems occurring in patients with leukemia  
class6	chylous ascites due to sarcoidosis  a 33 yr old black female with systemic sarcoidosis developed chylous ascites  a ct scan showed extensive mesenteric lymphadenopathy  at laparotomy  the mesenteric and para aortic lymph nodes were enlarged and diffusely matted  histologically  normal lymph node morphology was virtually replaced with noncaseating granulomas  corticosteroids and dietary manipulations were unsuccessful in managing the ascites  and repeated large volume paracentesis was necessary to provide symptomatic treatment  this is the first reported case of chylous ascites caused by sarcoidosis  
class6	enteroliths causing intermittent obstruction in a patient with crohn s disease  calcified enteroliths as a cause of intermittent small bowel obstruction is an uncommon clinical entity  the pathophysiological mechanism involves stasis of intestinal contents and has been associated with meckel s diverticulum  tuberculosis  and regional enteritis  this case describes prophylactic operative intervention in a symptomatic patient with enteroliths as a result of crohn s disease  
class6	successful prophylaxis for fungal peritonitis in patients on continuous ambulatory peritoneal dialysis  six years  experience  published erratum appears in am j kidney dis 1991 jun 17 6  726  fungal peritonitis as a serious complication of continuous ambulatory peritoneal dialysis  capd  is often associated with severe morbidity  capd  drop out  and  occasionally  death  most episodes of fungal peritonitis occur during or after a period of antibiotic treatment of various bacterial infections  usually bacterial peritonitis  from april 1979 to december 1982  period i   10 episodes of fungal peritonitis occurred during 415 patient months  ie  10 5  of all peritonitis episodes recorded in our capd program  after the introduction of oral prophylaxis with 3 x 500 000 iu  corrected  nystatin during every course of antibiotic treatment  only four episodes of fungal peritonitis occurred during 2 102 patient months  ie  3 1  of all peritonitis episodes from january 1983 to march 1989  period ii   this difference between the first and second periods is significant  p less than 0 05   moreover  none of the four patients who contracted fungal peritonitis in the second period received nystatin prophylaxis  thus  the simple measure of oral prophylaxis using this nonabsorbable antifungal agent in every case of an antibiotic treatment largely eliminates the risk of fungal peritonitis in patients on capd  
class6	chemical peritonitis secondary to intraperitoneal vancomycin  although previously reported in the literature  the existence of chemical peritonitis due to vancomycin in patients on peritoneal dialysis remains controversial  we report four similar episodes of sterile peritonitis in three patients receiving intraperitoneal  ip  vancomycin  the prior report implicated a change in the brand of vancomycin preparation  from vancocin to vancoled  as a contributing factor  we noted the occurrence of such episodes following a switch from vancocin to a generic preparation from abbott laboratories  high performance liquid chromatographic  hplc  profiles of the three preparations show vancocin to have a lower level of impurities than the other two  the presence of certain contaminants in the other brands may be contributing to the clinical difference observed  we conclude that chemical peritonitis due to ip vancomycin administration does occur  and that increased awareness of this entity could allow other cases to be identified  
class6	ascites revealing peritoneal and hepatic extramedullary hematopoiesis with peliosis in agnogenic myeloid metaplasia  case report and review of the literature  a 61 year old man presented with ascites in the course of agnogenic myeloid metaplasia  amm   ascitic fluid was exudative and contained mature and immature leukocytes  erythroid cells  and megakaryocytes as observed on a bone marrow smear  peritoneal biopsy showed myeloid metaplasia  and liver biopsy revealed intrasinusoidal myeloid metaplasia and peliosis  ascites cleared after abdominal radiotherapy but treatment resulted in transient aplasia  subsequently  portal hypertension was demonstrated by hepatic transjugular catheterization  complications of splenomegaly led to splenectomy and splenorenal shunt followed by fatal acute hepatitis and septic shock  a review of the literature and an analysis of mechanisms of ascites occurring in amm  especially peritoneal implants of myeloid tissue and occurrence of peliosis in myeloproliferative disorders  are presented  
class6	endoscopic sclerotherapy in extrahepatic portal hypertension in pregnancy  extrahepatic portal hypertension usually occurs during childhood  but a substantial number of patients may reach adult life  there is a general agreement that pregnancy may become hazardous to these patients  and some authors even consider this condition as a contraindication to conceiving  a case of endoscopic sclerotherapy in such a patient is herein presented  and the approach to such patients is discussed  
class6	a comparative study of gastrointestinal infections in united states soldiers receiving doxycycline or mefloquine for malaria prophylaxis  a double blind study of daily doxycycline  100 mg  vs  weekly mefloquine  250 mg  was performed on united states soldiers training in thailand to assess the effect of doxycycline malaria prophylaxis on the incidence of gastrointestinal infections  during a 5 week period  49   58 119  of soldiers receiving doxycycline and 48   64 134  of soldiers receiving mefloquine reported an episode of diarrhea  infection with bacterial enteric pathogens was identified in 39   47 119  of soldiers taking doxycycline and 46   62 134  of soldiers taking mefloquine  forty four percent  59 134  of soldiers receiving mefloquine and 36   43 119  of soldiers receiving doxycycline were infected with enterotoxigenic escherichia coli  etec   while 9   12 134  of soldiers receiving mefloquine and 4  of soldiers receiving doxycycline were infected with campylobacter  side effects from either medication were minimal  after 5 weeks in thailand  the percent of non etec strains resistant to greater than or equal to 2 antibiotics increased from 65   77 119  to 86   95 111  in soldiers on mefloquine and from 79   84 106  to 93   88 95  in soldiers on doxycycline  doxycycline prophylaxis did not prevent or increase diarrheal disease in soldiers deployed to thailand where etec and other bacterial pathogens are often resistant to tetracyclines  
class6	transmission of rift valley fever virus by adult mosquitoes after ingestion of virus as larvae  published erratum appears in am j trop med hyg 1991 jun 44 6  580  we studied the ability of culex pipiens  aedes circumluteolus  and ae  mcintoshi  exposed as larvae to liver tissue from a rift valley fever  rvf  virus infected hamster  to become infected and transstadially transmit virus to the adult and for the adults to transmit virus by bite to hamsters  after exposure as larvae  9   5 54  of adult cx  pipiens and 8   38 505  of the adult ae   neomelaniconion  species were infected  all of the infected cx  pipiens and about half of the infected ae  circumluteolus and ae  mcintoshi tested transmitted rvf virus by bite to hamsters  transmission rates for mosquitoes orally infected as larvae were higher than those for mosquitoes orally infected as adults  animals infected with rvf virus may abort or die in the vicinity of mosquito larvae breeding habitats and infected tissue from these animals may contaminate the water  
class6	the current spectrum of peptic ulcer disease in the older age groups  not only has there been a relative increase in the prevalence of peptic ulcer disease  pud  among america s older age groups  but the characteristics of pud in these patients differ significantly from those of the general population  seventy two consecutive patients 60 years of age or older who underwent operation for pud between 1984 and 1989 were studied  the unusual features in these patients were 1  92 per cent required emergency operation  2  57 per cent with perforated pud were female  3  85 per cent had duodenal pathology  4  28 per cent were currently taking nonsteroidal anti inflammatory agents  and 5  over one half of all patients had serious postoperative complications  the increasing incidence and associated serious complications of pud in the elderly population present new challenges to physicians in the diagnosis and treatment of this disease  
class6	sinistral  left sided  portal hypertension  between 1953 and 1988  21 patients with splenic vein thrombosis  svt   12 of whom had sinistral portal hypertension  sph  were treated at our institution  svt was identified at autopsy in nine patients  twelve additional patients presented with sph  bleeding esophageal varices  svt and normal hepatic function  svt was caused by pancreatic neoplasm  5   chronic pancreatitis  5   and pancreatic pseudocyst  2   svt was diagnosed by splanchnic angiography  splenoportography  computerized tomography  and ultrasonography  gastric varices were diagnosed by endoscopy  10  and barium swallow  2   splenectomy was performed as primary therapy in 10 patients  three of these 10 had en block distal pancreatectomy  two high risk patients had splenic artery embolization  one as a prelude to splenectomy performed 48 hours later and the other as definitive therapy  one splenectomized patient continued to bleed  no further bleeding occurred in 10 splenectomized patients in follow up from 1 week to 14 years  sinistral portal hypertension is a clinical syndrome of splenic vein thrombosis caused by pancreatic pathology and manifests as bleeding gastric varices in patients with a patent portal vein and normal hepatic function  splanchnic arteriography is necessary for accurate diagnosis  splenectomy is the effective treatment of choice  
class6	fine needle aspiration of pancreatic fluid collections  the complications of pancreatitis remain diagnostic and therapeutic challenges  patients with simple pancreatitis  pancreatic necrosis  pseudocyst  noninfected fluid collection or abscess may all have similar clinical pictures  during the last decade computerized tomography  ct  guided needle aspiration of peripancreatic fluid collections has been increasingly used as a diagnostic tool for pancreatic abscesses  this study reviewed the effectiveness of ct guided needle aspiration of peripancreatic fluid collections at our institution in terms of diagnostic accuracy  correlation with eventual outcome  and safety  charts of patients who underwent needle aspiration of de novo peripancreatic fluid collections over the past 2 years were reviewed  thirty five patients underwent 50 aspirations  eleven patients  31   had a positive aspirate culture  seven of these had a positive gram s stain  there were no false positive gram s stains but four false negatives  twenty four  69   patients had negative aspirate gram s stains and cultures  patients with positive aspirate cultures were treated with antibiotics only  2   ct guided drain placement  7   or surgical drainage  3   the mortality related to each of these therapeutic modalities was 50 per cent  0 per cent  and 33 per cent  respectively  of the 24 patients with negative aspirate cultures  five had no further treatment  12 received antibiotics  and six underwent ct drain placement  all these patients survived  there was one false negative aspirate culture  this patient underwent delayed surgical drainage but expired  there were no major complications from ct guided aspiration  ct guided aspiration appears to be a safe and reliable method of diagnosing infection in peripancreatic fluid collections  
class6	the intracolonic bypass tube for left colon and rectal trauma  the avoidance of a colostomy  traumatic perforations of the left colon and rectum are most frequently managed by procedures that include the formation of a colostomy  primary repair without colostomy is much less commonly employed  we report nine patients with traumatic perforations of the left colon and rectum treated with the intracolonic bypass tube  icbt  without concomitant colostomy  in all these patients we believe the standard treatment would have included fecal diversion  four patients sustained blunt trauma and five sustained penetrating trauma  healing of the colonic anastomosis occurred in all cases  and the icbts were passed per rectum between the tenth and nineteenth days postoperatively  on the basis of this study  we conclude that the icbt has a role in the treatment of selected injuries of the left colon and rectum as a safe means of avoiding a colostomy  
class6	one stage repair of colovaginal fistula complicating acute diverticulitis  fourteen patients with colovaginal fistula secondary to sigmoid diverticulitis were seen between 1964 and 1988  thirteen had undergone prior hysterectomy  three different operative approaches were used  three patients were treated with colostomy alone  one died and the fistula persisted in one  five patients underwent staged procedures  one patient died of complications after the second stage of a planned three stage procedure  four patients underwent a two stage procedure  fistula takedown  colectomy with colostomy and colostomy closure   all with good results  six patients were treated with one stage fistula takedown  colectomy and primary anastomosis  without major complication  we advocate this as the procedure of choice and emphasize the following principles of epidemiology and management  1  colovaginal fistula complicates diverticulitis in elderly women usually following hysterectomy  this association may be a factor in etiology  2  vaginography is useful in diagnosis  and 3  planned one stage repair is the best surgical approach  
class6	the importance of intraoperative cholangiography during laparoscopic cholecystectomy  laparoscopic cholecystectomy  lc  using electrocoagulation was successfully performed in 56 out of 58 selected patients  cholangiography was performed in 53 patients  six patients had common duct stones  five were unsuspected preoperatively  after the gallbladder was removed  three patients underwent open common duct exploration  in another five cases  anatomical anomalies were discovered  cholangiography performed via the cystic duct before any structures are divided can prevent the most serious complication  common duct injury  cholangiography should be attempted on all patients undergoing lc  
class6	the clinical significance of fluid collections in acute pancreatitis  computed tomography  ct  displays fluid collections in patients with acute pancreatitis as well defined intra  or extrapancreatic homogeneous areas with low attenuation numbers  we followed  prospectively  the clinical courses of 128 patients who had ct during an episode of acute pancreatitis  to determine the natural history and clinical significance of any fluid collections that developed  fluid collections were found in 48  37   of the 128 patients with pancreatitis  thirty eight developed in the 86  44   patients with alcoholic pancreatitis  five in the 33  15   with biliary pancreatitis and five in the nine  55   with other causes of pancreatitis  excluding chronic pancreatitis  trauma  or malignancy   on clinical follow up of the 48 patients with fluid collections  21 patients required operation  two died before an operation was done and 25 did not require operation  operations were done to treat pseudocysts  14   abscess  5   and necrosis  3   one patient had an operation for a pseudocyst and an abscess  all 14 patients requiring operation for pseudocyst had collections greater than 7 cm and 13 of these patients had alcoholic pancreatitis  of the 25 patients not requiring operation  five were lost to follow up  and 19 of the 20 who had spontaneous resolution of their fluid collection s  had collections less than 6 cm in diameter  the eight patients who required operative pancreatic debridement for abscess or necrosis had multiple small fluid collections  in summary  fluid collections were found in one third of patients with acute pancreatitis and were often associated with the development of local complications  
class6	inguinal hernia complicating flexible sigmoidoscopy  flexible sigmoidoscopy has become part of routine preoperative workup for patients over the age of fifty who present with an inguinal hernia  a recent experience with two patients with a left inguinal hernia allowing sigmoid colon to herniate into the scrotum bring awareness of the possibility for an increased risk of perforation of the sigmoid colon during flexible sigmoidoscopy  or possible iatrogenic incarceration of the hernia  these cases are presented so this clinical entity can be recognized and the complications prevented  
class6	gallbladder wall thickening  congestive cholecystopathy  in chronic liver disease  a sign of portal hypertension  a thickened gallbladder wall is often seen with ultrasound in alcoholic cirrhosis  hypoalbuminaemia is thought to be the cause since there is a strong association between bowel wall thickening and low serum albumin  to determine the role of portal hypertension in producing gallbladder wall thickening we studied 40 consecutive stable patients 37 with cirrhosis and three with portal hypertension due to primary biliary cirrhosis  ultrasound assessment of the gallbladder wall was made after an overnight fast using a technicare autosector  wall thickness 4 mm or greater was considered abnormal  twenty seven patients had a thickened gallbladder wall and all had evidence of portal hypertension  hypoalbuminaemia was not an important factor since it was only present in six cases with thickened walls  in two cases reduction in portal pressure with oral propranolol was associated with a decrease in gallbladder wall thickness  these results suggest that portal hypertension  not hypoalbuminaemia  is the dominant factor causing gallbladder wall thickening in cirrhosis  ultrasound demonstration of gallbladder wall thickening in chronic liver disease should suggest the presence of portal hypertension  
class6	microsurgical epididymovasostomy by tubule intussusception  a new technique in rat model  this experimental study on 15 adult male rats with bilateral epididymovasostomies evaluates a new technique of tubule intussusception as an improved form of end to end anastomosis  this paper describes in detail the steps in this technique and offers physiological  anatomical  and histological follow up after 3 months  with this technique there is a 97  patency rate and a 23 3  incidence of macroscopic spermatic granuloma  complications are discussed in detail  
class6	plasma glucagon concentration in cirrhosis is related to liver function but not to portal systemic shunting  systemic vascular resistance  or urinary sodium excretion  we tested the hypothesis that increased plasma glucagon concentration resulting from portal systemic shunting or liver dysfunction causes arterial vasodilation and thereby stimulates sodium retention in cirrhosis  twenty seven studies were performed in patients with alcoholic liver disease  11 of whom had ascites  liver function was quantitated as the elimination rate of antipyrine  caffeine  and stable isotopes of cholic acid administered both orally  2 2 4 4 2h  and intravenously  24 13c   portal systemic shunt fraction was calculated as the ratio of the intravenous and oral clearances of the isotopes of cholic acid  cardiac output was measured by using doppler echocardiography  plasma glucagon concentration was increased in patients with ascites when compared with that in patients without ascites  474     180 pg ml vs 245     120 pg ml  p   0 0007  but was unrelated to urinary sodium excretion  heart rate  mean arterial pressure  cardiac output  and systemic vascular resistance  r    0 48  0 35   0 13  0 18  and 0 22  respectively   plasma glucagon concentration correlated with the half lives of all model compounds  r   0 58  p   0 002  r   0 62  p   0 0008  r   0 62  p   0 001  and r   0 64  p   0 0005  for caffeine  antipyrine  oral and intravenous cholic acid  respectively  but not with shunt fraction  r   0 14   increased plasma glucagon concentration in cirrhosis is probably a result of diminished hepatic clearance  however  increased plasma concentration of glucagon does not appear to cause a hyperdynamic circulatory state or sodium retention  
class6	mesenteric blood flow in patients with diabetic neuropathy  we examined flow velocities in the superior mesenteric artery and celiac artery in normal controls  group c  n   11   diabetic patients  group d  n   8   and diabetic patients with clinically evident autonomic neuropathy  group dn  n   6  to further define the usefulness of duplex examination in the evaluation of the mesenteric circulation in normal and disease states  by use of a 3 mhz duplex scanner  peak systolic velocity  peak diastolic forward velocity  end diastolic forward velocity  and peak diastolic reverse velocity were measured in centimeters per second before and after a standardized meal  the vessels  diameters in centimeters were also measured  after the meal peak diastolic reverse velocity disappeared in all patients  the average vessel diameter in the superior mesenteric artery  0 7 cm  and celiac artery  0 8 cm  did not change  flow velocities in the celiac artery were not significantly altered by the meal  in the control group  peak systolic velocity in the superior mesenteric artery increased 38   peak diastolic forward velocity rose 66   and end diastolic forward velocity increased by 70   in the diabetic nonneuropathic group the changes were 15   98   and 100   respectively  these changes were statistically significant  p less than 0 01   on the other hand  the patients with diabetic autonomic neuropathy presenting a picture of gastroparesis did not exhibit the expected increases in postprandial velocities  moreover  this alteration in blood flow velocity  although similar to that encountered in patients with intestinal angina  did not appear to be due to occlusive arterial disease on the basis of clinical examination and b mode scanning  
class6	the effects of nonthyroid disease and drugs on thyroid function tests  serious nonthyroid illness and caloric deprivation  which so often accompany systemic illness  have diverse and still incompletely understood effects on thyroid hormone economy  we have discussed the pathophysiologic basis for the most common pattern of alterations in routine thyroid function tests  a decreased serum t3 concentration  normal or  in critically ill patients  a low total serum t4 level  and a normal free t4 concentration  another  less frequent pattern  high total and free t4 with a normal serum t3  can be encountered transiently in the acutely ill medical or psychiatric patient  with the recent advent of sensitive assays for tsh and better methods for serum free t4  it is now possible to define more quickly and accurately the thyroid metabolic status of most of these sick patients  the vast majority are euthyroid  certain drugs confound the picture  the most important of these include dopamine and high dose glucocorticoids  both of which suppress tsh secretion from the pituitary and may actually cause a state of central hypothyroidism  other drugs have multiple effects on thyroid hormone indices  e g   amiodarone   knowledge of all of the ways in which systemic illness  starvation  and certain drugs may influence thyroid function tests is crucial in assessing the thyroid status of patients with serious nonthyroid disease  
class6	elevated plasma aluminum levels in normal infants receiving antacids containing aluminum  aluminum toxicity is a documented cause of encephalopathy  anemia  and osteomalacia  excretion is primarily renal  therefore  patients with renal insufficiency are at risk for aluminum accumulation and toxicity  this has been demonstrated in uremic children treated with aluminum containing antacids  the purpose of this study was to determine whether plasma aluminum levels were elevated in infants with normal renal function during prolonged aluminum containing antacid use  ten study infants  mean age   5 8 months   who had been receiving antacids for at least 1 week  were compared with 16 control infants  mean age   9 8 months  not receiving antacids  the study patients consumed 123     16 mg kg per day  mean     sem  of elemental aluminum for an average of 4 7 weeks  their plasma aluminum level  37 2     7 13 micrograms l  was significantly greater than that of the control group  4 13     0 66 micrograms l   p less than  005   it is concluded that plasma aluminum levels may become elevated in infants with normal renal function who are consuming high doses of aluminum containing antacids  the safety of antacids containing aluminum should not be assumed and they should be used judiciously in infants  with careful monitoring of the aluminum dose and plasma level  
class6	gi symptoms  function  and psychophysiological arousal in dysmenorrheic women  in a previous study  gastrointestinal  gi  symptoms and stool characteristics were found to be influenced by menstrual cycle phase  the current study was designed to replicate initial work regarding gi symptoms and stool characteristics and to explore the relationships between gi symptoms  stool characteristics  ovarian hormone levels  and indicators of psychophysiological arousal  fifty women  dysmenorrheic  n   22  nondysmenorrheic  n   28  maintained a daily dairy for recording stool characteristics  gi symptoms  and daily anxiety level  first morning void urine specimens for catecholamine assays and serum samples for ovarian hormone and cortisol determinations were obtained at menses  follicular  and luteal phases  results showed menstrual cycle related differences in stool characteristics and report of gi symptoms  with the greatest changes occurring at menses in the total sample  dysmenorrheic women reported higher levels of all gi symptoms at menses as compared to nondysmenorrheic women  in addition  cycle related differences in serum cortisol  urine catecholamines  and report of anxiety were also noted  particularly in dysmenorrheic women  however  looser stools and gi symptoms at menses were not correlated with absolute levels of ovarian hormones or indicators of psychophysiological arousal  
class6	pancreatic response to percutaneous biliary drainage  a prospective study  to evaluate the effects of percutaneous biliary drainage  pbd  on the pancreas  serum amylase levels were measured for 7 consecutive days after pbd and compared with baseline values in 50 patients who underwent a total of 53 pbd procedures  of the 45 patients with normal baseline serum amylase levels  12 patients  24   developed postprocedural hyperamylasemia without clinical symptoms and five patients  10   developed postprocedural hyperamylasemia with clinical signs of pancreatitis  five patients who presented with elevated baseline serum amylase levels demonstrated decreases into the normal range after placement of stents without initiation of bowel rest or liquid diet  the level of biliary obstruction proved insignificant  as did the nature of the obstructing disease  in determining which patients would experience hyperamylasemia or pancreatitis after pbd  it is concluded that the frequency of pancreatic insult from pbd may be more common than previously reported and that patient susceptibility is not dependent on the level of biliary obstruction or the nature of the disease  
class6	gastric emptying in infants and children  limited utility of 1 hour measurement  gastric emptying measurements were performed in infants and children at 1 and 2 hours after a liquid feeding  the 1 hour measurements were predictive of only 58  of the variability in the 2 hour measurements  indicating that the 1 hour measurement was not a good predictor of the 2 hour measurement  gastric emptying measurements in children should be continued until 2 hours after feeding unless rapid emptying is observed during the 1st hour of the study  
class6	gallstone lithotripsy  relevant physical principles and technical issues  a basic understanding of shock wave generation is essential for the radiologist who performs gallstone lithotripsy  shock waves differ from ordinary acoustic waves in that they have a rapid rise time  a positive pressure component that gives rise to compressive forces approaching 1 000 atm  and a low amplitude sustained negative pressure  rarefactive  component  shock waves are created by means of three different types of shock wave generators  spark gap  electromagnetic  and piezoelectric  the authors describe and compare these three types of shock wave generators with regard to equipment selection  regardless of how shock waves are generated  they share common interactions with tissue  these interactions are reviewed along with the proposed mechanisms of stone fragmentation  
class6	rectal strictures  treatment with fluoroscopically guided balloon dilation  the authors performed 25 fluoroscopically guided balloon dilation procedures in nine patients with rectal strictures  in all cases  the stricture developed after rectal surgery  four patients underwent ileoanal anastomosis after total colectomy for various conditions  five patients underwent rectosigmoid end to end anastomosis after resection of a tumor or as treatment for diverticulitis  maximal stricture dilatation was attained in 20 instances with a single 15 30 mm balloon  in five procedures  two balloons  20 or 15 mm  were inflated simultaneously   kissing balloons  technique  to dilate the strictures  in five patients  only one dilation procedure was required for effective treatment of the strictures  with no clinical evidence of strictures after follow up of 1 5 56 months  mean  29 5 months   in the other four patients  multiple procedures were performed  nine in one patient  five in one patient  and three in two patients  in these patients  no recurrent symptoms developed during follow up of 1 25 18 months  mean  8 1 months  after the last dilation  complicating leaks  infection  or hemorrhage did not occur after any of the procedures  fluoroscopically guided balloon dilation is a safe and effective procedure for the treatment of rectal strictures  
class6	air in the fissure for the ligamentum teres  new sign of intraperitoneal air on plain radiographs  in each of four patients in whom an acute spontaneous pneumoperitoneum developed  a vertically directed area of hyperlucency in the right upper quadrant was seen on radiographs of the abdomen obtained with the patient supine  this finding  which appeared in the absence of other characteristic signs of free air on plain radiographs and which  to the authors  knowledge  has not been previously recognized  represented intraperitoneal gas confined to the fissure for the ligamentum teres  flt   the location of the hyperlucent area was confirmed with computed tomography or laparotomy in each patient  the distinctive configuration of air in the flt is a subtle but reliable indicator of pneumoperitoneum  
class6	benign and malignant nodules in cirrhotic livers  distinction based on blood supply  the blood supplies of nodular lesions associated with liver cirrhosis were analyzed in vivo with various imaging modalities  the portal blood supply was evaluated with computed tomography  ct  during arterial portography  ctap   the arterial blood supply was evaluated with hepatic angiography  ct angiography  ct following intraarterial injection of iodized oil  or ultrasound following intraarterial injection of carbon dioxide microbubbles  a total of 84 surgically confirmed hepatocellular carcinomas  hccs   less than or equal to 3 cm  and 25 areas of adenomatous hyperplasia  ah  were included in the study  at ctap  a portal blood supply was seen in 96  of cases of ah and only 6  of hccs  chi 2  p less than  005   in contrast  an arterial supply greater than that of the surrounding liver was verified in 94  of the hccs and only 4  of the cases of ah  chi 2  p less than  005   the blood supply of areas of ah with atypical hepatocytes and the blood supply of well differentiated hccs  edmondson grade 1  tended to be intermediate between that of ah without atypia and that of hcc that was edmondson and steiner grade 2 or greater  evaluation of the blood supply of the nodular lesions associated with liver cirrhosis is considered to be useful in the differential diagnosis and treatment of early stage hcc  
class6	extracorporeal shock wave lithotripsy of gallstones  results and 6 month follow up in 141 patients  a study of biliary shock wave lithotripsy of gallstones sponsored by dornier medical systems  munich  began in the united states in may 1988 to evaluate the efficacy and safety of extracorporeal shock wave lithotripsy  eswl  and the need for adjunctive therapy with ursodeoxycholic acid  udca   one hundred forty one symptomatic patients with one to three gallstones 5 30 mm in diameter were randomized to treatment  one week before eswl  patients were given either udca or placebo  this treatment was continued for 6 months  all patients underwent follow up at predetermined intervals  according to the protocol  re treatment for fragments larger than 5 mm in diameter could be performed only at 6 weeks  26  18   of the 141 patients were retreated  at 6 months  the stone free rates for single stones were as follows  patients with noncalcified stones receiving udca  29   patients with noncalcified stones receiving placebo  24   and patients with partially calcified stones receiving either udca or placebo  6   no significant difference was noted between the udca and placebo groups  at 6 months  the stone free rates in patients with single  noncalcified stones 20 mm or less in diameter were 40   udca  and 32   placebo   which is superior to rates for those with solitary  noncalcified gallstones 21 30 mm in diameter and those with two or three stones  
class6	liver cirrhosis  changes of doppler waveform of hepatic veins  published erratum appears in radiology 1991 aug 100 2  586  the authors compared the doppler ultrasonographic pattern of hepatic veins  hvs  in a group of 60 patients affected by liver cirrhosis and in 65 healthy subjects comparable for sex and age to  a  detect possible differences in hv waveform in the two groups and  b  investigate the relationship of these differences with the severity of the disease  according to child pugh classification  and the modifications of systemic hemodynamics  the waveform of hvs was arbitrarily classified into three patterns  hv0  a normal waveform  hv1  lower oscillations without the reversed phase  and hv2  completely flat waveform  the resistivity index of the superior mesenteric artery  reflecting the peripheral splanchnic impedance and the hyperdynamic circulation  was also measured in a subgroup of 45 cirrhotic patients  the waveform of hvs in all healthy subjects corresponded to the hv0 pattern  among cirrhotic patients  hv0 was found in 30  50    hv1 in 19  31 7    and hv2 in 11  81 3    the severity of functional impairment was greatest in the hv2 group and least in the hv0 group  this was significantly correlated with the decrease of the resistivity index in the superior mesenteric artery in the subgroup of 45 patients  changes in the normal hv waveform could be considered a useful adjunctive tool for the noninvasive evaluation of liver disease  the pathophysiology of these changes in hv blood flow is still unclear  the significant correlation with the severity of the disease and with the decrease of splanchnic resistances indicates that these changes in the hv waveform occur in the presence of marked rearrangements of liver tissue and of hyperdynamic systemic circulation  
class6	gastric antral vascular ectasia   watermelon stomach    radiologic findings  radiologic findings in a patient with gastric antral vascular ectasia are described on computed tomographic scans  upper gastrointestinal series  and specimen radiographs  findings include prominent  scalloped antral folds radiating to the pylorus and thickening of the gastric antrum  pathognomonic red vascular folds  likened to stripes on a watermelon  can be seen endoscopically  
class6	acute lower respiratory tract infections in hospitalized patients with diarrhea in dhaka  bangladesh  this study focused on 401 children less than 5 years old who were hospitalized with acute lower respiratory tract infection  alri  and diarrhea in dhaka  bangladesh  and who were investigated for the presence of both bacterial and viral respiratory tract pathogens as well as for selected diarrheal pathogens  the most common manifestations of alri were pneumonia  374 cases   bronchiolitis  12 cases   and tracheobronchitis  11 cases   the majority  77   of the illnesses were in children less than 2 years of age  and 88  of the children were malnourished  a respiratory tract pathogen was identified in 30  of the patients  and a diarrheal pathogen was identified in 34   the overall case fatality rate in children with alri and diarrhea was 8   the case fatality rate was 14  in children with bacterial pneumonia and diarrhea  3  in those with viral pneumonia and diarrhea  and 14  in malnourished children with shigellosis and alri  the most common respiratory tract pathogens were respiratory syncytial virus  streptococcus pneumoniae  influenza viruses  and haemophilus influenzae type b  
class6	achieving ph control in the critically ill patient  the role of continuous infusion of h2 receptor antagonists  stress related gastric mucosal damage is a common occurrence in intensive care unit  icu  patients  because of the significant morbidity and mortality associated with this mucosal damage  many icu patients routinely receive prophylactic therapy  usually with histamine h2 receptor antagonists  h2ras   gastric acid secretion occurs in a circadian pattern  with late afternoon and evening surges  h2ras by continuous infusion may control this uneven pattern of secretion more effectively than h2ras given by bolus injection  more studies are needed to identify the target icu population for prophylactic treatment  
class6	hemodynamic effects of h2 receptor antagonists  histamine h2 receptor antagonists  h2ras  often are administered to intensive care unit patients in an attempt to reduce gastric acidity and to prevent stress related mucosal damage  these agents have an extremely low overall incidence and severity of adverse reactions  however  hemodynamically significant hypotension has been noted  clinical studies with rapidly administered intravenous cimetidine in critically ill patients have demonstrated a depression in blood pressure in up to 75 percent of patients  ranitidine  also studied in this setting  does not appear to induce similar hemodynamic changes  the newer h2ras  famotidine and nizatidine  have not been evaluated in critically ill patients  
class6	use of h2 receptor antagonists in children  h2 receptor antagonists  h2ras  have evolved into the mainstay of anti acid therapy for pediatric patients  replacing antacids and other modes of therapy  much of the experience and data used for therapeutic decisions in children  however  have been extrapolated from adult studies  ranitidine and cimetidine have been studied most extensively in the adult and pediatric populations  both raise gastric ph and achieve other therapeutic endpoints  however  cimetidine appears to have a greater frequency of both adversed effects and drug interactions  h2ras are the preferred agents for prevention of stress ulcers  ulcer disease  and reflux esophagitis in the pediatric population  
class6	sclerotherapy for esophageal varices  endoscopic injection sclerotherapy  eis  frequently is used for patients with esophageal varices  both for controlling acute hemorrhage and for prophylaxis  an old technique  interest in eis increased when other methods did not improve patient outcomes  clinical trials of eis for acute hemorrhage demonstrated efficacy and improved outcome  although some researchers disagree with these findings  recent data on prophylaxis with eis fail to support the value of eis for this indication  ethanolamine oleate compares favorably with other sclerosing agents  and is the only one currently approved for eis  the intravariceal method is used more frequently than the paravariceal method because it has better efficacy and can be performed more rapidly  the percentage of patients developing significant complications from eis may be as high as 15 percent  common complications include retrosternal pain  pyrexia  and sepsis  eis is currently an important clinical tool in the management of esophageal varices  
class6	pathophysiologic changes in the critically ill patient  risk factors for ulceration and altered drug metabolism  virtually all patients who are under the physiologic stress of an intensive care unit  icu  are vulnerable to stress related mucosal damage and ulceration  although clinically significant hemorrhage from stress ulceration occurs in only 5 20 percent of patients in the icu  the associated mortality is greater than 50 percent  the pathophysiologic mechanisms of stress ulcer are not well understood  however  a number of risk factors such as intraluminal gastric acidity and mucosal ischemia have been implicated  to prevent the development of stress ulcers and subsequent complications  it is important to identify and correct these underlying risk factors  improving mucosal blood flow  i e   fluid resuscitation and low dose dopamine  and providing adequate nutritional support are invaluable adjuncts in minimizing the risk of stress ulcer formation  the use of pharmacologic prophylaxis controls the gastric acidity and prevents the formation of stress ulcers  the potential for drug induced adverse effects and drug drug interactions are of particular concern in the care of critically ill patients  multiple organ system dysfunction or failure  malnutrition  fluid and electrolyte abnormalities  as well as the use of multiple pharmacologic agents predispose these patients to alterations in drug pharmacokinetics  drug induced adverse effects and drug drug interactions  these changes may alter the pharmacodynamic response to therapy and must be considered when designing drug dosage regimens for critically ill patients  
class6	ondansetron  a new entity in emesis control  nausea and vomiting are serious problems for patients receiving cancer chemotherapy  dopamine receptor and cholinergic receptor antagonism have been the target mechanism for agents used to combat drug induced nausea and vomiting  more recently  blockade of serotonin receptors has been used for this indication  current therapies are limited by extrapyramidal adverse effects  as well as drowsiness  sedation  respiratory depression  and cardiac effects  ondansetron is an investigational serotonin antagonist that has documented effectiveness for cancer chemotherapy induced emesis  ondansetron appears to be well tolerated  with the possible exception of headaches and transient increases in liver enzymes  no extrapyramidal toxicities have been reported with this agent  while ondansetron looks promising  further studies are needed to fully define its role as an antiemetic  
class6	pathophysiology  monitoring  and management of the ventilator dependent patient  considerations for drug therapy  emphasis on stress ulcer prophylaxis  adult respiratory distress syndrome  ards   or noncardiac pulmonary edema  is a form of acute hypoxemic respiratory failure  the goals of treatment for patients with ards are to provide supportive therapy  to reverse the underlying etiology or pathology  and to prevent subsequent complications  supportive therapy consists of supplemental oxygen  positive end expiratory pressure  and  often  mechanical ventilation  the reversal of the underlying pathology varies according to the etiologic origin of ards  complications from ards include stress ulcers  which occur when gastric aggressive and defensive functions become unbalanced  antacids and cytoprotective agents are used for stress ulcer prophylaxis  but histamine h2 receptor antagonists are now regarded as the standard of care  because all the marketed h2 receptor antagonists are efficacious  choice of the agent is based on the adverse effect profile and drug interactions  no definitive data currently exist linking stress ulcer prophylaxis regimens that raise intragastric ph to a significant risk for nosocomial pneumonia  
class6	surgical management of nonparasitic cystic liver disease  we report clinical features  surgical management  recurrences  and follow up study of 12 patients with simple hepatic cyst  11 patients with polycystic liver disease  and 19 patients with cystadenoma who were surgically treated over a 25 year period  the median age of patients was 48 years  and 37 women and 5 men were in the series  the most common presenting symptom and physical finding were chronic abdominal pain and tenderness in the right upper quadrant  the most commonly associated disease was polycystic kidney disease  which was an associated finding in 5 of the 11 patients with polycystic liver disease  45    the most valuable diagnostic studies in all groups were computed tomography and ultrasonography  the location of the disease was bilobar in patients with polycystic liver disease  with a right lobe predominance in 18  of patients  the right lobe was also predominant in 83  of patients with simple hepatic cyst and 58  of patients with cystadenoma  of all solitary cystic lesions in the left lobe  75  of them were cystadenomas  of the 66 surgical procedures performed  aspiration was associated with a failure rate of 100   partial excision  a failure rate of 61   and total excision and liver resection  a failure rate of 0   orthotopic liver transplantation was performed in three patients and was associated with two early deaths  partial excision relieved symptoms in three patients  43   with polycystic liver disease  total excision  enucleation  or liver resection with cyst s  is the treatment of choice for non parasitic cystic lesions of the liver  
class6	glucose intolerance and hyperinsulinemia of cirrhosis are not results of spontaneous or surgical portosystemic shunting  to assess if spontaneous portosystemic shunting from collaterals contributes to the hyperinsulinemia of cirrhosis  12 patients with alcoholic cirrhosis underwent a 5 hour oral glucose tolerance test 1 day before and 10 days after an elective side to side portacaval shunt  the glucose  insulin  and c peptide responses to oral glucose post shunt were exaggerated but comparable to preoperative values  compared with preoperative values  the fasting molar ratio of c peptide to insulin postoperatively had increased 40   6 0     1 2 versus 8 4     0 7   indicating improved hepatic function  these results suggest that extrahepatic portosystemic shunting secondary to spontaneous splanchnic collaterals plays little or no role in the hyperinsulinemia of cirrhosis  it appears that decreased hepatic degradation of insulin in these patients is secondary to hepatocellular dysfunction rather than a result of shunting of portal blood around the liver  
class6	prospective study of a prosthetic h graft portacaval shunt  this study was undertaken to prospectively evaluate the 8 mm gore tex interposition h graft portacaval shunt  thirty six high risk patients at the university of south florida affiliated hospitals received small diameter shunts because of bleeding esophagogastric varices over a recent 2 year period  portal vein and portal vein inferior vena cava gradients were significantly reduced after shunting  these pressure changes were manifested clinically by the absence of variceal rebleeding and improvement of ascites  in addition  the incidence of encephalopathy was low  the 8 mm graft maintained hepatopedal flow in 67  of the patients  but reversal of flow did not result in complications commonly associated with poor portal perfusion  graft thrombosis occurred in four  11   patients  all grafts were successfully revised  three by operative revision and one by an interventional radiologist  operative mortality was low  11    and morbidity was unusual  the small diameter h graft portacaval shunt is a safe and effective method of treatment for bleeding esophagogastric varices  
class6	why does somatostatin cause gallstones  long term administration of the somatostatin analogue  octreotide  is complicated by gallstone formation  somatostatin is known to inhibit hepatic bile secretion and gallbladder emptying  however  the effect of octreotide on gallbladder bile composition remains unknown  therefore  we tested the hypothesis that octretide would alter hepatic bile composition and cause gallbladder stasis  thereby increasing gallbladder bile solute concentrations  fourteen control prairie dogs received daily saline injections  whereas 10 animals received 1 micrograms of octreotide subcutaneously three times per day for 5 days  cholecystectomy and common bile duct cannulation were then performed  octreotide increased hepatic bile concentrations of bilirubin monoglucuronide  p less than 0 05   total bilirubin  p less than 0 05   and total protein  p less than 0 01   rsa  an index of gallbladder stasis  was decreased  p less than 0 01  in the octreotide group  gallbladder bile total calcium  p less than 0 05   bilirubin monoglucuronide  p less than 0 05   total bilirubin  p less than 0 01   total protein  p less than 0 05   and total lipids  p less than 0 05  were increased in the octreotide group  animals receiving octreotide also had decreased hepatic  p less than 0 05  and gallbladder  p less than 0 001  bile ph  no differences in cholesterol saturation index were observed  these data suggest that in the prairie dog  octreotide  1  alters hepatic bile composition   2  causes gallbladder stasis  and  3  increases gallbladder bile calcium  bilirubin  protein  lipid  and hydrogen ion concentrations  we conclude that octreotide causes alterations in gallbladder bile composition that increase the likelihood of cholesterol and calcium bilirubinate precipitation  
class6	a prospective longitudinal study of observation versus surgical intervention in the management of necrotizing pancreatitis  pancreatic necrosis is now recognized as a principal determinant of survival in acute pancreatitis  however  it is currently unknown how frequently pancreatic necrosis develops in acute pancreatitis  how often pancreatic necrosis becomes secondarily infected  and whether sterile pancreatic necrosis represents an indication for surgery or can be treated by conservative means  in 194 patients with unequivocal acute pancreatitis  pancreatic necrosis developed in 38  20    as documented by dynamic pancreatography  and was confirmed by histologic diagnosis at surgery in 28  all patients were prospectively treated by medical means  patients with pancreatic necrosis who remained persistently febrile underwent fine needle aspiration for bacterial culture  infected pancreatic necrosis was demonstrated in 27 of the 38 patients  71   with pancreatic necrosis and was treated by open drainage  yielding a mortality rate of 15   all 11 patients with demonstrated sterile pancreatic necrosis  including 6 with pulmonary and renal insufficiency  were successfully treated without surgery  pancreatic necrosis occurs in approximately 20  of patients with acute pancreatitis and is necessary for the development of secondary pancreatic infection  however  pancreatic necrosis by itself  even when accompanied by organ failure  is not an absolute indication for surgery  a trial of medical treatment for all patients with sterile pancreatic necrosis is in order  
class6	proximal gastric vagotomy in the emergency treatment of bleeding duodenal ulcer  proximal gastric vagotomy for bleeding duodenal ulcer was performed in 52 low risk patients between 1973 and 1986  duodenotomy without violation of the pylorus was done in all patients to allow inspection and control of the bleeding site  the median duration of operation was 3 hours and 20 minutes  although 25  of the procedures required 4 or more hours  there was no postoperative mortality and no early reoperations  among the six patients with postoperative complications  one rebled from the ulcer and two developed prolonged gastric atony  at the time of follow up  median  2 9 years   48 of the patients were alive and 4 had died of non ulcer causes  no patient had significant postvagotomy sequelae  ulcer recurrence was documented in six patients  and three required reoperation  proximal gastric vagotomy is a safe  effective therapy for bleeding duodenal ulcer  because of the length of the operation  it should be restricted to low risk patients who are hemodynamically stable at the time of operation  
class6	nonsteroidal anti inflammatory drug use and increased risk for peptic ulcer disease in elderly persons  objective  to evaluate the relative risk for peptic ulcer disease that is associated with the use of nonaspirin nonsteroidal anti inflammatory drugs  design  nested case control study  setting  tennessee medicaid program  participants  medicaid enrollees 65 years of age or older were included in the study  the 1415 case patients had been hospitalized for confirmed peptic ulcer disease at some point from 1984 through 1986  the 7063 control persons represented a stratified random sample of other medicaid enrollees  measurements and main results  the estimated relative risk for the development of peptic ulcer disease among current users of nonaspirin nonsteroidal anti inflammatory drugs  compared with that among nonusers  was 4 1  95  ci  3 5 to 4 7   for current users  the risk increased with increasing dose  from a relative risk of 2 8  ci  1 8 to 4 3  for the lowest to a relative risk of 8 0  ci  4 4 to 14 8  for the highest dose category  the risk was greatest in the first month of use  relative risk  7 2  ci  4 9 to 10 5   if the association is fully causal  29  of peptic ulcers in the study sample resulted from the use of these drugs  and the excess risk associated with such use was 17 4 hospitalizations for ulcer disease per 1000 person years of exposure  conclusions  these data support other findings indicating that a clinically significant risk for serious ulcer disease is associated with the use of nonaspirin nonsteroidal anti inflammatory drugs  the data show that this risk increases with dose and recency of use and that use of these drugs may be responsible for a large proportion of peptic ulcer disease among elderly persons  
class6	the munich gallbladder lithotripsy study  results of the first 5 years with 711 patients  objective  to evaluate the long term results of three types of shock wave treatment in patients with radiolucent gallbladder stones  design  cohort study  setting  single center trial  patients  of 5824 patients with gallstones  19  were eligible  711 patients were treated  interventions  patients received extracorporeal shock wave lithotripsy as well as adjuvant therapy with bile acids  results  lithotripsy was done in three ways  using a water tank lithotriptor  group a   a water cushion lithotriptor at low energy levels  group b   and a water cushion lithotriptor at high energy levels  group c   the rate of complete fragment clearance 9 to 12 months after lithotripsy was done differed significantly among the three groups  among patients with single stones of 20 mm or less in diameter  the rate of fragment clearance for group a was 76   for group b  it was 60   and for group c  it was 83   p   0 03   among patients with single stones of 21 to 30 mm  the rate of fragment clearance for group a was 63   for group b  it was 32   and for group c  it was 58   p less than 0 005   among patients with two or three stones  the rate of fragment clearance for group a was 38   for group b  it was 16   and for group c  it was 46   p   0 01   patients with fragments of 3 mm or less 24 hours after lithotripsy was done showed a higher probability of fragment disappearance than did those with larger fragments  p less than 0 001   the clearance rate was higher in patients who were compliant than in those who were noncompliant with bile acid therapy  p less than 0 001   adverse effects included liver hematoma in 1 patients  biliary pain attacks in 253 patients  36    mild biliary pancreatitis in 13 patients  2    and cholestasis in 7 patients  1    elective cholecystectomy was done in 16 patients  2    and endoscopic sphincterotomy was done in 4 patients  1    conclusions  the rate of complete disappearance of stones after shock wave therapy depends on the size and the number of the initial stones  the diameter of the largest fragment  and the mode of shock wave treatment  adjuvant therapy with bile acids appears to be important for complete fragment clearance  
class6	nonsteroidal anti inflammatory drugs and peptic ulcer disease  evidence has accumulated that nonsteroidal anti inflammatory drugs  nsaids  cause clinically important gastroduodenal ulcers  the pathogenesis  which involves the impairment of mucosal resistance to injury in an acid peptic environment  is multifactorial and controversial  ulcers caused by nsaids can occur either in mucosa inflamed because of infection with helicobacter pylori or in histologically normal mucosa  the use of these drugs has been linked to an unexpectedly high incidence of ulcer complications  and a history of peptic ulcer disease is common in such cases  nonsteroidal anti inflammatory drugs thus appear both to exacerbate an underlying peptic diathesis and to cause de novo ulcers  the association between the use of these drugs and ulcer complications is supported by ulcer prevalence data from cross sectional studies  and by data from case controlled and cohort studies  and from randomized  experimental trials  drug induced gastric ulcers have been prevented by misoprostol  but not by h2 blocker therapy  several therapies have been reported to promote ulcer healing despite continued use of nsaids  but adequate controlled trials have not been done  small gastric and duodenal ulcers readily heal  whereas larger gastric ulcers require vigorous and prolonged therapy  the relative efficacies of various therapies in preventing ulcers  healing ulcers  or preventing complications remain to be established  
class6	microbiological studies of the enterocolitis of hirschsprung s disease  the results of a prospective study of 20 cases of newly diagnosed hirschsprung s disease  nine of whom developed enterocolitis  and 10 normal controls showed no variations in the bacterial flora  including clostridium difficile  in the stools of the groups studied  viral studies showed that rotavirus was present in the stools of seven of the nine cases of enterocolitis during the episode  we suggest that hirschsprung s enterocolitis may have a complex infective aetiology and that rotavirus plays a part  
class6	psychological characteristics of children with shwachman syndrome  twelve children and young adults with shwachman syndrome were compared with their unaffected siblings and with controls suffering from cystic fibrosis in terms of intellectual ability  motor skills  and behaviour  there were highly significant differences in intelligence quotient between those with shwachman syndrome and the other two groups  four of the index subjects but none of the control subjects were below the normal range  the differences between groups on other tests of cognitive and motor skills were not significant  though those with shwachman syndrome tended to have the lowest scores  there was no evidence that those with shwachman syndrome had more behavioural difficulties than the control subjects  we suggest that the intellectual difficulties of patients with shwachman syndrome may be of neurological rather than social origin and that they may originate before birth  
class6	fatal embolization of intestinal contents through a duodenocaval fistula  embolization of intestinal contents to the lung is an exceedingly rare event  which to our knowledge  has never been reported as a cause of death  equally rare is duodenocaval fistula resulting from a penetrating duodenal peptic ulcer  we present the case of a 51 year old man whose duodenal ulcer led to a fistulous tract with the inferior vena cava and subsequently to progressive pulmonary embolization of intestinal contents  ultimately resulting in death from respiratory failure  
class6	early antibiotic treatment of reactive arthritis associated with enteric infections  clinical and serological study  objective  to find out whether a 10 14 days  course of antibiotics early in the course of reactive arthritis associated with enteric infections could reduce the severity and duration of the disease and whether the antibody response in patients with reactive arthritis associated with yersinia infection differed between those treated and those not treated with the antibiotics  design  prospective multicentre trial in which patients were randomised to treatment or no treatment with antibiotics  patients were seen at three and six weeks and three  six  nine  12  and 18 months after their first visit  setting  departments of infectious diseases in three hospitals in linkoping  malmo  and stockholm  sweden  patients  40 consecutive patients who had had symptoms of reactive arthritis associated with enteric infection for less than four weeks  interventions  20 patients were allocated to treatment with antibiotics and 20 patients did not receive antibiotics  all patients received non steroidal anti inflammatory drugs  and four also received intra articular steroid injections after at least six weeks  observation  main outcome measures  arthritic symptoms assessed clinically and by using ritchies  index  blood measurements reflecting inflammatory activity  serum igg  igm  and iga antibody titres  hla tissue type  results  no difference was observed concerning duration of arthritis  grade of inflammation  and number of joints affected between patients treated and those not treated with antibiotics  furthermore  there was no significant difference between the two groups in erythrocyte sedimentation rate and haptoglobin  igg  and iga concentrations  all values had returned to normal within three months  no patient developed chronic arthritis  but sustained slight arthralgia occurred in three patients  the hla b27 antigen was found in 23  58   of the patients  and its presence did not affect clinical outcome  the igg  igm  and iga antibody responses were similar in patients treated with antibiotics and those not treated  conclusion  short term antibiotic treatment has no beneficial effect on the clinical outcome of reactive arthritis associated with enteric infection  
class6	stationary vs  mapping manometry in evaluating dysphagia  two methods are used to assess esophageal motility  the mapping technique uses catheter withdrawal at 1 cm steps until the entire esophagus is evaluated  a simpler method is commonly used that involves keeping the catheter stationary for the entire evaluation  we compared these 2 techniques in 30 patients referred for the evaluation of dysphagia  emphasis was placed on the distal 10 cm of the esophagus because this is the primary location of esophageal motility disorders  there was excellent correlation between techniques for mean distal amplitude  r   0 945   mean distal duration  r   0 942   and percentage of non peristaltic contractions  r   0 967   the overall manometry diagnosis was similar by both methods in 27  90   patients  three patients had different manometry diagnoses resulting from use of the two techniques  however  the change in diagnosis was only clinically important in one patient in whom the mapping technique identified a segmental motility disorder that had been missed by the stationary technique  stationary manometry had a 94  sensitivity and 93  specificity rate for identifying motility disorders compared to mapping manometry  we conclude that stationary manometry is a simple and accurate method for evaluating esophageal pressures and distal disorders  only those patients with normal results of stationary studies may benefit by further mapping to identify rare segmental motility disorders  
class6	radiographic techniques and efficacy in evaluating esophageal dysphagia  the radiographic examination of the esophagus to determine structural and or functional causes of dysphagia is best performed with multiple techniques  these include full column studies to produce distended films with or without the use of a solid bolus  mucosal relief films to identify mucosal defects such as esophagitis or the presence of varices  double contrast films  and motion recording  fluoroscopy   the efficacy of each technique depends on the quality of the study and the specific disorder to be detected  esophageal lesions producing dysphagia are classified into extrinsic structural lesions  intrinsic structural lesions  and esophageal motility disorders  radiographic studies are the preferred screening techniques for patients with dysphagia  although not as sensitive for the evaluation of mucosal lesions  radiographic studies are superior to endoscopy for the detection of abnormal motility  esophageal rings  and strictures  
class6	scleroderma esophagus  scleroderma  systemic sclerosis  is a connective tissue disorder characterized by thickening and fibrosis of the skin and visceral involvement that may include the heart  lungs  kidneys  and gastrointestinal tract  at least 40 50  of patients with scleroderma experience esophageal symptoms such as heartburn and dysphagia  while up to 90  of patients have esophageal dysfunction on objective testing at some point in their disease  the disease results in smooth muscle dysfunction that causes esophageal aperistalsis and reduced lower esophageal sphincter pressures  gastroesophageal reflux with poor acid clearance results with an increased incidence of complications such as peptic stricture and barrett s esophagus  aggressive medical therapy is necessary to prevent these and other complications of gastroesophageal reflux  
class6	esophageal motility  heartburn  and gastroesophageal reflux  variations in clinical presentation of esophageal dysphagia  dysphagia is a potentially important symptom  often leading to the finding of an anatomical or motility disorder of the esophagus  dysphagia and heartburn represent two of the most common symptoms associated with esophageal motility disorders  to explore the relationship of symptomatic esophageal dysphagia and heartburn and their association with primary esophageal motor disorders  we have performed a retrospective assessment of 1035 patient evaluations performed at our gastrointestinal laboratory  a clear statistical association of symptomatic dysphagia and heartburn was established  however  no pattern diagnostic of a specific motility disorder was discernible  a sizable fraction of our patient population with dysphagia demonstrated normal esophageal motility  a significant portion of dyspeptic patients exhibited both normal motility and acid exposure  the differences observed between the incidence of subjective symptoms and objective dysfunction may be explained in part by an altered or increased esophageal sensitivity of these patients  
class6	symptoms of achalasia in young women mistaken as indicating primary anorexia nervosa  the case of a young women with dysphagia  regurgitation  and weight loss  who was diagnosed as having anorexia nervosa but in whom reevaluation showed that achalasia was causing the symptoms  is presented together with related observations  misinterpretation of esophageal symptoms may occur not only as a consequence of inadequate history taking and of being biased by a patient s emaciation  age  and gender  which leads to view certain aspects of the patient s history and behavior as suggesting a pathologic attitude towards eating and body weight  but also as a consequence of a misinterpretation of the symptoms as indicative of an eating disorder by the patients themselves  in some cases a disordered attitude toward eating and body weight may develop together or coexist with achalasia  the clinical evaluation of patients with symptoms suggestive of anorexia nervosa but also of bulimia nervosa should include the taking of a thorough history regarding swallowing and vomiting in order to recognize a possible esophageal motor disorder  
class6	palliation of malignant esophageal obstruction  progressive dysphagia is common in patients with advanced esophageal carcinoma  multiple nonsurgical techniques are available to provide palliation and improved nutrition  simple dilatation is the oldest technique and newer methods may offer greater efficacy  laser therapy now provides an excellent opportunity to treat obstructing tumors  placement of an esophageal prosthesis may become particularly useful when dilatation must be performed too frequently or has become ineffective or in the patient with an esophageal pulmonary fistula  newer techniques including bicap tumor probe  intracavitary radiotherapy  or absolute alcohol injection offer promise  this review discusses the advantages and disadvantages of these different palliative techniques for patients with the extremely poor prognosis associated with esophageal cancer  
class6	esophageal perforation during pneumatic dilatation for achalasia  a possible association with malnutrition  pneumatic balloon dilatation of the lower esophageal sphincter is commonly utilized as primary therapy for achalasia  perforation related to pneumatic dilatation is uncommon  2 6   but may result in severe morbidity  factors associated with risk of perforation are not well defined  we noted perforation in three patients undergoing forceful balloon dilatation  all these patients had clinical evidence of significant malnutrition  recent marked weight loss and severe hypoalbuminemia   malnutrition may be a causal factor for perforation in patients with achalasia undergoing dilatation  
class6	prevalence of helicobacter pylori in specific forms of gastritis  further evidence supporting a pathogenic role for h  pylori in chronic nonspecific gastritis  helicobacter pylori colonization of the gastric mucosa is strongly associated with chronic nonspecific gastritis  moreover  there is evidence to suggest that h  pylori may cause this form of gastritis  however  there is little or no information on the prevalence of h  pylori in specific forms of gastritis  our hypothesis was that if h  pylori was pathogenic in chronic nonspecific gastritis  organisms would be found frequently in this type of gastritis but infrequently in specific forms of gastritis  prevalence rates of h  pylori were determined independently in patients with eosinophilic and crohn s gastritis  menetrier s disease  and chronic nonspecific gastritis  the prevalence of h  pylori in patients with chronic nonspecific gastritis was 71   whereas the organism was not identified in patients with any form of specific gastritis  this finding further supports the accumulating evidence that h  pylori is a primary pathogenic factor in chronic nonspecific gastritis  
class6	modulation of mediator release from human intestinal mast cells by sulfasalazine and 5 aminosalicylic acid  intestinal mast cells are thought to contribute to the mucosal inflammation in ulcerative colitis and crohn s disease through release of inflammatory mediators  since sulfasalazine and its metabolite 5 aminosalicylic acid are effective therapeutic agents in inflammatory bowel disease and have been shown to inhibit generation of inflammatory products in other cells  we examined the effect of these agents in vitro on human intestinal mast cell mediator release  sulfasalazine  5 x 10  4  10  3  m  was found to significantly enhance goat anti human ige induced histamine release from intestinal mast cells  which is the same response as seen in human blood basophils  whereas its metabolite 5 aminosalicylic acid was an effective inhibitor of stimulated histamine release in both mast cells and basophils  5 aminosalicylic acid also inhibited production of prostaglandin d2 by the stimulated intestinal mast cells  sulfasalazine alone  without immunologic stimulation  did not induce histamine release from mast cells or basophils  but the enhancement of ongoing mast cell activation by sulfasalazine may explain some cases of adverse reactions to the drug  the inhibition of mast cell histamine release and prostaglandin generation by 5 aminosalicylic acid demonstrates a potential therapeutic modality of this agent  
class6	rectal irrigation with short chain fatty acids for distal ulcerative colitis  preliminary report  colon cells from patients with ulcerative colitis utilize short chain fatty acids inefficiently and may be exposed to decreased concentrations of these compounds  to test whether irrigation of the inflamed mucosa with short chain fatty acids is useful  we conducted a six week preliminary trial in 12 patients with distal colitis  each patient used twice daily rectal irrigations with 100 ml of a solution containing acetate  80 mm   propionate  30 mm   and butyrate  40 mm   two patients stopped at three weeks  one because of no improvement and the other because of complete resolution of symptoms  of the 10 who completed the trial  nine were judged to be at least much improved and showed a change in a mean disease activity index score from 7 9     0 3  se  to 1 8     0 6  se   p less than or equal to 0 002  and in a mucosal histology score from 7 7     0 7  se  to 2 6     0 7  se   p less than or equal to 0 002   thus  ulcerative colitis patients appear to benefit from increased contact with or higher than usual levels of these critical energy substrates  
class6	gallstone dissolution with methyl tert butyl ether in 120 patients  efficacy and safety  of 612 patients with cholesterol gallbladder stones  120 were eligible for percutaneous transhepatic litholysis with methyl tert butyl ether  mtbe   puncture of the gallbladder was successful in 117 120  97 5    in 113 117  96 6   the stones dissolved  with solitary stones  treatment lasted for an average of 4 hr  with multiple stones 10 hr  mean hospitalization was 3 6 days  in 3 117  2 6   patients a bile leakage developed  33  reported mild complaints  after the end of treatment 34  had some residue in the gallbladder  two of these patients developed recurrent stones  mtbe is exhaled  is distributed in fatty tissue  and is excreted renally together with its metabolite tert butanol  methanol was found only in traces  gallbladder histology of six patients showed chronic cholecystitis  since these findings were independent of treatment time and the interval between treatment end and operation  they are most consistent with stone related changes rather than caused by mtbe  
class6	medical dissolution of gallstones  clinical experience of d limonene as a simple  safe  and effective solvent  retained gallstones in the bile ducts account for 60 70  of all the cases of postcholecystectomy syndromes  a solvent d limonene preparation was injected directly to the biliary system of 200 patients to dissolve or disintegrate the retained gallstones  the outcomes were  retained stones completely disappeared in 96 cases  48    partial dissolution in 29  14 5    chelating agent was also used with partial dissolution in 16  8    ineffective in 59  24 5    to make this method more effective  several guidelines should be observed including an in vitro trial dissolution test  cautious observation for possible side effects and frequent hepatic and pancreatic function tests during the treatment with this preparation also should be performed  
class6	evaluation of portal systemic shunting in rats from mesenteric and splenic beds  in rats with partial portal vein ligation  95     0 9  of the splenic blood flow is shunted from the portal to the systemic circulation when an intrasplenic injection of microspheres is used to determine the degree of shunting  despite this magnitude of portal systemic shunting  several biochemical and endocrine consequences of portal systemic shunting occur at levels below what is expected for the degree of shunting found  in an effort to resolve these discordant findings  shunting from both the splenic and the mesenteric bed was studied in anesthetized portal hypertensive rats with various degrees and or duration of portal vein stenosis  the shunting from the mesenteric bed averaged 66 7     29 9   range 5 1 99 1   and was influenced both by the degree and duration of portal vein stenosis  in contrast  shunting from the splenic bed averaged 97 3     4 0   range 79 99 9   and demonstrated no variation between groups determined by the degree of portal vein stenosis  the shunting from the splenic bed was consistently greater than that found from the mesenteric bed  mesenteric but not splenic shunting correlated with serum bile acid levels  mesenteric shunting was related inversely to the weight adjusted liver mass and to serum testosterone levels  based upon these data obtained in portal hypertensive rats  it is concluded that splenic injections of microspheres overestimate portal systemic shunting  in contrast  mesenteric injections of microspheres yield values for shunting that correlate well with independently determined biochemical and endocrine consequences of shunting  these observations support the validity of the mesenteric shunting measurements obtained  
class6	treatment of pruritus of primary biliary cirrhosis with rifampin  pruritus can be a debilitating symptom in patients with chronic cholestasis  based on previous reports of its efficacy  we evaluated the impact of rifampin on the pruritus associated with primary biliary cirrhosis  fourteen patients were included in a randomized  crossover study  after a 15 day washout period  subjects were followed for three weeks  during the first and third week  patients received 600 mg of rifampin or placebo  no treatment was administered during the second week  pruritus was subjectively scored on a scale from 0 to 100  with rifampin  pruritus disappeared in 11 patients and partially improved in three  with placebo  only two had a partial response  p less than 0 001   six patients with a prior poor or no response to cholestyramine improved with rifampin  no changes in biochemical tests or side effects were observed during this period  we conclude that short term administration of rifampin relieves pruritus in primary biliary cirrhosis  when administered over a period of eight months in an open study  the relief of pruritus was maintained  while one individual developed an allergic reaction  rifampin appears to be a safe drug in the management of the pruritus of primary biliary cirrhosis  
class6	achalasia in the elderly  effects of aging on clinical presentation and outcome  clinical and manometric data from 13 elderly subjects with idiopathic achalasia  mean age 79     2 years  were compared with findings from younger subjects with the same disease  n   79  to see if aging altered the presentation and outcome of this motor disorder  fewer elderly subjects complained of chest pain  27  vs 53    and the pain was significantly less severe  p less than 0 01   other presenting features  including sex  duration of symptoms  and presence and severity of dysphagia  did not differ between the groups  across all patients  age weakly and inversely correlated with residual postdeglutitive lower esophageal sphincter   les  pressure  r    0 34   and residual pressure was significantly lower in the older subjects  8 0     1 3 mm hg vs  11 9     0 8 mm hg  p   0 02   no differences in basal les pressure or esophageal body contraction amplitudes were present between the groups  initial success with pneumatic dilation was similar in the two subject groups  but the number of older subjects available for analysis was too small to draw strong conclusions  these results indicate that aging decreases the elevation of les residual pressure that occurs with achalasia  as elderly achalasia patients also present with less chest pain  the findings may be interrelated  
class6	prospective study on prevalence of esophageal chest pain in patients referred on an elective basis to a cardiac unit for suspected myocardial ischemia  the prevalence of esophageal chest pain was studied prospectively in patients referred on an elective basis to a cardiac unit for suspected myocardial ischemia  a group of 248 consecutive patients without previously documented heart disease was admitted for elective diagnostic coronary angiography  the clinical history classified 185 patients as having anginal pain and the coronary angiogram was normal in 48 of them  in 37 of these 48 patients full esophageal testing was performed including 24 hr intraesophageal ph and pressure recordings with indication of chest pain episodes as well as a number of esophageal provocation tests  ie  acid perfusion  edrophonium stimulation  balloon distension  and ergonovine stimulation  all performed under continuous esophageal manometric and electrocardiographic monitoring  in 19 of these 37 patients  the familiar chest pain could be reproduced by esophageal provocative testing without ischemic st t segment alterations  six of these 19 patients had also a positive 24 hr ph and pressure recording  these data strongly suggest an esophageal origin of chest pain in half the patients with typical angina and a normal coronary angiogram  
class6	ischemic colitis in a crack abuser  we report a case of acute colitis temporally associated with smoking crack  colonoscopy revealed a patchy left sided hemorrhagic inflammation from the rectosigmoid colon to the splenic flexure  biopsy specimens were consistent with resolving ischemic colitis  this entity should be considered in the differential diagnosis of acute bloody diarrhea in recreational drug users  
class6	islet cell carcinoma of the pancreas presenting as bleeding from isolated gastric varices  report of a case and review of the literature  gastrointestinal hemorrhage from left sided portal hypertension and gastric varices is an unusual presentation for islet cell carcinoma of the pancreas  islet cell tumors of the pancreas themselves are rare  they present in a variety of ways  those that elaborate functional hormones cause specific neuroendocrine syndromes  nonfunctional tumors characteristically present later with symptoms of metastatic disease or as a result of local enlargement  we present a case of islet cell carcinoma of the pancreas presenting with recurrent gastrointestinal bleeding from gastric varices and review the literature for this rare presentation  we emphasize the importance of a careful initial diagnostic work up that may enable curative surgery  
class6	pancreatic ascites presenting in infancy  with review of the literature  we report a 4 month old boy with massive ascites in whom a diagnosis of pancreatitis was made on a raised ascitic amylase level after two inconclusive laparotomies  he developed a pseudocyst which was managed with repeated percutaneous needle aspirations  nutrition being maintained intravenously  endoscopic retrograde cholangiopancreatography  ercp  demonstrated a congenital intra pancreatic cyst  he thrived after operation drainage for recurrent pseudocyst  but repeat ercp shows that the cyst in the head of the pancreas remains  pancreatic ascites is rare in children and diagnosis is frequently delayed  a third of reported cases in childhood present in the first year of life  a search for the underlying cause should include an ercp to demonstrate abnormalities of the pancreaticobiliary ducts  
class6	levels of the human hepatocyte growth factor in serum of patients with various liver diseases determined by an enzyme linked immunosorbent assay  we have found a hepatotrophic factor in plasma or sera of patients with fulminant hepatic failure and have purified human hepatocyte growth factor from plasma of these patients  in this study we developed an enzyme linked immunosorbent assay with high specificity and sensitivity for human hepatocyte growth factor in human serum  this assay for serum human hepatocyte growth factor is a sandwich method consisting of three steps  the standard curve for human hepatocyte growth factor appeared to be linear in the range of 0 20 to 12 50 ng purified human hepatocyte growth factor ml  2 35 to 147 pmol l   the assay took about 4 hr  serum human hepatocyte growth factor values in patients with fulminant hepatic failure measured by enzyme linked immunosorbent assay showed a strong positive correlation with that by bioassay using rat hepatocytes in primary culture  the mean value of serum human hepatocyte growth factor for 30 normal subjects was 0 24     0 12  s d   ng ml  that for 23 patients with fulminant hepatic failure was 8 06     1 76  s e m   ng ml  greater than 30 times greater than the mean value for normal subjects  serum human hepatocyte growth factor levels in patients with acute hepatitis  chronic hepatitis and cirrhosis were found to be slightly higher than those in normal subjects  but only the increase in serum human hepatocyte growth factor of acute hepatitis patients was statistically significant  the enzyme linked immunosorbent assay for serum human hepatocyte growth factor should prove useful for serum human hepatocyte growth factor level measurement in patients with various liver diseases  
class6	distribution of cholesterol between vesicles and micelles in human gallbladder bile  influence of treatment with chenodeoxycholic acid and ursodeoxycholic acid  the present study aimed at determining the relative distribution of cholesterol between the vesicular and micellar phases in gallbladder bile of gallstone patients  n   23  and gallstone free subjects  n   7   nine of the gallstone patients were treated with chenodeoxycholic acid and seven were treated with ursodeoxycholic acid  15 mg kg day  for 3 wk before cholecystectomy  the vesicular and micellar fractions in bile were separated by sucrose density gradient ultracentrifugation  and a clear separation between the two phases was obtained  the vesicles were further identified by quasielastic light scattering spectroscopy and appeared to be of a uniform size with a mean hydrodynamic radius of 760 a  the proportion of cholesterol in the vesicular fraction was significantly higher in the untreated gallstone group  40      4   compared with the gallstone free  28      3    ursodeoxycholic acid  28      3   and chenodeoxycholic acid  18      4   groups  despite a low cholesterol saturation of bile in the latter three groups  88      12   51      9  and 65      5   respectively   a considerable part of the biliary cholesterol was carried in the vesicular fraction  the cholesterol phospholipid ratio in the vesicular fraction averaged between 0 49 and 0 58 in the gallstone  gallstone free and chenodeoxycholic acid groups  whereas the ursodeoxycholic acid group had a significantly lower ratio of 0 24  the nucleation time of bile from the gallstone group was short  2     1 days  compared with the gallstone free  chenodeoxycholic acid and ursodeoxycholic acid groups  23     3  24     6 and 14     3 days  respectively  
class6	selective dopamine da1 stimulation with fenoldopam in cirrhotic patients with ascites  a systemic  splanchnic and renal hemodynamic study  we studied the effects of fenoldopam  a selective dopamine da1 agonist on systemic and splanchnic hemodynamics  renal blood flow and sodium excretion in 12 patients with alcoholic cirrhosis and ascites  hepatic  azygos and renal veins were catheterized before and after intravenous administration of fenoldopam  0 05 micrograms kg min for 1 hr and increased to 0 1 micrograms kg min for another hour  mean arterial pressure progressively decreased  from 83     7 to a minimum of 77     8 mm hg 100 min after starting the infusion  but returned to baseline level at 120 min  plasma norepinephrine and renin activity increased  respectively from 567     297 to 919     375 pg ml  p less than 0 05  and from 17     14 to 23     15 ng ml hr  p less than 0 05   renal blood flow  urine output or sodium excretion did not change  sodium output decreased at 1 hr from 6 9 mumol min to 4 0 mumol min  p less than 0 05  both hepatic venous pressure gradient and azygos blood flow significantly increased by 21   we conclude that the acute administration of fenoldopam did not improve renal hemodynamics or function in patients with cirrhosis and ascites  in addition  dopamine da1 agonism caused further increases in norepinephrine concentration and plasma renin activity  portal pressure also increased  probably because of an increase in mesenteric blood flow  these results question the renal benefit and raise concern about the use of dopamine agonists in patients with cirrhosis and ascites  
class6	prophylactic sclerotherapy for esophageal varices  long term results of a single center trial  survival after prophylactic sclerotherapy was assessed in a single center study involving 99 cirrhotic  41 alcoholic  patients enrolled over 8 yr  the wedged hepatic vein pressure gradient was measured  those with pressure greater than or equal to 12 mm hg were randomized to receive sclerotherapy or no treatment  the rest were not randomized  patients in all three groups who bled were treated with emergency endoscopy and sclerotherapy  stratification according to presence of ascites was also undertaken  median follow up was 61 mo  range   14 to 107 mo   survival among unrandomized patients was significantly longer than among randomized patients  p less than 0 006   but there was no significant difference between those treated by sclerotherapy and the controls  p   0 27   alcoholic cirrhotic patients undergoing sclerotherapy had better 2 yr survival than did the controls  80  vs  43   p   0 09   but this benefit was not sustained at 5 yr  survival in the nonalcoholic patient groups was identical  only 10 of 50 deaths were caused by variceal bleeding  forty eight percent of patients with large varices bled  compared with 20  of patients with small varices  wedged hepatic vein pressure less than 12 mm hg accurately identified alcoholic patients at low risk of variceal bleeding but not nonalcoholic patients  only four episodes of variceal bleeding were attributable to elective sclerotherapy  we conclude that in our population  prophylactic sclerotherapy alone does not improve survival  the discrepancy in survival between alcoholic and nonalcoholic cirrhotic patients suggests that factors other than variceal hemorrhage may be responsible for the difference  
class6	dual association of hla dr2 and dr3 with primary sclerosing cholangitis  human leukocyte antigen typing was performed in 81 patients with primary sclerosing cholangitis to investigate reported associations between human leukocyte antigen type and this disease  the results showed a significant increase in the frequency of the antigens b8 and dr3 compared with controls  53  vs  23   p less than 0 0005  and 56  vs  21   p less than 0 0005   this was caused by a significant rise in the frequency of the human leukocyte antigen a1 b8 dr3 haplotype  32 of 81 patients  40  vs  12 of 100 patients  12   p less than 0 0005   by contrast  a significant reduction was seen in the frequency of the antigens b44 and dr4  12  vs  31   p less than 0 005  and 12  vs  34   p less than 0 001  pc less than 0 011  because of the complete absence of the b44 dr4 haplotype in the patient group  p   0 027  fisher s exact test   when all the dr3 positive individuals  including the dr2 dr3 heterozygotes  were eliminated  a significant secondary association with dr2 was noted  25  69   of 36 remaining patients being dr2 positive compared with 27  34   of 79 dr3 negative controls  p less than 0 0005  pc less than 0 006   only 9  of the patients were dr2 positive and dr3 positive  kaplan meier analysis demonstrated that survival was not influenced by the presence of either haplotype nor by the individual antigens  patients who were dr3 positive were first seen at a significantly younger age than those who were dr2 positive  mean ages   33 yr and 44 yr  respectively  p less than 0 002  student s t test   
class6	significance of natural polymerized albumin and its receptor in hepatitis b infection of hepatocytes  lack of information regarding the presence of native albumin polymer in serum and its structural similarity to the one produced by glutaraldehyde treatment casts doubt on the postulate that hepatitis b virus attachment to hepatocytes is mediated through polymerized albumin  we used a sandwich enzyme linked immunosorbent assay with murine monoclonal antibodies raised against glutaraldehyde polymerized albumin to detect native albumin polymer in human serum and its cross reactivity with other albumin polymers  presence of polymerized albumin receptor on the hepg2 cell was studied by radioreceptor assay  purified hepatitis b virus and synthetic peptide analogous to part of pre s2 sequence  120 145  were used to study polymerized albumin dependent attachment of the virus to hepg2 cells  antibodies raised against pre s2 peptide were used to inhibit the pre s2 and hepatitis b virus attachment to hepg2 cells  glutaraldehyde treated polymerized albumin was found to be immunologically cross reactive with native albumin polymer  its levels were found to be significantly raised in sera of patients with liver diseases  polymerized albumin has specific saturable receptor on hepg2 cells with two classes of binding sites of different equilibrium dissociation constant  kd1    16     9 6 pmol l and kd2    1 019     172 pmol l  albumin monomer was unable to compete for the polymerized albumin receptor sites on hepg2 cells  anti pre s2 antibodies inhibit hepatitis b virus and pre s2 binding to hepatocyte by 40  and 70   respectively  added extraneous polymerized albumin and the antibody against it did not interfere with virus attachment to hepg2 cells  
class6	significance of anti hbx antibodies in hepatitis b virus infection  serological responses to hepatitis b virus x determinants have been noted in human sera  but conflicting findings concerning the correlation of anti hbx antibodies with different stages of hepatitis b virus infection or pathological sequelae have been reported  using an adenovirus based eukaryotic vector  the 17 kd x protein was efficiently expressed in 293 cells  cellular extracts containing the eukaryotic x protein have been used to screen for anti hbx antibodies by immunoblot analysis in a large panel of sera from patients affected by hepatitis b virus chronic hepatitis  hepatocellular carcinoma and acute viral hepatitis  sera from 32 of 171  19   chronic hepatitis b virus patients were positive for anti hbx antibodies  only one of thirty two  3   hbsag negative  anti hbs anti hbc positive chronic hepatitis serum was anti hbx positive  very few sera from primary hepatocellular carcinoma patients showed positivity for anti hbx  8 of 149 or 5    anti hbx were also detected in 8 of 48  17   acute viral hepatitis patients  in the four cases that were followed up weekly  anti hbx antibodies appeared 3 to 4 wk after the onset of the clinical signs  to compare the x protein expressed in eukaryotic and prokaryotic cells as a substrate for anti hbx antibody detection  171 sera were screened with hbx fusion proteins expressed in escherichia coli  the prokaryotic cell extract test seems to be more sensitive  during the chronic phase of hepatitis b virus infection  the presence of anti hbx antibodies detected with the eukaryotic cell extract correlates with the presence of well established markers of ongoing viral replication  serum hepatitis b virus dna  p less than 0 001  and intrahepatic hbcag expression  p less than 0 001   
class6	hepatic histological findings after transplantation for chronic hepatitis b virus infection  including a unique pattern of fibrosing cholestatic hepatitis  long term follow up of 27 patients with hepatitis b virus related chronic liver disease treated by transplantation showed that 23 had hepatitis b virus recurrence  in 13 patients late changes in the grafts were similar to those described in other series  minor abnormalities in five cases  chronic active hepatitis in five cases and non hepatitis b virus related graft dysfunction in three cases  three patients had incomplete histological follow up  analysis of the histological changes and viral antigen expression in six cases revealed a distinct and novel pattern termed fibrosing cholestatic hepatitis  development of fibrosing cholestatic hepatitis was associated with rapidly progressive graft dysfunction  it is postulated that this pattern of fibrosing cholestatic hepatitis develops because of a high cytoplasmic expression of viral antigens  including hbsag  the remaining case had some features of fibrosing cholestatic hepatitis  the main histological features of this unique syndrome include thin  perisinusoidal bands of fibrosis extending from portal tracts to surround plates of ductular type epithelium  prominent cholestasis  ground glass transformation  and ballooning of hepatocytes with cell loss and mild mixed inflammatory reaction  
class6	assay of hepatitis b virus dna by polymerase chain reaction and its relationship to pre s  and s encoded viral surface antigens  the polymerase chain reaction was evaluated as a diagnostic tool in 72 chronic hepatitis b virus carriers  hepatitis b virus dna was detectable in the serum of hbsag positive virus carriers using aliquots as small as 100 al  the detection limit for cloned hepatitis b virus dna was 100 ag  primer pairs for different regions of the hbv genome resulted in different sensitivity  detection of the amplified hepatitis b virus dna by southern blotting and subsequent scintillation counting or densitometry allowed a semiquantitative assay  using several primer pairs in parallel for optimal detection  all hbeag positive hbsag carriers  80  of hbe antibody positive symptomatic hbsag carriers and 57  of asymptomatic hbe antibody positive hbsag carriers were found to have hepatitis b virus dna in the serum  during antiviral therapy hepatitis b virus dna disappeared by the polymerase chain reaction assay in patients who became hbeag negative  but polymerase chain reaction detected a relapse earlier than did the conventional dot blot  pre s antigens were assayed in serum and liver samples from most chronic carriers by enzyme linked immunosorbent assay and or immunoblot  although most viremic carriers were strongly positive for pre s1 and pre s2 antigens  some hepatitis b virus dna positive hbsag carriers did not have detectable pre s antigens  and vice versa  our data show that assay of hepatitis b virus dna in the serum by polymerase chain reaction is by far more proficient than by dot blot and that it cannot be replaced by serological assays of hbeag or pre s antigen  
class6	antibodies in anti hbe positive patient sera bind to an hbe protein expressed on the cell surface of human hepatoma cells  implications for virus clearance  the relevance of the recently described membrane bound form of the hbe protein for the antiviral immune response was examined  the data show that antibodies in anti hbe  but not in anti hbc positive human sera efficiently bind to the membrane expressed hbe  no evidence was obtained that the hbc can reach the cell surface in a form that can be detected with human antibodies  the findings suggest that the decline of virus titer that is usually observed after seroconversion from hbe to anti hbe might be the result of an antibody mediated elimination of infected cells  
class6	the ver as a diagnostic marker for childhood abdominal migraine  abdominal migraine is a common childhood migraine equivalent  for which diagnostic criteria have not been defined  as in other children with migraine equivalents this leads to difficulties in diagnosis and determination of prevalence  by recording the fast wave activity  beta rhythmn  in the visual evoked response  ver  to red and white flash  the pattern stimulation  27 out of 28 children with clinically diagnosed abdominal migraine revealed significant differences compared with normal controls  outside the attack phase  comparisons with children diagnosed as migraine with or without aura revealed  from the ver findings of higher amplitude fast wave activity and the presence of paroxysmal sharp wave activity  that abdominal migraine appears to be a specific form of childhood migraine  we found that both clinically and electrophysiologically  abdominal migraine changes with age  older children exhibiting a shorter duration of abdominal pain during attacks  and less evidence of sharp wave activity in the ver  
class6	detection of hepatitis b virus dna by polymerase chain reaction in plasma of volunteer blood donors negative for hepatitis b surface antigen  plasma samples from 206 volunteer blood donors were tested for hepatitis b virus  hbv  dna by dot blot hybridization and polymerase chain reaction  pcr   all donors were negative for hepatitis b surface antigen  hbsag  and had normal serum alanine aminotransferase levels  none of the 206 plasma samples was positive for hbv dna by dot blot hybridization assay  however  nine samples were positive for hbv dna by pcr using two primer pairs specific for surface and core regions  nine persons received the hbv dna positive plasma  and one developed posttransfusion non a  non b hepatitis  the others remained well 6 months later  therefore  approximately 4  of blood donors in taiwan have low titers of hbv dna  and a more sensitive method to screen donors may be needed in the future  although the current serologic test remains the most practical at present  
class6	hepatopathy thrombocytopenia syndrome  a complication of dactinomycin therapy for wilms  tumor  a report from the united kingdom childrens cancer study group  we have observed hepatopathy  associated with thrombocytopenia  in children receiving chemotherapy for wilms  tumor  we have studied this hepatopathy thrombocytopenia syndrome  hts  in patients enrolled in the united kingdom childrens  cancer study group  ukccsg  wilms  tumor trials  ukw1 and ukw2   at the time of this study  501 patients had completed therapy  treatment flow sheets were examined for evidence of hepatopathy  hepatomegaly with abnormal liver function tests  and severe thrombocytopenia  platelet count less than 25 x 10 9  l   no child who developed the syndrome had received irradiation  hts was seen in five of 355  1 4   of patients treated with combination chemotherapy but in none of the 146 patients treated with vincristine alone  in each instance  the onset was less than 10 weeks after diagnosis  in two children  hepatopathy was severe with jaundice  ascites  transaminases greater than 1 000 iu l  and prolongation of prothrombin time  on average  hts lasted 12 days  and resolved with supportive treatment  after recovery  the children tolerated chemotherapy  mostly at reduced dosage  without recurrence  there was no evident long term morbidity  dactinomycin is the probable cause of this syndrome  we conclude that the hts is a rare but important complication of dactinomycin containing combination chemotherapy for wilms  tumor  children developing  isolated  thrombocytopenia following dactinomycin are  at risk  of developing the full blown syndrome and should have their treatment modified accordingly  
class6	comparison of shunt fraction estimation using transcolonic iodine 123 iodoamphetamine and technetium 99m pertechnetate in a group of dogs with experimentally induced chronic biliary cirrhosis  portosystemic shunt fraction estimation using transcolonic iodine 123 iodoamphetamine  imp  has been previously validated relative to portal vein macroaggregated albumin injections using an experimental model of cirrhosis  transcolonic technetium 99m pertechnetate  tco4   has been proposed as an alternative tracer to imp to study portal circulation in cirrhotic patients  we compared shunt fraction estimates from paired transcolonic imp and tco4  studies performed on a group of dogs before and after common bile duct ligation surgery  pertechnetate over estimated shunt fraction in 6 7 postoperative studies relative to imp  a good correlation between the two methods was demonstrated  however  the slope of the regression line was substantially less than 1 0 with tco4  values reaching 100  at imp shunt values of approximately 60   this apparent inability to accurately assess high shunt flows may limit the quantitative aspects of tco4  studies on patients with severe portosystemic shunting  
class6	bronchobiliary fistula detected by cholescintigraphy  we present a case of a bronchobiliary fistula initially detected by hepatobiliary scintigraphy  the patient developed bilioptysis 18 mo after undergoing a right hepatic lobectomy and resection of the common bile duct for cholangiocarcinoma  the procedure was complicated by the development of a subphrenic abscess that required percutaneous biliary drainage  
class6	quantification of hepatobiliary function as an integral part of imaging with technetium 99m mebrofenin in health and disease  a study was undertaken to check the feasibility of measuring the hepatic extraction fraction  hef  and excretion t 1 2 values as an integral part of hepatobiliary imaging with technetium 99m mebrofenin in health and disease  in 18 controls subjects  the hef was 100  and the t 1 2 excretion mean     s e  value was 15 23     1 4 min  the mean appearance times of the common bile duct  cbd   gallbladder  gb   and small intestine were 15 8     1 52  20 2     2 7  and 23 8     3 08 min  respectively  rising serum bilirubin in patients decreased hef and increased t 1 2 excretion value resulting in delayed appearance of cbd  gb  and small intestine  in control subjects and patients with bilirubin less than 5 mg   t 1 2 excretion values at 30  40  and 50 min were similar to those values calculated using the entire 60 min of data  suggesting that the hepatic phase study time could be reduced to 30 40 min and still use the normal reference values established for 60 min  in patients with bilirubin greater than 5 mg   the data collection duration should be continued for 60 min  
class6	sjogren s syndrome and primary biliary cirrhosis  presence of autoantibodies to purified mitochondrial 2 oxo acid dehydrogenases  sjogren s syndrome is well known for the presence of antibodies directed at specific nuclear antigens  however  the presence of antibodies reacting with a variety of other self antigens  including antimitochondrial antibodies  has often been reported although their significance is unknown  moreover  patients with sjogren s syndrome have been occasionally reported to be concordant with primary biliary cirrhosis  to address this issue we studied in a group of 96 patients with sjogren s syndrome the presence of autoantibodies to the dihydrolipoamide acetyltransferases of both pyruvate dehydrogenase and branch chain ketoacid dehydrogenase and to alpha ketoglutarate dehydrogenase  these latter enzymes are the mitochondrial target antigens of primary biliary cirrhosis  we report that 7 of the 96 patients reacted with the mitochondrial antigens that are prominent in primary biliary cirrhosis  moreover  in those patients showing reactivity with mitochondrial antigens  the autoantibodies were directed at the same immunodominant epitopes that have been previously characterized in primary biliary cirrhosis  one of the 7 positive patients was known to have primary biliary cirrhosis  we hypothesize that the remaining 6 patients are at clinical risk for the development of primary biliary cirrhosis and or that abnormalities would be found on liver biopsy  
class6	macroscopic and microscopic gut lesions in seronegative spondyloarthropathies  a retrospective study by ileocolonoscopy and multiple biopsies was performed on 96 patients with seronegative spondylarthropathy  17 patients with osteoarthritis  oa  and 19 patients with chronic abdominal discomfort  under these conditions  inflammatory gut lesions were detected in 66 7  of the patients with spondyloarthropathy  12 5  with oa and 15 8  with chronic abdominal discomfort  in 10 patients treated by sulfasalazine  salazopyrine   pathologic lesions disappeared simultaneously with an improvement of the rheumatic conditions  comparison between patients treated and untreated with nonsteroidal inflammatory drugs  nsaid  demonstrated that nsaid did not enter into the etiopathology of the intestinal lesions  our study therefore confirms the high incidence of inflammatory gut lesions among patients with spondylarthropathy which seems not to be related to nsaid therapy  
class6	intestinal obstruction by distension of a foley jejunostomy catheter  jejunostomies can be effective in permitting postoperative nutritional support  particularly in the patient with complicated gastrointestinal disease  in the case presented  however  distension of the foley balloon catheter  used as the jejunostomy tube  led to intestinal obstruction which was not initially detected  following radiographic identification of the problem  removal of the air from the foley balloon allowed the patient to complete his convalescence from surgery  the possibility of obstruction from the foley jejunostomy catheter should be recognized as a potential problem in the postoperative period  
class6	association of escherichia coli hep 2 adherence patterns with type and duration of diarrhoea  373  59   out of 636 faecal specimens obtained during the first 2 years of life of 72 mexican children yielded adherent escherichia coli  hep 2 cells   strains with localised adherence were significantly associated with acute non bloody diarrhoea  whereas strains with aggregative adherence were significantly associated with persistent diarrhoea  half the strains with localised adherence were not enteropathogenic e coli serotypes nor did they hybridise with an enteropathogenic e coli adherence factor dna probe  all strains with localised adherence gave a positive fluorescent actin staining  fas  assay  irrespective of serotype  one third of children colonised by aggregative strains had bloody diarrhoea  isolation of strains with diffuse adherence was not related to type or duration of diarrhoea but was generally associated with isolation of another pathogenic organism  
class6	syncytial giant cell hepatitis  sporadic hepatitis with distinctive pathological features  a severe clinical course  and paramyxoviral features  background and methods  we describe a new form of hepatitis  occurring in 10 patients over a period of six years  characterized clinically by manifestations of severe hepatitis  histologically by large syncytial giant hepatocytes  and ultrastructurally by intracytoplasmic structures consistent with paramyxoviral nucleocapsids  results  the patients ranged in age from 5 months to 41 years  the tentative clinical diagnosis before biopsy was non a  non b hepatitis in five patients and autoimmune chronic active hepatitis in the others  five patients underwent liver transplantation  the others died  the diagnosis of syncytial giant cell hepatitis was established pathologically  the liver cords were replaced in all 10 patients by syncytial giant cells with up to 30 nuclei  in 8 of the 10 the cytoplasm contained pleomorphic particles of 150 to 250 microns  filamentous strands  and particles of 14 to 17 nm with peripherally disposed spikes resembling paramyxoviral nucleocapsids  structures resembling degenerated forms were found in the other two patients  one of two chimpanzees injected with a liver homogenate from the index patient had an increase in the titer of paramyxoviral antibodies  probably an anamnestic reaction to previous paramyxoviral infection  suggesting that a paramyxoviral antigen but not viable virus was present in the liver homogenate  conclusions  although further virologic studies will be required for precise classification  we believe that paramyxoviruses should be considered in patients with severe sporadic hepatitis  
class6	spontaneous rupture of liver during pregnancy  current therapy  spontaneous hepatic rupture secondary to severe pregnancy induced hypertension is associated with a high rate of maternal and fetal mortality  numerous types of surgical management have been described  but a uniform surgical approach has not been accepted  the purpose of this review was to examine modes of surgical therapy reported in the literature since 1976  as well as the 11 year experience at our institution  twenty eight cases were extracted from the literature and seven more were identified at our institution  the incidence in our population was one per 45 145 live births  among 27 cases managed by packing and drainage  an 82  overall survival was achieved  whereas only 25  of eight patients undergoing hepatic lobectomy survived  p    006   hepatic hemorrhage with persistent hypotension unresponsive to blood products should be managed by evacuating the hematoma  packing the damaged liver  and draining the operative site  more aggressive surgical techniques  such as hepatic artery ligation or hepatic lobectomy  should be reserved for refractory cases  
class6	norwalk virus genome cloning and characterization  major epidemic outbreaks of acute gastroenteritis result from infections with norwalk or norwalk like viruses  virus purified from stool specimens of volunteers experimentally infected with norwalk virus was used to construct recombinant complementary dna  cdna  and derive clones representing most of the viral genome  the specificity of the clones was shown by their hybridization with post   but not pre   infection stool samples from volunteers infected with norwalk virus and with purified norwalk virus  a correlation was observed between the appearance of hybridization signals in stool samples and clinical symptoms of acute gastroenteritis in volunteers  hybridization assays between overlapping clones  restriction enzyme analyses  and partial nucleotide sequence information of the clones indicated that norwalk virus contains a single stranded rna genome of positive sense  with a polyadenylated tail at the 3  end and a size of at least 7 5 kilobases  a consensus amino acid sequence motif typical of viral rna dependent rna polymerases was identified in one of the norwalk virus clones  the availability of norwalk specific cdna and the new sequence information of the viral genome should permit the development of sensitive diagnostic assays and studies of the molecular biology of the virus  
class6	variceal rebleeding after portosystemic shunting  strategies and solutions to a vexing problem  the purpose of this review was to discuss an approach to the treatment of recurrent bleeding from esophageal or gastric varices after portosystemic shunt  from our own clinical experience  as well as that of others  it appears that re establishment of portal decompression should offer the best chance at long term survival  luckily  innovations in angiographic technique have allowed attainment of this goal without the inordinate risk of an operative procedure  however  not all patients  situations will be amenable to such treatment  for some of them  operative decompression of the portal venous system can be carried out in an anatomic area previously untouched  for those patients in whom no decompression is possible  direct endoscopic treatment of the varices will offer an alternative  albeit temporizing  approach  
class6	repeat operation for failure of antireflux procedures  the majority of patients who receive modern antireflux operations obtain substantial long term relief of their symptoms  about 10  to 15  will have persistent or recurrent problems  some severe enough to warrant reoperation for correction  with careful symptom review  barium study  endoscopy  and manometry  the mechanism of failure becomes evident  and remedial surgical treatment may proceed  the results at reoperation are not as good as those of the primary procedure  which emphasizes the need for proper diagnosis and choice of procedure and for reliable execution of technique at the initial treatment  
class6	reoperation for small intestinal obstruction  today  intestinal adhesions represent the most frequent etiology for complete or partial intestinal obstruction  although partial obstruction can be treated nonoperatively with a considerable likelihood of success  intestinal strangulation cannot uniformly be predicted or prevented  complete intestinal obstruction is associated with a significant incidence of strangulation if not treated by a vigorous surgical approach  consequently  complete intestinal obstruction secondary to adhesions is still a surgical disease  attempts at control of the adhesion process include mechanical methods to prevent subsequent obstruction and chemical methods to prevent the adhesion process itself  the invasive mechanical methods appear dated  a variety of agents have been used either systemically or in the peritoneal cavity to prevent the establishment of intra abdominal adhesions  agents that do not contribute to subsequent morbidity or impede the native host defense mechanisms should be utilized  high molecular weight dextran and nonsteroidal anti inflammatory agents show some promise of being both safe and effective  as is frequently the case  the bottom line in preventing and treating intra abdominal adhesions is appropriate surgical technique  intestinal adhesions can be related clearly to leaving damaged  devitalized  or ischemic tissue in the peritoneal cavity or to excessive roughness in handling of tissues  steps such as avoidance of excessive suture material and unnecessary handling of the bowel will do much to prevent subsequent adhesion generation  likewise  the surgical lysis of intraperitoneal adhesions is frequently fraught with complications such as intra abdominal abscess or postoperative incisional failure  this is again related to surgical technique and most directly to the use of blunt dissection to divide adhesions  knife dissection in the lysis of adhesions is recommended  this technique  combined with excellent intraoperative hemostasis  can be associated with a marked diminution in the incidence of postoperative fistulas and abscesses  
class6	alkaline reflux gastritis  alkaline reflux gastritis and the symptoms associated with alkaline reflux gastritis have been reported in the medical literature since shortly after billroth successfully performed his first gastrectomy in the 1880s  the disease process is produced by  or at least is associated with  the reflux of alkaline secretions into the gastric remnant  although it occurs after any procedure that ablates the pylorus including pyloroplasty  it would appear to be most common after a billroth ii gastrojejunostomy  how the alkaline secretions cause the gastritis is still controversial  clearly  the most effective therapy is to reroute the secretions from the biliary tract  pancreas  and duodenum so that they will not reflux into the gastric remnant  this is most effectively accomplished by a roux en y gastrojejunostomy with the afferent limb measuring at least 18 inches  40 cm   the surgeon and the patient should be aware that the construction of such a gastric outlet channel is associated with delayed gastric emptying  the etiology of this impaired emptying is also controversial  if the patient has symptoms of dumping  either early or late   these symptoms may also be abated using the roux limb  at least 40  of patients will have gastric outlet obstruction  supportive therapy is appropriate in the majority of these patients  
class6	reoperation for failed gastric bypass procedures for obesity  reoperation is worthwhile when there is an obvious defect in the gastric reduction operation that has failed to control weight  reoperation occasionally is necessary to correct a complication of gastric bypass  vertical banded gastroplasty is the operation of choice for reoperations  as it provides weight control while eliminating the problems of bypass  conversion of a horizontal to a vertical pouch is safe but requires careful attention to the technique to avoid injury to the other organs in the area and preservation of blood supply to the stomach  the gastrogastrostomy across the old horizontal staple line in the vertical pouch can be constructed in a way that will minimize the risk of obstruction  vertical banded gastroplasty is now the only operation in use at uihc for the treatment of obesity and is used not only as the primary operation but in all reoperations  bypass of the stomach and duodenum is not necessary for weight control and adds some risk of malabsorption and duodenal and stomal ulcer plus a lifetime of inaccessibility of the excluded areas for diagnostic and therapeutic measures  
class6	surgical options in postgastrectomy syndromes  the various operations performed for the treatment of peptic ulcer disease can lead to a variety of iatrogenic disorders collectively referred to as the  postgastrectomy syndromes   although the etiology of most of these disorders remains unclear  loss of vagal innervation and bypass  ablation  or destruction of the pylorus clearly are involved in the pathogenesis of most  if not all  of these disorders  unfortunately  there often is also a poorly understood psychological element involved in the pathogenesis  of all ulcer operations  proximal gastric vagotomy results in the fewest physiologic abnormalities and the mildest postoperative symptoms  the continued popularity of this operation should effect a marked reduction in the incidence of disabling postgastrectomy syndromes  fortunately  symptoms severe enough to necessitate remedial operation are uncommon  and conservative medical management is always indicated and usually suffices  when disabling symptoms are refractory  a thorough evaluation of the patient and an accurate classification of the syndrome are essential to guarantee a satisfactory result from surgical intervention  although numerous surgical procedures have been developed to deal with the different syndromes  with varied results  the roux en y procedure has emerged as the operation of choice for most  if not all  postgastrectomy syndromes  however  the roux en y procedure has not been universally successful  and this operation can itself lead to the recently recognized postgastrectomy state of roux en y stasis syndrome  prevention therefore remains the best form of therapy  and remedial operation should not be undertaken until adequate time has elapsed since the original operation and all forms of conservative treatment have failed  
class6	reoperation for recurrent peptic ulcer disease  the patient with recurrent peptic ulcer evidences failure of an initial operation to control the ulcer diathesis  a trial of aggressive medical therapy is warranted in elective presentations and has a moderate chance of success  failing this  we believe that reoperation should be tailored to the patient s physiologic status and previous operation  table 5   nevertheless  in most cases  we believe that the second operation should be the final operation and should consist of the procedure with the lowest recurrence rates  therefore  we believe that the assurance of an adequate antrectomy and complete vagal section is the preferred procedure for most patients with recurrent peptic ulcer  
class6	reoperation versus alternatives in retained biliary calculi  retained common bile duct stones can be treated by operation  dissolution  extraction  fragmentation  papillotomy  and reoperation  each approach requires some expertise  and the likelihood of success of most depends on the composition and size of the stones  good results often can be obtained nonoperatively  especially with a multidisciplinary team  reoperation is rarely necessary  
class6	emergency surgical treatment for nonvariceal bleeding of the upper part of the gastrointestinal tract  endoscopic and biochemical data were collected prospectively from 1 530 patients admitted with nonvariceal bleeding of the upper part of the gastrointestinal tract between september 1985 and june 1989  therapeutic endoscopy was done for 93 patients who underwent emergency surgical treatment for bleeding  subsequently required in 29 patients with seven postoperative fatalities  in contrast  31  15 7 per cent  of 198 patients  mortality rate of 9 6 per cent at 30 days  died in the hospital who had undergone emergency operation in whom therapeutic endoscopy had not been performed  data for this latter group is now presented  at admission  a greater likelihood of emergency operation was associated with a systolic blood pressure of 100 millimeters of mercury and endoscopic stigmatas of recent hemorrhage  esrh   p less than 0 001   rebleeding rates for the presence of fresh blood  active spurting and oozing hemorrhage or visible vessel in an ulcer base were 26 5  28 9 and 35 9 per cent  respectively  endoscopic stigmatas were thus associated with an increased risk of bleeding  p less than 0 0001  and rebleeding led to a sixfold increase in the mortality rate  congestive cardiac failure  chronic obstructive airway disease  chronic renal failure and a history of previous malignant disease were each associated with postoperative mortality rates of more than 50 per cent  an increased risk of mortality after emergency operation was related to age  p less than 0 0001   preoperative  p less than 0 002  and total  p less than 0 0001  blood transfusion requirement  immediate operation after resuscitation and endoscopy was required in 87 patients  11 deaths  hospital mortality rate of 12 7 per cent and 9 2 per cent at 30 days  occurred in this group compared with 20 fatalities  18 0 per cent  documented in 111 patients  9 9 per cent at 30 days  who underwent surgical treatment for rebleeding  we conclude that age  concomitant medical illness and preoperative and total transfusion requirements are each related to outcome after emergency operations  such urgent intervention is best avoided if at all possible in patients with severe concomitant medical illness  
class6	mechanical sutures in perforation of the thoracic esophagus as a safe procedure in patients seen late  between 1976 and 1988  we treated 13 perforations of the thoracic esophagus  excluding ruptured carcinoma and intraoperative wounds  by mechanical sutures without exclusion  the delay between perforation and treatment ranged from eight to 168 hours  more than 24 hours in 11  the length of perforation was 0 5 to 15 0 centimeters  suture was covered with a flap in ten instances  an antireflux procedure was associated with five instances  no digestive ostomies were performed  there was one death  a patient who was comatose upon arrival  the results of this small series suggest that myotomy exposing the mucosa and a flap are two essential elements of the technique  perforations of less than 6 centimeters  even when seen late  may be treated by primary surgical closure  
class6	incisional hernioplasty with mersilene  thirty large incisional abdominal hernias  myoaponeurotic defects greater than 10 centimeters  were successfully repaired by a technique of incisional hernioplasty which implants a large mersilene  polyester fiber  prosthesis in the space between the abdominal muscles and the peritoneum  the prosthesis extends far beyond the borders of the myoaponeurotic defect  and is solidly held in place by intra abdominal pressure and later by fibrous ingrowth  the prosthesis protects against recurrence in two ways  first  it prevents peritoneal eventration by adhering to the visceral sac and rendering it indistensible  second  the prosthesis unites and consolidates the abdominal wall  consequently  the procedure uniquely exploits the very force which caused the hernia to prevent a recurrence  a prosthesis of mersilene is essential for success because it is supple and elastic enough to conform freely to the curvatures of the visceral sac  has the necessary grainy texture to grip the peritoneum and prevent slippage and is reactive enough to induce a rapid fibroblastic response to ensure fixation  
class6	gastroesophageal reflux and respiratory symptoms  is there an association  proposed mechanisms and treatment  gastroesophageal reflux  ger  is a dysfunction of the distal esophagus causing movement of stomach contents into the esophagus  patients may develop heartburn  regurgitation  dysphagia  odynophagia  and hemorrhage  respiratory symptoms occur in 10 60 percent of patients with ger or hiatal hernia  although there is evidence associating pulmonary symptoms and ger  causality has not been proven  the appropriate use of antireflux therapy or surgery to treat ger may consequently alleviate respiratory symptoms  
class6	death  after swallowing and aspiration of a high number of foreign bodies  in a schizophrenic woman  a 46 year old woman who had had a long term schizoid psychosis collapsed on the street  upon admission to the hospital  she was determined to have an acute abdomen  the chest radiograph showed metallic foreign bodies in both main bronchi  foreign bodies in the stomach were not observed clinically  the woman died from repeated cardiac arrest shortly after hospital admission  at the autopsy a screw and a nail were found in both main bronchi  the abdominal cavity contained 2 l of greenish purulent fluid and a massive fibrinoid peritonitis was observed  two perforations of the stomach  each 1 cm in diameter  were detected  the stomach was completely filled with a mass of metallic foreign bodies  greenish fluid  and a bezoar of a total weight of 1 400 g  422 distinguishable and mostly metallic foreign bodies were counted  death was attributed to cardiac arrest in delayed shock after massive purulent peritonitis caused by two gastric perforations combined with obstruction of the airways by aspirated foreign bodies  cases of massive swallowing of foreign bodies are mainly restricted to mentally handicapped persons  especially schizophrenics  whereas acute impaction of the larynx by large food particles occurs nearly exclusively in heavily intoxicated adults  
class6	late volume changes in retrosternal colon bypass  esophageal obstruction by malignancy  chemical burns  or other less common entities presents a challenge for the surgeon  either for esophageal substitution after esophageal resection or as a bypass for the obstructed esophagus  colon interposition is often the best available option  massive colonic enlargement requiring resection of the interposed dilated colon developed recently in 2 of our patients who had a colon bypass 22 and 10 years earlier  respectively  
class6	stercoral perforation of the colon  stercoral perforation of the colon is rare  the 64 reported cases are reviewed to define the syndrome of stercoral perforation  and to facilitate accurate diagnosis and treatment  features of localized or generalized peritonitis were universal  however  only 11 per cent were correctly diagnosed before operation  recognition that the disease involves a segment of colon rather than only the focal point of perforation is essential to adequate surgical treatment  it is postulated that this is the reason for the higher postoperative mortality following closure of the perforation and proximal colostomy  57 per cent  or exteriorization alone  43 per cent   compared with resection of the diseased segment and exteriorization  32 per cent   resection and exteriorization is therefore the treatment of choice is most situations  
class6	adrenergic control of the internal anal sphincter is abnormal in patients with idiopathic faecal incontinence  there is histological and functional evidence that the internal anal sphincter is abnormal in patients with idiopathic faecal incontinence  the in vitro responsiveness of the internal anal sphincter to noradrenaline  an important sympathetic neurotransmitter  and electrical field stimulation  known to stimulate the intrinsic innervation  has been studied  muscle strips from eight patients with incontinence undergoing postanal repair and five controls undergoing resection for low rectal carcinoma were studied  the contraction response curves for noradrenaline were significantly different  and the ec50  the concentration required to produce 50 per cent of maximum contraction  was higher in incontinent patients  p less than 0 001   electrical field stimulation produced initial contractions in four of the control group which were blocked by phentolamine  this contraction was not present in the incontinent patients  p less than 0 01   these results indicate an abnormality in the adrenergic innervation of the internal anal sphincter in patients with idiopathic faecal incontinence  
class6	paraileostomy hernia  a clinical and radiological study  forty six patients who underwent colectomy with end ileostomy for ulcerative colitis  n   33  or crohn s disease  n   13  have been reviewed for paraileostomy hernia  pih  formation 1 16 years after surgery  pih developed in 13 of these patients  28 per cent  and was not related to the original disease or excessive weight gain  twenty eight patients underwent limited computed tomography  ct  scanning of the stomal region  eight of these had a clinically detectable pih  which was demonstrated on ct  a further two patients had pih demonstrated on ct which was not detected by clinical examination  the rate of pih was similar where the stoma emerged lateral to the rectus abdominis muscle  six out of 16 patients  37 per cent  to where the stoma emerged through the rectus  four out of 12 patients  33 per cent   recurrence following operative repair of pih was common  pih occurs more frequently than previously supposed  ct can detect pih and may be useful in evaluating a patient with stoma related symptoms for occult pih formation  
class6	risk of cancer death in first degree relatives of patients with hereditary non polyposis cancer syndrome  lynch type ii   a study of 130 kindreds in the united kingdom  to estimate the relative risks of cancer in first degree relatives of index patients  130 pedigrees of dominantly inherited lynch type ii cancer family syndrome have been analysed  the risk of death from all causes was significantly increased in women over 45 years of age and the overall liability to cancer in women was greater than for men  a sevenfold increase in risk of colon cancer was found in both sexes  in female relatives the risk of breast cancer was increased fivefold and lifetime risk of breast cancer was 1 in 3 7  a screening programme based on estimated risks could be offered to first degree relatives of index patients with lynch type ii cancer family syndrome  
class6	achalasia of the cardia  long term results of oesophagomyotomy and posterior partial fundoplication  forty eight patients with achalasia of the cardia were treated by heller s myotomy with a posterior fundoplication of approximately 270 degrees  suturing the gastric fundus to the edges of the myotomy  the mean s d   postoperative follow up period was 5 4 2 8  years  the clinical results were good to excellent in 44 cases  92 per cent  and fair in four cases  8 per cent   two with residual dysphagia and two with gastrooesophageal reflux   barium studies showed a decrease in oesophageal diameter and disappearance of distal narrowing but normal oesophageal emptying did not occur  postoperative manometric studies  29 patients  revealed a significant decrease in lower oesophageal sphincter pressure and a significant increase in the length of the infradiaphragmatic segment  in the oesophageal body a recovery of peristaltic waves in the proximal third was seen in ten of the patients  34 per cent   twenty four hour ph monitoring showed pathological reflux in only three of 25 patients studied  and one of these was asymptomatic  this technique is effective  improving oesophageal symptoms and controlling long term reflux  
class6	surgical results of intrathoracic gastric volvulus complicating hiatal hernia  from 1981 to 1988  138 patients with hiatal hernia were treated surgically at our centre  twenty one  mean age 76 6 years  17 women  four men  had an associated intrathoracic gastric volvulus  eleven patients  mean age 73 2 years   of whom eight were asymptomatic  had an elective procedure  ten patients  mean age 80 3 years  had emergency surgery  six for acute complications of the volvulus  five cases of strangulation and one of perforated ulcer  and four because of other  unrelated causes of acute abdomen  there were four deaths after operation  all in the emergency surgery group  four other patients had significant morbidity  all in the emergency group  in the elective cases  all hernias were easily reduced  in one emergency case a gastrotomy was necessary for decompression  and in another gastrectomy was necessary because of gastric gangrene  our results indicate the need for elective intervention when intrathoracic gastric volvulus is first diagnosed  
class6	serum gastrin and blood glucose levels during halothane nitrous oxide anaesthesia and strabismus surgery in children  the purpose of this study was to determine whether serum gastrin levels are increased by reflexogenic stimuli applied to the extrinsic muscles of the eye  serum gastrin and blood glucose concentrations were measured in ten normal children aged between 5 and 12 yr during general anaesthesia with halothane and nitrous oxide and during strabismus surgery  fasting basal concentrations of gastrin  33 6     14 8 pg ml 1  and of glucose  4 43     0 72 mmol l 1  were in the normal range of values for children  intravenous atropine  0 01 mg kg 1   general anaesthesia with halothane in nitrous oxide and oxygen by mask for three minutes  tracheal intubation  extraocular muscle stimulation and surgical stress did not cause any variation in the mean serum gastrin concentration  on the contrary  tracheal intubation and surgical stress increased blood glucose concentrations  p less than 0 05   there was no difference in the serum gastrin levels after extraocular muscle stimulation between children with positive or negative oculocardiac reflexes  44 5     16 7 pg ml 1 vs 38     14 7 pg ml 1  respectively   the incidence of vomiting predischarge was 60 per cent  serum gastrin levels did not differ between children who vomited and children who did not  44 3     18 5 pg ml 1 vs 47 1     16 9 pg ml 1  respectively   vomiting after strabismus surgery cannot be attributed to high gastrin serum levels  consequently  it is unlikely that vomiting after strabismus surgery is linked to an  oculogastric reflex  with the vagus nerve as the efferent pathway  
class6	antiemetic prophylaxis with promethazine or droperidol in paediatric outpatient strabismus surgery  this randomized  double blind study evaluated the antiemetic efficacy and the side effects of promethazine pretreatment  0 5 mg kg 1 iv   0 5 mg kg 1 im  versus droperidol   placebo pretreatment  droperidol  0 075 mg kg 1 iv   physiological saline  0 02 ml kg 1 im   one hundred unpremedicated asa physical status i children ranging from two to ten years  and undergoing outpatient strabismus surgery were studied  all children received inhalational anaesthesia with halothane  nitrous oxide and oxygen  neither opioids nor muscle relaxants were used  the incidence of vomiting and or retching and the incidence of side effects were determined in the post anaesthesia recovery room  parr   in the short stay surgical unit  sssu   and after discharge from the hospital  including the journey and the stay at home during the first postoperative day   promethazine and droperidol were equally effective in reducing the incidence of vomiting before discharge to two and eight per cent respectively  on the contrary  the incidence of vomiting after discharge and overall were significantly less with promethazine  ten and ten per cent  than with droperidol pretreatment  54 and 56 per cent   p less than 0 0001   promethazine permitted the time to discharge from the hospital to be reduced to an average of three hours  without increasing the incidence of vomiting postdischarge  promethazine pretreatment is much less expensive than droperidol pretreatment  the incidence of restlessness was significantly less with droperidol  eight per cent  than with promethazine  36 per cent   p less than 0 001   promethazine pretreatment demands the use of an analgesic like acetaminophen in order to reduce the incidence of postoperative pain and restlessness  
class6	maternal outcome after open fetal surgery  a review of the first 17 human cases  a few fetal diseases may benefit from surgical treatment before birth  but hysterotomy and subsequent delivery by cesarean section pose a risk to the otherwise unaffected mother  to assess maternal risk of mortality  morbidity  and reproductive potential after fetal surgery  we reviewed our experience with 17 highly selected women who underwent fetal surgery  fifteen of these procedures were performed for one of two congenital anomalies  severe bilateral hydronephrosis and congenital diaphragmatic hernia  there were no deaths or serious maternal injuries  in the 14 women who continued pregnancy after hysterotomy  uterine irritability and preterm labor were frequent complications  requiring early confinement in most cases  there has been no detectable effect on future fertility  as indicated by eight subsequent normal pregnancies  we conclude that hysterotomy for fetal surgery can be accomplished without unduly endangering the mother s life or her future reproductive potential  however  morbidity related to premature labor remains a serious problem  and our ability to control uterine contractions after hysterotomy remains the limiting factor in human fetal surgery  
class6	gallstone pancreatitis  choosing and timing treatment  patients with gallstone pancreatitis are often seen initially by primary care physicians  prompt diagnosis and timely intervention are crucial in reducing morbidity and mortality  initial management should include supportive medical care and surgical consultation  the timing of surgery is then dictated by serum enzyme levels and liver function test results as well as by the patient s condition  the role of endoscopic intervention is currently evolving  whether surgery or endoscopic sphincterotomy is preferable as primary therapy for gallstone pancreatitis remains unresolved  however  sphincterotomy with stone extraction is a viable option in selected cases  especially in patients who have severe gallstone pancreatitis  
class6	gynecomastia  a bothersome but readily treatable problem  although breast enlargement in boys and men can cause both psychological and physical distress  the disorder is rarely serious and is readily treatable  several factors can lead to the estrogenic excess that causes growth of breast tissue  dr jacobs describes a patient with gynecomastia related to cirrhosis of the liver who responded promptly to a brief course of tamoxifen citrate therapy  
class6	endoscopy versus x ray studies of the gastrointestinal tract  future health care implications  i did esophagogastroduodenoscopy in 147 patients and colonoscopy in 59 patients who had had gastrointestinal x ray studies  the endoscopic procedure was done within 7 days after the x ray study and or while the patient was still symptomatic  the barium swallow findings were confirmed in only 40   in the other 60   the x ray findings could not be confirmed  these unconfirmed x ray findings were false positive in 37 4   false negative in 16 3   and suboptimal or nondiagnostic in 6 2   the barium enema findings were confirmed in 32   in the other 68   the x ray findings were false positive in 42 3   false negative in 22   and suboptimal in 3 3   we conclude that in clinical or private practice  relying on x ray studies alone may be associated with a high margin of diagnostic errors  when all factors are considered  the initial cost advantage of the x ray studies appears to be lost  in future recommendations on the continuing dilemma of x ray studies versus endoscopy  consideration should be given to factors other than the initial lower price of the x ray studies  
class6	high mortality among patients with the leukemoid reaction and alcoholic hepatitis  we describe a patient with severe alcoholic hepatitis  markedly elevated white blood cell count  and high fever  after review of the english literature  we discovered reports of other cases similar to our case  the striking feature in all of these cases was a high short term mortality rate  despite predictions of a favorable outcome  we therefore believe these patients represent a subgroup of patients with alcoholic hepatitis and that the leukemoid reaction is a poor prognostic sign in this disease  
class6	hepatocyte transplantation into the lung for treatment of acute hepatic failure in the rat  the lung was investigated as a matrix for transplanted hepatocytes in the rat model  surgically induced fulminant hepatic failure was successfully treated by injection of 5 to 7 x 10 7  isolated hepatocytes into the pulmonary parenchyma in 86  of the animals  no animal  however  survived injection of hepatocytes into the jugular vein  it was found that liver failure is a prerequisite for the intrapulmonary survival of hepatocytes  after regeneration of the native liver  the majority of hepatocytes are cleared away within 6 months  
class6	contributions of the zollinger ellison syndrome  the salient contributions of the zollinger ellison syndrome have made it unique  no pancreatic endocrine tumor described before  insulinoma  or subsequently  glucagonoma  somatostatinoma  vipoma  pancreatic polypeptidoma  has been the topic of such a variety of studies  or has been such an inspiration and rich source of new ideas for investigation and ultimate improvement in patient care  
class6	transduodenal sphincteroplasty with transampullary septectomy for stenosing papillitis  the papilla of vater and its sphincter of oddi  lying at the confluence of the bile and pancreatic ducts in man  have long been suspected as a source of upper abdominal pain  enlarging the opening of the transpapillary segment of the bile and major pancreatic ducts by using a transduodenal sphincteroplasty with transampullary septectomy resulted in death in a patient with a peripapillary diverticulum and pancreas divisum  eight six patients followed for 1 to 10 years experienced a 75  success rate  thirty six patients had a marked stenosis of their duct of wirsung  suggesting that their pain was primarily from the pancreas  the remainder had either a generalized narrowing  40 patients  or a normal  7 patients  papilla  pain was not satisfactorily resolved in patients with an associated pancreas divisum  chronic pancreatitis  and recurrent episodes of acute pancreatitis with alcoholism  
class6	historical review of pancreaticoduodenectomy  the performance of pancreaticoduodenectomy by whipple in 1935 demonstrated that the operation was feasible technically and compatible with reasonable function after recovery  from the mid  to late 1940s until the last 10 years  the procedure was condemned by many because of its associated mortality and morbidity  for reasons that are not clear  the risk of pancreaticoduodenectomy in the last 10 years has fallen to less than 10  and in several centers  less than 5   postoperative complications have been reduced and blood transfusions are unnecessary in an increasing number of patients  furthermore  a normal productive life without the need for medication and with no digestive disorder is expected  seventy one percent of patients are able to return to their preoperative occupation  
class6	neuroendocrine design of the gut  the enteric nervous system  ens  can be thought of as the third component of the autonomic nervous system  it is a vast network of neurons widely dispersed throughout the gut  the ens is a dominant regulator of gut function through the action of peptide and non peptide neurotransmitters  the most intensively studied roles of the ens have been the regulation of secretory processes  such as gastric acid secretion  and motility  it is clear  however  that the ens plays a broader role in the regulation of other gut functions  including mucosal defense  the gut immune response  and sphincter function  alterations in the regulation of gut function by the ens are likely or suspected in a number of conditions  including achalasia  hirschsprung s disease  inflammatory bowel disease  chagas  disease  chronic intestinal pseudoobstruction  biliary dyskinesia  tachygastria  and irritable bowel syndrome  improved knowledge of the pathophysiology of these troublesome conditions makes effective therapy more likely in the future  
class6	the roux operation for postgastrectomy syndromes  the aim of this paper is to describe the technique  indications  and results of the roux operation as used in the treatment of postgastrectomy syndromes  a roux gastrojejunostomy with a 40 cm roux limb is the procedure of choice for alkaline reflux gastritis  because it virtually eliminates reflux of bile and pancreatic juice into the stomach  the slow transit through a roux limb can also be used to good advantage to slow gastric emptying in patients with dumping  patients with delayed gastric emptying respond to the combination of near total gastric resection  which removes the atonic gastric remnant and speeds emptying  and roux y gastrojejunostomy  which prevents reflux esophagitis and provides a reservoir for ingesta in the upper gut  after all roux operations  however  the roux limb may slow emptying so much that pain  fullness  nausea  and food vomiting result  the so called roux stasis syndrome  prevention of the roux stasis syndrome with an  uncut  roux limb and the treatment of the syndrome by using electrical pacing to suppress the ectopic pacemakers that emerge in the limb offer possible new solutions to this vexing problem  
class6	germfree animals and technics in surgical research  germfree animals have been reared to a size  weight  and age permitting the performance of major surgical procedures and the pursuit of a variety of surgical research problems  germfree dogs have been maintained in the isolator system through three generations  indicating that life  reproduction  and growth are all possible in the absence of microbial contamination  the value of the germfree approach to surgical problems has been utilized in studies of a variety of gastrointestinal problems  shock  cancer  immunology  burns  wound healing  and in direct patient application  patients have been maintained in isolator environments for prevention of infection  for operative procedures  for treatment of extensive burns  and for management of immune suppressed individuals  we conclude that germfree animals and germfree technics provide a valuable addition to the armamentarium of the surgeon in both research and clinical applications  
class6	gastro oesophageal reflux during elective laparoscopy  an oesophageal ph electrode was used to record gastro oesophageal reflux in 73 women who had elective laparoscopy for various gynaecological procedures  no refluxes were recorded during the 63 procedures from which results could be analysed  the upper 95  confidence limit from this observation is 3 in 63  4 8    two of the excluded women refluxed during episodes of hiccough that occurred shortly after induction of anaesthesia  tracheal intubation may be required during laparoscopy  although the need to protect against the possibility of aspiration of gastric contents may not be a valid reason unless  with the same logic  it is suggested that all patients who hiccough should be intubated  
class6	ichthyosis  exocrine pancreatic insufficiency  impaired neutrophil chemotaxis  growth retardation  and metaphyseal dysplasia  shwachman syndrome   report of a case with extensive skin lesions  clinical  histological  and ultrastructural findings   the shwachman syndrome comprises exocrine pancreatic insufficiency  growth retardation  and bone marrow hypoplasia resulting in neutropenia  clinical  morphological  and ultrastructural studies  as well as hair analysis  were performed in a patient with shwachman s syndrome and severe ichthyosis  clinical findings were lamellar ichthyosiform desquamation on the extremities  the hair was scanty and short on the scalp  in the eyelashes  and in the eyebrows  the nails were hyperkeratotic  morphologic findings were slight  regular acanthosis and severe diffuse hyperkeratosis with variable parakeratosis  the granular layer was thickened  the papillary dermis showed very slight perivascular lymphocyte infiltration  the most prominent ultrastructural finding was the presence of solitary or multiple droplets of varying size in the cytoplasm of the keratinocytes  hair analysis revealed no abnormalities  the cystine concentration in hair specimens was normal  
class6	a videofluoroscopy chair for the evaluation of dysphagia in patients with severe neuromotor disease  due to the difficulties encountered in positioning severely neurologically impaired individuals for videofluoroscopic studies  the rehab tech video fluorochair was developed  the purpose of the chair is to provide the severely disabled patient with safe  stable postural support in an upright position for videofluoroscopic studies  with anterior posterior  lateral  and rotational views easily performed  the chair features a removable headrest  a full back support  armrests  lateral truncal supports  and a patented base which is clamped to the footboard of the radiology table and allows for 200 degrees rotation of the patient  two case studies illustrate the practical use and versatility of the rehab tech video fluorochair  
class6	serological evidence of infection with helicobacter pylori may predict gastrointestinal intolerance to non steroidal anti inflammatory drug  nsaid  treatment in rheumatoid arthritis  specific circulating antibodies to the spiral gastric organism  helicobacter pylori  hp  were detectable in 43  of 68 patients with rheumatoid arthritis by complement fixation test  cft  and enzyme linked immunosorbent assay  elisa   a frequency comparable with that of a normal  age matched population  presence of these antibodies correlated strongly with a previous history of peptic ulcer disease  pud  and to the severity of nsaid related dyspeptic symptoms  the latter often leading to multiple drug intolerance  this contrasts with short term  prospective nsaid toxicity data  which show little relationship between ulceration and hp carriage  this result suggests  however  that hp may have a definite role in the pathogenesis of symptomatic pud associated with more chronic nsaid usage  and may have important implications for ulcer prophylaxis in these patients  
class6	the long term effects of radiation therapy on patients with ovarian dysgerminoma  a retrospective chart review and questionnaire study was undertaken to look at the long term effects of radiation therapy in ovarian dysgerminoma patients  forty three patients and 55 controls responded to a questionnaire that detailed bowel  bladder  thyroid  menstrual  reproductive  sexual  and growth function  statistically significant differences in the number of bowel movements were noticed when comparing patients with controls  the authors noticed no significant differences between cases and controls in bladder function  no thyroid disorders were attributable to mediastinal radiation therapy  most patients with intact uteri bleed monthly on hormonal replacement  three patients with a remaining ovary and uterus resumed menstrual function after substantial doses of abdominopelvic radiation therapy  no patients have conceived  the authors noticed a slight increase in dyspareunia in the treated group  but most patients were satisfied with their sexual function  one premenarchal patient exhibited a growth disorder  
class6	primary and metastatic pulmonary meningioma  patient 1 was a 53 year old man who had a very rare primary pulmonary meningioma that developed in the left lingular segment  when this report was written  7 years had passed since he underwent operation  and no recurrence of the meningioma had been detected  in patient 2  a 61 year old woman  multiple pulmonary metastases were confirmed 19 years after she had undergone operation for multiple cerebellar meningiomas  and the metastases were resected  after 2 years  multiple intraperitoneal metastases were found  and thus aggressive surgery was performed  currently  22 years after the operation for the primary cerebellar meningioma  the patient is alive without any subjective symptoms  although intraperitoneal metastases have recurred  to date  only four cases  all in women  of primary pulmonary meningioma have been reported  case 1 reported in this article is thus the first case in a male patient to be reported  and  in addition  this patient also has the first reported case to have been evaluated for more than 5 years  in case 2  however  each of the excised extracranial tumor lesions was histologically homogeneous and showed a hemangiopericytomatous pattern  the histologic picture of those tumor lesions was exactly the same as the picture of a small portion of the cerebellar meningiomas excised 19 years earlier  thus  all those extracranial tumor lesions were diagnosed to be metastatic meningiomas  however  it is difficult to explain why there had been no symptoms for as long as 19 years until the pulmonary metastases were discovered  
class6	functional comparison between double and triple ileal loop pouches  ileal pouch function in 35 patients operated upon by the same surgeon were compared  seventeen of the patients had a double loop  j  ileal pouch anal anastomosis  ipaa  and 18 a triple loop  s  pouch  the patients were examined a mean of 27 9 months and 5 1 months  respectively  after ileostomy closure  ten of the s pouch patients were evaluated more than 6 months  s greater than 6 months   mean 9 1 after ileostomy closure  there were no differences in the mean maximum resting pressures or maximum squeeze pressures between the groups  the incidence of daytime and nocturnal leakage was lower in the s pouch group  22 and 29 percent  than in the j group 29  and 53 percent  though the mean maximum tolerated volume  mtv  of the s pouch group was greater than the j group  the difference was not statistically significant  the difference in the mean compliance between the j  and s pouch groups and the j and s greater than 6 months group was statistically significant  p less than 0 01  and  p less than 0 008   all the patients could evacuate spontaneously  the difference in the 24 hour frequency of defecation between the s greater than 6 months and j group was significant  p less than 0 05   but not between the s and j groups  the median frequency of nocturnal defecation between the s greater than 6 months and j pouch groups was significant  p less than 0 005   but not between the s and j groups  the triple loop s pouches were more compliant than the j pouches and had a better functional result as shown by a lower incidence of nocturnal leakage  and a lower frequency of defecation during the day and night  
class6	the role of sphincteroplasty for fecal incontinence reevaluated  a prospective physiologic and functional review  sixteen female patients  mean age 54 1 years  range 34 74 years  with a 9 8 year  range 1 25 years  history of incontinence to solid stool underwent overlapping sphincteroplasty with internal sphincter imbrication without fecal diversion  all patients were prospectively evaluated with preoperative anorectal manometry  electromyography  and pudendal nerve motor latency assessment  postoperative anorectal manometry  and preoperative and postoperative functional evaluation  mean and maximal resting pressures increased from 30 mm hg and 49 mm hg preoperatively to 40 mm hg and 57 mm hg  respectively  postoperatively  likewise  mean and maximal squeeze pressures increased from 27 mm hg and 48 mm hg preoperatively to 39 mm hg and 73 mm hg  respectively  postoperatively  p less than 0 01   furthermore  anal canal high pressure zone length was increased by sphincteroplasty from a mean of 0 9 cm  range 0 3 cm  to a mean of 2 1 cm  range 1 4 cm   these objective physiologic improvements correlated well with subjective functional improvement  subjectively  functional outcome was rated by patients as excellent in 38 percent  good in 38 percent  fair in 19 percent  and poor in only 5 percent of cases  overlapping sphincteroplasty with internal sphincter imbrication improves both the anal sphincter physiologic profile and fecal continence  
class6	rectopexy is an ineffective treatment for obstructed defecation  the symptoms of obstructed defecation have been attributed to rectal intussusception  and thus rectopexy has been advocated in the surgical management  in this study  patients with obstructed defecation underwent manometry and proctography before and after rectopexy  seventeen patients  16 females and one male  mean age 51 6 years  were studied  eleven underwent anterior and posterior fixation of the rectum and six had posterior fixation only  preoperatively five patients demonstrated rectoanal intussusceptions  fifteen had significant pelvic descent  no significant change in maximum resting pressure  maximum voluntary contraction  pelvic descent  or anorectal angle was seen postoperatively  in the initial follow up  many patients had significant amelioration of symptoms  however  on longer follow up  mean 30 8 months  only two had long term improvement  the remainder had a poor clinical result in spite of complete resolution of rectal intussusception  many reported a worsening of symptoms as reflected by an increase in tenesmus and stool frequency  in the two cases with a satisfactory result  both could empty the rectum completely and demonstrated rectoanal intussusception on preoperative evacuation proctography  in those with poor results  four had complete emptying and three had rectoanal intussusception  in conclusion rectopexy is an ineffective treatment for obstructive defecation in most patients  
class6	treatment of anorectal abscess with or without primary fistulectomy  results of a prospective randomized trial  to determine whether primary fistulectomy should be performed or not at the time of incision and drainage  a prospective  randomized study in 70 patients with anorectal abscess was conducted  thirty six patients underwent incision  drainage and fistulectomy with primary partial internal spincterectomy  group i   whereas in 34 patients anorectal abscess was treated by incision and drainage alone  group ii   after a median follow up of 42 5 months  the combined recurrence or persistence rate was 2 9 percent in group i and 40 6 percent in group ii  p less than 0 0003  log rank test   recurrent abscesses or persistent fistulas were treated by secondary partial internal sphincterectomy  comparing anal continence before and 1 year after definite treatment  we found increased anal function disturbances in 39 4 percent of the patients in group i and in 21 4 percent of the patients in group ii  p less than 0 106  fisher exact test   the combined recurrence or persistence rate of 40 6 percent indicates that more than half of the patients with anorectal abscess will have no further problems after simple incision and drainage  this finding  as well as the increased anal function disturbances after partial internal sphincterectomy  either primary or secondary  are the main reasons to reserve fistulectomy as a second stage procedure if necessary  
class6	anal sphincter function after intersphincteric resection and stapled ileal pouch anal anastomosis  this study was done to determine the effect of the direct ileal pouch anal anastomosis upon pressure and sensory components of the anal canal and ileal pouch  these findings were related to postoperative continence  thirty three patients with ileal pouch anal anastomosis  25 continent  eight with episodic minor incontinence  were studied 3     0 3 and 25     5 months after ileostomy takedown  the maximum resting pressure in the anal canal was significantly lower in patients with an imperfect result  35     5 mm hg  than in continent patients  44     5 mm hg   p less than 0 05   postoperatively the maximum squeeze anal pressure was slightly greater in continent than in incontinent patients  99     8 mm hg vs  87     7 mm hg   p greater than 0 05   the postoperative recto  ileo  anal inhibitory reflex was present in 27 percent  the linear correlation between strength of rectal  ileal  distension and depth resp  duration of internal sphincter relaxation as preoperatively observed disappeared postoperatively in every group of patients  simultaneous measurements of pouch and anal pressure in patients with imperfect results revealed a reduced positive pouch anal pressure gradient compared to the continent group  this low pouch anal pressure gradient is thought to be responsible for the increased incidence of soiling in some of our patients  
class6	a case of cecocolic intussusception with complete invagination and intussusception of the appendix with villous adenoma  villous adenoma of the appendix is a rare neoplasm and intussusception of the appendix is a rare pathologic condition  a very rare case seen in a 35 year old male with pain in the right lateral abdomen is reported  in this patient  the appendix along with the villous adenoma intussuscepted and invaginated into the cecal lumen  and presented as cecocolic intussusception  a polypoid lesion was diagnosed in the cecum by fiberoptic colonoscopy  unlike polypoid lesions at other sites in the large intestine  polypoid lesions of the cecum may accompany intussusception and invagination of the appendix  consequently  caution is required in performing endoscopic polypectomy in cases of polypoid lesions of the cecum  
class6	treatment of obstructive pneumatosis coli with endoscopic sclerotherapy  report of a case  the case of an 86 year old man with cardiac and pulmonary failure  in whom pneumatosis cystoides intestinalis caused segmental obstruction of the sigmoid colon is described  the patient was treated with endoscopic puncture and sclerotherapy of the cyst walls in four sessions  giving endoscopic and radiologic regress of the lesions and symptomatic relief  
class6	effect of motilin on gastric emptying in patients with diabetic gastroparesis  objectives  because disturbances of gastric emptying are a serious complication in insulin dependent diabetic subjects with regard to the maintenance of good metabolic control  we wanted to assess the effectiveness of motilin as a potential treatment for gastric emptying disturbances  research design and methods  the intestinal hormone motilin has been shown to accelerate gastric emptying in healthy subjects  therefore  we examined the effect of intravenous motilin on gastric emptying of a 99mtc colloid labeled semisolid test meal in 9 insulin dependent diabetic patients with diabetic gastroparesis  all patients had a significantly delayed gastric emptying rate compared with a group of 11 healthy control subjects  results  during the infusion of motilin  gastric emptying was accelerated  and it was no longer significantly different from control values  conclusions  these data demonstrate that motilin and related compounds such as erythromycin derivatives could be useful for the treatment of disturbed gastric emptying in diabetic subjects  
class6	studies on autoimmunity for initiation of beta cell destruction  vii  evidence for antigenic changes on beta cells leading to autoimmune destruction of beta cells in bb rats  the diabetic syndrome in biobreeding  bb  rats is believed to result from the destruction of beta cells by autoimmune responses  however  the initial events that cause the autoimmune destruction of beta cells remain largely unknown  this investigation was initiated to see whether there are any antigenic changes on the beta cells from neonatal to adult bb rats that may lead to the autoimmune destruction of beta cells  pancreatic grafts from neonatal bb rats remained largely intact without insulitis when transplanted into the renal subcapsular space of acutely diabetic bb rats  similarly transplanted islet grafts from neonatal bb rats were also not subject to autoimmune destruction  in contrast  islet grafts obtained from adult bb rats  which had been treated with silica to prevent insulitis  were rapidly destroyed in diabetic recipients  these results indicate that beta cells from neonatal bb rats are different from beta cells from adult bb rats  at least regarding their recognition by immunologic effectors  considering our observations and previous information on the initial role of macrophages dendritic cells in the development of insulitis in bb rats  we suggest that beta cell specific antigenic changes that precede insulitis may result in the autoimmune destruction of beta cells in bb rats  
class6	minor papilla cannulation and dorsal ductography in pancreas divisum  until recently  pancreas divisum represented a major technical barrier to a complete evaluation of pancreatic ductal anatomy  technical refinements have now made it possible to achieve minor papilla cannulation and dorsal ductography in more than 90  of attempts  in 120 consecutive dorsal ductograms  structural pathology was demonstrated in 36 subjects  30    chronic pancreatitis in 23  pancreatic stones in 10  pseudocyst s  in 4  ductal  cut off  in 7  pancreatic cancer in 3  and partial agenesis in 1  some patients had more than one finding   for patients in whom alcohol abuse was excluded  ductal pathology was present in 25   abnormal ventral ductograms were present in only 8  of cases  demonstrating that dorsal ductography has an appreciable additional diagnostic yield  when the clinical situation indicates the need for pancreatography  minor papilla cannulation should be performed if major papilla cannulation fails or reveals only the ventral pancreatogram of pancreas divisum  
class6	long term follow up in patients who have undergone balloon dilation for gastric outlet obstruction  although balloon dilation for gastric outlet obstruction has supplanted vagotomy plus drainage or resective therapy in some institutions  there are no long term data which demonstrate what percentage of patients ultimately requires surgical intervention  of 23 evaluable patients treated with hydrostatic balloon dilation in our institution  70  were asymptomatic at a mean follow up of 2 5 years  five patients required surgery  one for acute perforation and the other four for symptoms of continued obstruction  despite one to three additional attempts at dilation  only three of seven patients with previous gastric resection had a satisfactory long term result  whereas endoscopic therapy initially cost one tenth to one fifth that of surgical intervention  such figures do not factor for loss of productivity  on the one hand  or potential need for chronic h2 blockade  on the other  despite instruction to the contrary  only 6 of 15  40   active patients continue acid suppressive therapy  we conclude that balloon dilation remains a viable alternative for selected patients with gastric outlet obstruction  
class6	endoscopic ultrasonography in diagnosis of the extent of gallbladder carcinoma  endoscopic ultrasonography  eus  was performed preoperatively in 39 patients with gallbladder carcinoma  diagnosis of the anatomical extent of gallbladder carcinoma was compared with histologic analysis  and staging accuracy was evaluated according to the tnm classification  carcinoma considered to be at an early stage with no lymph node metastasis was correctly diagnosed in 87 5   differential diagnosis between early and advanced staged tumors was possible in 79 5   overall accuracy for depth of tumor invasion  t  was 76 9   limitations were due to many stones in the gallbladder and microinfiltration of carcinoma  assessment of regional lymph node metastasis  n  was at a sensitivity of 81 8  and specificity of 92 9   for an overall accuracy of 89 7   we believe endoscopic ultrasonography is useful in the clinical staging of gallbladder carcinoma  
class6	prospective randomized comparison of esophageal variceal sclerotherapy agents  sodium tetradecyl sulfate versus sodium morrhuate  we designed a prospective randomized study to evaluate differences in efficacy and complication rate between the two most commonly used sclerosing agents  sodium tetradecyl sulfate  std  and sodium morrhuate  mor   of 41 patients with acute index variceal bleeding initially evaluated  21 were randomized to receive 0 75  std and 20 to receive 1 6  mor diluted with 50  dextrose  overall mortality for the std group was 38  and that for the mor group was 25   ns   control of acute bleeding was achieved in 86  of the std patients and 90  of the mor patients  ns   overall  obliteration was achieved in only 33  of the std group and 25  of the mor group  but in those patients who remained in the study over 3 months  obliteration was achieved in 87 and 83   respectively  ns   there was a trend toward higher rebleeding in the std group compared with the mor group  81  vs  51    p   0 078   but there was no significant difference between the std and mor patients with regard to transfusion requirements  8 4 units patient vs  8 7 units patient   ulceration  53  vs  40    or stricture formation  9 5  vs  0 0    the results of this study suggest that std and mor are clinically equivalent sclerosing solutions  and that bias favoring use of one agent over the other may be unfounded  
class6	endoscopic variceal ligation in patients who have failed endoscopic sclerotherapy  endoscopic variceal ligation has been developed as an alternative to endoscopic sclerotherapy  we report a series of 12 men with a history of bleeding esophageal varices who were treated with endoscopic variceal ligation after they had failed sclerotherapy  hemostasis was achieved in all 10 patients who were bleeding at the time of initial endoscopy and again in those who subsequently re bled  over a follow up period of up to 22 months  varices have been and remain eradicated in five patients  in four others  a reduction in grade was noted before death  two patients   liver transplant  or loss to follow up  one patient each   two patients died before they could be re evaluated  while in the remaining patient  no reduction in variceal grade was noted before loss to follow up  no complication was recorded after 35 endoscopic treatment sessions involving a total of 245 rubber band ligations  our results indicate that endoscopic variceal ligation may be used with success in patients who fail sclerotherapy  
class6	endoscopic and histologic appearance of the gastric mucosa in patients with portal hypertension  to assess reliability of the endoscopic and histologic appearance of the gastric mucosa for diagnosing portal hypertension  50 patients with portal hypertension and 1323 controls were studied  endoscopic evidence of mild gastritis was seen more frequently in patients with portal hypertension than in the control group  42  vs  13 1   p less than 0 001   the mosaic sign was also seen more frequently in patients with portal hypertension compared with controls  14  vs  0 9   p less than 0 001   however  the mosaic sign was found to be nonspecific  and the sensitivity for diagnosis of portal hypertension was only 14   biopsy specimens from the stomach of all patients with portal hypertension and 100 controls with a normal endoscopic appearance revealed mucosal vascular congestion in 72  of patients with portal hypertension compared with 59  of controls  ns   there was no correlation between endoscopic and histologic evidence of congestive gastropathy  similarly  there was no correlation between the severity of mucosal vascular congestion and the degree of inflammatory changes observed in the biopsy specimens  both in the control  r   0 1  and in patients with portal hypertension  r   0 14   it is concluded that endoscopic and histologic features of the gastric mucosa in patients with portal hypertension are of low sensitivity and nonspecific and cannot be used to diagnose portal hypertension  
class6	endoscopic findings in yersinia enterocolitica enterocolitis  the endoscopic findings in the colon and terminal ileum in eight cases of yersinia enterocolitica enterocolitis infection were studied  the diagnosis was based on the isolation of y  enterocolitica in the feces and or elevated serum antibody titers to the organism  total colonoscopy was performed between 7 and 38 days  mean  24 days  after the onset of symptoms  in all patients  the terminal ileum was affected  followed by frequent involvement of the ileocecal valve and the cecum  and less frequently  the ascending colon  in the terminal ileum  round or oval elevations with or without ulcers were detected  small ulcers were detected on the ileocecal valve and in the cecum  these findings were observed even 4 to 5 weeks after the onset of symptoms  suggesting a relatively long course for this disease  
class6	twelve hour overnight oesophageal ph monitoring in patients with reflux symptoms  results of continuous 12 hour overnight ph monitoring  duration of ph less than 4  were reviewed in 112 patients with heartburn or regurgitation  or both  and in 56 normal subjects  patients had more reflux than normal subjects  medically controlled patients  n   51  had less acid reflux than patients who subsequently underwent reflux surgery  n   61   but there was a considerable overlap between those two groups  surgery was followed by a reduction in acid reflux to a value similar to that in normal subjects  patients in whom surgery was deemed to have failed had more reflux after the operation than those in whom it was successful  but no difference could be found in the preoperative reflux values of these two subgroups  monitoring ph is not of value in selecting candidates for surgery since the results are not a good predictor of outcome  but it is useful in the objective evaluation of surgical results  
class6	effect of increasing helicobacter pylori ammonia production by urea infusion on plasma gastrin concentrations  it has been proposed that the hypergastrinaemia in subjects with helicobacter pylori infection is caused by the action of the ammonia produced by the organism s urease activity on the antral g cells  to investigate this hypothesis we examined the effect on plasma gastrin of increasing the bacterium s ammonia production by infusing urea intragastrically to eight h pylori positive duodenal ulcer patients  after a 60 minute control intragastric infusion of dextrose solution at 2 ml minute  a similar infusion containing urea  50 mmol l  was continued for four hours  during the urea infusion  the median gastric juice urea concentration rose from 1 1 mmol l  range 0 3 1 6  to 15 5 mmol l  range 7 9 21 3  and this resulted in an increase in the ammonium concentration from 2 3 mmol l  range 1 3 5 9  to 6 1 mmol l  range 4 2 11 9   p less than 0 01   this appreciable rise in ammonia production did not result in any change in the plasma gastrin concentration  the experiment was repeated one month after eradication of h pylori  at which time the median basal gastrin was 20 ng l  range 15 25   significantly less than the value before eradication  30 ng l range 15 60   p less than 0 05   on this occasion  the gastric juice ammonium concentration was considerably reduced at 0 4 mmol l  range 0 1 0 9  and the urea infusion did not raise the ammonium concentration or change the plasma gastrin concentration  in conclusion  augmenting h pylori ammonia production does not cause any early change in plasma gastrin  
class6	dissociation between systemic and mucosal humoral immune responses in coeliac disease  we examined humoral immunity in coeliac disease as expressed in serum  systemic immunity   and in saliva  jejunal aspirate  and whole gut lavage fluid  mucosal immunity   the aims were to define features of the secretory immune response  iga and igm concentrations and antibody values to gliadin and other food proteins measured by enzyme linked immunosorbent assay  elisa   in active disease and remission  and to establish whether secretions obtained by relatively non invasive techniques  saliva and gut lavage fluid  can be used for indirect measurements of events in the jejunum  serum  saliva  and jejunal aspirate from 26 adults with untreated coeliac disease  22 treated patients  and 28 immunologically normal control subjects were studied  together with intestinal secretions obtained by gut lavage from 15 untreated and 19 treated patients with coeliac disease and 25 control subjects  jejunal aspirate iga and igm and gut lavage fluid igm concentrations were significantly raised in patients with untreated coeliac disease  the lavage fluid igm concentration remained higher in patients with treated coeliac disease than in controls  serum and salivary immunoglobulin concentrations were similar in the three groups  patients with untreated coeliac disease had higher values of antibodies to gliadin compared with treated patients and control subjects in all body fluids tested  these were predominantly of iga and igg classes in serum  and of iga and igm classes in jejunal aspirate and gut lavage fluid  values of salivary iga antibodies to gliadin were significantly higher in untreated coeliacs  though antibody values were generally low  with a large overlap between coeliac disease patients and control subjects  
class6	autoimmune enteropathy and colitis  is there a generalised autoimmune gut disorder  children with protracted diarrhoea  circulating enterocyte autoantibodies  and an enteropathy showing features of inappropriate hla molecule expression on the jejunal crypt epithelium  often present with persistent blood and mucus in their stools  eight children with autoimmune enteropathy were investigated for the presence of associated colonic disease  six children with protracted diarrhoea  no circulating autoantibodies  and an enteropathy  in five of them  undergoing colonoscopy were used as control subjects  in all eight patients  but not in the control subjects  there was macroscopic and microscopic evidence of an accompanying colitis of variable severity  thus indicating that a more generalised intestinal disorder was present  which might affect the whole intestine  aberrant expression of dr molecules on the colonic surface and crypt epithelium was also detected  autoimmunity may play a role in the colitis  
class6	mycobacterium paratuberculosis and crohn s disease  the possible aetiological role of mycobacterium paratuberculosis in crohn s disease was investigated  the immunological response was studied using an enzyme linked immunosorbent assay  elisa   western blotting  and immunocytochemistry  the antibody response to two protoplasmic antigen preparations of m paratuberculosis in the sera of patients with inflammatory bowel disease was measured by elisa  igg and igm antibodies to these antigens were measured in serum samples from 52 patients with crohn s disease  15 patients with ulcerative colitis  and 41 control patients without inflammatory bowel disease  although there was wide variation in the concentrations of antibody detected  patients with crohn s disease had concentrations that were not significantly different from those of the other two groups  in addition  mycobacterial antigens were separated by sodium dodecyl sulphate polyacrylamide gel electrophoresis and the immune response to each antigen was then examined separately and assayed for igg and igm in 10 patients from each of the three groups  an indirect peroxidase test was also used to detect m paratuberculosis in sections of tissue from 18 patients with crohn s disease and 10 with ulcerative colitis  the results were negative in all cases  this study does not support a role for m paratuberculosis in crohn s disease  
class6	impaired sulphation of phenol by the colonic mucosa in quiescent and active ulcerative colitis  substantial amounts of phenols are produced in the human colon by bacterial fermentation of protein  in the colonic mucosa of animals  phenols are inactivated predominantly by conjugation with sulphate  the purpose of this study was to confirm sulphation of phenols by isolated colonocytes from man and to evaluate mucosal sulphation in inflammatory bowel disease using the phenol  paracetamol  in rectal dialysis bags  the incubation of paracetamol with colonocytes isolated from resected colon specimens  n   7  yielded a mean  se  value of 7 0  0 9  mumols g dry weight of paracetamol sulphate after 60 minutes but virtually undetectable values of paracetamol glucuronide  paracetamol sulphate was detected in rectal dialysates from all control subjects  with a mean  se  value of 4 2  0 8  nmol hour  sulphation was significantly impaired  p less than 0 01  in 19 patients with active ulcerative colitis  0 6  0 2  nmol hour  and in 17 patients with ulcerative colitis in remission  1 1  0 4  nmol hour   sulphation in eight patients with crohn s colitis  4 3  2 1  nmol hour  was similar to that in control subjects  impairment of the capacity of the mucosa to sulphate phenols in quiescent and active ulcerative colitis may pose a metabolic burden on colonic epithelial cells  which are continuously exposed to endogenous phenols from the colonic lumen  
class6	5 aminosalicylic acid is a potent inhibitor of interleukin 1 beta production in organ culture of colonic biopsy specimens from patients with inflammatory bowel disease  interleukin 1 beta in biopsy specimens from inflamed colonic mucosa of patients with active inflammatory bowel disease was studied  compared with normal colonic mucosal biopsy specimens  a significantly greater amount of interleukin 1 beta was present in rectal mucosa before  median  range  4 3  2 0 11 8  v 119 2  30 1 286 8  pg mg  p less than 0 01  and produced during organ culture  39 1  9 4 106 8  v 97 6  28 2 991 6  pg mg  p less than 0 01   values of interleukin 1 beta after culture correlated with concentrations of thromboxane b2  organ culture of inflamed biopsy specimens in the presence of 5 aminosalicylic acid and dexamethasone reduced the amount of interleukin 1 beta detected  at the doses studied  5 aminosalicylic acid also reduced the amount of leukotriene b4 detected after culture  
class6	candidacidal activity of crohn s disease neutrophils  the ability of normal and crohn s disease neutrophils to kill candida albicans has been studied using neutrophils isolated from peripheral blood and suspended in phosphate buffered saline at 5 x 10 6  cells per ml  c albicans was grown to a stationary phase in broth culture and suspended in phosphate buffered saline at 10 7  organisms ml  neutrophils and candida were then incubated together at 37 degrees c in a shaking water bath in the presence of fresh serum  at 30 and 60 minutes samples were withdrawn  neutrophils lysed  and candida survival assessed by colony counting  results were compared with control suspensions of candida incubated with serum alone  after 30 and 60 minutes in the presence of autologous serum normal neutrophils had killed significantly more candida than crohn s disease neutrophils  mean  sd  61 0  16 7   v 40 5  16 2   at 30 minutes  p less than 0 0001  83 2  7   v 70 8  16   at 60 minutes  p less than 0 005   the results did not alter significantly when normal neutrophils were incubated with candida in the presence of crohn s disease serum instead of normal serum  when crohn s disease neutrophils were incubated with candida in the presence of normal serum instead of autologous serum there was some improvement in candidacidal ability at 30 minutes  48 9  20 6   v 40 5  16 2    p less than 0 03  but not at 60 minutes  phagocytosis  measured using a radiometric assay  was normal  neutrophils from patients with crohn s disease have an impaired ability to kill this granuloma provoking organism  it is not due to serum inhibitors or defective phagocytosis  
class6	mucosal characteristics of pelvic ileal pouches  this study aimed to investigate the degree of colonic metaplasia in ileo   anal pouches  biopsy specimens from 25 patients with functioning pouches  eight of whom had pouchitis  were studied using routine histology  mucosal morphometry  mucin histochemistry  and immunoperoxidase staining with monoclonal antibodies directed towards a 40kd colonic protein and a small bowel specific disaccharidase sucrase isomaltase  thirteen patients  including all eight with pouchitis  had subtotal or total villous atrophy and crypt hyperplasia  in this group  nine had colorectal type sulphomucin and the 40kd colonic protein was detected in two  these changes were not observed in patients with less severe villous abnormalities  sucrase isomaltase activity was  however  present in all 25 pouch specimens  we conclude that although some ileal pouches acquire certain colonic characteristics  complete colonic metaplasia does not occur  
class6	alcohol consumption in patients with colorectal adenomatous polyps  the risk of developing colorectal adenomatous polyps is probably increased by a variety of dietary and environmental factors  we found an association with current alcohol and cigarette consumption  the risk of polyps was increased three times in drinkers who did not smoke and two times in smokers who did not drink  with those who both drank and smoked having 12 times the risk of total abstainers  since colonic adenomatous polyps are generally regarded as premalignant lesions  these results lend support to the view that alcohol consumption may be an important factor in the pathogenesis of colorectal neoplasia  thus reinforcing the proposed polyp carcinoma sequence in colorectal carcinogenesis  the role of smoking  however  is less clear particularly since the lack of association of colorectal carcinoma and smoking has been reported in many other studies  
class6	how bad are the symptoms and bowel dysfunction of patients with the irritable bowel syndrome  a prospective  controlled study with emphasis on stool form  since it is not known whether the symptoms and bowel function of patients with the irritable bowel syndrome are truly abnormal we used diaries and frequent telephone interviews over a 31 day period to assess symptoms  defecation  and stool types in 26 unselected female hospital patients with the irritable bowel syndrome  27 women who admitted to recurrent colonic pain but had not consulted a doctor  non complainers   and 27 healthy control subjects  unexpectedly  abdominal pain and bloating occurred in most of the control subjects  pain  however  was six times more frequent in the patients and was more often considered severe  bloating occurred three times more often  defecation was more frequent  more erratic in timing and stool form  and more likely to produce stools of extreme forms  indicating rapid fluctuations in intestinal transit time  urgency was four times more prevalent in patients than control subjects  straining to finish defecating was nine times more prevalent and was often accompanied by feelings of incomplete evacuation  a combination which could lead to the misdiagnosis of constipation  the normal relation between stool form and the above symptoms was distorted  possibly due to rectal irritability  non complainers were intermediate between patients and control subjects in almost every parameter but were closer to control subjects than to patients  patients with the irritable bowel syndrome have real cause for complaint and their bowel function is truly abnormal  
class6	coeliac disease and malignancy of the duodenum  diagnosis by endoscopy  successful treatment of the malignancy  and response to a gluten free diet  a patient presented with subtotal villous atrophy and a malignant duodenal tumour of uncertain histogenesis  he was successfully treated by resection and chemotherapy and the small bowel mucosa recovered on a gluten free diet  the tumour was diagnosed at upper gastrointestinal endoscopy when barium studies and abdominal computed tomography were normal  thus making this one of the earliest coeliac malignancies diagnosed  
class6	successful control of bleeding from gastric antral vascular ectasia  watermelon stomach  by laser photocoagulation  we report a case of gastric antral vascular ectasia in a patient with primary biliary cirrhosis in whom chronic blood loss was a major problem  she required repeated blood transfusions that were complicated by reactions and still had persistent anaemia  she was treated with laser phototherapy in the form of quadrantic photocoagulation with a neodynium yttrium aluminium garnet laser  this greatly improved the endoscopic appearance of the gastric lesions and effectively controlled blood loss  she required no further transfusions  bleeding recurred after 11 months which was controlled by further laser photocoagulation  
class6	provision of gastrointestinal endoscopy and related services for a district general hospital  working party of the clinical services committee of the british society of gastroenterology   1  the number of endoscopic examinations performed is rising  epidemiological data and the workload of well developed units show that annual requirements per head of population are approaching  upper gastrointestinal 1 in 100 flexible sigmoidoscopy 1 in 500 colonoscopy 1 in 500 ercp 1 in 2000  2  open access endoscopy to general practitioners is desirable and increasingly sought  for a district general hospital serving a population of 250 000  this workload entails about 3500 procedures annually  performed during 10 half day routine sessions plus emergency work   3  high standards of training and experience are needed by all staff  who must work in purpose built accommodation designed to promote efficient and safe practice   4  the endoscopy unit should be adjacent to day care facilities and near the x ray department  there should be easy access to wards   5  an endoscopy unit needs at least two endoscopy rooms  a fully ventilated cleaning disinfection area  rooms for patient reception  preparation  and recovery  and accommodation for administration  storage  and staff amenities   6  the service should be consultant based  at least 10 clinical sessions are required  made up of six or more consultant sessions and two to four clinical assistant  hospital practitioner  or staff specialist sessions  each consultant should be expected to commit at least two sessions weekly to endoscopy  extra consultant sessions may be needed to provide an efficient service   7  a specially trained nursing sister  grade g or h  and five other endoscopy nurses are needed to care for the patients  their work may be supplemented by care assistants   8  a new post of endoscopy department assistant  analogous to an operating department assistant  is proposed to maintain and prepare instruments  and to give technical assistance during procedures   9  a full time secretary should be employed  records  appointments  and audit should be computer based   10  ercp needs the collaboration of an interventional radiologist working with high quality x ray equipment in a specially prepared radiology screening room  this facility may need to serve more than one hospital   11  a gastrointestinal measurement laboratory can conveniently be combined with the endoscopy unit  in some hospitals one or more gastrointestinal measurement technicians may staff this laboratory   12  an endoscopy unit is a service department analogous to a radiology department  it needs an annual budget  
class6	role of mast cells in ion transport abnormalities associated with intestinal anaphylaxis  correction of the diminished secretory response in genetically mast cell deficient w wv mice by bone marrow transplantation  to investigate the role of mast cells in transport abnormalities during intestinal anaphylaxis  we examined responses to antigen in isolated intestinal preparations from ovalbumin sensitized genetically mast cell deficient wbb6f1 w wv  w wv  mice and congenic normal wbbgf1             mice  changes in ion transport  primarily secretion of chloride ions  were indicated by increases in short circuit current  isc   in tissues from     mice  antigen caused increases in isc which were significantly inhibited by antagonists to histamine  diphenhydramine  and serotonin  ketanserin   by a cyclooxygenase inhibitor  piroxicam  and by a neurotoxin  tetrodotoxin   in preparations from w wv mice  antigen stimulated responses were approximately 30  of that in     mice and were inhibited only by piroxicam  responses to electrical transmural stimulation of nerves were approximately 50  in w wv versus     mice  and were inhibited by antagonists of mast cell mediators in     but not w wv mice  reconstitution of mast cells in w wv mice by intravenous injection of     bone marrow cells restored the normal responses to both antigen and nerve stimulation  our results indicate that mast cell dependent mechanisms are primarily responsible for the ion secretion associated with intestinal anaphylaxis  but that other cells are also involved  in addition  our data provide evidence for the functional importance of bidirectional communication between nerves and mast cells in the regulation of ion transport in the gastrointestinal tract  
class6	association between primary pulmonary hypertension and portal hypertension  analysis of its pathophysiology and clinical  laboratory and hemodynamic manifestations  to determine the clinical  laboratory and hemodynamic profile in patients with primary pulmonary hypertension and associated portal hypertension  7 new cases and 71 previously reported cases were analyzed  there was no gender predilection and the average age at diagnosis was 41 years  liver cirrhosis was the most frequent cause of hypertension  82   and a surgical portosystemic shunt was present in 29   almost invariably  portal hypertension either preceded or was diagnosed concurrently with pulmonary hypertension  favoring the hypothesis that in portal hypertension  the pulmonary vasculature may be exposed to vasoactive substances normally metabolized or produced by the diseased liver  possibly inducing vasoconstriction or direct toxic damage to the pulmonary arteries  clinically  exertional dyspnea was the most frequent presenting symptom  81    other symptoms  such as syncope  chest pain and fatigue  were present in less than 33   an accentuated pulmonary component of the second heart sound  82   and a systolic murmur  69   were the most common physical findings  at least 75  of these patients had evidence of pulmonary hypertension on electrocardiography  right ventricular hypertrophy  or roentgenography  cardiomegaly or dilated main pulmonary arteries  or both   hemodynamic findings included severe pulmonary hypertension  mean pulmonary artery pressure 59     19 mm hg  with normal pulmonary capillary wedge pressure and cardiac output  treatment was basically palliative and the mean and median survival times were 15 and 6 months  respectively  in brief  on the basis of clinical presentation and laboratory features  patients with combined primary pulmonary hypertension and portal hypertension seldom represent a diagnostic challenge  further research is needed on treatment  which remains palliative  the survival rate is poor and worse than that seen in isolated primary pulmonary hypertension  
class6	the prevalence of gallstone disease in very old institutionalized persons  we present the results of a study that was undertaken at a large geriatric nursing home to assess the prevalence of gallstone disease in very old institutionalized persons  one hundred seventeen residents underwent ultrasound examination of the gallbladder  two thirds of 82 women and half of 35 men had gallstone disease  when stratified for age  80  of women and men over the age of 90 years were positive for the disease  in summary  the prevalence of gallstone disease in our very old nursing home population was found to be unexpectedly high  
class6	immune competent cells of regional lymph nodes in colorectal cancer patients  i  flow cytometric analysis of lymphocyte subpopulation  lymphocyte subpopulations of the regional lymph nodes in 20 colorectal cancer patients were measured by flow cytometry to analyze nodal lymphocytes phenotypically  eleven patients with cholelithiasis were used as controls  comparison of lymphocyte subpopulations between colorectal cancer and control groups revealed a significantly increased rate of leu 12  cells in the cancer patients  furthermore  a significant increase of leu 3a  leu 8  cells and a significant decrease of leu 3a  leu 8  cells were also found in the paracolic nodes of the cancer patients  however  leu 2a  leu 15  cells were not different between the both groups  meanwhile  in the cancer patients  the rates of leu 4   leu 3a   and leu 3a  leu 8  cells were higher in the paracolic nodes compared with the intermediate nodes  additional investigation of the correlation between clinicopathological features of the tumors and lymphocyte subpopulations  showed that leu 12  cells were related to the tumor size and leu 2a  15  cells related to the histopathological type  the foregoing results indicate that the rates of both b and helper t cells  which may specifically participate in the antibody production  increase in the regional lymph nodes of colorectal cancer patients  
class6	clinical management of gastric cancer and concomitant esophagogastric varices  we report the late results of treatment of 13 consecutive patients with gastric cancer and concomitant esophagogastric varices  of seven good risk patients classified as child s class a or b  gastrectomy together with selective shunt operation was performed in two  total gastrectomy with splenectomy in three  and distal partial gastrectomy with paraesophageal devascularization without splenectomy in one  the remaining patient with early gastric cancer underwent distal partial gastrectomy following repeated endoscopic injection sclerotherapy  eis  for treatment of the esophageal varices  although the majority of patients who underwent surgical repair of varices  i e   shunt  splenectomy  or devascularization  died  total gastrectomy with splenectomy was the only procedure that led to control of the esophageal varices  since partial gastrectomy combined with eis limits the morbidity and mortality of an extensive resection and at the same time controls esophageal variceal bleeding  it is probably the procedure of choice for patients with a carcinoma in the lower two thirds of the stomach  concerning non surgical cases  two patients were effectively treated using laser endoscopy and eis  without the occurrence of variceal bleeding  the remaining four patients  given chemotherapy or irradiation for treatment of gastric carcinoma  died within 4 months with variceal bleeding or liver failure  for the poor risk patients with evidence of severe liver dysfunction  laser treatment and eis would be the treatment of choice  
class6	self management of dietary compliance in coeliac disease by means of elisa  home test  to detect gluten  to improve compliance with a gluten free diet in coeliac disease a simple prototype test kit was developed to detect gluten in foods for use at home  the test is based on monoclonal antibodies to heat stable gluten proteins which crossreact appropriately with barley and rye proteins  it is suitable for use with a wide range of raw or cooked foods  the food is extracted with dilute hydrochloric acid and 1 drop of the extract transferred to an antibody coated tube  enzyme labelled gluten detection antibody is added and after 3 min the tube is washed and colour developer is added  the reaction is stopped after 2 min  stabilising the blue colour  the home kit was compared with a quantitative laboratory kit  and the qualitative agreement was very good  the kit could distinguish foods with trace gluten contents  acceptable for a  gluten free  diet  from those with a slightly higher but unacceptable gluten content  in a trial of the prototype kit by 47 coeliac disease patients of diverse ages and educational backgrounds  93  of tests correctly identified foods as acceptable or unacceptable  
class6	rice based oral electrolyte solutions for the management of infantile diarrhea background  in infants the treatment of acute diarrhea with glucose based solutions results in rehydration but does not reduce the severity of diarrhea  oral rehydration with solutions based on rice powder may reduce stool output as well as restore fluid volume  methods  we designed a prospective  randomized  double blind study to evaluate the efficacy of two rice based rehydration solutions and a conventional glucose based solution  solution a contained only rice syrup solids  solution b contained rice syrup solids and casein hydrolysate  and solution c  the glucose based solution  served as control  the study subjects were 86 mildly to moderately dehydrated infant boys  3 to 18 months old  who were admitted to a children s hospital with acute diarrhea  we measured fluid intake  fecal and urine output  and absorption and retention of fluid  sodium  and potassium at intervals for 48 hours in all 86 infants  results  the mean      se  fecal output was significantly lower in the infants given solution a  group a infants  than in the infants given solution c  group c   29     4 vs  46     7 ml per kilogram of body weight  p less than 0 05  during the first six hours of therapy  the infants in group a also had greater fluid absorption  221     16 vs  167     9 ml per kilogram  p less than 0 05  over the entire 48 hours of therapy and greater potassium absorption  1 6     0 2 vs  0 6     0 1 mmol per kilogram  p less than 0 05  during the first six hours than the infants in group c  solution b offered no advantages over solution a  conclusions  solutions containing rice syrup solids were effective in the rehydration of infants with acute diarrhea  they decreased stool output and promoted greater absorption and retention of fluid and electrolytes than did a glucose based solution  
class6	evidence for role of prostacyclin as a systemic hormone in portal hypertension  the possibility that prostacyclin could be a systemic hormone and could mediate the splanchnic hyperemia of chronic portal hypertension was evaluated in rabbits in a normotensive state and in rabbits with chronic partial ligation of the portal vein  in rabbits with portal hypertension  pht   6 keto prostaglandin f1 alpha  pgf1 alpha  a prostacyclin degradation product  was elevated twofold in all vascular beds  systemic arterial  systemic venous  and portal venous  when compared with levels in control animals  in pht rabbits  exogenous prostacyclin infusion after cyclooxygenase blockade through the systemic arterial  systemic venous  or portal venous route resulted in an equal elevation of 6 keto pgf1 alpha in the reciprocal vascular beds and restored the original precyclooxygenase blockade hemodynamics  these hemodynamic changes were of equal magnitude irrespective of site of infusion in pht  in controls there was no significant change in 6 keto pgf1 alpha or hemodynamics with intraportal infusion  we conclude that prostacyclin achieves systemic levels by escaping hepatic degradation resulting from portosystemic shunting in the animal with chronic portal hypertension  
class6	a new method for mapping hepatic subsegment  counterstaining identification technique  hepatic subsegmentectomy requires identification of the borders of tumor bearing subsegment  usually achieved by injecting dye into the portal veins feeding the domain  we describe an alternative technique for performing systematic subsegmentectomy in patients with cirrhosis and hepatocellular carcinoma  in whom hepatic arterial and portal venous embolizations were already performed as a preoperative adjuvant  under ultrasonic guidance  each of the neighboring portal units is sequentially stained  thus defining the avascular subsegment to be resected as the nonstaining area  this allows the subsegment to be totally resected  this counterstaining identification technique can be used for all subsegments undergoing complete embolization and for other situations in which the usual staining method is impossible because of the presence of arterioportal shunting or portal tumor thrombus  
class6	cytologic criteria to distinguish hepatocellular carcinoma from nonneoplastic liver  the authors reviewed a series of fine needle aspiration biopsy  fnab  specimens of the liver to identify useful cytologic criteria to distinguish hepatocellular carcinoma  hcc  from nonneoplastic liver  ten cytologic features were examined in this study  high cellularity  acinar pattern  trabecular pattern  hyperchromasia  pleomorphism  irregularly granular chromatin  uniformly prominent nucleoli  multiple nucleoli  increased nuclear cytoplasmic ratio  and atypical naked hepatocytic nuclei  these features were examined in a series of 82 fnab specimens from 52 patients with hcc and 30 patients with nonneoplastic lesions  with the use of a step wise logistic regression analysis  three features were identified as predictive of hcc  increased nuclear cytoplasmic ratio  p   0 001   trabecular pattern  p   0 002   and atypical naked hepatocytic nuclei  p   0 03   when these three criteria were used  the sensitivity of diagnosing hcc by fnab was 100   and the specificity was 87   
class6	nonpropulsive esophageal contractions and gastroesophageal reflux  nonpropulsive esophageal contractions radiologically described as tertiary contractions or  corkscrew  esophagus suggest the presence of an underlying motility disorder and may lead to impaired acid clearance  the goals of this study were to determine the prevalence and role of gastroesophageal reflux  ger  in patients with tertiary contractions  thirty five consecutive patients with spontaneous  repetitive  nonpropulsive esophageal contractions noted on esophagography were studied with endoscopy  infusion esophageal manometry  and 24 h ambulatory ph monitoring  all patients had esophageal symptoms  mainly dysphagia  heartburn  and chest pain  but only three were found to have esophagitis by endoscopy and biopsy  nineteen patients had repetitive  nonlumen obliterating  nonperistaltic  tertiary  contractions  six had corkscrew esophagus  and 10 had forceful  lumen obliterating simultaneous contractions  rosary bead esophagus   twenty patients  58   had ger by ph criteria with mean values    time ph less than 4  40 9   upright ph less than 4  41   supine ph less than 4  44 3   number of episodes with greater than 5 min of ph less than 4  12  esophageal motility revealed  nutcracker  esophagus in eight  low lesp in two  and nonspecific esophageal motility disorder in 10  symptoms or severity of nonperistaltic contractions did not correlate with ger  radiologically demonstrable free reflux or the presence of heartburn did not predict ger  we conclude that 1  ger occurs in up to 58  of patients with nonpropulsive  tertiary  esophageal contractions on esophagography  and may play a role in the induction of abnormal peristaltic activity of the esophageal body  2  ger is usually not associated with endoscopic evidence of esophagitis or characteristic symptoms  and is recognized by 24 h ph monitoring  we speculate that detection and treatment of ger may improve the symptomatic management of patients with nonpropulsive esophageal contractions  
class6	the symptom sensitivity index  a valuable additional parameter in 24 hour esophageal ph recording  twenty four hour esophageal ph monitoring is useful for the quantitative measurement of gastroesophageal reflux and for the demonstration of a temporal relationship between symptoms and reflux  the symptom index  a numerical score  was developed to quantify the association between symptoms and reflux  because the symptom index primarily assesses the specificity of a patient s reflux symptoms  we propose to refer to this score as the symptom specificity index  because of certain limitations of this score  we developed and evaluated a new score  the symptom sensitivity index  that quantifies the subject s sensitivity for reflux  fifty two consecutive patients  referred to our laboratory for ambulatory 24 h ph recording were studied  beside the conventional reflux variables  both indexes were calculated  although a statistically significant correlation between the indexes was found  discordance between the specificity and sensitivity indexes was seen in 17 patients  33    based on the findings in this study we advocate that the symptom sensitivity index should be used  in addition to the symptom specificity index  and incorporated in future ph studies to optimalize the interpretation of the results  
class6	radiographic evaluation of suspected small bowel obstruction  plain abdominal radiographs and enteroclysis studies were reviewed blindly in 117 consecutive patients undergoing enteroclysis for suspected small bowel obstruction  plain radiographs were unreliably predictive of the presence of obstruction as determined by enteroclysis and surgery  among patients with normal or abnormal nonspecific plain radiographs  varying degrees of small bowel obstruction were demonstrated by enteroclysis in 22   conversely  of patients with obstruction on plain radiographs  42  had either normal enteroclysis studies or only minor adhesions  enteroclysis correctly predicted the presence of obstruction in 100   the absence of obstruction in 88   the level  proximal vs distal  of obstruction in 89   and the etiology of obstruction in 86  of operated patients  enteroclysis is advocated as the definitive study in patients with clinical uncertainty about the diagnosis of small bowel obstruction  
class6	fine structure of active and healed duodenal ulcer  in order to characterize the fine structure of active and healed duodenal ulcers  we examined tissue specimens of patients with active duodenal ulcer disease  n   30  before and after treatment with either antacids  n   16  or h2 receptor antagonists  n   14   by light microscopy and various electron microscopic techniques  e g   scanning and transmission electron microscopy  the characteristic histological feature of both the active and healed duodenal ulcer was the appearance of periodic acid schiff  pas  positive epithelial cells at the edge of the ulcers  electron microscopy revealed that these cells were similar to a special type of mucus secreting cell in the antrum  surface mucous cell   their mucus granules contained mainly neutral glycoproteins  helicobacter pylori were found attached to these cells in tissue specimens from 12 of 30 patients  40    the mucous structure destroyed during the ulcerative phase regained its normal net like structure after treatment  the ultrastructural healing process of duodenal ulcer was characterized by the presence of gastric metaplasia  by stunted microvilli of the duodenal epithelium  p less than 0 001 vs  control group   and an increased number of lysosome like bodies  p less than 0 001 vs  control group  of the epithelial cells  these results were independent of the type of treatment  and showed that the repair mechanisms were incomplete after a 4 wk period of treatment  
class6	colonoscopy during an attack of severe ulcerative colitis is a safe procedure and of great value in clinical decision making  thirty four patients who had severe ulcerative colitis had a colonoscopic examination during the attack  the indications were resistance to therapy and or differential diagnostic purposes  total colonoscopy was performed in 25 cases and less extensive examination in nine  biopsy was taken in 22 cases  no clinically significant complications occurred  the procedure helped us to postpone immediate surgical intervention in 19 cases  fourteen of these patients have maintenance treatment and are still well after a follow up median time of 5 yr  6 months to 10 yr   
class6	extracorporeal piezoelectric lithotripsy for complicated bile duct stones  today  common bile duct stones are extracted endoscopically  after endoscopic sphincterotomy  nearly 90  of all stones can be removed with a dormia basket or a mechanical lithotripter  problems are encountered if there are larger stones or a duct stenosis  new conservative therapies do serve as an alternative to surgical intervention for those few patients in whom endoscopic measures have failed  stone fragmentation can be achieved by extracorporeal shock wave lithotripsy  and remaining fragments can be removed endoscopically  so far  authors of most reports on the successful disintegration of common bile duct stones used the dornier lithotripter  stone localization is thus achieved with x rays  and the shock waves are generated by an underwater spark discharge  we report on our experiences and results with extracorporeal piezoelectric shock wave lithotripsy  epl  in 19 patients with complicated bile duct stones  with this lithotripter  stones are visualized by ultrasound  and shock waves are produced by a piezoelectric acoustic generator  fragmentation was achieved in 84 2   and complete stone removal in 78 9   these results show that piezoelectric lithotripsy is also a useful method for the treatment of complicated bile duct stones  as has already been proved for the electrohydraulic  and electromagnetic generated shock waves systems  however  the renunciation of general anesthesia and the need for analgesia or sedation in only 25  of the treatments render this lithotripter system attractive  especially for elderly and frail patients  
class6	exocrine pancreatic function in chronic liver diseases  to confirm the respective influence of chronic alcoholism and liver disease on exocrine pancreatic function in cholecystokinin secretin  cs   tests were performed on patients with chronic liver cirrhosis  lc  and non cirrhotic  nlc  disease of alcoholic  a  and nonalcoholic  na  etiology  results were compared in four subgroups  alc  n   26  anlc  n   45  nalc  n   18  and nanlc  n   43   volume of duodenal juice and bicarbonate output  bo  were increased and maximal bicarbonate concentration was decreased in alc  compared with those in normal controls  comparison of lc and nlc indicated that the volume  bo  and amylase output  ao  were greater in lc than in nlc of alcoholic etiology  but not in those of nonalcoholic etiology  the initial disappearance rate  kicg  of indocyanine green  icg  excretion correlated with a parameter of cs test in alcoholic liver disease  vs  volume  r    0 51  p less than 0 01 vs bo  r    0 40  p less than 0 01   but not in nonalcoholic liver disease  concurrent chronic pancreatitis with pain and definite exocrine insufficiency was observed in only one alc patient and in four anlc patients  but in none of the nonalcoholics  in alcoholic liver disease  exocrine pancreatic secretion tends to increase with severity of liver damage  but concurrence of definite chronic pancreatitis is not correlated with the severity  
class6	prognostic factors in alcoholic liver disease  va cooperative study group  two hundred eighty one alcoholic patients were prospectively evaluated by clinical  biochemical  and histologic parameters during a 4 yr period to assess their prognosis  they were stratified into four categories of injury  1  fatty liver  26 patients   2  acute alcoholic hepatitis  106   3  cirrhosis  39   and 4  cirrhosis with superimposed alcoholic hepatitis  111   the rate of survival and variables correlating with survival varied according to the group  at 48 months  70  of the patients with fatty liver were alive  58  in the alcoholic hepatitis group  49  in cirrhosis  and 35  in alcoholic hepatitis superimposed upon cirrhosis  within group one  deaths were due to causes unrelated to liver disease  in the alcoholic hepatitis group  factors significantly correlating with survival were ascites  alanine amino transferase levels  grams of alcohol consumed  continuation of alcohol intake  and clinical severity of disease  survival in patients of group three correlated significantly with prothrombin time and histologic severity score  patients with combined cirrhosis and alcoholic hepatitis exhibited the worst prognosis  with the most significant predictors of survival being age  grams of alcohol consumed  the ratio of serum aminotransferases  ast alt  and the histologic and clinical severity of the disease  although a different pattern of correlates was observed for each pathologic level of injury  knowledge of the various correlates aids in prognostic assessment  
class6	hemolytic anemia associated with the use of omeprazole  omeprazole is the first drug designed to block the final step in the acid secretory process within the parietal cell  it has been shown to be extremely effective in the treatment of peptic ulcer disease  reflux esophagitis  and the zollinger ellison syndrome  although clinical experience with omeprazole is still limited  many controlled studies have established the short term safety of this drug  we report the first case of a serious short term adverse reaction with the use of omeprazole  hemolytic anemia  the patient developed weakness  lethargy  and shortness of breath 2 days after starting therapy with omeprazole  two weeks after the initiation of therapy  her hematocrit had decreased from 44 1  to 20 4   and she had a positive direct coombs antiglobulin test and an elevated indirect bilirubin  after she discontinued the omeprazole  her hemoglobin and hematocrit gradually returned to normal  the mechanism by which omeprazole caused the patient s hemolytic anemia is uncertain  but physicians should be alerted to this possible adverse effect  
class6	kawasaki like syndrome after treatment with mesalazine  we report a patient who developed a severe hypersensitivity reaction  including rash  lymph node enlargement  fever  hepatitis  and eosinophilia  after sulphasalazine therapy  five years later  he developed a similar reaction after exposure to mesalazine  the salicylic compound of sulphasalazine  we conclude that patients with known severe systemic reaction to sulphasalazine therapy are also at risk for such a reaction when treated with a 5 asa preparation  
class6	congenital duodenal diaphragm  conversion of stable chronic symptoms to subacute gastric outlet obstruction by penetrating foreign body  congenital duodenal diaphragms  cdd  are rare lesions that usually become symptomatic and require surgery in childhood  we report a patient  who  although symptomatic since early childhood  had accommodated to the condition and finally required surgical correction in late life after an ingested foreign body traumatized the diaphragm  producing subacute gastric outlet obstruction  the condition  including the reconstruction of the precipitating event  was diagnosed endoscopically prior to surgery  
class6	annular pancreas as a cause of extrahepatic biliary obstruction  annular pancreas is a rare congenital abnormality that is increasingly diagnosed by endoscopic retrograde cholangiopancreatography  ercp  in the adult  in this population  it can present with duodenal or gastric ulceration  duodenal obstruction  pancreatitis  and  rarely  with associated congenital abnormalities  although it has been suggested that biliary obstruction may result from associated pancreatitis  such cases have not been reported  primary extrahepatic biliary obstruction from a constricting annulus also has not been reported  we report such a case  and describe resolution of symptoms and a return to normal biochemical tests in a patient  the literature and embryology of annular pancreas are reviewed  we suggest that this entity be added to the differential diagnosis of extrahepatic biliary obstruction  
class6	endoscopic management of retained cystic duct stones  the finding of residual common bile duct stones after cholecystectomy is a relatively frequently encountered problem for which effective nonoperative therapy exists  retained stones in a cystic duct remnant are very rare  we present a case of multiple retained stones in a long variant cystic duct remnant following cholecystectomy and common duct exploration  which was successfully managed with endoscopic sphincterotomy and balloon extraction  
class6	ten years  experience with continuous ambulatory peritoneal dialysis  up to january 1989  171 patients were trained at our center on continuous ambulatory peritoneal dialysis  capd   and 17 on continuous cyclic peritoneal dialysis  ccpd   over 10 years  we have gained 5 068 patient months experience  patient survival was 60  and 31  at 5 and 10 years  respectively  in contrast  diabetics had a survival of 32  at 5 years  major complications included 499 new episodes of peritonitis  304 exit site infections  22 hernias  five bowel perforations  one hydrothorax  and three episodes of sclerosing encapsulating peritonitis  our technique survival has been 62  and 40  at 5 and 10 years  respectively  we believe that capd is a viable dialysis technique for long term treatment of chronic renal failure and it should be offered as an option to intermittent hemodialysis  
class6	group b streptococcus  an unusual cause of severe peritonitis in young children treated with continuous ambulatory peritoneal dialysis  peritonitis in continuous ambulatory peritoneal dialysis  capd  patients is only rarely caused by beta hemolytical streptococci species  we describe two young children  aged 15 months and 5 years  respectively  who presented an unusually severe course of peritonitis due to group b beta hemolytical streptococci  this course of the disease showed a strong similarity with neonatal streptococcal septicemia  in neonates  igg2 deficiency is thought to be partly responsible for the severity of this condition  this may also be true for young children treated with capd  since igg2 deficiency has been established for children  
class6	umbilical cord ulceration and intestinal atresia  a new association  in three fetuses  congenital intestinal atresia was associated with linear ulcerations of the umbilical cord  in two cases  hemorrhage was seen from the cord ulcer  both fetuses required emergency cesarean section for fetal distress and were born anemic  the third fetus was mildly hydropic  attributed to hemorrhage  and was stillborn  the mechanism of the association could not be determined  these cases suggest a risk of prenatal umbilical cord hemorrhage in infants with intestinal atresia  
class6	estrogen receptors in the external anal sphincter  inasmuch as anal competence in women is reduced after the age of 50 years  it may be dependent on effects of estrogens  in this study  samples of the external anal sphincter were analyzed for the presence of estrogen receptors and were found to be present at a median concentration of 5 0 fmol per milligram of protein  range  1 9 to 13  in women  n   7   and 1 1 fmol per milligram of protein  range  0 to 3 2  in men  n   7   these findings are of interest with regard to the treatment of idiopathic anal incontinence  
class6	longitudinal histopathologic assessment of rejection after bladder drained canine pancreas allograft transplantation  in preparation for assessment of percutaneous biopsies in our clinical pancreas transplant program  a working knowledge of the histopathologic changes after transplantation was obtained in a longitudinal open biopsy study of 16 dogs receiving bladder drained whole pancreas allografts  edema  extravasation of polymorphs  and lymphocytes associated with focal parenchymal injury were early  invariable  and probably nonspecific findings  the initial feature of unmodified rejection was the appearance of capillary and small vein endothelial changes with mainly perivascular inflammatory cell infiltration  acinar cell loss occurred early and was progressive  whereas islets and ducts were relatively preserved  indicating that acinar tissue may be more vulnerable to lytic necrosis when damaged  functional rejection  determined by fasting urinary amylase levels  was at a stage of extensive and irreversible necrosis  functioning grafts in immunosuppressed dogs had minor and transient endothelial changes with absence of class ii antigen staining of parenchymal cells  
class6	ischemic colitis  an ever changing spectrum  ischemic colitis  or more properly colonic ischemia  became a clear clinical entity in the past 25 years  yet  early diagnosis of this disease with its various presentations remains a difficult task  a 10 year review at our hospital identified 38 patients with colonic ischemia for comparison with the authors  previous experience and with data from the literature  several important factors emerge   1  twice as many cases occurred after operations  34  in this series vs  16  in the past   probably because fewer and fewer spontaneous cases were hospitalized   2  sixteen patients required operative intervention for colonic ischemia with a mortality of 62 per cent  while those treated nonoperatively had a mortality of 14 per cent  seven of eight postoperative patients who required a second operative procedure for their colonic ischemia died  a high clinical suspicion is necessary in the postoperative patient  as colonic ischemia appears to be more severe among these patients  moreover  the high incidence of associated cardiovascular disease indicates that early diagnosis  as well as monitoring of the  at risk  patient  is needed for improvement in survival to occur  new monitoring methods  such as tonometry  may help accomplish this goal  
class6	effect of oxygen free radical scavengers on survival in sepsis  sepsis remains a leading cause of death in the surgical intensive care unit  sicu  patient following major surgery or trauma  recent work has demonstrated that oxygen free radicals  ofr  generated during sepsis contribute to the pathogenesis of this syndrome  the purpose of this study was to evaluate the effect of various new free radical scavengers on survival in sepsis  a total of 85 male sprague dawley rats were placed into one of the following treatment groups  control  cecal ligation and puncture  clp   pre at  pretreatment with alpha tocopherol  at  10 mg 100 gm sc x 3 days  and 5 mg 100 gm iv prior to clp  at  20 mg 100 gm at time of clp and 4 hours following clp  u74006f   21 aminosteroid which inhibits lipid peroxidation  3 mg kg iv at the time of and 4 hours following clp  u78517f   alpha tocopherol analogue  3 mg kg at the time of and 4 hours following clp  survival was determined at various time points up to 72 hours  pretreatment with at resulted in improved survival  whereas the novel ofr scavengers u78517f and u74006f significantly improved survival and were efficacious without pretreatment  it was concluded that ofr scavengers can improve survival in sepsis  
class6	ileal pouch anal anastomosis  the emory university experience  the ileal pouch anal anastomosis has become a practical alternative to proctocolectomy for the treatment of ulcerative colitis and polyposis coli  to evaluate its success  the emory university affiliated hospital experience from february 1984 to march 1989 was retrospectively reviewed  there were a total of 50 patients identified  84 per cent had ulcerative colitis  and 16 per cent had polyposis coli  familial polyposis and gardner s syndrome   the majority of these patients underwent a two stage operation  but one third required a three stage procedure due to difficulty in mucosal proctectomy or toxic megacolon  j pouch construction was performed in 72 per cent of patients  s pouch construction in 14 per cent  straight ileo anal anastomosis in 8 per cent  and lateral isoperistaltic ileo anal anastomosis in 6 per cent  of the 50 patients  36  72   have had closure of the temporary ileostomy  fourteen patients have not had ileostomy closure due to change in diagnosis to crohn s disease  operative complications  or ileostomy closure pending  the combined operative morbidity per patient for the ileal pouch anal anastomosis and the closure of the ileostomy was 32 per cent  this included bowel obstruction  16 per cent  pelvic abscess  6 per cent  and ileo anal separation  4 per cent  follow up on patients with ileostomy closure ranged from 6 months to 4 years  mean  1 3 years   stool frequency was 5 9 stools per 24 hours at 6 months and improved with time  during the follow up period  all patients were eventually completely continent of stool during the day  and most became completely continent of stool at night  
class6	aids enteropathy  occult enteric infections and duodenal mucosal alterations in chronic diarrhea objective  to investigate occult enteric infections and morphologic changes in the small intestine in patients with advanced human immunodeficiency virus  hiv  infection and chronic diarrhea of undefined cause  design  case control study  setting  referral based clinic and hospital in tertiary care center  patients  twenty two patients with advanced hiv infection  19 with the acquired immunodeficiency syndrome  aids   3 with aids related complex  with chronic diarrhea  selected because of previously negative stool evaluations for bacterial or parasitic pathogens  were compared with 13 patients with advanced hiv infection  9 with aids  4 with aids related complex  without diarrhea by analysis of endoscopic biopsies using light and electron microscopy  viral culture  and morphometric studies  both groups were convenience samples and had at least 7 months follow up  measurements and main results  eleven of twenty two patients with hiv infection and chronic diarrhea but only 1 of 13 patients without diarrhea showed occult enteric pathogens  that is  undetected by routine studies  after extensive evaluation of duodenal and colorectal biopsies  mycobacterium avium intracellulare and microsporidia were the most common occult agents in study patients with diarrhea  5 each   patients with diarrhea and occult enteric infections had greater weight loss  mean  14 3 kg compared with 6 2 kg  p less than 0 05  and shorter survival  1 of 11 compared with 8 of 11 still alive  p less than 0 004  than those with diarrhea but no identified pathogens  defined as  aids enteropathy    duodenal morphometry showed decreased villus to crypt ratios because of villus atrophy and crypt elongation in hiv infected patients both with and without diarrhea compared with normal controls  p less than 0 001 for each   all three groups showed comparable frequencies of epithelial mitoses  conclusions  further endoscopic biopsy evaluation of patients with aids who had unexplained chronic diarrhea showed an occult infectious cause in half of the cases  however  altered villus and crypt architecture in advanced hiv infection was independent of the presence of diarrhea or enteric infection and therefore did not correlate with aids enteropathy  subnormal epithelial proliferation in response to injury could be a factor  but the underlying cause of the architectural changes remains obscure  we suggest that t cell dysfunction may play a role  
class6	increased sympathetic outflow in cirrhosis and ascites  direct evidence from intraneural recordings  objective  to determine if central sympathetic outflow is increased in patients with cirrhosis and ascites  patients  eleven patients with cirrhosis and ascites  8 patients with cirrhosis but without ascites  and 7 age matched and 8 young healthy volunteers  methods  with subjects supine  direct microneurographic recordings of efferent post ganglionic muscle sympathetic nerve activity were obtained from the peroneal nerve  and sympathetic burst frequency was compared with subjects  blood pressure  heart rate  sodium excretion  catecholamines  and plasma renin activity  all patients with cirrhosis were studied at least 5 days after withdrawal from all medications and after 7 days of a 20 mmol d sodium  1 l fluid restricted diet  age matched volunteers were studied after 7 days of 20 mmol d sodium intake and young healthy volunteers after 7 days of 150 mmol d sodium intake  results  sympathetic nerve activity in ascitic patients  65     15 bursts min  mean     sd  was markedly increased  whether compared with patients with cirrhosis but without ascites  34     16 bursts min  p less than 0 001   age matched healthy volunteers on similar sodium intake  27     22 bursts min  p less than 0 001   or young healthy subjects  21     10 bursts min  p less than 0 001   the frequency of muscle sympathetic nerve discharge was directly related to plasma norepinephrine and epinephrine concentrations  plasma renin activity  and heart rate  all of which were increased in those patients with cirrhosis and ascites  and inversely related to 24 hour urinary sodium excretion  the fractional excretion of sodium  and subjects  pulse pressures  sympathetic nerve activity fell from 78 to 6 bursts min in one patient after liver transplantation  conclusions  this study provides the first direct evidence that elevated plasma norepinephrine concentrations in patients with cirrhosis and ascites are due to increased central sympathetic outflow  sympathetic nerve activity is not increased in patients with cirrhosis but without ascites  because there were direct positive correlations of sympathetic nerve activity with plasma norepinephrine concentrations  plasma epinephrine concentrations  plasma renin activity  and heart rate  the increase in central sympathetic outflow in patients with cirrhosis and ascites appears generalized and not restricted to muscle nerves  the anti natriuretic effects of parallel increases in renal and muscle sympathetic nerve activity could account for the inverse correlation between muscle sympathetic nerve activity and sodium excretion  
class6	do life events or depression exacerbate inflammatory bowel disease  a prospective study  objective  to determine whether depressed mood or life events are associated with an exacerbation of inflammatory bowel disease  design  a prospective study of a consecutive sample of patients with relapsing inflammatory bowel disease  followed by monthly questionnaires and periodic office visits  setting  a referral based gastroenterology clinic at a medical school  patients  a consecutive sample of 32 patients with inflammatory bowel disease who had had at least one relapse in a 2 year period after entry into the study  measurements and main results  the social readjustment rating scale  measuring life events   the beck depression inventory  a visual analog scale for depressed mood  and an inventory of intestinal symptoms were completed monthly by each subject with a 78  rate of compliance  a mean of 2 2 exacerbations was seen per subject during the study period  life events were not temporally associated with changes in intestinal symptoms  significant associations were found between intestinal symptoms and the two mood scales  p less than 0 05 for each   but no directionality in symptom occurrence could be detected in a time lagged analysis  the results were similar when the months preceding exacerbations of inflammatory bowel disease were analyzed separately  conclusions  although these findings suggest that mood changed concurrently with exacerbation of inflammatory bowel disease  no evidence indicated that stressful life events or depressed mood precipitated exacerbations in this study group  
class6	transvaginal approach for repair of rectovaginal fistulae complicating crohn s disease  the management of rectovaginal fistulae complicating crohn s disease is difficult and often unsatisfactory  between december 1983 and november 1988  13 patients with crohn s disease underwent repair of rectovaginal fistulae via a transvaginal approach  all patients had a diverting intestinal stoma either as part of the initial step in the staged management of intractable perianal disease or concurrent with the repair of the rectovaginal fistula  each of the patients had low or mid septal fistulae  high fistulae generally are treated transabdominally and are not the focus of this discussion  fistulae were eradicated in 12 of the 13 women and did not recur during the follow up period  which averaged 50 months  range  9 to 68 months   the only treatment failure was a patient who had a markedly diseased colon from the cecum to the rectum and a very low lying fistula  it is concluded that a modified transvaginal approach is an effective method for repair of rectovaginal fistulae secondary to crohn s disease  
class6	alanine aminotransferase in clinical practice  a review  alanine aminotransferase is an enzyme produced mainly in the liver  when serum activity is measured  it provides a marker of hepatic disease  this review explores the biochemistry and laboratory analysis of alanine aminotransferase in terms of its significance in human health and disease  cut off levels that define abnormality are rather arbitrary and this decreases the specificity of the test in apparently healthy patients  a small  but important  group of patients with alanine aminotransferase abnormality have underlying liver disease that may be treatable  most can be diagnosed based on history  physical examination  and biochemical serological profiles  liver biopsy can complement the diagnostic process in selected circumstances  literature pertaining to this is critically reviewed  
class6	parathyroid hormone secretion and target organ response in experimental acute pancreatitis  to determine changes in parathyroid hormone secretion and target organ response caused by acute pancreatitis before the development of systemic toxic conditions  experimental acute pancreatitis was induced in rats with a choline deficient  ethionine supplemented diet  after 7 days  the rats were weighed and bled  and one kidney was assayed for 25 hydroxyvitamin d1 hydroxylase activity  several manifestations of pancreatitis were observed in rats given the diet  weight loss  from 29 6 to 26 3 g vs that for control rats  from 29 to 52 8 g  and lower dietary intake  15 5 vs 47 g per rat per 7 days   serum amylase levels fell from 1794 to 350 u l in rats given the choline deficient  ethionine supplemented diet compared with levels of 1800 to 2100 u l in control rats  the pancreases of rats given the choline deficient  ethionine supplemented diet showed degeneration  necrosis  and hemorrhaging  serum levels of calcium  phosphorus  chloride  and parathyroid hormone did not change significantly throughout the experiment  renal 25 hydroxyvitamin d1 hydroxylase activity was higher than in control rats  8 9     0 8 vs 7 6     0 6 fmol mg of kidney per minute   acute pancreatitis in this experimental animal model does not alter serum levels of calcium and parathyroid hormone or reduce target organ responsiveness to the hormone  
class6	transient and distant infections alter later intraperitoneal abscess formation  transient nosocomial infections  such as line sepsis and pneumonia  are common in today s critical care patient population  although generally well treated  the effect of these transient antigen exposures on the immune system is unclear  we have previously shown that prior intraperitoneal inoculation with live bacteria leads to increased numbers of intraperitoneal abscesses  data presented here demonstrate in a murine model that two immunizations with live escherichia coli  bacteroides fragilis  or both  administered systemically via intracardiac injection or at a focal distant site in subcutaneous tissue  significantly increased the number of mixed e coli b fragilis intraperitoneal abscesses when induced 1 week later  further  immunization with e coli  either alone or in combination with b fragilis  increased the total number of anaerobes recovered per mouse  transient or focal sublethal infections can significantly alter an animal s immune response to later infectious insults  particularly the formation of intraperitoneal abscesses  
class6	pneumonia complicating abdominal sepsis  an independent risk factor for mortality  nosocomial pneumonia  np  is associated with a significant mortality  66  in a previous retrospective study of np complicating intra abdominal sepsis  ias   we prospectively compared the outcome of np complicating ias with that of recurrent ias  r ias  in the absence of np  data were collected prospectively on 300 patients with ias  34 patients who presented with pneumonia were excluded from the analysis  44  mortality   one hundred seventy one patients with no np and no r ias  group 1  had a hospital mortality of 20   34 patients   36 without np in whom r ias developed  group 2  had a 17  mortality  six patients   and 47 with np but no r ias  group 3  had a 53  mortality  25 patients   finally  12 patients who had both np and r ias suffered a 75  mortality  nine patients   we examined the relationships among the following putative risk factors and mortality  apache  acute physiology and chronic health evaluation  ii score  at initial presentation with ias   the need for mechanical ventilatory assistance following initial treatment for peritonitis  steroid requirement  generalized peritonitis vs abscess  and the need for surgical as opposed to percutaneous treatment  using mortality as the dependent variable  group 2 vs 3 as the explanatory variable  and the risk factors as confounders  logistic regression analysis indicated that the group difference was significant after controlling for confounders  we conclude that np complicating ias is an independent risk factor associated with a significant mortality compared with r ias  these data challenge the notion that death in ias is usually due to recurrent or persistent intra abdominal infection  
class6	diagnosis and treatment of cytomegalovirus disease in transplant patients based on gastrointestinal tract manifestations  infection due to cytomegalovirus is a substantial cause of morbidity and mortality in immunocompromised patients  in particular  cytomegalovirus infection has been associated with a significant detrimental effect on patient and allograft survival after solid organ transplantation  we are evaluating a new antiviral agent  ganciclovir 9  1 3 dihydroxy 2 2 propoxymethyl  guanine  dhpg   used in solid organ transplant recipients who developed life threatening cytomegalovirus infections  between march 1  1987  and june 30  1989  we treated 93 solid organ transplant patients who developed tissue invasive cytomegalovirus disease  from this group of patients we have identified 14 patients with primary gastrointestinal cytomegalovirus disease who received treatment with dhpg  tissue diagnosis was made by endoscopy of the upper gastrointestinal tract  11 patients  or colonoscopy  three patients   invasive cytomegalovirus disease was identified prior to severe complications of the gastrointestinal tract in all but one patient  who suffered colonic perforation prior to treatment with dhpg and subsequently died of bacterial sepsis  while 13 of the 14 patients improved after treatment with dhpg  four patients required additional treatments for recurrent cytomegalovirus disease and recovered  no dhpg toxicity was observed  we believe treatment with dhpg is indicated in this patient population  but that further studies are indicated to fully define the impact of this recommendation on both patient and allograft survival after solid organ transplantation  
class6	the vagus nerve  gastric secretions  and their relationship to peptic ulcer disease  although peptic ulcer disease was known to the ancients  the process by which the disease was produced remained a mystery  as advances were made in medicine and science  so too were advances made in the understanding of digestion and gastrointestinal disease  the treatment of peptic ulcer disease improved as our understanding of the digestive process grew  the current surgical treatment for peptic ulcer disease follows the principals articulated by lester r  dragstedt  md  phd  which he based on his observations in the research laboratory  we present a historical perspective of the role of the vagus nerve in the control of gastric secretions and its relationship to peptic ulcer disease  placing particular emphasis on dragstedt s contributions  
class6	sexual behavior before aids  the hepatitis b studies of homosexual and bisexual men  data on sexual practices  collected during studies of hepatitis b virus  hbv  infection in 1978 and 1979  were analyzed for 4910 homosexual and bisexual men from chicago  denver  los angeles  san francisco  and st louis  data on sexual practices in 1978 showed that white participants had larger numbers of non steady male sexual partners and engaged in oral genital activities more frequently but were equally likely to engage in anal intercourse as black and hispanic participants  san francisco participants had more non steady sex partners and were more likely to engage in receptive anal intercourse with non steady partners than participants from all other sites  analysis of data on 606 hbv antibody negative men interviewed on three occasions in 1978 and 1979 showed no changes in risk indices for insertive and receptive anal intercourse between these years  except in san francisco where significant declines occurred in insertive anal intercourse and receptive anal intercourse without ejacultion in a small  highly select group of participants  
class6	recovery from disturbed colonic transit time after alcohol withdrawal  the effects of alcohol withdrawal on total and segmental transit time were evaluated in 20 chronic alcoholic subjects  after withdrawal  colorectal transit time significantly increased from 24 9     3 6 to 33 3     4 5 hours mean     se  p less than 0 01   this was the result of an exclusive increase in rectosigmoid transit time from 2 8     0 7 to 9 8     2 1 hours  p less than 0 001   no variations were found in right or left colon transit time  distal colonic motility is thus a crucial factor in the genesis of diarrhea in chronic alcoholic subjects  
class6	water and electrolyte balance after ileoanal anastomosis  water and electrolyte balance was studied in 30 patients with ileoanal anastomosis and j pouch  10 patients with conventional ileostomy  and nine nonoperated patients with quiescent ulcerative colitis  serum electrolyte concentrations  daily urinary volume  and daily losses of sodium  potassium  and chloride were measured in all patients  daily fecal weight and daily losses of sodium and potassium were analyzed in patients with ileoanal anastomosis or conventional ileostomy  serum chloride in patients with ileoanal anastomosis was significantly lower  p less than 0 05  than in those with conventional ileostomy or in nonoperated patients  daily urinary loss of sodium in nonoperated patients was significantly higher than in patients with ileoanal anastomosis  p less than 0 01  or conventional ileostomy  p less than 0 05   daily urinary loss of chloride in patients with ileoanal anastomosis was significantly lower  p less than 0 05  than in nonoperated patients  daily fecal loss of potassium in patients with ileoanal anastomosis was significantly higher  p less than 0 05  than in those with conventional ileostomy  daily urinary volume and fecal weight did not differ significantly in patients with ileoanal anastomosis or conventional ileostomy  the present study indicates that changes in water and sodium balance after ileoanal anastomosis are similar to those after conventional ileostomy but chloride balance is more altered after ileoanal anastomosis  
class6	 mini perforation  of the colon  not all postpolypectomy perforations require laparotomy  in a 10 year experience with 4 784 consecutive colonoscopic polypectomies  the need for operative intervention in just two of seven perforations indicates that patients with specially defined  limited perforations can usually be treated nonoperatively  this specific complication  which has been termed  mini perforation   is generally detected within 6 24 hours of polypectomy  and is characterized by local pain and tenderness  without signs of diffuse or spreading peritoneal irritation  free intra abdominal or retroperitoneal air on x ray documents the actual perforation  complete resolution of symptoms within 24 48 hours confirms the diagnosis of  mini perforation   success depends on good bowel preparation for colonoscopy  and early recognition of perforation  with institution of bowel rest and intravenous antibiotics  the  mini perforation  spontaneously closes  probably by omental adherence  frequent serial clinical examinations are mandatory so that frank perforation with advancing peritonitis will be promptly recognized and treated surgically  an understanding of the three levels of cautery injury to the colon wall   serosal burn    mini perforation   and  frank perforation  are essential in managing the complications of colonoscopic polypectomy  
class6	anorectal dysfunction in patients with urologic disturbance due to multiple sclerosis  anorectal function was evaluated in 11 patients with voiding dysfunction due to multiple sclerosis  in six patients with constipation  three also had symptoms of obstructed defecation and one patient was incontinent due to stercoral diarrhea  one patient was only fecal incontinent and one patient had obstructed defecation as the only symptom  three patients had no anorectal symptoms  anal manometry in the women compared with a control group revealed significant lower anal resting and squeeze pressures  although no significant difference of rectal sensation to distention with air was found  pudendal nerve terminal latencies were obtained in seven patients and were all normal  in four patients latency could not be demonstrated due to poor contraction of the sphincter on stimulation of the pudendal nerve  two of these patients were incontinent and two had both constipation and obstructed defecation  it is concluded that patients with voiding symptoms due to multiple sclerosis often reveal anorectal symptoms or motility disorders  although anal sphincter function is reduced  fecal incontinence is not prevalent in this group  the reason for this lies probably in the fact that many of the patients are constipated  thus securing fecal continence  
class6	the value of the rectus abdominis myocutaneous flap in the treatment of complex perineal fistula  complex perineal fistula and persistent perineal sinus are difficult to treat  we describe our experience with wide excision of the diseased perineum using a combined abdominoperineal approach  ten patients were reconstructed by a rectus abdominis myocutaneous flap  n   7   rectus abdominis muscle flap  n   2   and omental graft  n   1   primary healing was achieved in all cases  a median follow up of 18 months  range 6 54 months  has shown no recurrence of perineal disease or associated abdominal incisional hernia  there were no perioperative deaths  we propose that the rectus abdominis myocutaneous flap is indicated if large amounts of perineal skin has to be sacrificed  when less skin is removed a repair with greater omentum or rectus muscle alone is adequate  the abdominoperineal approach together with filling the residual pelvic cavity with well vascularized tissue allows definitive treatment to be carried out in one stage  
class6	the ileosigmoid knot  the ileosigmoid knot  isk  is a rare cause of intestinal obstruction  unfamiliarity with the condition could have disastrous consequence at surgery  over the past 20 years  we have encountered seven cases  analyzing the data gathered from these  and on reviewing the literature  we found it possible to arrive at a preoperative diagnosis in two patients  four patients were women  two of whom developed the obstruction in the postpartum period  one of the males was found to have an inflamed meckel s diverticulum included in the knotting  the symptoms and the clinical findings were nonspecific  the characteristic x ray findings of a double closed loop obstruction  was seen in only three patients  resection of gangrenous bowel with anastomoses was feasible in four  unlike in other series  primary anastomosis of the large gut was undertaken  there were two deaths early in the series  guidelines to the management have been suggested  
class6	crohn s disease and adenocarcinoma of the intestinal tract  report of four cases  four patients with intestinal adenocarcinoma complicating crohn s disease are reported  the youngest of the four patients was a 21 year old female with a 9 year history of crohn s disease of the terminal ileum as well as of the entire colon  she developed mucus producing moderately differentiated adenocarcinoma in the cecum  of the remaining three patients with crohn s disease  one presented an adenocarcinoma in the ascending colon  one in the rectum and the remaining one in the duodenum  all three colorectal adenocarcinomas originated in areas of high grade dysplasia and all four in areas with chronic transmural inflammation  the review of the literature indicates that a total of 174 small and large bowel cancers occurring in crohn s disease have been recorded  including the four reported herein   the vast majority of the reported cases have been found in the north american subcontinent  only in a few instances were bowel adenocarcinoma and crohn s disease observed in the european continent  it is therefore remarkable that three of our four cases were seen within a period of 12 months  interestingly  six patients having colorectal adenocarcinoma in association with crohn s disease were recently reported from a single hospital in england  the question therefore arises whether our cases and those reported recently from england are unrelated and merely coincidental or whether carcinomas are now also affecting european cd patients  if the latter is the case  the surveillance policy for patients with cd should be reconsidered at this hospital  
class6	colonic histoplasmosis in acquired immunodeficiency syndrome  report of two cases  colonic histoplasmosis is a rare entity  there have been four previous reported cases within the population of patients with human immunodeficiency virus  hiv  infection  because of the increasing incidence of hiv infection within regions where histoplasmosis is endemic  this condition may become more common  gastrointestinal histoplasmosis has protean clinical manifestations  and symptoms are often nonspecific  any patient with hiv infection who has unexplained gi symptoms should undergo evaluation for possible histoplasmosis  aggressive long term amphotericin b therapy has been effective in hiv patients with histoplasmosis  resection or diversion of symptomatic colonic strictures caused by histoplasmosis may be necessary in addition to medical therapy  
class6	incarceration of colonoscope in an inguinal hernia   pulley  technique of removal  because of its relative safety  colonoscopy has become an accepted diagnostic and therapeutic procedure in the evaluation of patients with colorectal disorders  many unusual complications of colonoscopy have been described  but only anecdotal reports of hernial incarceration have been published  we present a case of a right sided hernial incarceration of the colonoscope that would not permit reduction of the hernia nor removal of the instrument by conventional means  the mechanism of incarceration  which dictates the size of hernia at risk for incarceration  is explained  the  pulley  technique  which was used to remove the instrument without surgical intervention  is described  
class6	a rare cause of colitis  brucella melitensis  report of a case  documentation of gastrointestinal lesions in brucella infections is sparse  a case of brucella melitensis type 3 infection accompanied by erosive lesions of the colon  observed by endoscopy and histopathologic examination  is reported  such gastrointestinal lesions have not been described since 1934  before 1934 only postmortem observations are recorded  
class6	chronic anal fissure  a new method of treatment by anoplasty  chronic anal fissure is a common condition usually treated by maximal anal dilatation or lateral subcutaneous sphincterotomy  the following method is based on a common surgical principal  to widen a stenosed tube a longitudinal incision is made across the stenosed area and this is sutured transversely as in pyloroplasty  this method of anoplasty is simple and appears to have no resultant complications  further studies are necessary before its value can be established compared to the presently accepted methods of treatment  
class6	gender differences in manning criteria in the irritable bowel syndrome  the objective of this study was to determine if gender differences exist when using the manning criteria for diagnosis of irritable bowel syndrome  in an outpatient setting  61 women and 36 men with entry complaints of abdominal pain  altered bowel habits  or both underwent full evaluation by board certified eligible gastroenterologists who also systematically rated the presence or absence of the six manning criteria  irritable bowel syndrome was defined as the absence of an organic disease explanation for the entry complaints  this determination was made by two other board certified gastroenterologists after patients had been in the study for 9 months  these raters were independent of the study and rated the transcripts of patients  clinic visits  all other available clinical data from this and other clinics  all laboratory data obtained during the 9 month study period  and the results of a 9 month telephone follow up to patients and their physicians  sixty five percent of the study population had no organic disease explanation for the entry symptoms  thereby representing irritable bowel syndrome for this study  a similar proportion and type of organic disease and irritable bowel syndrome were experienced by men and women  for the total sample of 97 subjects  the correlation of the manning criteria with irritable bowel syndrome was 0 22  p less than 0 01   in the 61 women  correlation between the manning criteria and irritable bowel syndrome was significant  r   0 47  p less than 0 01   in the 36 men  however  the correlation was in the opposite direction  although it was not significant  r    0 16   it was concluded that significant gender differences exist when using the manning criteria for the diagnosis of irritable bowel syndrome and that the manning criteria were not of diagnostic value in men  
class6	impairment of esophageal emptying with hiatal hernia  concurrent videofluoroscopy and manometry were used to analyze esophageal emptying during barium swallows in 22 patients with axial hiatal hernias and in 14 volunteers  subjects were divided into three groups   a  volunteers with maximal phrenic ampullary length less than 2 cm  controls    b  patients or volunteers with maximal ampullary hiatal hernia length greater than or equal to 2 cm that reduced between swallows  reducing hernia group   and  c  patients with hernias that did not reduce between swallows  complete esophageal emptying without retrograde flow was achieved in 86  of test swallows in the controls  66  in the reducing hernia group  and 32  in the nonreducing hernia group  p less than 0 05   impaired emptying in the reducing hernia group was attributable to  late retrograde flow   whereby barium squirted retrograde from the hernia during emptying  impaired emptying in the nonreducing hernia group was attributable to  early retrograde flow  that occurred immediately after les relaxation  the nonreducing hernia group also had longer acid clearance times than the controls  p less than 0 05   we conclude that gastroesophageal junction competence is severely impaired in patients with nonreducing hiatal hernias  suggesting a mechanism whereby this subgroup of hiatal hernia is involved in the pathogenesis of reflux disease  
class6	role of leukotriene c4 in mucosal damage caused by necrotizing agents and indomethacin in the rat stomach  intragastric ethanol stimulates mucosal formation of leukotriene c4 in the rat stomach  the present study demonstrates that the increase in leukotriene c4 formation begins within 30 seconds and is maximal within 5 minutes  closely paralleled by the appearance of hemorrhagic lesions  leukotriene c4 formation returns to prechallenge levels within 3 hours  although erosions still persist  intragastric 0 2n naoh  acidified 100 mmol l taurocholate  25  nacl  or 0 6n hcl did not consistently increase leukotriene c4 formation despite severe mucosal injury  a number of sulfhydryl containing or sulfhydryl blocking agents as well as metals protected against mucosal damage and simultaneously prevented the stimulation of leukotriene c4 formation induced by ethanol  none of the agents increased and some virtually abolished mucosal formation of prostaglandin e2  indicating that gastroprotection can occur completely independently of the endogenous prostaglandin system  the leukotriene biosynthesis inhibitor mk 886 markedly suppressed gastric leukotriene c4 formation but did not protect against damage caused by ethanol  naoh  nacl  or acidified taurocholate  oral indomethacin reduced the ex vivo formation of both prostaglandin e2 and  to a lesser extent  leukotriene c4 in the gastric mucosa  inducing a shift in the balance from protective prostaglandins to proulcerogenic leukotriene c4  pretreatment with mk 886  however  did not significantly diminish indomethacin induced lesions  these data suggest that leukotriene c4 is not the exclusive mediator of gastric injury caused by necrotizing agents or indomethacin  on the other hand  certain protective compounds exhibit a striking parallelism between protection and inhibition of ethanol induced leukotriene c4 formation  suggesting that they may affect a target crucial for both mucosal injury and stimulation of 5 lipoxygenase  
class6	omeprazole 20 mg three days a week and 10 mg daily in prevention of duodenal ulcer relapse  double blind comparative trial  in a double blind  parallel group clinical trial of 195 patients with duodenal ulcers who after a short term study had relief of pain and healed ulcers proved endoscopically  65 were randomized to receive 20 mg omeprazole 3 days a week  once in the morning from friday to sunday   64 to receive 10 mg omeprazole once daily in the morning  and 66 to receive placebo for up to 6 months  the patients underwent repeat endoscopy with biopsy of the gastric fundic mucosa  qualitative assessment of argyrophilic cell population   assessment of symptoms  and laboratory screening with measurement of basal serum gastrin concentrations at 3 and 6 months or more often if indicated by recurrence of symptoms  at 3 months  endoscopically proved ulcer relapse occurred in 16  receiving 20 mg omeprazole 3 days a week  21  receiving 10 mg omeprazole daily  and 50  receiving placebo  at 6 months  corresponding rates were 23   27   and 67  with 95  confidence intervals of difference between the placebo group and omeprazole groups of 28  60  and 24  56   p less than 0 00001   respectively  and between omeprazole groups of  19  11   ns   no major clinical or laboratory side effects were noted  thus both omeprazole regimens are effective and safe in preventing duodenal ulcer relapse  
class6	small intestinal transit in the portal hypertensive rat  the purpose of this study was to determine the effects of portal hypertension on gastrointestinal transit  portal hypertension was induced in a group of 15 rats by the staged portal vein ligation technique  a control group of 15 rats underwent a sham operation  ten days later  a 51cr labeled krebs  buffer solution was instilled into the duodenum and the distribution or radioactivity along the length of the small intestine was determined after 15  30  and 60 minutes  portal hypertension was consistently established in the study group  splenic pulp pressure  mm hg  mean     sd  portal hypertensive vs  control  was 20 0     3 9 vs  12 7     3 9  p less than 0 002  various measures of intestinal transit revealed delayed transit in the portal hypertensive group  retention of radioactivity in the most proximal quartile of the intestine was greater  percentage retained  portal hypertensive vs  control  was 57 9     17 3 vs  31 2     15 3  p less than 0 02  49 1     15 5 vs  28 3     4 8  p   0 03  and 42 4     17 6 vs  29 0     8 8  p   0 08  at 15  30  and 60 minutes  respectively  and the geometric mean of transit was located more proximally  p less than 0 02  at each study interval in the portal hypertension group  it was concluded that portal hypertension is associated with delayed intestinal transit  this abnormality could predispose to bacterial overgrowth and contribute to altered digestion and absorption  
class6	l glutamine stimulates jejunal sodium and chloride absorption in pig rotavirus enteritis  rotavirus enteritis is the leading cause of diarrhea in infants worldwide  a research priority of the world health organization is to develop oral rehydration solutions containing amino acids or other additives that will stimulate intestinal absorption more efficiently than the current glucose based oral rehydration solutions  glutamine is the principal metabolic fuel of the small bowel and a putative stimulator of mucosal repair  this report describes the transport response to mucosal l glutamine following intestinal injury caused by porcine rotavirus  peak symptoms and mucosal damage were observed 2 7 days after oral rotavirus inoculation  in vitro transport studies of the maximally injured region  the midjejunum  80  reduction in lactase   surprisingly  showed transport responses to l glutamine  30 mmol l  and l alanine  30 mmol l  that were similar qualitatively and quantitatively to those observed in control tissue  subsequent application of mucosal d glucose  30 mmol l  caused additional stimulation of electrogenic na  transport  but the response to glucose was blunted  p less than 0 05  in the infected tissues  glutamine and alanine enhanced na  absorption to a similar degree  2 2 5 mueq cm 2 h 1   but glutamine stimulated equal amounts of electrogenic and electroneutral nacl absorption  whereas alanine had no significant effect on net cl  flux  glutamine is a potentially useful substrate for investigation in oral rehydration solutions for infant diarrhea  
class6	increased uptake of bromodeoxyuridine by hepatocytes from early stage of primary biliary cirrhosis  the relationship between dna synthesis activities of hepatocytes in biopsied specimens and liver volume was studied in various stages of primary biliary cirrhosis using an in vitro bromodeoxyuridine  a thymidine analogue  anti bromodeoxyuridine reaction and computed tomography  the mean bromodeoxyuridine      se  labeling index for 10 patients in an early histological stage  stage i  4  and stage ii  6  3 4      0 4   of primary biliary cirrhosis was 17 times that for 6 control subjects  0 2      0 1   p less than 0 001   and was significantly higher than that for 19 female patients with chronic aggressive hepatitis  0 9      0 2   p less than 0 001   14 compensated cirrhotic patients of viral origin  all female  1 1      0 3   p less than 0 01   and 5 patients with stage iii primary biliary cirrhosis  0 5      0 1   p less than 0 001   the mean      se  liver volume in the early stage of primary biliary cirrhosis  1225     40 cm3  was about 1 5 times that in control subjects  835     42 cm3  p less than 0 001   these results suggest that liver volume has already become large in the early stage of primary biliary cirrhosis perhaps because of markedly increased dna synthesis in hepatocytes  
class6	glucose and fat metabolism during short term starvation in cirrhosis  to evaluate the metabolic consequences of short term  i e   less than 24 hours  starvation  glucose and fat metabolism were studied in eight healthy subjects and in eight patients with stable cirrhosis after 16 hour and again after 22 hour starvation by 3  3h glucose and  14c palmitate turnover and by indirect calorimetry  although patients and controls showed significant increases in free fatty acid concentration  respectively  48      12  and 53      17   and turnover  55      14  and 71      21   during short term starvation  the values after 16  and after 22 hour starvation were higher in cirrhosis  fat oxidation was enhanced in the patients  but did not increase during fasting in contrast to controls  increase 19      17   p less than 0 05   net glucose oxidation was decreased in postabsorptive cirrhotics  p less than 0 05   although postabsorptive glucose turnover was not different from controls  starvation induced a greater decrease in glucose turnover in the patients  25      3  vs  10      3   p less than 0 05   this was not reflected in plasma glucose concentrations  in conclusion  the effects of starvation on glucose and fat metabolism are enhanced in cirrhosis  fasting hypoglycemia is prevented by decreased use of glucose  it remains to be established whether these changes are merely explained by defective liver function  per se  
class6	ascites increases the resting energy expenditure in liver cirrhosis  the purpose of this study was to investigate the effect of ascites on the energy metabolism of patients with liver cirrhosis  the resting energy expenditure was determined in 10 patients with liver cirrhosis and ascites of moderate or large volume  the resting energy expenditure measurement was performed using indirect calorimetry and the resting energy expenditure predictive value was calculated with the harris benedict equation  both before and after removal of ascitic fluid by paracentesis  metabolic stress factors were absent in all cases  after an interval of 11 2     7 7 days between measurements  a weight loss of 16 6     10 3 kg was observed with paracentesis  the resting energy expenditure measured by indirect calorimetry showed a statistically significant decrease from 1682     291 to 1523     240 kcal day  p less than 0 005  after removal of ascites  the repeatability of our indirect calorimetry method only allowed for the analysis of the results in 4 of 10 patients in whom ascites removal produced a consistent decrease in resting energy expenditure  there were no statistically significant differences between the measurements obtained by indirect calorimetry and those provided by the harris benedict equation  but the latter had a moderate reliability in predicting the real resting energy expenditure of every patient  our results suggest that  far from being an inert volume  ascites may be associated  at least in some patients  with an increased resting energy expenditure and therefore accelerate the appearance of protein energy malnutrition with corresponding complications  
class6	high protein ascites in patients with the acquired immunodeficiency syndrome  diseases of the liver or peritoneum resulting in ascites have been infrequently reported in patients with the acquired immunodeficiency syndrome  since 1985  eight noncirrhotic patients with the acquired immunodeficiency syndrome presenting with new onset high protein ascites have been evaluated  all but one patient had nondiagnostic paracentesis studies  laparoscopy with biopsy of identified abnormalities or percutaneous omental biopsy were diagnostic in four patients  non hodgkin s lymphoma was the cause in three patients  and disseminated cryptococcosis occurred in one patient  in the four other patients  chronic nonspecific peritonitis was found at laparoscopy  follow up of these latter patients  including exploratory laparotomy in one patient and autopsy in two patients  disclosed no specific cause  patients with the acquired immunodeficiency syndrome and high protein ascites of uncertain etiology should undergo directed peritoneal evaluation as a potentially treatable disorder may be found  however  despite extensive evaluation  a subset of patients in whom no specific cause can be identified still remains  
class6	expression of leukocyte adhesion molecules in the liver of patients with chronic hepatitis b virus infection  virus specific t cell responses are believed to be involved in the pathogenesis of liver cell injury secondary to hepatitis b virus infection  in this study  liver biopsy specimens from patients with chronic hepatitis b virus infection were analyzed for expression of two major pathways of adhesion used by cytotoxic t cells to interact with target cells  the lymphocyte function associated antigen 3 was found preferentially expressed on hepatocytes of patients with active hepatitis b virus replication  whereas the expression of the intercellular adhesion molecule 1 on hepatocytes seemed more closely related with inflammatory activity  adhesion molecules were also highly expressed on t lymphocytes found in areas of piecemeal and spotty necrosis  indicating the presence of antigen specific  memory  t cells at the site of hepatocellular injury  this study suggests that the expression of the lymphocyte function associated antigen 3 on hepatocytes may be important for viral elimination  the coordinate expression of the intercellular adhesion molecule 1 may regulate inflammatory response and enhance viral antigen presentation to t cells  conversely  the absence of hepatocyte adhesion molecules might be a favorable factor for viral persistence  
class6	interferon alfa therapy in patients with chronic hepatitis b virus infection  effects on hepatitis b virus dna in the liver  pretrial and posttrial liver biopsy samples from 124 adult patients who participated in two randomized  controlled trials of interferon alfa therapy for chronic hepatitis b virus  hbv  infection were analyzed to determine the effects of interferon on the replication of hbv in the liver  replicative forms of hbv dna were detected in the pretrial biopsy samples from all and posttrial biopsy samples from 74  treated patients and 86  controls  replicative forms of hbv dna were detected in the posttrial biopsy samples from all patients who remained positive for hepatitis b e antigen and hbv dna in the serum  in 77  treated patients and 80  controls who cleared hbv dna in the serum but who remained positive for hepatitis b e antigen  but in only 19  treated patients and 40  controls who cleared hbv dna as well as hepatitis b e antigen in the serum  serum alanine aminotransferase levels were significantly lower in patients whose posttrial biopsies did not contain replicative forms of hbv dna  in summary  we demonstrated that in most patients with chronic hbv infection treated with interferon alfa  serological response was associated with the disappearance of replicative forms of hbv dna in the liver  
class6	prognosis of wilsonian chronic active hepatitis  twenty of 320 patients with wilson s disease initially presented with chemical and laboratory features of chronic active hepatitis  confirmed histologically in 17  when first seen  cirrhosis was present in all 20 and was complicated by ascites and or jaundice in 11  within 1 week to 8 years of the onset of over liver disease the diagnosis of wilson s disease was established  and treatment with d penicillamine was promptly initiated in 19 patients  one man refused treatment and died 4 months later  treated patients received d penicillamine or trientine for a total of 264 patient years  median  14 patient years   abnormal water retention  for which salt restriction and diuretics were added to penicillamine or trientine  disappeared in all but 1 of the patients so affected  symptomatic improvement and virtually normal levels of serum albumin  bilirubin  aspartate aminotransferase  and alanine aminotransferase followed within 1 year in the majority of subjects  one woman died after 9 months of treatment  two patients  who became noncompliant with the therapeutic regimen after 9 and 17 years of successful pharmacological treatment  required liver transplants  these results indicate that the prognosis of specifically treated wilsonian chronic active hepatitis is very good in spite of the presence of cirrhosis  
class6	characterization of a rat pancreatic secretory protein associated with pancreatitis  a new protein was purified from the pancreatic juice of rats with acute pancreatitis  that protein  not detectable in control animals  was called  pancreatitis associated protein   it was first observed 6 hours after induction of experimental pancreatitis with taurocholate or cerulein  reached maximal levels of 45 micrograms mg protein in zymogen granules and 1 8 micrograms mg protein in pancreatic tissue during the acute phase  48 hours   and disappeared during recovery  day 5   it was never detected in spleen  liver  kidney  heart  or lung  the detection limit of the assay system was 12 ng mg protein  so that pancreatitis associated protein levels increased at least 100 fold in pancreatic tissue during the acute phase  the molecular weight  12 000  and isoelectric point  8 2  were determined by two dimensional gel electrophoresis  subcellular fractionation and immunoelectron microscopy showed that the protein was synthesized on the rough endoplasmic reticulum and stored in zymogen granules before being secreted  similar to other pancreatic secretory proteins  immunoblotting and two dimensional gel electrophoresis revealed that the same protein was synthesized upon induction of pancreatitis by cerulein infusion  by retrograde injection of bile acids  or pancreatitis induced by pancreatic surgery  the pancreatitis associated protein is therefore an acute phase protein that differs from other proteins of that family because of its exocrine nature  
class6	incidence of gallstones in a danish population  five year incidence of gallstone disease was assessed by ultrasonography in an age  and sex stratified random population of danish origin aged 30  40  50  and 60 years  the response rate was 82 8   2987 3608   nonrespondents did not differ from respondents regarding variables concerning gallstone disease  the 5 year incidence of gallstone disease in men aged 30  40  50  and 60 years was 0 3   2 9   2 5   and 3 3   corresponding figures in women were 1 4   3 6   3 1   and 3 7   the incidence of gallstones was significantly higher in subjects aged 45 years or more compared with those aged 35 years  the sex difference in gallstone incidence decreased with increasing age  a significantly higher incidence of gallstone disease was found among subjects with former polyps in the gallbladder  spontaneous disappearance of gallstones was seen in 4 5   
class6	the role of continued drinking in loss of portal perfusion after distal splenorenal shunt  fifty percent of patients with alcoholic cirrhosis who undergo distal splenorenal shunting for variceal bleeding lose portal perfusion within 1 year  although it was previously considered that this loss of portal flow was irrevocable  the present study shows that with resolution of alcoholic hepatitis  portal perfusion can be restored  a 34 year old patient with alcoholic liver disease and a distal splenorenal shunt lost portal perfusion 1 year after the operation  he had continued to drink alcohol and had high sinusoidal pressure  following forced abstinence over the next 2 years  his sinusoidal pressure fell  liver volume decreased  results of liver biopsy improved  and portal perfusion was restored  shunt patency was documented  and the same collaterals from the portal vein to the shunt could still be visualized as had been seen when portal flow was absent  restoration of portal perfusion was attributed to decreased intrahepatic resistance secondary to abstinence from alcohol  a return to drinking in the next 9 months led to alcoholic hepatitis and once again loss of portal perfusion  this study places emphasis on increased intrahepatic resistance rather than the development of portal to shunt collaterals as important in the loss of portal flow in such patients  
class6	hereditary internal anal sphincter myopathy causing proctalgia fugax and constipation  a newly identified condition  a newly identified myopathy of the internal anal sphincter is described  in the affected family  at least one member from each of five generations had severe proctalgia fugax  onset was usually in the third to fifth decades of life  three members of the family have been studied in detail  each had severe pain intermittently during the day and hourly during the night  constipation was an associated symptom  in particular difficulty with rectal evacuation  clinically the internal anal sphincter was thickened and of decreased compliance  the maximum anal canal pressure was usually increased with marked ultraslow wave activity  anal endosonography confirmed a grossly thickened internal anal sphincter  two patients were treated by internal anal sphincter strip myectomy  one showed marked improvement and one was relieved of the constipation but had only slight improvement of the pain  the hypertrophied muscle in two of the patients showed unique myopathic changes  consisting of vacuolar changes with periodic acid schiff positive polyglycosan bodies in the smooth muscle fibers and increased endomysial fibrosis  in vitro organ bath studies showed insensitivity of the muscle to noradrenaline  isoprenaline  carbachol  dimethylpiperazinium  and electrical field stimulation  immunohistochemical studies for substance p  calcitonin gene related peptide  galanin  neuropeptide y  and vasoactive intestinal peptide showed staining in a similar distribution to that in control tissue  a specific autosomal dominant inherited myopathy of the internal anal sphincter that causes anal pain and constipation has been identified and characterized  
class6	microvillus inclusion disease  in vitro jejunal electrolyte transport  microvillus inclusion disease is an inherited intestinal brush border membrane defect that causes severe fluid and electrolyte malabsorption  in an infant with microvillus inclusion disease  confirmed by electron microscopic evaluation of rectal  jejunal  and gallbladder mucosae   basal stool output was massive  greater than 125 ml   kg 1   day 1  and was not altered by treatment with clonidine or octreotide  a proximal jejunostomy with mucous fistula was placed  allowing separation of proximal from distal tract outputs  60 ml   kg 1   day 1 and 100 ml   kg 1   day 1  respectively   a 10 cm jejunal segment was excised during surgery and mounted in ussing chambers for determination of transepithelial na  and cl fluxes  compared with intestine of normal infants  this infant s epithelium showed transmural conductance and unidirectional ion fluxes that were only 30  of normal  with respect to both na  and cl  the excised jejunum was in a net secretory state  theophylline  5 mmol l  increased net cl secretion slightly  in response to mucosal d glucose  30 mmol l   jejunal mucosal to serosal na  flux doubled  in the infant  glucose electrolyte solution administered intrajejunally did not significantly change stool output  suggesting that all of the solution  40 ml kg  was absorbed  subtotal enterocolectomy  in theory  could have decreased purging by 66  in this infant with microvillus inclusion disease  but diarrhea would still have been significant  
class6	primary biliary cirrhosis  paradigm or paradox for autoimmunity  primary biliary cirrhosis has been classified as a model autoimmune disease based on striking defects in immune regulation and the presence of autoantibodies to mitochondria  until recently the significance and definition of mitochondrial autoreactivity was unknown  since 1987  there has been a vast improvement in the understanding and definition of the biochemical and molecular target autoantigens  the cloning of complementary dnas for mitochondrial antigens has led to the identification of three enzymes of the 2 oxo acid dehydrogenase family as the targets of the autoantibodies to mitochondria in patients with primary biliary cirrhosis  the major reactive autoantigen is the e2 subunit of pyruvate dehydrogenase  immunodominant sites on pyruvate dehydrogenase e2  autoepitopes  have been mapped and have been shown to be the site of attachment of the functionally important lipoic acid prosthetic group  the autoepitope for the other enzymes probably occupies an equivalent site on the enzyme  the availability and definition of these mitochondrial autoepitopes have allowed specific questions to be addressed relating to the processing and targeting of these autoantigens as well as further studies on mechanisms of immunopathology  similarly  the availability of well defined autoantigens could contribute to the development of valid animal models in addition to the already described reproduction of the biliary ductular lesions by transfer of peripheral blood lymphocytes from patients with primary biliary cirrhosis into severe combined immunodeficient mice  such models will facilitate specific study of the role of major histocompatibility complex expression and the characterization of t cell reactivity  thus  primary biliary cirrhosis is a key example of significant progress in autoimmunity being made by use of recombinant dna technology  
class6	electrophysiology of motor pathways for sphincter control in multiple sclerosis  the central and peripheral motor pathways serving striated sphincter muscle function were studied using cortical and lumbar transcutaneous electrical stimulation  pudendal nerve stimulation and sphincter electromyography in 23 patients with multiple sclerosis  ms   and sphincter disturbance  including incontinence of urine or faeces  urinary voiding dysfunction  or constipation  the central motor conduction time was significantly increased in the ms group compared to controls  p less than 0 05   damage to both the upper and lower motor neuron pathways can contribute to sphincter disturbance in ms  the latter may be due to coexisting pathology or to involvement of the conus medullaris by ms  
class6	prognostic significance of proteinuria one year after onset of diarrhea associated hemolytic uremic syndrome  we examined the prognostic value of changes in the amount of proteinuria  measured as protein creatinine ratios in early morning urine samples  in 40 children who had had diarrhea associated hemolytic uremic syndrome  one year after diagnosis  87  of those who seemed to have fully recovered had normal urinary protein creatinine ratios  compared with none of those with poor outcomes  p less than 0 001   none of those with poor outcomes achieved normal protein creatinine ratios during follow up to a maximum of 5 1 2 years  but 93  of those who made a full clinical recovery no longer had proteinuria  measurement of the protein creatinine ratio in an early morning sample of urine is a simple  cost effective  and noninvasive means of monitoring the progress of patients with diarrhea associated hemolytic uremic syndrome  provided that a technique sensitive at low protein concentrations is employed  
class6	prostaglandin e2 induced diarrhea in mice  importance of colonic secretion  the present study has investigated the basis for induction of diarrhea by prostaglandin  pg e2 in mice  when given i p   pge2 induced a dose  and time dependent diarrhea  the shortest post treatment time for diarrhea onset was approximately 7 min  at a pge2 dose of 200 micrograms kg  at this dose  pge2 also produced accumulation of fluid in the small intestine and in the colon  enteropooling   the enteropooling reached its maximum by 9 min and did not decrease until approximately 11 min  i e   2 to 4 min after the mean time for diarrhea onset   pge2 treatment altered neither gastric emptying nor gastrointestinal propulsion  but strongly enhanced the expulsion of a glass bead from the colon  i e   decreased the time to bead expulsion   the shortest time to expulsion of the glass bead was observed at 200 micrograms kg i p  the induction of diarrhea by pge2 was unaffected by cecectomy  or sham cecectomy  but the dose response curve for time to onset of diarrhea by i p  pge2 was displaced to the right in animals with ligations of the ileo ceco colonic  icc  junctions  the intraluminal fluid accumulation in the colon  evaluated in mice with icc ligations  was increased by pge2 administration within 2 min and remained greater than in vehicle treated animals until the onset of diarrhea  the stimulation of colonic bead expulsion produced by i p  pge2 in control mice was not observed in animals with acute icc ligations  even at i p  doses up to 800 micrograms kg  
class6	hepatic portal venous gas identified by computed tomography in a patient with blunt abdominal trauma  a case report  an abdominal computed tomographic  ct  scan in a middle aged man injured in a high speed motor vehicle accident demonstrated the presence of portal venous gas  findings on initial peritoneal lavage were entirely negative  exploratory celiotomy performed because of increasing abdominal pain and leukocytosis revealed gangrene of the cecum  this report illustrates the importance of the finding of portal venous gas on ct scan in patients with blunt abdominal trauma  
class6	treatment of refractory oral candidiasis with fluconazole  a case report  we describe a patient with the acquired immunodeficiency syndrome who had persistent oral esophageal pseudomembranous candidiasis clinically refractory to nystatin  clotrimazole  and ketoconazole  in vitro resistance to clotrimazole was demonstrated as well  the patient received temporary relief with intravenous amphotericin b therapy  but this was associated with serious adverse effects  including transfusion requiring anemia  azotemia  and severe thrombophlebitis  despite two courses of intravenous amphotericin b therapy  the patient s highly symptomatic  recurrent oral and esophageal candidiasis continued  the patient was then treated with fluconazole and obtained immediate relief without associated adverse effects  
class6	enteroclysis and small bowel series  comparison of radiation dose and examination time  respective radiation doses and total examination and fluoroscopy times were compared for 50 patients  25 underwent enteroclysis and 25 underwent small bowel series with  n   17  and without  n   8  an examination of the upper gastrointestinal  gi  tract  for enteroclysis  the mean skin entry radiation dose  12 3 rad  123 mgy   and mean fluoroscopy time  18 4 minutes  were almost 1 1 2 times greater than those for the small bowel series with examination of the upper gi tract  8 4 rad  84 mgy   11 4 minutes  and almost three times greater than those for the small bowel series without upper gi examination  4 6 rad  46 mgy   6 3 minutes   however  the mean total examination completion time for enteroclysis  31 2 minutes  was almost half that of the small bowel series without upper gi examination  57 5 minutes  and almost four times shorter than that of the small bowel series with upper gi examination  114 minutes   the higher radiation dose of enteroclysis should be considered along with the short examination time  the age and clinical condition of the patient  and the reported higher accuracy when deciding on the appropriate radiographic examination of the small bowel  
class6	gallbladder perforation and bile leakage  percutaneous treatment  three patients with spontaneous gallbladder perforation and one with an iatrogenic bile leak causing bile peritonitis were treated successfully by means of percutaneous catheter drainage  three patients had cholelithiasis as the cause of perforation  the fourth patient had previously undergone gallstone dissolution with methyl tert butyl ether lavage and developed bile peritonitis a few hours after removal of the catheter  in three patients  a percutaneous cholecystostomy catheter provided successful decompression  in the fourth patient  drainage was performed with a percutaneous sump catheter in the subhepatic space adjacent to the gallbladder  no specific complications occurred  follow up was performed at 1  12  22  and 59 months  respectively  to date  one of the four patients has undergone elective cholecystectomy  1 month after drainage   the remainder of the patients are asymptomatic  this preliminary experience suggests that the severe complication of gallbladder perforation and bile leakage may be treated  at least temporarily  by means of percutaneous drainage  
class6	peptic ulcer disease  ct evaluation  the authors retrospectively describe the computed tomographic  ct  findings in 35 patients with peptic ulcer disease  three of eight patients with gastritis or duodenitis had bowel wall thickening  ten of the remaining 27 patients had ct evidence of ulcer perforation  n   2  or penetration  n   8   four cases of which were unsuspected clinically  both patients with acute free perforation had pneumoperitoneum  and one showed free extravasation of orally administered contrast material  the precise site of perforation could not be established in either case with ct  the eight patients with ulcer penetration had ct evidence of bowel wall thickening  n   3  and inflammatory changes in adjacent soft tissues and organs  n   8   including the pancreas  n   4   liver  n   1   and lesser omentum  n   1   ulcer craters were seen in only two  the ct findings of penetration can mimic other disease processes  ct was not useful in detecting uncomplicated peptic ulcer disease  
class6	diagnostic fine needle puncture of the gallbladder with us guidance from february 1988 to january 1990  118 fine needle diagnostic punctures of the gallbladder  dpg  were performed under continuous ultrasound  us  guidance on symptomatic patients with gallstones  the first attempt at gallbladder puncture and aspiration was successful in every patient with use of a 22 gauge needle and continuous us visualization of the needle tip  the aspirated volume varied between 3 and 88 ml  average     standard deviation  25 0 ml     15 3   biliary analysis revealed an elevation of the cholesterol saturation index in patients with cholesterol gallstones  attenuation at computed tomographic examination of 50 hu or less  relative to that in patients with pigment stones  attenuation more than 50 hu   1 3     0 2 vs 1 0     0 1  p less than  05   the nucleation time was prolonged in patients with pigment stones  19 3 days     3 5 vs 1 8 days     0 8 for patients with cholesterol stones  p less than  001   all patients remained hospitalized for 24 hours after dpg and were reexamined on an outpatient basis at 1 and 3 months thereafter  no complications were detected during either short term observation or long term follow up  the authors conclude that dpg is a safe and valuable technique in the diagnostic work up of gallstone patients to establish their suitability for nonoperative treatment  
class6	asialoglycoprotein receptor function in benign liver disease  evaluation with mr imaging  an arabinogalactan coated ultrasmall superparamagnetic iron oxide  ag uspio  preparation specific for asialoglycoprotein  asg  receptors on hepatocytes was used as a magnetic resonance  mr  imaging contrast agent in the evaluation of a spectrum of benign liver diseases in animal models  the activity of hepatocyte asg receptors  which directly reflects liver function  was directly assessed by measuring liver relaxation times in vitro and mr signal intensity in vivo  the following measurements allowed three dimensional assessment of liver function   a  liver relaxation time   b  native mr signal intensities of liver   c  response of liver to the ag uspio probe  percentage decrease of liver signal intensity after intravenous administration of 10 mumol kg of ag uspio  normal liver 55   fatty liver 57   acute hepatitis 36   chronic hepatitis 29   and cirrhosis 46    and  d  redistribution of hepatocyte specific ag uspio to the spleen  present in hepatitis and cirrhosis but not in normal liver and fatty liver   the results of this study indicate that cellular hepatic abnormalities can be detected and quantitated with mr receptor imaging  
class6	percutaneous rotational contact biliary lithotripsy  initial clinical results with the kensey nash lithotrite  the percutaneous rotary lithotrite introduces a new concept to fragmentation and percutaneous removal of gallstones  a fluid vortex is generated  pulling calculi into a high speed blade that fragments stones to predominantly under 500 microns  the results of treating the first 10 patients with this instrument reveal that large stone burdens as well as small stones  2 3 mm  of any composition can be removed if the gallbladder is of sufficient size to accommodate the six pronged basket  rotation times of 7 39 minutes were required  nine of 10 procedures were completed  access was lost in one case  one major complication occurred  at repeat oral cholecystography  the gallbladder was visualized after 3 6 weeks in eight of the nine patients  ursodeoxycholic acid was administered from 3 to 12 months to five patients with either residual stones or aggregates  the hospital stay ranged from 48 to 72 hours  all patients  except the patient who underwent surgery  resumed light activity in 3 4 days and strenuous activity and full diet within 3 weeks  
class6	extrauterine findings of ectopic pregnancy of transvaginal us  importance of echogenic fluid  transvaginal ultrasound  us  studies of 232 consecutive patients with positive serum pregnancy tests who were considered to be at risk for ectopic pregnancy were prospectively evaluated to determine the significance of various extrauterine findings  including echogenic fluid in the cul de sac  all patients were found to have a surgically proved ectopic gestation  group 1  68 patients  29 3     reliable evidence of intrauterine pregnancy at initial transvaginal us  group 2  83 patients  35 8     or no evidence of pregnancy at initial transvaginal us  but subsequent proof of an intrauterine pregnancy  group 3  81 patients  34 9     adnexal findings were demonstrated in 45  66   group 1 patients  including a living extrauterine embryo in 10  15    an extrauterine gestational sac in 21  31    and an adnexal mass in 14  21    intraperitoneal fluid was detected in 43  63   group 1 patients and in 81  31   group 3 patients  echogenic fluid was the only abnormal finding at us in 10  15   group 1 patients and added confidence to the diagnosis of ectopic pregnancy in many others  echogenic fluid correlated with hemoperitoneum at the time of surgery  the presence of echogenic fluid indicates a high risk for ectopic pregnancy in women referred with this clinical indication  
class6	antropyloric muscle thickness at us in infants  what is normal  the authors reviewed the ultrasonographic  us  images and medical records of 145 consecutive infants who were seen for evaluation of the upper gastrointestinal tract because of chronic vomiting and or regurgitation  at us  the antropyloric muscle of each patient was measured in the midlongitudinal plane  on the basis of this measurement  the patients were divided into the following categories  group 1  1 2 mm  99 patients   group 2  greater than or equal to 3 mm  40 patients   and group 3  2  less than 3 mm  six patients   patients in group 1 were considered to have normal antropyloric muscle thickness  those in group 2 had abnormal thickness  and those in group 3 had muscle thickness that was not definitely normal or abnormal  the final clinical diagnoses for all of the infants in the three groups confirmed the authors  initial impressions that antropyloric muscle thickness of less than 2 mm was anatomically normal  muscle measuring 3 mm or greater was abnormal and diagnostic for pyloric stenosis  and muscle from 2 to less than 3 mm was abnormal but not specifically diagnostic for pyloric stenosis  two of the six patients in group 3 eventually were diagnosed as having pyloric stenosis  thus  the authors believe that only those patients with antropyloric muscle less than 2 mm thick should be considered unequivocably normal  
class6	effect of portasystemic shunts on subsequent transplantation of the liver  portasystemic  ps  shunts have been regarded as a relative contraindication to hepatic transplantation  ht  because of the potential for increased technical difficulties during the transplant operation  we compared operative blood loss  morbidity and mortality in 27 patients with ps shunts and 147 patients with no shunts  ns  who underwent ht  the ps shunt group included 12 portocaval  pc   eight mesocaval  four central splenorenal and four distal splenorenal shunts  the ps shunt and ns groups were similar with respect to age  preoperative medical status and abo blood group matching between donors and recipients  there were no significant differences in the mean  plus or minus s d   intraoperative blood transfusion  9 1     7 6 versus 9 2     11 0 units   mean  plus or minus s d   duration of anesthesia  8 1     1 4 versus 7 8     1 5 hours  and operative mortality  7 versus 11 per cent  between the ps shunt and ns groups  respectively  complications of the biliary tract were significantly higher in the ps shunt group  22 0 versus 5 4 per cent  p less than 0 01  but they did not increase the mortality rate  we conclude that a prior ps shunt should not influence the decision to accept patients for ht  ps shunts remain a reasonable surgical option for patients with cirrhosis and variceal hemorrhage  refractory to sclerotherapy  who  by virtue of good hepatic function  do not merit immediate ht  
class6	modified technique of pringle s maneuver in resection of the liver  crushing of the hepatic parenchyma with hepatic clamps to minimize blood loss during resection of the liver leads to mechanical damage of hepatocytes  pringle s maneuver may precipitate liver failure by hepatic warm ischemia as well  therefore  we controlled bleeding from the surface of the resection by using light compression on the hepatic parenchyma with a band while applying a hepatic arterial clamp at the hepatic hilus  this vascular control method can be done because the portal pressure is about one tenth of the hepatic artery pressure and provides an efficient and harmless transection of the liver  
class6	late cholangitis after successful surgical repair of biliary atresia  bacterial cholangitis is a frequent complication of successful surgical repair of biliary atresia  occurring in 93  of patients before the age of 1 year  but thought to be rare after 2 years of age  among 76 children free of jaundice more than 5 years after operation  four presented with late cholangitis  7 to 13 5 years old   consisting of fever  jaundice  and abdominal pain with biochemical features of an inflammatory process and cholestasis  liver biopsy specimens consistently demonstrated histological features of cholangitis  growth of microorganism  or both  cholangitis subsided spontaneously in one patient or in response to intravenous administration of antibiotics  cholangiography consistently demonstrated biliary abnormalities but no definite obstruction to the bilioenteric anastomosis  all the children had good hepatic function 3 weeks to 4 years after the episode of cholangitis  these results suggest that cholangitis may occur several years after surgery but does not seem to alter prognosis  
class6	iron and the liver  iron is essential for life  but iron overload is toxic and potentially fatal  the liver is a major site of iron storage and is particularly susceptible to injury from iron overload  especially when  as in primary hemochromatosis  the iron accumulates in hepatocytes  iron can be taken up by the liver in several forms and by several pathways including   1  receptor mediated endocytosis of diferric or monoferric transferrin or ferritin   2  reduction and carrier facilitated internalization of iron from transferrin without internalization of the protein moiety of transferrin   3  electrogenic uptake of low molecular weight  non protein bound forms of iron  and  4  uptake of heme from heme albumin  heme hemopexin  or hemoglobin haptoglobin complexes  normally  pathway 2 is probably the major one for uptake of iron by hepatocytes  iron is stored in the liver in the cores of ferritin shells and as hemosiderin  an insoluble product derived from iron rich ferritin  iron in hepatocytes stimulates translation of ferritin mrna and represses transcription of dna for transferrin and transferrin receptors  the major pathologic effects of chronic hepatic iron overload are   1  fibrosis and cirrhosis   2  porphyria cutanea tarda  and  3  hepatocellular carcinoma  although precise pathogenetic mechanisms remain unknown  iron probably produces these and other toxic effects by increasing oxidative stress and lysosomal lability  vigorous efforts at diagnosis and treatment of iron overload are essential since the pathologic effects of iron are totally preventable by early vigorous iron removal and prevention of iron re accumulation  
class6	sulphasalazine and prednisone compared with sulphasalazine for treating active crohn disease  a double blind  randomized  multicenter trial  objective  to determine whether sulphasalazine plus prednisone is more effective than sulphasalazine alone in treating active crohn disease  design  randomized  double blind  placebo controlled trial  setting  multicenter trial in one university hospital and nine general hospitals  patients  patients with active crohn disease and a van hees activity index of 140 or more  of 71 patients who were randomly assigned  60 completed treatment and were analyzed  interventions  for 16 weeks  30 patients received sulphasalazine  6 g d  or 4 g d if adverse effects occurred  and prednisone  30 mg d initially  prednisone therapy was tapered in increments of 5 mg 2 wk to 10 mg d after 8 weeks  thirty other patients received sulphasalazine and a placebo  measurements and main results  in the first 6 weeks of treatment  the van hees activity index decreased to a median of 70   interquartile range  57  to 81   of the initial value in patients treated with sulphasalazine and prednisone and to a median of 87   interquartile range  70  to 94   in patients treated with sulphasalazine alone  p   0 001   in the last 4 weeks of treatment  the corresponding figures were 63   interquartile range  40  to 75   and 70   interquartile range  54  to 90    p   0 10   the crohn s disease activity index decreased in the first 6 weeks to a median of 65   interquartile range  57  to 86   in patients receiving sulphasalazine and prednisone and to a median of 75   interquartile range  58  to 101   in patients receiving sulphasalazine alone  p   0 13   in the last 4 weeks of treatment  the corresponding figures were 65   interquartile range  42  to 90   and 76   interquartile range  49  to 110    p   0 19   conclusions  the use of prednisone in addition to sulphasalazine in patients with active crohn disease results in a significantly faster initial improvement  but not in a significantly better result after 16 weeks of treatment  when disease activity is measured by the van hees activity index  
class6	endoscopic retrograde cholangiopancreatography in infantile cholestasis  the difficulty of distinguishing surgically correctable causes of conjugated hyperbilirubinaemia in infants from other causes means that some infants may undergo laparotomy and intraoperative cholangiography unnecessarily  and others may be referred for surgery too late  in an attempt to improve the diagnostic accuracy in infants with conjugated hyperbilirubinaemia when standard methods produced equivocal results  we have been using prototype paediatric duodenoscopes  pjf 7 5 and xpjf 8 0  olympus  to perform endoscopic retrograde cholangiopancreatography  ercp   from 159 infants with conjugated hyperbilirubinaemia  11 were referred for ercp  which was performed in nine  in four in whom bile ducts were definitely visualised laparotomy was avoided  operative cholangiography confirmed patent bile ducts in one in whom visualisation had been uncertain  three of four in whom bile ducts were not seen had extrahepatic biliary atresia  visible bile drainage in the fourth excluded atresia  no major complications ensued but there was radiological evidence of gall bladder perforation in one  common hepatic duct block  and overinflation with air was a problem until finer cannulae  wilson cook  were introduced  in appropriately selected patients with conjugated hyperbilirubinaemia  ercp with paediatric duodenoscopes in experienced hands may provide useful diagnostic information  
class6	audit of results of operations for infantile pyloric stenosis in a district general hospital because of the proposal that infants with hypertrophic pyloric stenosis should only be treated by surgeons with an interest in paediatric surgery  we carried out a retrospective study to audit our experience in a district general hospital  forty six infants over a five year period underwent pyloromyotomy  there were no deaths  and 36 infants  78   made uneventful recoveries  perforation of the duodenal mucosa occurred during the operation in 11 patients  and eight complications developed in six of these infants  there were seven wound infections  and two patients had vomiting that lasted four days or longer after their operations  there were no long term feeding problems  the results of this study show that such patients can be successfully treated in district general hospitals  and three areas merit special attention  meticulous surgical technique  the use of prophylactic antibiotics  and early graduated feeding  
class6	bleeding from duodenal lymphangiectasia  an 8 year old girl with recurrent upper gastrointestinal bleeding was found to have localised duodenal lymphangiectasia by fibreoptic endoscopy  she did not show physical signs or laboratory evidence of significant enteric protein loss  a low fat diet seemed to prevent further bleeding  duodenal lymphangiectasia may be associated with gastrointestinal bleeding in children  
class6	intraperitoneal femoral venous catheter insertion with free blood return in presence of tense hemoperitoneum  the authors report a case of intraperitoneal insertion of a femoral venous catheter  with blood return  in a patient with hemoperitoneum  in such patients  skin puncture at or below the inguinal ligament is important  aspiration of unusually dark blood and medial catheter location should raise the possibility of intraperitoneal catheter placement  
class6	miliary tuberculosis presenting as hepatic and renal failure  a 67 year old man developed hepatic and renal failure over a six day period  despite full supportive measures  he died on his 11th day of hospitalization with fulminant dic and hepatic  renal  and respiratory failure  postmortem examination revealed acid fast bacilli in virtually all organ systems  miliary tuberculosis should be considered as a potentially treatable cause of hepatic failure  
class6	management of an extensive tracheoesophageal fistula by cervical esophageal exclusion  giant tracheoesophageal fistulae occurring in ventilator dependent patients usually result in significant ventilatory embarrassment  cervical exclusion of the fistula can safely control the fistula and quickly restore adequate ventilation to these critically ill patients  
class6	medical treatment of esophageal achalasia  double blind crossover study with oral nifedipine  verapamil  and placebo calcium channel blockers have been previously shown to decrease lower esophageal sphincter  les  pressure and improve symptoms in achalasia  we performed a placebo controlled  double blind  crossover study to assess the effects of oral nifedipine and verapamil on les pressure  amplitude of esophageal body contraction  and clinical symptomatology in eight patients with symptomatic achalasia diagnosed by endoscopy  barium swallow  and manometry  patients were randomized to receive up to 20 mg nifedipine  160 mg verapamil  or placebo and underwent esophageal manometry before  baseline  and after four weeks on each drug  diary cards were kept to record and grade symptoms and drug plasma level determinations were correlated with manometric and clinical findings  both nifedipine and verapamil caused a statistically significant decrease in mean les pressure  but only nifedipine caused a significant decrease in the amplitude of contractions of the smooth muscle portion of the esophagus  no statistically significant differences in the overall clinical symptomatology were noted with any of the drugs  although some individual improvements in dysphagia and chest pain were noted  we conclude that  despite the reduction in les pressure and contraction amplitude of the distal esophageal body  oral nifedipine and verapamil do not significantly alter the clinical symptomatology of patients with achalasia  
class6	management of dysphagia in suspected esophageal motor disorders fifty three patients suffering from dysphagia because of suspected esophageal motor disorders were treated by pneumatic dilatation using the rider moeller technique  fifteen had achalasia demonstrated by manometric studies  forty nine of them had remarkable clinical improvement after the procedure  during the mean period of follow up  average 5 years  range 1 11   75  of the patients needed a new dilatation  with a delay of two years  the results of the dilatation were excellent or good in 80  of the cases  early complications consisted in two esophageal perforations surgically treated  there was no mortality  we did not observe late complications of the procedure  we conclude that pneumatic dilatation should be the initial procedure in the treatment of dysphagia in suspected esophageal motor disorders  
class6	reevaluation of manometric criteria for vigorous achalasia  is this a distinct clinical disorder  clinical and manometric data from 97 consecutive patients with idiopathic achalasia were analyzed to see if a distinct subset with vigorous achalasia could be identified  statistical analyses failed to detect a unique group of subjects based on the distribution of contraction wave amplitudes alone  because of this  patients falling above the 95th percentile  n   4  mean wave amplitude greater than 100 mm hg for each  were compared with those having mean amplitudes above the conventional threshold for the diagnosis of vigorous achalasia  mean amplitude 60 100 mm hg  n   4   and with the remainder  n   89  mean amplitude less than 60 mm hg   subjects with mean amplitudes less than 60 mm hg and with mean amplitudes 60 100 mm hg closely resembled each other in all measured clinical features  whereas subjects with mean amplitudes greater than 100 mm hg were all male  were older  67     4 years vs 47     2 years  p less than 0 01   and appeared to have somewhat longer duration of symptoms when compared with the remainder  82     41 vs 44     10 months  p   0 4   chest pain and other esophageal symptoms  basal and residual lower sphincter pressures  and response to first treatment did not differ among the three groups  these data indicate that high fidelity manometry techniques identify a rare subset of achalasia patients with mean contraction amplitudes exceeding 100 mm hg that  although older and possibly with greater duration of symptoms  presents similarly to others with idiopathic achalasia  outcome from conventional treatment is also similar for the  vigorous  and  nonvigorous  patients  making the distinction of questionable value  
class6	esophageal candidiasis in aids  successful therapy with clotrimazole vaginal tablets taken by mouth  in this paper we describe the results of oral therapy of esophageal candidiasis with clotrimazole vaginal tablets in 25 homosexual men with aids  of whom 19 had oral candidiasis and 16 had esophageal symptoms  therapy with clotrimazole vaginal tablets  100 mg  taken by mouth cleared the esophageal symptoms  oral candidiasis  and esophageal lesions completely in all 25 men  clotrimazole vaginal tablets are a useful alternative to other antifungal agents for the treatment of esophageal candidiasis in aids patients  
class6	effect of intraesophageal location and muscarinic blockade on balloon distension induced chest pain  intraesophageal balloon distension has been introduced recently as a provocative test in the assessment of patients with noncardiac chest pain  in order to examine the effect of balloon location and muscarinic blockade on distension induced pain  10 asymptomatic male volunteers were studied on two separate days using a low compliance perfused manometry system that incorporated a silicone rubber balloon  five second duration balloon distensions using balloon volumes of 2 5  5  7 5  and 10 ml of air were performed with the balloon located both 16 cm  proximal site  and 6 cm  distal site  above the lower esophageal sphincter  les  before and after administration of atropine  10 micrograms kg intravenously  or placebo in a randomized double blind fashion  a standardized scoring system was used to assess the balloon distension induced pain  pain scores varied directly with balloon volume but were consistently higher with the balloon located at the proximal site versus the distal site  this was not associated with any differences in intraballoon pressures between the two sites  however  contraction amplitude orad to the balloon was greater with balloon distension at the proximal site  atropine significantly decreased pain sensation scores with the balloon located distally but not proximally  this attenuation was not associated with significant changes in intraballoon pressures  however  contractions orad to the balloon were markedly inhibited by atropine with distal but not with proximal distension  these studies indicate that balloon distension induced pain varies depending on the location of distension  this difference is not explained by differences in esophageal wall tension at the site of distension  
class6	natural killer cell activity in patients with liver cirrhosis relative to severity of liver damage  to evaluate the role of severe liver damage on natural killer cell activity  29 patients with liver cirrhosis were examined  the natural killer cell activity was measured with a 4 hr chromium release assay  and the k562 cell line was employed as target cells  the natural killer cell activity was significantly decreased in cirrhotic patients compared with normal controls and patients with chronic active hepatitis  cirrhotic patients with pugh s c grade of severity of liver disease had lower natural killer cell activity  the depression of natural killer cell activity in cirrhotic patients was inversely correlated with prothrombin time ratios  and the natural killer cell activity in cirrhotic patients with hepatic encephalopathy was lower than in patients without hepatic encephalopathy  thus  the diminished natural killer cell activity in cirrhotic patients might be related to the severity of liver damage  
class6	demonstration of two distinct subsets of gastric varices  observations during a seven year study of endoscopic sclerotherapy  over a seven year period  assessment of gastric varices was made on 225 patients receiving endoscopic sclerotherapy for variceal hemorrhage  of 170 patients with complete data  gastric varices were observed in 26  15 3    importantly  two distinct subsets of gastric varices were identified  varices distal to the gastroesophageal junction without extension into the fundus  termed  junctional varices   occurred in 11 2   and varices that were confined only to the fundus  termed  fundal varices   occurred less frequently in 4 1   although rebleeding was increased in both subsets of gastric varices  junctional varices were more amenable to sclerotherapy  patients with fundal varices  n   7  had a significantly higher rebleeding rate  increased complications with sclerotherapy  and significantly decreased survival  p less than 0 005  when compared to patients with esophageal varices alone  n   87  who were followed for more than three months  cumulative survival was not significantly different  p less than 0 08  in patients with junctional varices  n   19  when compared with patients with esophageal varices alone  we conclude that not all patients with gastric varices have a poor result with sclerotherapy  recognition of these subsets may improve treatment strategies in patients with gastric varices  
class6	bile acids in human plasma interfere with cholecystokinin bioassay using dispersed pancreatic acini  a bioassay using dispersed pancreatic acini was used to measure fasting plasma cholecystokinin  cck  concentrations in 105 patients with various kinds of gastrointestinal diseases  17 patients with diabetes mellitus  and 6 healthy volunteers  high plasma cck bioactivities were observed in patients with obstructive jaundice  choledocolithiasis  and primary biliary cirrhosis  twenty three samples with high cck bioactivities were assayed by the same bioassay after the addition of a specific cck antagonist and by a cck radioimmunoassay in order to determine whether the high cck like bioactivity was due to circulating cck or other factors  high cck bioactivities were partially inhibited by the specific cck antagonist  cr 1409  but the activities were not totally abolished  the residual bioactivities  not inhibited by cr 1409  correlated with plasma bile acid concentrations  the inhibitable cck bioactivities correlated with plasma cck levels obtained by radioimmunoassay  although the bioassay using dispersed pancreatic acini has several advantages for measuring plasma cck  this method overestimates cck bioactivities in patients with high plasma bile acid concentrations  
class6	biliary pain in postcholecystectomy patients without biliary obstruction  a prospective radionuclide study  biliary pain without obvious biliary obstruction is common in postcholecystectomy patients  we studied 20 symptomatic patients with episodes of biliary type pain after cholecystectomy  all having undergone endoscopic retrograde cholangiography   and in 18 asymptomatic postcholecystectomy controls  we performed quantitative hepatobiliary radionuclide analysis with dimethyl imidodiacetic acid  from a series of 90 dynamic images at 1 min intervals using a gamma camera coupled to a computer  time activity curves were produced in regions of interest in the liver  intrahepatic biliary tree  common duct  and heart  from which quantitative biliary excretion indexes were obtained  the results demonstrate a biliary kinetic dysfunction in patients with postcholecystectomy pain without morphological abnormalities  
class6	ulcerative colitis disease activity as subjectively assessed by patient completed questionnaires following orthotopic liver transplantation for sclerosing cholangitis  to assess whether or not liver transplantation and subsequent immunosuppression with cyclosporine and prednisone affect ulcerative colitis symptomatology  we surveyed by questionnaire all 23 surviving patients with pretransplant colonoscopy documented ulcerative colitis who were transplanted for primary sclerosing cholangitis between june 1982 and september 1985  at follow up  89 8     7 6 weeks  mean     sem   all six patients who had had asymptomatic colonoscopy documented ulcerative colitis reported continued ulcerative colitis quiescence  among the 17 patients who had had symptomatic colonoscopy documented ulcerative colitis at time of liver transplantation  88 2  reported improvement in overall ulcerative colitis severity  p less than 0 001   with significant improvement in the frequency of bowel movements reported by 100   in crampy abdominal pain by 87 5   in bowel urgency by 75   in the occurrence of pus or mucus in stool by 87 5   in the incidence of ulcerative colitis flares by 81 8   and in the number of days unable to function normally due to ulcerative colitis symptoms by 78 6   all at least p less than 0 01   these data demonstrate that ulcerative colitis symptom severity significantly improves following liver transplantation with immunosuppression with cyclosporine and prednisone  
class6	usefulness of fecal alpha 1 antitrypsin clearance and fecal concentration as early indicator of postoperative asymptomatic recurrence in crohn s disease  the aim of this study was to evaluate in crohn s disease the possible usefulness of alpha 1 antitrypsin clearance and fecal concentration in the early detection of postoperative asymptomatic recurrence  eleven adult patients with small bowel crohn s disease undergoing elective resection were enrolled in the study and prospectively followed for one year  three  six  and 12 months after surgery the alpha 1 antitrypsin clearance and fecal concentration were measured  and the disease activity was assessed  all patients were free of active symptoms throughout the study  one year after surgery small bowel radiology was performed in all patients  radiographic evidence of recurrent macroscopic disease was found in five of the 11 patients  three months after surgery both alpha 1 antitrypsin clearance and fecal concentration were significantly lower  p less than 0 01  than before surgery  there was no difference at this time between patients with recurrence and those with no recurrence  in patients with recurrence both alpha 1 antitrypsin clearance and fecal concentration significantly increased at six months in comparison with the values at three months  p less than 0 02   both measurements were significantly higher at six and 12 months in this group of patients than in those with no recurrence and in normal controls  p less than 0 01   at six and 12 months alpha 1 antitrypsin clearance was above the upper normal limit in all patients with recurrence  we conclude that fecal alpha 1 antitrypsin clearance is a noninvasive  inexpensive  sensitive marker of asymptomatic recurrence in cd patients who are under regular supervision after surgery  
class6	endometriosis  an important condition in clinical gastroenterology  endometriosis  a condition defined by the presence of ectopic endometrium  is a disorder of increasing incidence and a significant cause of gastroenterologic distress in young women  although clinical manifestations vary considerably depending upon the anatomic extent of disease  characteristic abdominal complaints and typical physical findings continue to be associated with misdiagnosis and delayed recognition of gastrointestinal involvement  the authors of this paper review the medical literature concerning endometriosis of the digestive tract  emphasizing modes of presentation  risk factors  diagnostic testing  complications  and therapy  greater familiarity with the disease and heightened awareness of its sequellae are needed and prerequisite to improved medical management  
class6	acute porphyria presenting with hyperamylasemia  an elevation of serum amylase and lipase has not been reported previously to occur with porphyria  in this report  we describe a patient who presented with the clinical and laboratory picture of pancreatitis  elevated amylase  lipase  amylase creatinine clearance ratio  and with abdominal pain  only after extensive evaluation  was the patient found to have porphyria  on two separate occasions  with hematin therapy  her serum amylase decreased  as did her clinical symptoms of porphyria and her urinary quantitative porphyrins  this suggests an association between elevation of the serum amylase and lipase with acute porphyria  moreover  this association can lead to delay in establishing the diagnosis of acute porphyria  
class6	severe hemorrhagic radiation proctitis advancing to gradual cessation with hyperbaric oxygen  we report a case of a male patient suffering from a severe hemorrhagic radiation proctitis which gradually ceased with hyperbaric oxygen  we discuss the mechanisms of chronic radiation injury and the effect of the hyperbaric oxygen  this therapy is proposed as an alternative to surgical intervention for this abnormality  
class6	duodenal caval fistula  duodenal caval fistula is a rare  often lethal disease that requires prompt diagnosis and surgical correction  a case of duodenal caval fistula due to duodenal ulceration is presented and discussed  
class6	elevated intracranial pressure and computed tomography of the brain in fulminant hepatocellular failure  cerebral herniation is a leading cause of death in patients with fulminant hepatocellular failure  classical signs of elevated intracranial pressure are often absent in these patients  a reliable noninvasive method by which the presence of cerebral edema could be determined is much needed  to assess the efficacy of computed tomography of the brain in this setting  we compared the radiographic findings to the intracranial pressure measured by an epidural monitor in patients with fulminant hepatic failure  unfortunately  a considerable difference existed between the presence of cerebral edema diagnosed by computed tomography of the brain and elevation of the intracranial pressure  our observations suggest that in patients with fulminant hepatic failure and advanced hepatic encephalopathy  computed tomography of the brain is of little value in detecting cerebral edema  pressure monitoring is most important to establish the presence and guide the therapy of intracranial hypertension  
class6	carbon tetrachloride induced alterations of hepatic calmodulin and free calcium levels in rats pretreated with chlordecone  calmodulin  a low molecular weight ca2  binding protein  regulates a large number of cell activities including cell division  previous studies from our laboratory indicated excessive accumulation of ca2  in hepatocytes succeeded by rapid glycogen breakdown and suppressed cell division in rats receiving ccl4 after previous dietary exposure to 10 ppm chlordecone  since calmodulin plays a major role in ca2    regulated events and has been reported to be localized in mitotic apparatus during cell division  we have assessed subcellular distribution of calmodulin and estimated cytosolic phosphorylase a to indicate cytosolic free ca2  levels in livers of rats fed 0 ppm or 10 ppm  chlordecone  in the diet for 15 days before ccl4  100 microliters kg  administration to understand the role of ca2    calmodulin in chlordecone   ccl4 toxicity  hepatotoxicity was assessed by determining serum ast and alt succeeded by histopathological observations of liver sections  serum aminotransferases were significantly elevated 6 hr after ccl4 administration to normal rats and returned to control level by 24 hr  however  serum ast and alt elevations were severalfold higher  and progressive increase was observed starting 4 hr after ccl4 administration to chlordecone rats  histopathological observations of liver sections for necrotic  swollen and lipid laden cells provided findings commensurate with the serum enzyme data  these data indicate that normal rats do recover from ccl4 hepatotoxicity  however  the ccl4 hepatotoxicity is progressive in chlordecone rats without recovery  in normal rats  ccl4 administration resulted in a slight increase in phosphorylase a starting at 6 hr  
class6	circulating tumor necrosis factor  interleukin 1 and interleukin 6 concentrations in chronic alcoholic patients  although altered cytokine homeostasis has been implicated in the pathogenesis of alcoholic liver disease  the relationship between cytokines and metabolic consequences of alcoholic liver disease is unknown  we  therefore  sought to correlate circulating concentrations of tumor necrosis factor alpha  interleukin 1 and interleukin 6 to clinical and biochemical parameters of liver disease in chronic alcoholic patients  we used an enzyme linked immunosorbent assay to measure plasma tumor necrosis factor and interleukin 1 and a bioassay to measure serum interleukin 6 in three groups of alcoholic men as follows   a  actively drinking alcoholic men without evidence of chronic liver disease   b  nondrinking alcoholic men with stable cirrhosis and  c  patients with acute alcoholic hepatitis  mean cytokine concentrations were elevated in cirrhotic patients and alcoholic hepatitis patients compared with controls and alcoholic patients without liver disease  tumor necrosis factor alpha and interleukin 1 alpha concentrations remained elevated for up to 6 mo after diagnosis of alcoholic hepatitis  whereas interleukin 6 normalized in parallel with clinical recovery  concentrations of all three cytokines were correlated with biochemical parameters of liver injury and hepatic protein synthesis plus serum immunoglobulin concentrations  we could not demonstrate a relationship between cytokine concentrations and peripheral endotoxemia  percentages of peripheral blood monocytes that reacted with monoclonal antibodies to cd25  interleukin 2 receptor  and human lymphocyte antigen dr were similar for alcoholic patients and controls  these data suggest that tumor necrosis factor alpha and interleukin 1 alpha are related to some of the metabolic consequences of both acute and chronic alcohol induced liver disease  whereas interleukin 6 is related to abnormalities seen in acute liver injury  
class6	regulation of insulin like growth factor ii gene expression by hepatitis b virus in hepatocellular carcinoma  in this study we investigated the regulation of insulin like growth factor ii gene expression to explain a role for this growth factor in concert with hepatitis b virus involvement in the development of hepatocellular carcinoma from cirrhosis  sections of normal liver and tumor and non tumor bearing liver disease tissue were hybridized in situ with  35s  labeled insulin like growth factor ii oligonucleotide probe  parallel sections were tested for presence of insulin like growth factor ii polypeptide using immunohistochemistry  to investigate a possible role for hepatitis b virus in insulin like growth factor ii gene expression in hepatocellular carcinoma  results were analyzed against patient seropositivity for hepatitis b virus  levels of insulin like growth factor ii transcripts in normal liver  n   4  sections and in those from non tumor bearing individuals  n   10  were so low that specific signal was not detectable above homogeneous tissue background  in contrast  4 of 8  50   of the sections of hepatocellular carcinoma arising from cirrhosis or noncirrhotic chronic liver disease with hepatitis b virus involvement showed increased expression of insulin like growth factor ii messenger rna transcripts  up regulation was observed in cell foci in the hepatocellular regions of the surrounding cirrhotic lobular cells and the fibrous septa  numerous cell foci were observed in patch distribution in the tumor areas  the level of insulin like growth factor ii messenger rna transcripts in sections of hepatocellular carcinoma arising from cirrhotic and noncirrhotic tissues obtained from patients seronegative for hepatitis b virus was similar to that of normal liver  
class6	interferon alpha receptor expression and regulation in chronic hepatitis b virus infection  interferon alpha elicits antiviral and immunoregulatory activities by binding to specific receptors on the cell surface  in this study  binding characteristics of interferon alpha to peripheral blood mononuclear cells in patients with chronic hepatitis b virus infection were studied using radioiodinated recombinant interferon alpha 2b to determine interferon alpha receptor numbers and dissociation constants  a single class of interferon alpha receptor was demonstrated on peripheral blood mononuclear cells and mononuclear subsets  peripheral blood mononuclear cells from patients with chronic hepatitis b virus infection  n   20  and controls  n   16  expressed a similar number of interferon alpha receptors  484     175 vs  511     168 sites cell respectively  p   ns  with a similar dissociation constant  dissociation constant approximately 0 2 to 0 7 nmol l   expression of interferon alpha receptors was similar in monocyte enriched and lymphocyte enriched fractions in both groups  similar changes were observed in patients receiving alpha interferon therapy  there was no correlation between interferon alpha receptors expression and serum transaminase  serum hbsag  serum hbv dna  liver histological findings or the response to interferon alpha therapy  after incubation of lymphocytes in vitro with interferon alpha 2b  10 to 1 000 u ml   interferon alpha receptors number dropped by 42  to 80   but this was associated with an increase in binding affinity  dissociation constant approximately 0 05 to 0 15 nmol l  in both patients and controls  there was significant delay in the initial phase of receptor recovery in the patients with chronic hepatitis b virus infection compared with normal controls  days 1 and 2  p less than 0 05   
class6	a rat model of esophageal varices  we have developed a new method for inducing portal hypertension and esophageal varices in rats  partial ligation of the portal vein after devascularization of the circumference of the left renal vein and complete ligation of the portal vein on the fifth day thereafter  thirty rats were separated into groups of 10  control  sham operation   complete portal ligation only and complete portal ligation plus devascularization  two weeks after the surgery  the presence of esophageal varices in rats with complete portal ligation plus devascularization was confirmed by portography and by the histological findings  the diameter  mean     sd  of the submucosal veins of the lower esophagus in the complete portal ligation plus devascularization group  219 4     86 6 microns  was significantly larger than that in the complete portal ligation group  99 8     53 4 microns  or in the control group  30 5     16 6 microns   p less than 0 01   vascular structures of the lower esophagus closely resembled those in humans with esophageal varices  this new technique is simple  rapid and reliable  and application can be made to various experimental studies on portal hypertension  
class6	pancreatic pseudocyst in the left hepatic lobe  a report of two cases  the ultrasound and computed tomographic imaging features in a rare pancreatic pseudocyst of the liver are described in two patients  the pseudocysts occurred in the left lobe in both cases  one after a traumatic injury and the other after alcoholic pancreatitis  the possible topographical sequences with which pancreatic secretions entered the left hepatic lobe to form a cyst are discussed  
class6	outcome of hepatitis b virus infection in homosexual men and its relation to prior human immunodeficiency virus infection  to investigate the effect of human immunodeficiency virus type 1  hiv 1  infection on subsequent hepatitis b virus  hbv  infection  hiv antibody was sought in homosexual men who developed hbv infection during a hepatitis b vaccine trial  among 134 unvaccinated hiv 1 negative men  7  became hbv carriers  64  had viremia  and 42  had clinical illness  among vaccinated hiv 1 negative men  hbv infection severity decreased with number of vaccine doses administered  when adjusted for prior hepatitis b vaccination status  persons with hiv 1 infection preceding hbv infection had a significantly higher risk of developing hbv carriage  viremia  prolonged alt elevation  and clinical illness  among hiv 1 infected men  the risk of hbv carriage was increased in unvaccinated persons  21   and those who failed to respond to vaccination  31   and further increased in those who received vaccine doses at the time they developed new hbv infection  56  80    suggesting inactivated hepatitis b vaccine may temporarily impair the immune response to hbv infection in hiv 1 infected persons  hiv 1 infection was also associated with reduced alanine aminotransferase elevations during the first 36 months of follow up of men who became hbv carriers  
class6	a field study of the safety and efficacy of two candidate rotavirus vaccines in a native american population  a double blind  randomized  placebo controlled trial was conducted to evaluate the safety and efficacy of a rhesus rotavirus vaccine and rit 4237  a bovine rotavirus vaccine  in a navajo population  infants aged 2 5 months were randomized to receive one dose of either 10 4  pfu of the rhesus rotavirus vaccine or 10 8  pfu of the rit 4237 vaccine or placebo  eleven  10 2   of 108 infants in the rhesus vaccine group  11  10 4   of 106 in the rit 4237 group  and 9  8 4   of 107 in the placebo group experienced rotavirus diarrhea during the follow up period of 17 months  thus  in this population  neither vaccine was efficacious in preventing rotavirus diarrhea  
class6	measles associated diarrhea in hospitalized children in lima  peru  pathogenic agents and impact on growth  because the causes of measles associated diarrhea are not well known  0  to 5 year old children presenting to the hospital with measles associated diarrhea  cases  n   77  or acute diarrhea only  controls  n   77  were compared  growth and diarrheal morbidity were evaluated for 1 month after acute illness  campylobacter jejuni was more frequently isolated from cases  31   than controls  16   p    03   rotavirus was absent in all cases versus 28  of controls  p less than  001   incidence density for new episodes of diarrhea was significantly greater in cases  6 5 vs  4 1  odds ratio  1 6  confidence intervals  1 09 2 34  p    01   as was duration of episodes  3 vs  2 days  p    02   both groups showed similar positive cumulative percentage weight gains throughout follow up  these data support the theory of measles as a risk factor for developing diarrhea  the bacteriologic and virologic findings may reflect the immunologic response of the host to measles infection  
class6	diffuse adhering escherichia coli  daec  as a putative cause of diarrhea in mayan children in mexico  diarrhea is a major cause of infantile morbidity and mortality in developing countries  a community based  case control study was conducted in a southern mexican mayan village for 3 weeks during the peak diarrhea period to prospectively identify the infectious agents associated with childhood diarrheal disease  several enteropathogens were isolated from stools of 34 of 58 cases  although none was significantly associated with diarrhea  for the 24 cases from which no enteropathogens were isolated  diffuse adhering escherichia coli  daec  strains were significantly associated with diarrheal disease  p less than  02  odds ratio   6  95  confidence limit  1 08 99 0   daec were highly heterogeneous with respect to plasmid content and serotype  three dna probes designed to differentiate e  coli exhibiting localized  diffuse  or aggregative adherence were compared with results from a standard hela cell binding assay to assess the utility of these probes in the field  this study provides evidence for the potential pathogenic capacity of daec and underscores the variety of diarrheal agents operating within a community  
class6	yersinia enterocolitica o 3  an emerging cause of pediatric gastroenteritis in the united states  the yersinia enterocolitica collaborative study group  after an outbreak of yersinia enterocolitica infections among black children in atlanta  a seven hospital study was conducted to determine the importance of this pathogen in other communities with large black populations  of 4841 stool specimens from patients with gastroenteritis examined between november 1989 and january 1990  y  enterocolitica  shigella  campylobacter  and salmonella were identified in 38  49  60  and 98 specimens  respectively  34  92   of 37 y  enterocolitica isolates were serotype o 3  of the 38 patients with yersiniosis  37  97   were children  illnesses were clustered around the holidays  and 20  62   of 32 patients had been exposed to raw pork intestines in the 2 weeks before onset  exposure was significantly associated with illness in a case control study of eight patients identified at one hospital  p    004   infants less than or equal to 6 months old with yersiniosis were more likely to have immature to total neutrophil ratios greater than 0 50 than were infants of comparable age with salmonellosis  p    02   infrequently isolated in the past  y  enterocolitica o 3 is emerging as an important enteric pathogen in this country  particularly among black children  
class6	preexposure of the peritoneum to live bacteria increases later mixed intraabdominal abscess formation and delays mortality  intraabdominal infections are a major source of morbidity and mortality for the trauma and postoperative patient  transient peritoneal contamination with bacteria after either intentional or unintentional violation of the gut are common  the effect of this intermittent antigen exposure upon later formation of intraabdominal abscesses is unclear  previous experiments by others have demonstrated that repeated exposure to bacteroides fragilis capsular polysaccharide can induce a t lymphocyte mediated immunity to subsequent induction of pure b  fragilis abscess formation  in a murine mixed intraabdominal abscess model  preexposure to live escherichia coli  b  fragilis  or both increased the number of later abscesses and in some cases their bacterial composition  further  immunization with e  coli alone increased late mortality without altering overall mortality  these data suggest that the alterations of immune function produced by live  transient bacteria upon subsequent mixed intraabdominal abscess induction result in fundamentally different consequences from those observed after specific polysaccharide antigen exposure and subsequent monomicrobial abscess induction  
class6	obesity and colorectal adenomatous polyps  obesity has been investigated as a risk factor for various malignancies  including colon cancer  a case control study was conducted on patients in three colonoscopy practices in new york city to determine possible risk factors for colorectal adenomatous polyps  a known precursor lesion for most cases of colorectal cancer  among 301 case subjects with incidence adenomatous polyps  174 men and 127 women  and 506 control subjects  223 men and 283 women   an increased risk was observed with increasing body mass index in women  odds ratio 2 1  95  confidence interval 1 1 4 0  for highest versus lowest quartile  linear trend p    02   a nonsignificant trend was observed for men  the increased risk seen in women is consistent with prior observations regarding reproductive hormonal and dietary risk factors for colorectal cancer  
class6	should alcoholics compete equally for liver transplantation  the circumstances of liver transplantation are unique among organ transplantation because of the dire  absolute scarcity of donor livers and the predominance of one disease  alcohol related end stage liver disease  as the principal cause of liver failure  we propose that patients who develop end stage liver disease through no fault of their own should have higher priority for receiving a liver transplant than those whose end stage liver disease results from failure to obtain treatment for alcoholism  we base our proposal on considerations of fairness and on whether public support for liver transplantation can be maintained if  as a result of a first come  first served approach  patients with alcohol related end stage liver disease receive more than half the available donor livers  we conclude that since not all can live  priorities must be established for the use of scarce health care resources  
class6	alcoholics and liver transplantation  the ethics and social impact committee of the transplant and health policy center  two arguments underlie a widespread unwillingness to consider patients with alcoholic cirrhosis of the liver as candidates for transplantation  first  alcoholics are morally blameworthy  their condition the result of their own misconduct  such blameworthiness disqualifies alcoholics in unavoidable competition for organs with others who are equally sick but blameless  second  because of their habits  alcoholics will not exhibit satisfactory rates of survival after transplantation  good stewardship of a scarce lifesaving resource therefore requires that alcoholics not be considered for liver transplantation  these arguments are carefully analyzed and shown to be defective  there is not good moral or medical reason for categorically precluding alcoholics as candidates for liver transplantation  it would  in addition  be unjust to implement such a preclusion simply because others might respond negatively if we do not  
class6	collagenous colitis as a cause of chronic diarrhea  when the usual workup for chronic diarrhea fails to provide a diagnosis and the endoscopic findings are normal  alternative etiologies must be considered  this case of collagenous colitis represents such an alternative diagnosis  the patient is a 65 year old woman who complained of abdominal cramps and watery diarrhea for an 8 month span  the key element to her diagnosis was subepithelial collagen deposits of the mucosa of the colon  her symptoms were resolved with supportive care  diet  and diphenoxylate  essential features and treatment of collagenous colitis are reviewed  
class6	recurrent peritonitis  evidence for possible viral etiology  a 45 year old woman who was treated with continuous ambulatory peritoneal dialysis  capd  developed recurrent peritonitis characterized by cloudy effluents  elevated white blood cell  wbc  counts  predominantly lymphocytes   and negative culture results  this case report suggests that she may have had viral peritonitis as indicated by a positive viral culture  the presence of viral antibodies in serum and peritoneal dialysis effluent  pde   hematological findings  and cell surface receptor studies  the possibility of a viral cause should be considered in patients with culture negative peritonitis  especially if they do not respond to antibiotics  
class6	two cases of adult t cell leukemia associated with acute pancreatitis due to hypercalcemia  we report two cases of adult t cell leukemia associated with acute pancreatitis and hypercalcemia  after sudden onset of epigastralgia  acute pancreatitis and hypercalcemia were found in both patients  there were no diseases that could explain the acute pancreatitis except for hypercalcemia probably due to adult t cell leukemia  thus we considered that hypercalcemia due to adult t cell leukemia had led to acute pancreatitis  this is the first report of such a complication in adult t cell leukemia  
class6	intestinal cryptosporidiosis  pathophysiologic alterations and specific cellular and humoral immune responses in rnu   and rnu rnu  athymic  rats  in order to develop an experimental model of symptomatic cryptosporidiosis in an immunosuppressed mammal  we investigated the pathophysiology of infection with cryptosporidium and the humoral and cellular host responses in rnu rnu  athymic  rats and their heterozygous  rnu    littermates by challenging suckling rats with greater than or equal to 2 5 x 10 6  cryptosporidium oocytes oro gastrically  normal and immunodeficient animals were followed for onset and duration of infection  fecal oocysts   physiologic consequences  diarrhea  impaired weight gain  brush border enzyme activities   and immunologic response  both b  and t lymphocyte mediated   homozygosity for the rnu gene was associated with protracted cryptosporidial infections  shedding for up to 52 days occurred  and delay in weight gain was noted in rnu rnu infected compared with rnu rnu uninfected rats  p less than 0 05   in contrast  cryptosporidial challenge of rnu   rats resulted in self resolving infections  occasionally with transient diarrhea lasting four days or less occurring 10 15 days after oro gastric challenge  the latter animals mounted a cell mediated immune response to cryptosporidium  three months after challenge  five of five rnu   rats demonstrated positive skin test responses to a subcutaneous 3 5 micrograms dose of cryptosporidial antigen  further  sera from 6 rnu   rats taken two to three months after oro gastric oocyst challenge exhibited specific anticryptosporidial immunoglobulin binding  a405   0 96   compared to that of seven uninfected rnu   controls  a405   0 09  p less than 0 02   macromolecules of 150  105  and 88 kd in the cryptosporidium antigen preparation were bound by serum immunoglobulin from previously infected  recovered rnu   rats  two brush border enzymes  lactase and alkaline phosphatase  were markedly reduced in the ileum 8 10 days after oro gastric challenge in rats with diarrhea and oocyst shedding  we find the rnu rnu  athymic  nude  rat provides a useful model for study of prolonged cryptosporidial infection with impaired weight loss  brush border enzyme alteration and intermittent diarrhea  these studies further suggest that a t lymphocyte population is involved in recovery from cryptosporidium infection and that this recovery is associated with both cellular and humoral immune responses to specific cryptosporidial antigenic macromolecules  this model should open further avenues for the study of the pathogenesis and protective immunity in cryptosporidial infection  
class6	isoenzyme profiles of four strains of giardia lamblia and their infectivity to jirds  the infectivity to jirds  meriones unguiculatus  and the cyst excretion pattern of a recently isolated strain of giardia lamblia from egypt  strain cdc 1088 1  egy   were compared to those of three well established strains  all five jirds inoculated orally with strain uno 0487 1  uno  became infected and began excreting cysts 3 6 days post infection  dpi   no cysts were detected between 8 12 dpi after which time cysts were produced through day 19  four of the five jirds infected with strain atcc 30957  wb  and three of the five jirds infected with strain cdc 0284 1  va  excreted cysts from 6 20 dpi and 6 22 dpi  respectively  one of five jirds inoculated with egy excreted cysts on 8 dpi only  at necropsy  trophozoites were recovered from only three uno infected jirds but from all wb  and va infected jirds that excreted cysts  the one jird which excreted cysts of egy was negative at necropsy  but egy trophozoites were found in one non patient jird  isoelectric focusing indicated that these four strains of g  lamblia represented three zymodemes  wb and va were assigned to one zymodeme  egy to a second  and uno  which shared common bands with both other zymodemes  to the third  although the similarities and differences in infectivity and cyst excretion patterns appear to coincide with the zymodemes to which the strains can be assigned  further study is needed to examine the parasitologic behavior of these strains in relation to isoenzyme patterns  
class6	rupture of the oesophagus during cricoid pressure rupture of the oesophagus occurred during the application of cricoid pressure at induction of anaesthesia when the patient vomited  the patient  who was bleeding from a gastric ulcer  was found to have a lower oesophageal tear which  although repaired at operation  resulted in a fatal mediastinitis  
class6	the role of a critical care unit in an epidemic  the role of a critical care unit in life threatening situations is well established  the management of 52 children with acute gastroenteritis and 22 children with acute paralytic poliomyelitis as part of recent epidemics is described  the solutions to the problems in the critical care management of these 74 victims  out of a total of 6197 patients admitted during the epidemics  are discussed  
class6	poisoning with equine phenylbutazone in a racetrack worker  phenylbutazone is a potent nonsteroidal  anti inflammatory drug often used by veterinarians to treat racetrack animals  its use in human beings is limited because of significant adverse effects and the availability of newer  safer drugs  we report the case of a 24 year old man who ingested 17 g of equine phenylbutazone over a 24 hour period to treat the pain of a toothache  he developed grand mal seizures  coma  hypotension  respiratory and renal failure  and hepatic injury  serum phenylbutazone concentration obtained approximately eight hours after presentation was 900 micrograms ml  the patient recovered during six weeks of intensive supportive care and repeated hemodialysis  
class6	propofol as an i v  anaesthetic induction agent in variegate porphyria  the choice of an i v  anaesthetic induction poses problems for the anaesthetist confronted with a patient with one of the acute porphyrias  we undertook a prospective clinical trial in 13 variegate porphyric subjects using propofol as an anaesthetic induction agent  urinary porphyrin precursors and porphyrins were measured before operation and 1 5 days after operation  stool and plasma porphyrin concentrations were measured over the same period  comparison of these data in the porphyric patients and in 21 control subjects over the trial period revealed no significant change in porphyrin or porphyrin precursor output after operation  urinary porphyrin precursor concentrations did not exceed the limits established for variegate porphyric patients in remission  and there were no changes in the stool and plasma porphyrin profiles or any symptoms of an acute porphyric attack  we conclude that propofol did not appear to be porphyrinogenic when used for the induction of anaesthesia in 13 patients with variegate porphyria  
class6	a simple score for the identification of patients at high risk of organic diseases of the colon in the family doctor consulting room  the local ibs study group  in order to develop a scoring system for selecting patients at high risk of organic diseases of the colon  who would need a colonoscopy or a barium enema  we conducted a study with 14 gps in the local health care district of modena  over one year  254 consecutive patients who consulted their gp for chronic abdominal pain were asked to answer a guided questionnaire  a checklist of simple parameters suggestive of the presence of organic diseases of the colon was also registered by the gp  for the final diagnosis  the patients underwent either a colonoscopy or a barium enema  data collected were analysed by means of a stepwise logistic regression analysis to obtain a weighted score for the diagnosis of either irritable bowel syndrome  score less than 0  or organic disease  score greater than 0   out of the 25 parameters explored  six were significantly more common among patients with organic disease and weighted as positive score  namely esr greater than 17 mm  first hour  history of blood in the stool  leukocytosis greater than 10 000 cm3  age greater than 45 years  slight fever and presence of neoplastic colonic diseases in first degree relatives   on the contrary  five parameters were more frequent among patients with irritable bowel syndrome and weighted as negative score  namely visible distension of the abdomen  feeling of distension  presence of irritable bowel syndrome in first degree relatives  flatulence and irregularities of bowel movement   our scoring system correctly classified 83 5  of the cases  and it was very sensitive  82 4   for the diagnosis of organic disease  
class6	hepatocyte expression of hbcag and serum hbeag in hepatitis b  comparison of polyclonal and monoclonal antibodies during a trial of interferon  the distribution and quantitative expression of hbcag in relation to serum hbeag and liver histology before and after a trial of interferon in 50 patients with chronic type b hepatitis were evaluated using polyclonal and monoclonal antibodies  in general  both antisera showed a similar pattern in terms of the distribution of hbcag  with predominant localisation of hbcag in the cytoplasm in hbeag positive patients with chronic active hepatitis  semiquantitative analysis showed  however  that there was a higher degree of cytoplasmic expression of hbcag with polyclonal than with monoclonal anti hbc  some of the hbeag positive patients with only a focal expression of hbcag in the cytoplasm by polyclonal anti hbc showed no expression of hbcag with monoclonal anti hbc  the expression of hbcag with polyclonal anti hbc correlated better with the histological features of chronic active hepatitis or the persistence of serum hbeag on follow up  suggesting that it did not result from non specific or false positive staining  all of the hbeag negative patients with minimal histological changes or inactive cirrhosis were hbcag negative with both antisera  in conclusion  though both polyclonal and monoclonal antibodies produced a quite similar distribution of hbcag in patients with chronic type b hepatitis  polyclonal antibody seemed to be more sensitive in detecting hbcag in the cytoplasm than did monoclonal anti hbc  and the expression of hbcag with polyclonal anti hbc correlated better with the clinical and histological outcome  
class6	evaluation of the pre s  pre s 1 ag pre s 2 ab  system in hepatitis b virus infection  the diagnostic and prognostic value of pre s 1 ag and pre s 2 ab was investigated in 69 hbsag surface antigen positive patients  14 with acute hepatitis b  30 with chronic liver disease  six chronic persistent hepatitis  14 chronic active hepatitis  10 with cirrhosis  and in 25 asymptomatic carriers  pre s 1 ag was found in all patients with chronic hepatitis b virus  hbv  infection regardless of viral replication  in contrast  pre s 2 ab was not detected in any patients  acute hepatitis was studied sequentially with periodic controls at 20 day intervals  pre s 1 ag cleared before hbsag in six of 14  43   patients who progressed favourably  and the two antigens cleared simultaneously in eight of 14  57   cases  patients with early clearance of pre s 1 ag progressed favourably  thus indicating the prognostic value of this test  which  however  is still of limited practical application given the small temporal difference between the moment of clearance of the two antigens  the first markers to clear  however  were hbeag and dna hbv  which showed significant differences with respect to the clearance of hbsag  moreover  pre s 2 ab appeared before hbsab in 57 1  of our patients and was found in some patients before pre s 1 ag and hbsag had cleared  42 8    thus allowing complete viral clearance and acute hbv infection to be predicted earlier  
class6	breakdown of gastric mucus in presence of helicobacter pylori  the potential of helicobacter pylori to degrade gastric mucus was examined  colonies of h pylori cultured from antral mucosal biopsy specimens of patients with non autoimmune gastritis were washed with sterile saline  passed through a sterilisation filter  and the filtrate examined for urease  protease  and mucolytic activity  the filtrate failed to hydrolyse bovine serum albumin  or to degrade stable mucus glycoprotein structures of high particle weight that had been separated from human gastric mucus on sepharose 2b  the high particle weight mucus glycoprotein was  however  extensively degraded when incubated with h pylori filtrate  which possessed urease activity  in the presence of 2 m urea  to release fragments of mr approximately 2 x 10 6   the high particle weight mucus glycoprotein was also broken down to a comparable extent when incubated with jack bean urease in the presence of 2 m urea  or 1 m ammonium carbonate  or 40 mm carbonate bicarbonate buffer  ph 8 7   but not when treated with 4 m urea alone  or jack bean urease alone  these results indicate that the loss of high particle weight mucus glycoprotein in gastric mucus from patients with gastritis and gastric ulcers is unlikely to be due to the mucolytic action of an extra cellular protease produced by h pylori  but it may result from the destabilising effects of a carbonate bicarbonate buffer  generated at the mucosal surface when h pylori urease hydrolyses transuded plasma urea  
class6	retrospective application of prognostic indices to pancreatitis discovered at necropsy  six prognostic indices  which were developed to assess inpatients with acute pancreatitis  were evaluated for possible retrospective application  when applied to a series of 14 cases in whom pancreatitis was first diagnosed at necropsy  the index devised by jacobs et al was found to be the most useful  because in nine of these cases eight or more of the variables required were available for assessment from the case records  in the other indices evaluated fewer than eight of the required variables were available for retrospective assessment in most cases  although undiagnosed pancreatitis is probably uncommon as a sole cause of death  the retrospective use of one or more of these indices may help assess the severity of the patient s condition on admission to hospital  
class6	gross and microscopic changes in the viscera induced by photodynamic therapy applied to the lower abdomen of intact rats  photodynamic therapy  pdt  is a promising approach to the treatment of cancer  preferential retention of the photosensitizer by malignant tissue has been considered a hallmark of this treatment modality  however  photosensitivity can be observed in normal  non neoplastic tissues  and the present study investigated the effects of pdt treatment on the abdomen of intact rats  a circular region  1 cm diameter  on the shaved abdomen of fischer rats  pretreated 24 h prior with photofrin ii  was irradiated for 30 min at 632 nm  control animals received either photoradiation or photofrin ii administration  subsequent lesions were observed in the irradiated skin  its associated abdominal wall  and the underlying gut in rats receiving photofrin ii and laser irradiation  all tissues were not equally sensitive to pdt treatment  gut lesions were consistently more severe than were skin and abdominal wall injuries  by 24 hr after treatment  the gut manifested a transmural hemorrhagic necrosis  while the irradiated skin and abdominal wall were edematous  with an inflammatory infiltrate in the dermis and around occasional swollen myocytes  these results indicate that superficial lesions induced by pdt may not be reliable indicators of the extent of deeper pdt tissue damage  further  it may be possible to take advantage of this discrepancy in tissue sensitivity and treat deep tissues through less sensitive superficial tissues  
class6	valproate metabolism during hepatotoxicity associated with the drug  plasma concentrations of valproate and certain of its metabolites and their patterns of excretion in urine are described in three adults who developed hepatotoxicity during treatment of epilepsy with sodium valproate  one patient also developed a degree of reversible renal insufficiency  whilst another may have had associated infectious mononucleosis  all three cases showed evidence of impaired mitochondrial beta oxidation of valproate  in one the impairment was at the stage catalysed by fatty acyl coa dehydrogenase  in another at the stage catalysed by 3 hydroxyacyl coa dehydrogenase and in the third at the stage catalysed by enoyl coa hydratase and possibly also at the next stage catalysed by 3 hydroxyacyl coa dehydrogenase  the impaired beta oxidation meant that valproate metabolism was diverted into various alternative pathways  plasma concentrations of the suspected hepatotoxic metabolite 4 en valproate were normal for the valproate treated population in all cases  by analogy with certain spontaneous and acquired human disorders of branched chain amino acid metabolism  it is suggested that valproate associated hepatotoxicity may represent the consequences of a valproate overload on a limited mitochondrial beta oxidation capacity  causing accumulation of a toxic product of endogenous branched chain amino acid metabolism  
class6	diltiazem therapy for symptoms associated with nutcracker esophagus  a randomized double blind  cross over prospective trial in 22 patients was designed to evaluate possible effect of an oral calcium channel blocker  diltiazem  on symptoms of chest pain and or dysphagia in patients with nutcracker esophagus  we studied 22 consecutive patients referred to an esophageal diagnostic center for evaluation of noncardiac chest pain or dysphagia having high amplitude esophageal contractions  14 of whom completed the study  diltiazem  60 90 mg qid  was compared with placebo  each being administered for 8 wk  patients were evaluated with esophageal motility pre  and posttreatment periods and with regular symptom assessment throughout each 8 wk treatment  active diltiazem therapy resulted in significantly lower  p less than 0 05  mean distal esophageal peristaltic pressure  128     20 mm hg      se  than placebo  158     16 mm hg   mean chest pains scores were significantly  p less than 0 05  lower with diltiazem therapy than with placebo  only nine of the 14 patients fulfilled presently acceptable criteria for diagnosing nutcracker esophagus  and the diltiazem effect was similar  although not significant  because of the smaller sample  conclusions  in this preliminary study involving 14 patients  the oral calcium channel blocker  diltiazem  appeared to improve noncardiac chest pain associated with strong esophageal contraction  the nutcracker esophagus  these improved symptoms were associated with significant decreases in contraction pressure  
class6	colon interposition for esophageal disease  histologic finding of colonic mucosa after a follow up of 5 months to 15 years  thirty six patients  subjected to colon interposition for benign esophageal disease or carcinoma of the esophagus or gastric cardia  were studied by endoscopy for signs of mucosal disease in the interposed colon  five months to 15 yr  mean 57 months  after the operation  endoscopic finding of the interposed colon was macroscopically normal in 28 patients  signs of inflammation  including hyperemia or hyperemia and friability  were observed in seven patients  histologic specimens obtained at endoscopy were examined microscopically  and the findings were compared with those seen in the preoperative graft  in two patients  chronic inflammatory changes were observed in the graft mucosa  consisting of mononuclear cell infiltration of the lamina propria accompanied by crypt dilatation and deformation  in one of these patients  the inflammation was in the proximal third of the graft  and it was also seen at the endoscopy  in the remaining 34 patients  the graft mucosa was microscopically comparable to normal  the alterations were unexpectedly few and mild considering the marked change in the location and function of the colonic segment  
class6	a topographical relationship between helicobacter pylori and gastritis  quantitative assessment of helicobacter pylori in the gastric mucosa  a topographical relationship between the number of helicobacter pylori in the gastric mucosa and the histological severity of gastritis was studied in 902 pairs of biopsy specimens taken from 314 patients  a pair of biopsies were taken from the antrum  the lesser curvature of the middle body  and the greater curvature of the upper body of the stomach  the quantitative assessment of h  pylori was made based on smear  culture  and tissue section  the histological severity of gastritis was assessed as to the degrees of mononuclear cell and polymorphonuclear leukocyte infiltration  a positive correlation was confirmed between the number of h  pylori and the severity of polymorphonuclear leukocyte infiltration  the degrees of inflammatory cells infiltration in the specimens with h  pylori colonization were significantly lower in the upper body than in the antrum  
class6	gluten challenge in patients with celiac disease  evaluation of alpha 1 antitrypsin clearance  our aim in this study was to monitor changes of the intestinal structure by alpha 1 antitrypsin clearance  alpha 1 atcl  in order to offer an alternative to the gluten challenge biopsy  in addition  we evaluated the possibility of reducing the time of gluten challenge  twelve patients had a presumptive diagnosis of celiac disease based on clinical and histological grounds  they were studied when the jejunal histology was normal after gluten free diet and an alpha 1 atcl was normal  the gluten was introduced by returning to a normal diet  the challenge lasted 4 wk  we measured alpha 1 atcl at the end of the 1st and 4th wk  and a new jejunal biopsy was obtained at the end of the 4th wk  by wk 1  alpha 1 atcl was abnormal in 11 patients but normal in one  by wk 4  alpha 1 atcl was abnormal in 10 patients and still normal in one  the post challenge biopsies showed atrophy in 11 and was normal only in the patient with normal alpha 1 atcl at wk 1 and 4  one patient with abnormal alpha 1 atcl had to stop the challenge at the first week  the patient with normal clearance at wk 1 and 4 and normal biopsy at wk 4 had abnormal results at 6 months  these data support our hypothesis that alpha 1 atcl can be used as evidence of gluten toxicity after gluten challenge  and that this test can be abnormal as early as 1 wk after gluten is reintroduced  
class6	undetected fatal acute pancreatitis  why is the disease so frequently overlooked  an analysis of postmortem investigations between 1980 and 1985 revealed 43 patients with acute pancreatitis  in 13  30 2   of them  the diagnosis was first established at autopsy  in eight of the latter patients  the diagnosis could have been present on admission  the etiology was alcoholism in three patients  hypothermia in one  biliary tract disease in one  and unknown in three patients  in five patients  acute pancreatitis developed after gastric  pancreatic  or biliary tract surgery  abdominal pain was present in only one patient  amylase levels had been estimated in 11 patients  but the level was in the diagnostic range  greater than or equal to 3 times of upper normal level  in only four  consequently  ultrasound examination was performed in only two of the latter four patients  but failed to show the pancreas because of intestinal gas  to diagnose acute pancreatitis at an earlier stage and to improve therapy and prognosis  we recommend that serum amylase levels be measured and ultrasound examination be performed  if the results are inconclusive  this should be followed by computed tomography for all abdominal emergency cases and for patients who have undergone cardiopulmonary or upper abdominal surgery  especially when the patients deteriorate or fail to improve postoperatively  
class6	prolonged treatment of children with chronic hepatitis b with recombinant alpha 2a interferon  a controlled  randomized study  a prospective study was conducted to evaluate the efficacy and tolerance of alpha interferon in 20 children with biopsy proven hbsag hbeag hbv dna positive  anti delta negative chronic hepatitis  patients were randomized to receive alpha 2a interferon  inf   3 mu im three times weekly for 12 months  or no treatment  10 patients per group   five patients receiving ifn showed a marked decrease or negativization of hbv dna during treatment  at the end of the study  after 18 month   three patients lost hbv dna permanently  and two of them seroconverted to hbeab 10 and 11 months after disappearance of hbv dna with normalization of aminotransferase values  in the control group  one patient had spontaneous clearance of hbv dna with conversion to hbeab and normalization of aminotransferase levels  all treated patients had a febrile reaction in the first month of treatment  the dose of ifn had to be decreased in two patients and was discontinued for persistent intolerance in one of them  patients who showed a decreased viral replication had higher initial biochemical and histological activity than nonresponders  the data suggest that ifn treatment may favorably influence the progression of chronic b hepatitis in children with a history of acute hepatitis and active chronic disease  
class6	cluster of fulminant hepatitis b in crack users  fulminant hepatitis occurs in only 1  of acute hepatitis b patients  requiring hospitalization  but coinfection with delta virus increases the incidence  hepatitis b and d infection are commonly associated with intravenous drug abuse  but there have been no previous reports of an association with nonparenteral cocaine  crack use  via sexual promiscuity  is associated with an increased risk for human immunodeficiency virus infection  but has never been associated with viral hepatitis  we report four fatal cases of fulminant hepatitis b including  one with delta virus coinfection and one with human immunodeficiency virus  hiv  infection  in young  sexually active  heterosexual crack users  these patients denied a history of intravenous drug abuse  our patients probably contracted hepatitis b infection via heterosexual contact  chronic cocaine exposure may or may not have contributed to the fulminant outcome  crack users may be at increased risk of developing hepatitis b and d infection  epidemiological studies are needed to evaluate their risk of viral hepatitis and the effect of cocaine on its outcome  
class6	the effects of vitamin k on the generation of des gamma carboxy prothrombin  pivka ii  in patients with hepatocellular carcinoma  the clinical significance of des gamma carboxy prothrombin  pivka ii  in hepatocellular carcinoma  hcc  was investigated in 112 patients with and without vitamin k administration  the positivity rate of pivka ii was significantly decreased in patients receiving vitamin k  28 5    compared with those without vitamin k administration  54 5   p less than 0 05   the plasma levels of vitamin k derivatives  phylloquinone  vk1   menaquinone 4  mk4   and menaquinone 7  mk7   measured were not decreased in patients with hcc  but were significantly increased in mk4 and vk1   mk4   mk7  the amount of pivka ii in plasma did not correlate with the plasma levels of vitamin k derivatives  however  pivka ii was decreased by the administration of vitamin k  and all of the six patients with more than 5 0 ng ml of vk1   mk4   mk7 were within normal limits  whereas half of 32 patients with less than that had abnormal levels of pivka ii  thus  it was suggested that pivka ii was not elevated due to vitamin k deficiency  but might result from the impaired metabolism or availability of vitamin k in the tumor  therefore  pivka ii should be measured without vitamin k administration  
class6	gaucher s disease complicated by bleeding esophageal varices and colonic infiltration by gaucher cells  we report a 10 yr old child with gaucher s disease who developed upper gastrointestinal bleeding from esophageal varices  as well as hemorrhage from a colonic polyp infiltrated with gaucher cells  both the varices and polyp were treated endoscopically  and the outcome was successful  although gastrointestinal hemorrhage due to portal hypertension is considered a rare complication of gaucher s disease  colonic infiltration with gaucher cells has not been recognized previously  
class6	use of plasmid profiles in the investigation of a patient with helicobacter pylori infection and peptic ulcer disease  plasmids may effect bacterial virulence and antibiotic resistance  and serve as epidemiologic markers  in this study  plasmid dna profiles of serial isolates of helicobacter pylori showed persistence of an identical strain of this organism in a patient with duodenal ulcer disease  three control strains of h  pylori isolated from other patients contained plasmids different from each other and from that of the original patient  two of these strains had two plasmids each  these data have important implications for further study of the epidemiology and pathogenesis of h  pylori related diseases  
class6	peritoneal blastomycosis  blastomycosis is a systemic fungal infection caused by blastomyces dermatitidis  involvement of the peritoneum is unusual  with only two previously reported cases that occurred in association with disseminated disease  a single case of histopathologically proven blastomycosis involving the peritoneum is presented  as well as a short overview of previously published cases on gastrointestinal and peritoneal blastomycosis  the case is unique in that chronic peritonitis was the only manifestation of disease  the diagnosis was made by laparoscopy  
class6	ehlers danlos syndrome type iv  diagnosis and therapy of associated bowel perforation  ehlers danlos syndrome type iv is a heritable disease of type iii collagen metabolism  this diagnosis is suspected in a patient with a combination of clinical manifestations and family history  but it is confirmed only by culture of the patient s skin fibroblasts and demonstration of a defect in type iii collagen metabolism  the disease may rarely present with spontaneous colonic perforation  a complication traditionally treated by primary closure of the perforated segment and creation of an end colostomy  attempts at bowel reanastomosis have often resulted in repeated colon perforations  we present the first patient with ehlers danlos type iv syndrome to develop a colon perforation proximal to an end colostomy  and discuss the surgical strategy to prevent recurrences of this and other postoperative complications associated with the syndrome  
class6	perforation and tumor formation of the intestine in primary amyloidosis  we report a case of primary amyloidosis with repeated bowel perforations  this patient also had localized amyloid deposition creating a tumorous region mimicking malignancy in the rectum  perforation of the intestine is common in systemic amyloidosis  the ischemic change due to amyloid infiltration into the vessel wall may lead to perforation of the affected bowel  amyloid tumors occur more often in localized amyloid than in systemic amyloidosis  macroscopically  it is difficult to distinguish amyloid tumor of the intestine from neoplasia  
class6	cerebrovascular complications of inflammatory bowel disease  there is an increased incidence of central nervous system thromboembolic events in young patients with inflammatory bowel disease  a 33 yr old woman previously diagnosed with pseudotumor cerebri suffered superior sagittal and transverse sinus thromboses during a severe flare of ulcerative colitis  these were documented on contrast computed tomographic  ct  and magnetic resonance imaging  mri  scans  stroke may be more common in patients with ulcerative colitis than in patients with crohn s disease  arterial disease is more prevalent than venous and dural sinus disease  and is correlated with an active phase of inflammatory bowel disease  it is difficult to assess whether there is a relationship to concurrent steroid use  and a consistent relationship to duration of inflammatory bowel disease or to other extraintestinal manifestations is not apparent  
class6	giardia lamblia infestation reveals underlying whipple s disease in a patient with longstanding constipation  whipple s disease is an uncommon disorder  generally associated with gastrointestinal symptoms  of these  diarrhea is a common feature  we report a case of whipple s disease associated with chronic constipation which was not diagnosed until after giardia lamblia infestation had caused diarrhea  to the best of our knowledge this association has not previously been reported  the clinical  laboratory  endoscopic  and manometric aspects are described and discussed  
class6	epidermolysis bullosa acquisita and associated symptomatic esophageal webs  epidermolysis bullosa acquisita  eba  is a well characterized  subepidermal blistering disorder associated with autoimmunity to type vii collagen  which is the collagen localized to anchoring fibrils within the dermoepidermal junction of skin  although the full clinical spectrum of eba is still being defined  it is known that the clinical features of eba may be reminiscent of hereditary dystrophic epidermolysis bullosa  a scarring blistering disease of children that is commonly associated with esophageal stenosis  we describe a patient with eba who had both an acral predominant mechanobullous disease akin to dystrophic epidermolysis bullosa and an inflammatory  widespread bullous eruption reminiscent of bullous pemphigoid in association with esophageal webs and dysphagia  although esophageal involvement is common in dystrophic epidermolysis bullosa  a review of the literature shows that this is the first bonafide case of eba with symptomatic esophageal disease  
class6	severe gastrointestinal hemorrhage in crohn s disease  twenty one of fifteen hundred twenty six patients with crohn s disease  cd  treated at the mount sinai hospital between 1960 and 1986 developed severe gastrointestinal hemorrhage  there were 26 separate episodes of severe hemorrhage  17 patients bled only once  three bled twice and one bled three times  the frequency of bleeding was significantly higher among patients with colonic involvement  17 of 929  1 9   than among those with small bowel disease alone  4 of 597  0 7    p less than 0 001   twelve patients required surgery on 13 occasions  which involved colon resection in all but one case  eleven of these patients underwent surgery during their first hemorrhagic episodes  and 1 of 11 had a second operation for recurrent bleeding  the 12th patient  whose first hemorrhage had been treated medically  had surgery during a repeated episode of hemorrhage  the precise bleeding points could be located in only 2 of the 26 bleeding episodes  both at the ileocecal area  three patients died  of whom two had not undergone surgery when they had bled a few weeks earlier  primary bleeding episodes subsided without surgery in 10 of 21 cases  but 3 of these 10 patients  30   rebled massively  by contrast primary excisional surgery was followed by recurrent hemorrhage in only 1 of 11 cases  9    these differences in mortality and in recurrent bleeding rates  although not statistically significant  seem to favor removal of diseased bowel at the time of the first episode of massive hemorrhage  
class6	human liver regeneration after major hepatectomy  a study of liver volume by computed tomography  regeneration of the remnant liver after major hepatectomy in humans was studied by computed axial tomography  ct  in 12 noncirrhotic and five cirrhotic patients  liver volumes were measured by abdominal ct 3 days  10 days  3 months  6 months  1 year  and 1 5 years after resection  of the 17 patients  liver remnant volume was increased in 21 2      6 7  and 30 6      12 7  at 3 months and 6 months after resection  respectively  noncirrhotic livers were 28 4      9 5  and 48 4      17 8  larger at 3 and 6 months  for cirrhotic livers  the increase was 8 5      3 6  and 12 9      4 5   in five patients with right hepatectomy  65  resection   the liver remnant volumes were increased 38 4      11 7   48 0      16 2  and 95 1      4 5  at 3 months  6 months  and 1 year after resection  respectively  in seven patients with right partial hepatectomy  30  to 35  resection   the percentages were 7 4      3 2   21 8      8 4   and 63 9      18 3  and in five patients with left lateral segmentectomy  15  resection   they were 15 6      8 2   27 8      12 2   and 33 0      14 5  3 months  6 months  and 1 year after resections  respectively  noncirrhotic livers showed better regeneration than cirrhotic livers  complete regeneration took about 1 year  the noncirrhotic liver that underwent right lobectomy also needed 1 year to double its postresection volume  
class6	a valved hepatic portoduodenal intestinal conduit for biliary atresia  forty six consecutive patients with biliary atresia were operated on at our institution during the 11 year period between 1978 and 1989  their ages at operation ranged from 18 to 153 days  mean  59 days   after dissecting the porta hepatis structures by kasai operation  a biliointestinal anastomosis was constructed with a valved hepatic portoduodenal intestinal conduit in all cases  the intestinal valve is an intussuscepted muscular valve  valvular function was examined radiologically  the upper gastrointestinal series demonstrated no reflux of contrast material into the conduit proximal to the valve and liver scintigraphy demonstrated that radioactive isotope drained readily into the duodenum through the valve  thirty nine of the forty six patients  85   had bile drainage after initial operation  at present 30 patients  65   are alive without jaundice  6  13   are alive with jaundice  and 10  22   are dead  the 5 year jaundice free survival rate was 64   cholangitis occurred in 9 of 39 patients  23   who had obtained apparent bile drainage  5 had tractable cholangitis and 4 had refractory cholangitis  reoperation restored bile flow in 2 of 8 patients who abruptly ceased to have bile drainage without cholangitis  in conclusion  with a valved hepatic portoduodenal intestinal conduit  the incidence of cholangitis was decreased  its medical control became easier  and the survival rate was improved  
class6	the peritoneal environment during infection  the effect of monomicrobial and polymicrobial bacteria on po2 and ph  intraperitoneal  ip  abscesses frequently are composed of aerobes and anaerobes  and  in experimental models  a particulate adjuvant  the environmental changes effected by these components  either singularly or in combination  have not been well defined  the ip po2  ph  and recoverable bacteria from the peritoneum of rats were quantified over 6 hours during simple aerobic and anaerobic infections and during mixed peritonitis with and without a sterile feces barium sulfate adjuvant  sfa   fourteen groups were studied  receiving intraperitoneally  at time of oxygen probe placement  1 ml normal saline  control   escherichia coli  ec   bacteroides fragilis  bf   sfa alone  or a mixture of ec and bf  ec and sfa  bf and sfa  or ec  bf  and sfa  control animals exhibited a stable ip po2 and ph during 6 hours  in monomicrobial ec peritonitis  inocula well below the ld50 produced an increased ip po2 and reduced arterial peritoneal gradient  apg   with a stable ip ph  by 6 hours lethal doses of ec produced a dramatic decline in ip po2  with no change in arterial po2 as well as acidic ip and arterial phs  simple bf peritonitis caused no or minor elevations in ip and arterial po2 with no change in ph  during mixed infections a significant decline in the ip po2 and ph at 6 hours in those groups infected with both sfa and ec of a moderate  normally sublethal inoculation was observed  while arterial po2 was unchanged and arterial ph was decreased only slightly  concomitantly there was a significant increased number of aerobic bacteria in those groups with sfa as adjuvant compared to similar inocula without sfa  this study demonstrates the complex interactions of bacteria  sterile particulate adjuvant  sfa   and the host peritoneum  it suggests that the combination of sfa and aerobic bacteria alter the peritoneal environment to one permitting anaerobic growth and promoting abscess formation  
class6	simultaneous bilateral hernia repair  a case against conventional wisdom  the timing of bilateral hernia repair remains controversial  because of reported high recurrence rates after simultaneous bilateral repair  staged procedures have been suggested  this study determined recurrence and complication rates of unilateral versus simultaneous bilateral repair  of 659 patients undergoing hernia repair between 1974 and 1980  333 underwent unilateral repair and 329 had simultaneous bilateral repair  more than 90  of patients were followed until death or a minimum of 60 months  median  104 months   perioperative complications were associated with 18  of repairs  more morbidity occurred in the bilateral group  however complication rates for specific events were not significantly different  except for urinary retention  which occurred in 20 patients  6 1   of the unilateral group and 49  15   of the bilateral group  p less than 0 001   overall 25 recurrences occurred in the unilateral group and 31 in the bilateral group  recurrence rates at 5 and 9 years were  respectively  4 8  and 8 8  in the unilateral group and 5 0  and 9 1  in the bilateral group  p   0 861   these data suggest that simultaneous bilateral inguinal herniorrhaphy does not result in increased rates of most postoperative complications or recurrence when compared with unilateral repair  
class6	technique of photodynamic therapy for disseminated intraperitoneal malignant neoplasms  phase i study  patients with disseminated intraperitoneal malignant neoplasms were given intra abdominal photodynamic therapy  patients received dihematoporphyrin ethers intravenously 48 to 72 hours before laparotomy at doses of 1 5 to 3 0 mg kg  at operation  as much tumor as possible was resected  red light  630 nm  was delivered to all peritoneal surfaces from an argon pumped dye laser at doses ranging from 0 2 to 3 0 j cm2 in an escalating fashion  viscera and peritoneal surfaces were anatomically isolated and exposed to light for intervals calculated to deliver the prescribed energy  light was delivered to mesentery and bowel by a flat cut optical fiber  while other areas  including diaphragm  viscera  omental bursa  gutters  and pelvis  were delivered light through a diffusing wand  twenty three patients  13 with ovarian cancer  eight with sarcoma  and two with pseudomyxoma peritoneii  underwent photodynamic therapy  five of eight patients cleared positive peritoneal cytologies after treatment  six patients remained clinically free of disease for up to 18 months  and five patients had treatment related complications  intraperitoneal phototherapy is technically feasible and deserving of clinical evaluation  
class6	nosocomial outbreak of cryptosporidiosis in aids patients  objective  to describe a nosocomial outbreak of cryptosporidiosis during four months after june 1989  setting  a department of infectious diseases in copenhagen  seeing about half the patients with aids in denmark  subjects  73 hiv antibody negative subjects and 60 antibody positive subjects admitted as inpatients during the transmission period of the outbreak  20 june 14 august   of whom 18  17 with aids  one with aids related complex   developed cryptosporidiosis  two further hiv negative subjects  one departmental secretary  one visiting relative  developed cryptosporidiosis  main outcome measures  cryptosporidia in stool samples  clinical symptoms  cd4 cell count  hiv antigen concentration  chemotherapeutic treatment  results  the source of the outbreak was identified as ice from an ice machine in the ward  contaminated by an incontinent  psychotic patient with cryptosporidiosis picking out ice for cold drinks  the mean incubation time was at least 13 days that is  twice that in hiv negative patients  of the 18 patients with aids who developed cryptosporidiosis  five recovered  two were symptomless carriers  three died of unrelated causes  and eight died after prolonged diarrhoea  among the 57 exposed hiv antibody positive inpatients  excluding two patients and the index case with cryptosporidiosis diagnosed elsewhere   significantly more of those who developed symptomatic cryptosporidiosis received oral sulphonamides than those who did not  91   10 11 v 48   21 44  p less than 0 05   conclusions  the clinical and epidemiological findings indicate that infection was the consequence of very small inocula  increased sensitivity to cryptosporidiosis may be an unrecognised side effect of oral sulphonamide treatment in patients with aids  
class6	magnetic resonance angiography of abdominal vessels  early experience using the three dimensional phase contrast technique  based on three dimensional acquisition of three sequences sensitive to one flow direction  abdominal magnetic resonance phase contrast angiography  mra  was performed in 13 volunteers and 20 patients  the subjects received no antiperistaltic medication and were allowed to breath normally during the three acquisition periods of 11 minutes  the frequency of demonstration of the normal aorta  superior mesenteric and right and left renal arteries was 100  100  91  100   and of the inferior vena cava  splenic  superior mesenteric and portal veins was 92  67  92  100   respectively  whereas other abdominal vessels were seen less constantly  in renal artery stenosis or occlusion  mra detected eight out of nine pathological arteries  missed only a minimal stenosis and was never false positive  in all 10 cases of portal hypertension  mra demonstrated the venous collaterals detected by conventional angiography and in six cases showed more collaterals  particularly paravertebral vessels  a budd chiari syndrome was investigated as well  if the accuracy of mra can be proved in larger studies  it may become an important diagnostic tool in evaluating abdominal vascular pathology  such as renal artery stenosis or portal hypertension  
class6	ultrasound in the investigation of the right iliac fossa mass  patients presenting with a right iliac fossa  rif  mass are a diagnostic problem  the objective of this study was to assess the role of ultrasound  us  in their investigation  a prospective series of 50 patients presenting with a clinically suspected rif mass was examined by us and the finding correlated with the final diagnosis  there was a positive finding in 34 patients  68    ultrasound correctly identified the organ of origin in 33  97   and was able to guide the patients  further management  in 12 cases no abnormality was found in the rif  of which 11 had no positive findings at follow up and one was shown to have an unrelated abnormality at laparotomy  in four cases the findings were due to normal variants  ultrasound is the imaging modality of first choice in patients presenting with a rif mass  
class6	recurrence of crohn s disease after resection  recurrent crohn s disease develops in most patients after surgical resection if the patient is followed for sufficient time  this review examines various aspects of recurrent crohn s disease  it is concluded that crohn s disease is a diffuse condition of the gastrointestinal tract and that radical resection of crohn s disease does not prevent recurrence  assorted factors thought to be associated with recurrence are examined and the relevance of these factors to the surgeon treating crohn s disease is discussed  
class6	importance of the omentum in the development of intra abdominal metastases  areas of trauma are preferred sites for metastatic tumour growth  in extensive intra abdominal tumour recurrence the omentum is invariably involved  the importance of the omentum in the development of tumours at sites of intra abdominal trauma has been investigated  colonic anastomoses were performed in hooded lister rats with and without omentectomy  animals received intraluminal or intraperitoneal injections of a syngeneic tumour  with intraluminal injection  tumour occurred at the anastomosis and in the omentum in 38 and 43 per cent of animals respectively but following omentectomy the values were 14 and 9 per cent  omental remnant   with intraperitoneal administration tumour occurred in 53 per cent at the anastomosis and in 79 per cent in the omentum compared with 16 and 29 per cent  in omental remnant  following omentectomy  in this model a reduced ability of an anastomosis to support  seeded  tumour following removal of the omentum is demonstrated and the development of local recurrence from spilled tumour cells during operation may be enhanced by  or be dependent on  the proximity of the omentum  
class6	proximal gastric vagotomy  follow up at 10 20 years  from august 1969 to december 1989  600 patients had elective proximal gastric vagotomy for duodenal ulceration with an operative mortality of 0 2 per cent  of these  372 patients had surgery over 10 years ago  three hundred and forty two patients survived for more than 10 years and  in a prospective study  305 were reviewed  forming the basis of this 10 20 year follow up report  forty six  15 per cent  have had recurrent ulceration  80 per cent of these developed symptoms within 5 years and no patient has had recurrence after 13 years  although 29 patients required reoperation for recurrent ulceration  the current patient satisfaction rate for visick grades i and ii is 92 per cent  only two patients required reoperation because of gastric stasis  it is concluded that proximal gastric vagotomy is a safe and satisfactory first choice operation for duodenal ulceration  
class6	gastric adaptive relaxation and symptoms after vagotomy  gastric adaptive relaxation is reported to be impaired after vagotomy  this abnormality has been implicated in the pathogenesis of postvagotomy symptoms  but no association has previously been demonstrated between the two  gastric adaptive relaxation was measured in 15 healthy volunteers and 33 patients more than 1 year after highly selective vagotomy or truncal vagotomy and drainage  seventeen patients were asymptomatic  the remainder were symptomatic including seven patients with persistent diarrhoea  fasted subjects were intubated with a ryle s tube containing a pressure microtransducer within a flaccid  800 ml  plastic bag  gastric corpus fundus pressure was recorded during distension of the bag with air  15 ml s  over 30 s  pressure indices were derived from the areas under the pressure curves  median  range  pressure indices were  healthy volunteers 12 7  7 5 17 1  cmh2o  highly selective vagotomy 14 0  9 8 15 9  cmh2o  n s    truncal vagotomy and drainage 14 5  8 6 26 8  cmh2o  p   0 04   all patients with diarrhoea had abnormally high pressure indices  p less than 0 001   pressure indices in all other patient groups were within the normal range  we conclude that gastric adaptive relaxation remains abnormal in patients with postvagotomy diarrhoea but not in those who are asymptomatic or who have other symptoms  
class6	peptic ulcer surgery during the h2 receptor antagonist era  a population based epidemiological study of ulcer surgery in helsinki from 1972 to 1987  to evaluate the effects of improvements in medical therapy on the incidence of  indications for and operative methods used in peptic ulcer surgery  all cases of primary peptic ulcer surgery among adults in the city of helsinki in the years 1972  1977  1982 and 1987 were analysed  there was a total of 565 such cases in a population which consisted of 5 2 x 10 5  individuals in 1972 and 4 8 x 10 5  individuals in 1987  the introduction of h2 receptor antagonists in 1979 was associated with a fall in the annual incidence of elective duodenal ulcer operations  from 15 5 to 6 7 per 10 5  individuals  and a fall in the annual incidence of elective gastric ulcer operations  from 9 4 to 3 1 per 10 5  individuals  p less than 0 05   the decrease was greatest among males with duodenal ulcer  in contrast  the annual incidence of emergency surgery for ulcer haemorrhage and perforation  all types of ulcers  remained relatively stable  varying from 7 2 to 10 2 per 10 5  inhabitants over the observation period  n s    the mean age of patients undergoing elective surgery remained essentially unchanged  the mean age of patients undergoing emergency surgery increased  the decrease in the annual incidence of elective duodenal ulcer surgery occurred mainly in relation to proximal gastric vagotomy  there was a concomitant relative increase in the incidence of gastric resection  the types of operative procedures used in cases of pyloric  prepyloric and gastric ulcer remained unchanged over the years 1972 to 1987  
class6	correlation between laboratory findings and clinical outcome after restorative proctocolectomy  serial studies in 20 patients with end to end pouch anal anastomosis  clinical function and anorectal physiological function were assessed and correlated in 20 patients with ulcerative colitis before restorative proctocolectomy and 3  7  and 12 months after operation  the entire anal sphincter was preserved by means of a stapled pouch anal anastomosis  before operation  the median resting anal pressure was 79 cmh2o  interquartile range 70 89 cmh2o   the rectoanal inhibitory reflex was present in all patients and anorectal  sampling  was noted in 16 of 20 patients  three months after operation  resting anal pressure was 68 cmh2o  range 50 87 cmh2o   p less than 0 001   the reflex was present in only three patients  p less than 0 001  and sampling was observed in one patient  after 7 months  resting anal pressure was 76 cmh2o  range 64 89 cmh2o   the reflex was present in 11 patients and sampling was observed in nine patients  at 12 months  resting anal pressure was 84 cmh2o  range 66 94 cmh2o   the reflex was present in 19 patients and sampling was observed in 17 patients  the compliance and capacity of the reservoir increased significantly  ability to discriminate flatus from faeces was associated with return of the rectoanal reflex and sampling  
class6	stools containing altered blood plasma urea  creatinine ratio as a simple test for the source of bleeding  the plasma urea creatinine ratio  u c ratio  is known to be elevated in cases of upper gastrointestinal bleeding  almost all patients with haematemesis have upper gastrointestinal  or generalized  bleeding so that in this study we characterized the diagnostic power of the u c ratio in patients with stools containing altered blood without haematemesis in the hope that this simple laboratory test  used in conjunction  perhaps  with clinical data  might reduce the number of patients subjected to an unrewarding gastroscopy or colonoscopy  of 76 cases seen in a provincial and a metropolitan hospital  42 and 34 patients had upper and lower gastrointestinal bleeding  respectively  fifty four per cent of those with upper gastrointestinal bleeding and none of those with lower gastrointestinal bleeding had u c ratios above 110 on admission  however  a discriminating level of 90 is considered to be more suitable  judged by the quadratic uncertainty score  at this level the odds for upper gastrointestinal bleeding were 15 1  
class6	changes in anal canal sensation after childbirth  obstetic trauma predisposes to faecal incontinence  anal canal sensation is impaired in incontinent patients  to assess the effect of childbirth on anal canal sensation anal mucosal electrosensitivity was measured in 122 primiparous patients in the immediate postnatal period and in 74 at 6 months postpartum  there were 35 normal vaginal deliveries  36 forceps deliveries  20 ventouse extractions  ten vaginal breech deliveries and 21 caesarean sections  sensation was impaired in the lower  mid and upper anal canal immediately after delivery in those patients who had a normal vaginal delivery or a forceps delivery when compared with controls or with those delivered by caesarean section  women who had ventouse deliveries had impaired sensation immediately after delivery in the mid anal canal compared with controls and those undergoing caesarean section  by 6 months there were no differences between any group  patients who sustained a division of the external anal sphincter at delivery had impaired sensation which persisted in the upper anal canal at 6 months  
class6	role of the protease antiprotease balance in peritoneal exudate during acute pancreatitis  the peritoneal exudate formed during experimental pancreatitis is toxic when administered intraperitoneally or intravenously to other animals  overwhelming of the peritoneal antiprotease defences by proteolytic enzymes released from the pancreas may be a key factor responsible for this toxicity and is examined in the current study  human pancreatitis exudates possessed tryptic amidase activity indicating trypsinogen activation  the trypsin inhibitory capacities of exudates were reduced indicating a degree of consumption of the peritoneal antiproteases  of 21 exudates examined  three showed marked reduction of their trypsin inhibitory capacity indicating almost complete consumption of their antiproteases  all three patients were shocked at the time of sampling  two dying of fulminant pancreatitis within 24 h  overwhelming of the peritoneal antiproteases was not confirmed  but may occur in a few instances where proteolytic enzyme release or zymogen activation continues  intraperitoneal administration of exogenous antiproteases prolongs survival in rats with pancreatitis and has been suggested as a therapy in man  the current data suggests that few patients are likely to benefit from such an approach  
class6	neonatal small bowel atresia  stenosis and segmental dilatation  in 8 years  44 neonates were treated for small bowel atresia  stenosis or segmental dilatation by one surgical team  there was a single lesion in 30 infants and 14 had two or more sites of intestinal obstruction  associated gastrointestinal abnormalities were found in 23  52 per cent  patients  resection of the atresia s  and primary anastomosis were performed in 34 infants and staged procedures were carried out in ten patients with complicated lesions  patients undergoing staged procedures had a higher complication rate than those having primary repair  six out of ten and 11 out of 34 respectively   the overall initial survival rate was 93 per cent  rising to 100 per cent in those without associated anomalies or prenatal complications  but more than a quarter  27 per cent  of survivors have long term disabilities  
class6	advantages of a narrow range  medium molecular weight hydroxyethyl starch for volume maintenance in a porcine model of fecal peritonitis objective  to compare the effectiveness of two hydroxyethyl starch solutions of different molecular weight ranges for volume maintenance in a porcine model of fecal peritonitis  design  randomized prospective trial  setting  laboratory investigation  subjects  adolescent female pigs weighing approximately 30 kg  interventions  we compared diafiltered 6  pentastarch with 6  high molecular weight hetastarch for volume maintenance in a porcine model of fecal peritonitis  the number average molecular weight of pentastarch is higher than hetastarch  although the weight average molecular weight is lower  i e   a narrow range of medium weight molecules  the infusion rate of each agent was adjusted to maintain baseline arterial hct for less than or equal to 7 hr after instrumentation and induction of fecal peritonitis  main outcome measurements  the volume of fluid required to maintain arterial hct was compared along with comparisons of hemodynamic and histologic responses associated with the two agents  results  significantly less pentastarch was required to prevent hemoconcentration than hetastarch  109     22 8 vs  150     10 3 ml kg  p less than  05  while hemodynamics  colloid osmotic pressure  and oxygen transport responses were similar  capillary patency was greater  21 99     3 68 vs  10 09     1 17   p less than  05  and mean alveolar capillary barrier thickness was less  2 36     0 13 vs  3 06     0 17 microns  p less than  05  with pentastarch than with hetastarch  as judged by electron microscopy  conclusions  these data suggest that pentastarch is better retained in the circulation in capillary leak syndromes compared with hetastarch  
class6	incontinence and rectal prolapse  a prospective manometric study  a prospective  manometric study has been performed on 23 female patients with rectal prolapse and varying degrees of incontinence  seven of the 14 incontinent patients regained continence after surgery  and a further two patients improved  improvement in internal and external sphincter function follows correction of rectal prolapse  preoperative resting anal pressure was significantly higher in continent patients than in incontinent patients  p less than 0 05   as was the maximum voluntary contraction pressure  p less than 0 027   postoperatively there was a significant increase in the resting anal pressure  p less than 0 0001  and maximum voluntary contraction pressure  p less than 0 003  in the whole group  the preoperative resting anorectal angle was significantly more acute  p less than 0 028  in continent patients than in incontinent patients  there was no significant change in the resting anorectal angle following prolapse repair  patients who remained incontinent had a significantly lower preoperative resting anal pressure  p less than 0 01  than patients who improved or regained continence  similarly  maximum voluntary contraction pressure was lower preoperatively in these patients  p less than 0 02   preoperative resting anal pressure below 10 mm hg and maximum voluntary contraction pressure below 50 mm hg are associated with persisting incontinence after surgery  
class6	vascular responsiveness in obstructed gut  multiorgan system failure due to hypotension and sepsis is an important cause of death in patients with bowel obstruction  we have investigated the pathophysiology of this entity in an animal model  after 5 days of bowel obstruction  blood flow in the superior mesenteric artery was measured with and without pitressin and norepinephrine given in separate experiments  in controls  pitressin in moderate dosages caused a substantial fall in gut blood flow  which was not seen in obstructed animals  blood flow reduction 52 percent vs  11 percent in sham and obstructed animals respectively  p less than 0 01   similarly  norepinephrine infusion had less of an effect on gut blood flow in obstructed animals  blood flow reduction 79 percent vs  58 percent sham vs  obstructed animals  p less than 0 05   thus  both agents had dose related effects on gut blood flow  which was maintained at a higher level throughout the drug infusion periods in the bowel of obstructed animals  demonstrating that splanchnic flow is less responsive to vasoactive drug infusion under these experimental conditions  because splanchnic vasoconstriction is an important feature of normal hemodynamic homeostasis  we suggest that these results may help explain some aspects of the pathophysiology of multiorgan failure caused or worsened by systemic hypotension seen in bowel obstruction  
class6	clostridium difficile  a common and costly colitis  clostridium difficile infection manifests as a self limiting diarrhea  protracted colitis  or toxic pseudomembranous colitis  the incidence of c  difficile in a 514 bed community hospital was studied retrospectively  155 patients of a total 18 262 admitted during 1988 were identified with c  difficile as an admitting or subsequent diagnosis  the method of diagnosis  mode of therapy  and related costs were analyzed  we have determined that education  with an emphasis on pathogenesis and prevention  is necessary to reduce the incidence in the hospital and the cost to the patient  
class6	loop ileostomy after ileal pouch anal anastomosis  is it necessary  construction of a loop ileostomy is usually advised in patients having an ileal pouch anal anastomosis to minimize the complication of chronic pelvic sepsis  formation and closure of a loop ileostomy was associated with a 41 percent and 30 percent complication rate  respectively  in a prospective series of 34 patients  this morbidity must now be assessed in relation to the benefits of avoiding temporary fecal diversion in restorative proctocolectomy  
class6	surgical treatment of low rectovaginal fistulas  forty women with low rectovaginal fistulas were operated upon over a 9 year period  the etiology of the fistula in the majority was obstetric  nine women had prior attempts to repair the fistula  all 40 women were managed with endorectal advancement flap with the addition of sphincteroplasty or perineal body reconstruction in 15 patients and rectocele repair in six patients  postoperative complications included urinary difficulties  two patients  and wound complications  three patients   there were two recurrences  all women treated with sphincteroplasty or perineal body reconstruction were continent  seven women complained of varying degrees of incontinence postoperatively  none had undergone sphincter or perineal body reconstruction  endorectal advancement flap is a safe and effective operation for women with rectovaginal fistulas  concomitant sphincteroplasty or perineal body reconstruction should be performed in women with historical  physical  or manometric evidence of incontinence  
class6	dysplasia and dna aneuploidy in a pelvic pouch  report of a case  a patient with an 18 year history of ulcerative colitis was operated on with colectomy  mucosal proctectomy  ileoanal anastomosis  and an s type pelvic pouch due to intractable chronic continuous disease  the patient was followed by endoscopic controls and biopsy sampling from the pouch at regular intervals  a gradual development of severe atrophy in the ileal mucosa was followed by the development of low grade dysplasia  at the most recent endoscopic control  4 years after the construction of the pouch  biopsies were sampled also for flow cytometric dna analyses  dna aneuploidy was detected in a biopsy from the center of the pouch  and a biopsy taken immediately adjacent showed low grade dysplasia  these findings underline the importance of endoscopic follow up after construction of a pelvic pouch and focus attention to the potential of malignant transformation of the mucosa  
class6	geriatric constipation  brief update on a common problem  constipation occurs frequently in the elderly and is often multifactorial in origin  a search for an underlying cause is necessary  and can often be found by taking an adequate history and performing a thorough physical examination  a minority of patients require further investigation  guided by the clinical setting  management should be directed at correcting the underlying cause and providing dietary advice and  less commonly  medication to allow restoration of a normal bowel habit  
class6	hyposensitivity to vasopressin in patients with hepatitis b related cirrhosis during acute variceal hemorrhage  it has been suggested that vasopressin given during hemorrhage may be less effective than when given during a stable state in a portal hypertensive rat model  this study was designed to evaluate the hemodynamic response to vasopressin infusion in 25 hbsag positive cirrhotic patients  nine patients had active variceal hemorrhage before vasopressin infusion  and the other 16 patients were in a stable condition at the time of infusion  the two groups of patients were similar in baseline values except that a higher heart rate was found in patients with hemorrhage  96     20 vs  73     10 beats min  mean     s d   p less than 0 01   thirty minutes after vasopressin infusion  0 66 units min   hepatic venous pressure gradient significantly decreased in both bleeding and stable patients  from 21     9 to 18     9 mm hg  p less than 0 05  and from 18     4 to 8     3 mm hg  p less than 0 0001  respectively   however  the decrease of hepatic venous pressure gradient was less obvious in bleeding patients as compared with stable patients  4     3 vs  9     2 mm hg  p less than 0 0001   a significant reduction of hepatic venous pressure gradient after vasopressin infusion was found in five bleeding patients without shock  from a median of 16 mm hg  range   12 to 26  to 11 mm hg  range   6 to 18   p less than 0 05   but not in four bleeding patients with shock  from 28  range   15 to 36  to 25  range   18 to 33  mm hg  p greater than 0 05   
class6	expression of x protein and hepatitis b virus replication in chronic hepatitis  the x protein can act on the enhancer of hepatitis b virus in an in vitro system and elevate the transcriptional level of hepatitis b virus  however  because no relationship had been reported between x protein expression and hepatitis b virus replication in patients with chronic hepatitis b  we focused on its expression in the liver in comparison with markers of hepatitis b virus replication  liver biopsy samples and sera from 59 carriers with hbsag were examined immunohistochemically for x protein using rabbit igg against recombinant x protein  there was a significant difference in the serum hepatitis b virus dna level between x protein positive and  negative patients  p less than 0 001   serum pre s1 and pre s2 antigens were also measured quantitatively by enzyme immunoassay using monoclonal antibodies specific against each antigen  the titers of pre s1 antigen in patients positive for x protein were significantly higher  p less than 0 001  than those of the x protein negative patients  3 02     0 99 vs  2 00     0 59  respectively   similarly  the titers of pre s2 antigen were 2 98     0 91 vs  1 94     0 54  respectively  p less than 0 001   the rate of positivity of the x protein was higher  38 of 49  77 6   in the replicative group  serum hbeag  serum hepatitis b virus dna or hbcag in liver positive  compared with that observed in the nonreplicative group  3 of 10  30   serum hbeag  serum hepatitis b virus dna and hbcag in liver negative   p less than 0 01   
class6	development and application of an in vitro model for screening anti hepatitis b virus therapeutics  the development of effective anti hepatitis b virus agents has been hampered by the lack of reliable in vitro systems for the screening of new therapeutics  in an effort to circumvent this problem  we have developed an in vitro system for screening anti hepatitis b virus drugs using hepatitis b virus dna transfected hep g2 cells  the cell line designated 2 2 15 produces replicative viral dna intermediates  mature dane particles and high levels of viral antigens  subconfluent 2 2 15 cells were treated with a variety of commonly used anti hepatitis b virus therapeutics  and their efficacy was determined by analyzing changes in the replicative cellular or extracellular hepatitis b virus dna content by southern blotting or slot blot hybridization  the slot blot method was sensitive  reproducible and rapid and correlated well with southern blotting  analysis of the media for hepatitis b virus dna was indicative of changes in intracellular  replicative hepatitis b virus dna  permitting sampling of the media  therefore 2 2 15 cells may provide a valuable method for identifying and monitoring effective anti hepatitis b virus therapeutics  using this system to test various agents  we confirm that 2  deoxyguanosine strongly inhibited viral replication  whereas others tested were less effective  correlation with in vivo systems is now needed  
class6	transcatheter oily chemoembolization in the management of advanced hepatocellular carcinoma in cirrhosis  results of a western comparative study in 60 patients  transcatheter oily chemoembolization is widely used as palliative therapy for inoperable hepatocellular carcinoma in high incidence asiatic areas  to assess its usefulness in the western form of this cancer  30 french patients were treated between 1987 and 1990 by intraarterial hepatic injection of a lipiodol doxorubicin emulsion followed by embolization with 0 5 to 1 mm gelatin sponge particles  the number of procedures ranged from one to five  all patients had advanced  symptomatic and inoperable hepatocellular carcinoma  okuda s staging  i  n   8  ii  n   14  iii  n   8   none was found under systematic screening  all had underlying cirrhosis  child pugh s class  a  n   15  b  n   12  c  n   3  that was alcoholic in origin in 27 cases and posthepatitic b in origin in 3 cases  the results of the treatment were assessed by comparison with a group of 30 untreated patients admitted to the same unit between 1984 and 1987  patients of both groups were closely matched for clinical presentation  global disease staging and precise anatomical extension  the overall 1  and 2 yr survival rate was 59  and 30   respectively  for the treated patients vs  0  at 1 yr for the untreated patients  the latter all died from local disease with end stage liver failure and or uncontrollable variceal bleeding  in the former  the three patients with child s class c cirrhosis died after the first procedure  during the follow up  range   3 to 26 mo   11 additional patients died  8 from metastatic generalization  
class6	the role of methanethiol in the pathogenesis of hepatic encephalopathy  mixed disulfides of methanethiol represent a relative estimate for an exposure to methanethiol  the concentrations of methanethiol mixed disulfides  methionine  4 methylthio 2 oxobutyrate and ammonia were measured in patients with different stages of hepatic encephalopathy  in patients with chronic kidney failure and in healthy subjects  in patients with hepatic encephalopathy  the mean serum concentrations of all these compounds were elevated  however  the elevations of methanethiol mixed disulfides were small and partly caused by decreased renal function  in addition  the levels of methanethiol mixed disulfides did not differ significantly between the different grades of hepatic encephalopathy  the concentrations of methanethiol mixed disulfides were substantially lower than those previously observed in healthy subjects after an oral methionine load or in a patient with a deficiency in methionine adenosyltransferase  the latter without causing encephalopathy  we concluded that the role of methanethiol in the pathogenesis of hepatic encephalopathy is probably minor  if not insignificant  in the patients with hepatic encephalopathy  a significant correlation was found between the concentrations of methionine and 4 methylthio 2 oxobutyrate and between 4 methylthio 2 oxobutyrate and methanethiol mixed disulfides  supporting the theory that methanethiol is formed by way of the methionine transamination pathway  evidence is provided that  besides the methionine transsulfuration pathway  the transamination pathway is also impaired in patients with hepatic encephalopathy  
class6	markers of chronic alcohol ingestion in patients with nonalcoholic steatohepatitis  an aid to diagnosis  we report here the use of the biochemical marker desialylated transferrin to aid in the diagnosis of nonalcoholic steatohepatitis  conventional biochemical tests used for the detection of chronic alcohol consumption fail to differentiate nonalcoholic steatohepatitis patients from alcoholic subjects  in addition  even in those alcoholic subjects with alcoholic liver disease in whom biopsy has been performed  it is impossible to differentiate these two disease states on the basis of morphological examination alone  in this study we have examined two new markers of excessive alcohol intake  desialylated transferrin and mitochondrial ast in subjects with nonalcoholic steatohepatitis and in patients consuming excessive amounts of alcohol  all nonalcoholic steatohepatitis patients consumed minimal or no alcohol and were diagnosed by morphological criteria based on liver biopsy specimens  alcoholic subjects were consuming in excess of 80 gm day ethanol  often with clinical evidence of overt alcoholism  control subjects included both healthy controls and patient controls with liver diseases unrelated to alcohol  the ratio of desialylated transferrin total transferrin was elevated only in patients who consumed excessive amounts of alcohol  whereas the ratio of mitochondrial ast to total ast  mitochondrial ast total ast  was not significantly different between alcoholic subjects and patients with nonalcoholic steatohepatitis  the sensitivity and specificity for the ratio desialylated transferrin total transferrin was 81  and 98   respectively  whereas the sensitivity for the mitochondrial ast total ast ratio was 92   the specificity was only 50   indicating that there were a large number of false positives  all the conventional markers were less sensitive and less specific than the ratio desialylated transferrin total transferrin  
class6	hepatic amino nitrogen clearance to urea nitrogen in control subjects and in patients with cirrhosis  a simplified method  the functional hepatic nitrogen clearance during amino acid infusion is a measure of liver cell mass  the clinical feasibility of the test has so far been limited by methodological problems  a simplified procedure was used to measure the urea nitrogen synthesis rate and functional hepatic nitrogen clearance in nine subjects with normal liver function and in nine patients with cirrhosis  the method was based on only four consecutive 2 hr urine collections and five blood samples  total body water was calculated from a nomogram based on age and anthropometric data  whereas the gut urea hydrolysis was assigned one fixed fraction of synthesis  0 17 in control subjects and 0 26 in patients with cirrhosis   finally  a solution of a single amino acid  alanine  was infused as substrate for urea synthesis  urea nitrogen synthesis rate increased linearly with increasing alpha amino nitrogen concentration  and the slope of the regression  functional hepatic nitrogen clearance  was reduced in cirrhosis from 37 5     7 0 l hr to 18 4     6 7 l hr  p less than 0 005  the hepatic nitrogen clearance was linearly related to the clinical status  child pugh score   to routine liver function tests and to galactose elimination capacity  r   0 869   a well established  quantitative  liver function measure  the simplified method makes the measurement of hepatic nitrogen clearance suitable for routine clinical use  the test might prove useful to study the alterations of nitrogen metabolism in cirrhosis  with special reference to hepatic encephalopathy  
class6	autoantibodies in primary biliary cirrhosis  analysis of reactivity against eukaryotic and prokaryotic 2 oxo acid dehydrogenase complexes  six components of the mammalian 2 oxo acid dehydrogenase complexes have previously been identified as m2 autoantigens in primary biliary cirrhosis  in this report  we present data showing that both polypeptide specific and cross reacting antibodies are present in patients  sera  antibodies reacting with e2 of the pyruvate dehydrogenase complex cross react with protein x but not with any other mammalian antigen  the main immunogenic region on protein x has been localized to within its single lipoyl domain  polypeptide specific antibodies bind to e1 alpha and e1 beta of the pyruvate dehydrogenase complex  antibodies reacting with the e2 polypeptides of the 2 oxoglutarate dehydrogenase complex and branched chain 2 oxo acid dehydrogenase complex show some cross reactivity but do not recognize any of the antigens of the pyruvate dehydrogenase complex  antibodies against the e2 component of the mammalian pyruvate dehydrogenase complex cross react effectively with the corresponding protein from yeast but not with e2 from escherichia coli  antibody titer against mammalian antigens is significantly higher than against the bacterial antigens  arguing against a bacterial origin for primary biliary cirrhosis  
class6	quantitation of intrinsic drug metabolizing capacity in human liver biopsy specimens  support for the intact hepatocyte theory  hepatic drug metabolism is decreased in patients with severe liver disease  but it is unclear to what extent this is due to altered hepatic blood flow or reduced intrinsic metabolic capacity  in this study we quantitated in needle biopsy specimens the intrinsic capacity of liver tissue from 67 patients with mild liver disease  n   36   chronic active hepatitis  n   16  and cirrhosis  n   15  to metabolize two model compounds in vitro  hydroxylation of the low extraction drug bufuralol resulted in the formation of 251     25 nmol 1 oh bufuralol gm wet wt hr in mildly diseased liver tissue and was significantly  p less than 0 01  reduced in liver tissue exhibiting chronic active hepatitis  166     23 nmol gm wet wt hr  and cirrhosis  124     21 nmol gm wet wt hr   the formation rates of monoethylglycinexylidide  the main metabolite of the high extraction drug lidocaine  varied widely and were not significantly different among the three groups  to relate the drug metabolizing capacity to the hepatocyte content of liver tissue  morphometrical study was performed in the biopsy pieces originally submitted  the metabolic activity of each biopsy piece was then related to the fractional volume of hepatocytes it was calculated to contain  in mildly diseased liver tissue 355     35 nmol 1 oh bufuralol ml hepatocytes x hr or 12 4     1 0 mumol monoethylglycinexylidide ml hepatocytes x hr  and in cirrhotic liver tissue 306     49 nmol 1 oh bufuralol ml hepatocytes x hr or 15 3     3 0 mumol monoethylglycinexylidide ml hepatocytes x hr  were formed  respectively  and these differences were not significant  
class6	in micronodular cirrhosis  hepatocytes retain a normal c 25 hydroxylation capacity toward vitamin d3  a study using the rat carbon tetrachloride induced cirrhotic model  to test further the competence of the cirrhotic liver to metabolize vitamin d3 at c 25  hepatocytes were isolated from controls and from ccl4 induced cirrhotic rat livers  as well as from partially hepatectomized rats  the transformation of d3 into 25 hydroxyvitamin d3 was studied in the presence of 10 7  hepatocytes at d3 concentrations of 20 nmol l to 15 4 mumol l  histologically  micronodular cirrhosis was present in all ccl4 treated rats  whereas controls had normal livers  portal venous pressure  p less than 0 008  and intrahepatic collagen content  p less than 0 0001  were significantly increased in ccl4 treated rats  whereas no difference was found between the two groups in the total and ionized serum calcium  d3 metabolites  alt  ast and alkaline phosphatase  cytochrome p 450 was 0 27     0 02 and 0 25     0 02 nmol 10 6  hepatocytes in controls and cirrhotic rats  n s    and it significantly increased in both groups after phenobarbital or 3 methylcholanthrene administration  p less than 0 0001   25 hydroxyvitamin d3 formation was best described by power law equations and varied between 0 02     0 0004 and 29 57     2 8 in controls  and 0 024     0 0004 and 32 0     7 0 pmol hr 1 10 6  hepatocytes 1 in cirrhotic rats  no statistically significant difference was found in the slopes of the 25 hydroxyvitamin d3 formation  but the y axis intercept was found to be lower in cirrhotic rats under basal resting conditions  p less than 0 005   inducers of the mixed function oxidases significantly increased 25 hydroxyvitamin d3 formation in controls as well as in cirrhotic rats  p less than 0 005   moreover  both groups were found to respond similarly to the addition of modulators of the enzyme such as the calcium ionophore a23187 and parathyroid hormone  partial hepatectomy was also without effect on the activation of d3  furthermore  the cell sequestration of d3 was also found to be unperturbed in hepatocytes obtained from either cirrhotic or partially hepatectomized livers  the data indicate that in well compensated micronodular cirrhosis  the c 25 hydroxylation of d3 is generally intrinsically normal at the cellular level and that it also remains fully responsive to in vivo and in vitro modulators of its activity  
class6	rapid induction of hepatic fibrosis in the gerbil after the parenteral administration of iron dextran complex  the parenteral administration of iron dextran complex to gerbils caused hepatic hemosiderosis and fibrosis after 6 wk  type i and iii collagen synthesis in the liver developed from perisinusoidal stellate cells that are often referred to as myofibroblasts  immunohistologically these cells were shown to have large intracellular deposits of ferritin  the hepatic fibrosis appeared to be associated with aggregates of these cells rather than the aggregates of kupffer cells  which also occur in hemosiderosis in the liver  no appreciable necrosis of hepatocytes to trigger the fibrotic response was found  so that the fibrosis appeared to be related to the accumulation of ferritin in the perisinusoidal stellate cells  in contrast  rats and mice did not accumulate ferritin in their perisinusoidal cells or develop hepatic fibrosis in response to parenterally administered iron  although they accumulated similar or greater amounts of total iron in their livers  the rapid induction of hepatic fibrosis in gerbils in response to parenterally administered iron will provide a model to investigate the mechanism of induction of collagen deposition in response to iron overload and a means of quickly evaluating therapeutic treatments for iron overload induced fibrosis in vivo using iron chelating drugs  
class6	regulation of collagen production in freshly isolated cell populations from normal and cirrhotic rat liver  effect of lactate  previous work has shown that lactic acid  and to a lesser extent pyruvic acid  is able to increase collagen synthesis significantly in liver slices of ccl4 treated rats but not normal rats  the purpose of this report is to document which cells in the cirrhotic liver are responsible for the lactate stimulated increase in collagen synthesis  it was found that  a  incorporation of 3h proline into protein bound 3h hydroxyproline is increased threefold to fourfold in hepatocytes from ccl4 treated rats as compared with normal rat hepatocytes   b  neither the hepatocytes from normal nor those from ccl4 treated rats modify their collagen synthesizing capacity when 30 mmol l lactic acid was added to the incubation medium   c  nonparenchymal cells obtained from livers of ccl4 treated rats synthesize much less collagen than hepatocytes  but their synthesis is stimulated twofold by lactic acid   d  from the different nonparenchymal cells  only fat storing  ito  cells increase collagen synthesis when lactic acid is present in the incubation medium  these results suggest that the increased lactic acid levels observed in patients with alcoholic hepatic cirrhosis may play an important role in the development of fibrosis by stimulating collagen production by fat storing  ito  cells  
class6	trolox protects rat hepatocytes against oxyradical damage and the ischemic rat liver from reperfusion injury  trolox  a hydrophilic analog of vitamin e  was reported to scavenge peroxyl radicals from artificial systems better than its parent compound  here we examined the possible cytoprotective effect of trolox in cultured hepatocytes and in the rat liver  in cultured rat hepatocytes  0 5 to 16 mmol l trolox  with optimum between 1 to 2 mmol l  was observed to prolong the survival of cells exposed to oxyradicals generated with xanthine oxidase hypoxanthine  the protection by 1 mmol l trolox surpassed that provided by either ascorbate  mannitol  superoxide dismutase and or catalase  each at a level giving its maximal protection in the same system  in both a global and partial model of hepatic ischemia reperfusion in rats  infusion of trolox  7 5 to 10 mumol kg body weight  just before reflow reduced by greater than 80  the liver necrosis sustained in untreated  no trolox  control rats  such organ salvage was apparently accompanied by approximately 50  reduction in the amount of hepatic conjugated dienes  which were quantified by a highly specific radiochemical assay  since conjugated dienes are presumed to be good  markers  of oxyradical damage  our data may have provided a semiquantitative link between free radical induced necrosis and its chemical imprint in vivo  the data also indicated a relatively rapid and potent antioxidant like action by trolox on rat hepatocytes and on the postischemic reperfused rat liver  
class6	temporal relationship between the decrease in arterial pressure and sodium retention in conscious spontaneously hypertensive rats with carbon tetrachloride induced cirrhosis  it has been proposed that the initial event of sodium retention in cirrhosis is a peripheral arteriolar vasodilation causing underfilling of the arterial vascular compartment and stimulation of the renin aldosterone and sympathetic nervous systems  to test this hypothesis  systolic blood pressure  sodium balance and urinary excretion of sodium and aldosterone were sequentially measured in 13 conscious spontaneously hypertensive rats submitted to a cirrhosis induction program with carbon tetrachloride and phenobarbital and in 14 control hypertensive animals  no significant differences were found between control and cirrhotic rats in any of the measured parameters during the first 7 wk of the study  the eighth week sodium retention developed in cirrhotic rats as indicated by a positive sodium balance and a marked decrease of sodium excretion  at the same time a significant reduction in systolic blood pressure and a great increase in urinary excretion of aldosterone were detected  these changes were more marked the ninth week of the study  in cirrhotic rats there was a highly significant direct correlation between systolic blood pressure and urinary sodium excretion  postmortem examination showed a histological picture of cirrhosis in all animals given carbon tetrachloride and ascites in six of them  these results indicate that the onset of hyperaldosteronism and sodium retention in conscious spontaneously hypertensive rats with carbon tetrachloride induced cirrhosis is chronologically related to a significant decrease in arterial pressure  thus supporting the  peripheral arterial vasodilation hypothesis  of ascites  
class6	infantile form of carnitine palmitoyltransferase ii deficiency with hepatomuscular symptoms and sudden death  physiopathological approach to carnitine palmitoyltransferase ii deficiencies  reported cases of carnitine palmitoyltransferase ii  cpt ii  deficiency are characterized only by a muscular symptomatology in young adults although the defect is expressed in extra muscular tissues as well as in skeletal muscle  we describe here a cpt ii deficiency associating hypoketotic hypoglycemia  high plasma creatine kinase level  heart beat disorders  and sudden death in a 3 mo old boy  cpt ii defect   90   diagnosed in fibroblasts is qualitatively similar to that   75   of two  classical  cpt ii deficient patients previously studied  it resulted from a decreased amount of cpt ii probably arising from its reduced biosynthesis  consequences of cpt ii deficiency studied in fibroblasts differed in both sets of patients  an impaired oxidation of long chain fatty acids was found in the proband but not in patients with the  classical  form of the deficiency  the metabolic and clinical consequences of cpt ii deficiency might depend  in part  on the magnitude of residual cpt ii activity  with 25  residual activity cpt ii would become rate limiting in skeletal muscle but not in liver  heart  and fibroblasts  as observed in the patient described herein  cpt ii activity ought to be more reduced to induce an impaired oxidation of long chain fatty acids in these tissues  
class6	apical secretion of lysosomal enzymes in rabbit pancreas occurs via a secretagogue regulated pathway and is increased after pancreatic duct obstruction  lysosomal hydrolases such as cathepsin b are apically secreted from rabbit pancreatic acinar cells via a regulated as opposed to a constitutive pathway  intravenous infusion of the cholecystokinin analogue caerulein results in highly correlated apical secretion of digestive and lysosomal enzymes  suggesting that they are discharged from the same presecretory compartment  zymogen granules   lysosomal enzymes appear to enter that compartment as a result of missorting  after 7 h of duct obstruction is relieved  caerulein stimulated apical secretion of cathepsin b and amylase is increased  but the ratio of cathepsin b to amylase secretion is not different than that following caerulein stimulation of animals never obstructed  these findings indicate that duct obstruction causes an increased amount of both lysosomal and digestive enzymes to accumulate within the secretagogue releasable compartment but that duct obstruction does not increase the degree of lysosomal enzyme missorting into that compartment  pancreatic duct obstruction causes lysosomal hydrolases to become colocalized with digestive enzymes in organelles that  in size and distribution  resemble zymogen granules but that are not subject to secretion in response to secretagogue stimulation  these organelles may be of importance in the development of pancreatitis  
class6	gastrointestinal dysfunction and disaccharide intolerance in children infected with human immunodeficiency virus  because gastrointestinal dysfunction is a major problem in children with human immunodeficiency virus  hiv  infection  we utilized breath hydrogen measurements to determine the relationship between disaccharide malabsorption and gastrointestinal dysfunction in hiv infected children  we found a strong association between lactose intolerance and persistent diarrheal disease in this population  p less than 0 007  mann whitney u test   we also found evidence of sucrose malabsorption and persistent diarrheal disease in three of the children  extensive microbiologic evaluations failed to reveal an etiologic agent related to the occurrence of gastrointestinal symptoms  our findings indicate that disaccharide intolerance is a common occurrence in hiv infected children with persistent diarrheal disease  careful attention to dietary intake may be required to ameliorate clinical symptoms and to maintain adequate nutrition  
class6	fundoplication and gastrostomy in familial dysautonomia  fundoplication with gastrostomy has become a frequent treatment for patients with familial dysautonomia  so we evaluated the use of both procedures in 65 patients  although patients differed widely in presenting signs and age  from 5 weeks to 40 years  gastroesophageal reflux was documented in 95  of patients by cineradiography or ph monitoring  panendoscopy was a useful adjunct  preoperative symptoms of gastroesophageal reflux included vomiting  respiratory infections  and exaggerated autonomic dysfunction  severe oropharyngeal incoordination frequently coexisted and resulted in misdirected swallows with aspiration  dependence on gavage feedings  or poor weight gain and dehydration  follow up after surgical correction ranged from 3 months to 11 years  55 patients  85   were available for a 1 year postoperative assessment  we had no instances of surgical death  the long term mortality rate was 14   primarily related to severe preexisting respiratory disease  beyond the first postoperative year  30 patients had pneumonia attributed to continued aspiration  exacerbation of preexisting lung disease  or recurrence of gastroesophageal reflux  of 11 patients who vomited postoperatively  six had recurrence of reflux  recurrence of gastroesophageal reflux was documented in eight patients  12    and we revised the fundoplication in three patients  the number of patients with cyclic crises was reduced from 18 to 7  retching replaced overt vomiting in all but two of these seven patients  neither of whom had recurrence of reflux  because oropharyngeal incoordination was prominent  concomitant use of gastrostomy and an antireflux procedure was especially effective in the treatment of younger patients with familial dysautonomia  before the development of severe respiratory disease  despite the development of severe morning nausea in 15 patients  the combination procedure resulted in significantly improved nutritional status  decreased vomiting  and decreased respiratory problems  appropriate use of gastrostomy feedings also contributed to success of the operation  the generally good outcome of fundoplication with gastrostomy confirms the benefit of this procedure in familial dysautonomia  
class6	prune belly syndrome in females  a triad of abdominal musculature deficiency and anomalies of the urinary and genital systems  we describe seven female patients with deficient abdominal wall musculature and urinary tract and genital anomalies that represent the female equivalent of the prune belly syndrome  urethral atresia  uterine duplication  and anorectal anomalies occurred frequently  the perinatal mortality rate was high  of the four surviving patients  renal failure developed in two and renal transplantation was required  the analysis of these cases suggests that urethral obstruction is an important factor contributing to the development of the prune belly syndrome in females  
class6	relationships of somatic symptoms to behavioral and emotional risk in young adolescents  junior high students  n   1508  from a midwestern community completed a health behavioral questionnaire that asked the frequency of headache and abdominal pain and of a number of behavioral and emotional risk indicators  headache  24   and abdominal pain  13   were frequently reported among these young adolescents  particularly among girls  those reporting frequent somatic complaints also reported significantly more behavioral and emotional symptoms indicative of risk  p less than 0 001   further  the interaction between somatic complaint and gender significantly affected risk status  p less than 0 01   this interaction was greater with behavioral risk  boys with both abdominal pain and headaches reported higher behavioral risk than all other groups  p less than 0 0001   somatic symptoms continued to account for a significant amount of variance in behavioral risk after the effects of emotional risk and age were removed  this suggests that behavioral risk and emotional risk are independently associated with somatic complaints  the evaluation of persistent somatic complaints in adolescents  particularly in boys with abdominal symptoms  should include careful examination of emotional risk factors and other health endangering behaviors such as substance use  early sexual activity  and delinquency  
class6	blood contacts during surgical procedures operating room personnel are at risk for infection with blood borne pathogens through blood contact  to describe the nature and frequency of blood contact and its risk factors  trained observers monitored a sample of operations performed by six surgical services at grady memorial hospital  atlanta  ga  for 6 months  in 62  30 1   of 206 operations  at least one blood contact was observed  of 1828 operating room person procedures observed  96  5 3   had 147 blood contacts  133 skin contacts  90    10 percutaneous injuries  7    and four eye splashes  3     the mean number of blood contacts per 100 person procedures was highest for surgeons  18 6   the frequency of percutaneous injury was similar among surgeons and scrub staff  mean  1 2 per 100 worker procedures for each group   risk factors for surgeons  blood contacts were  1  performing a trauma  burn  or orthopedic emergency procedure  odds ratio  or   4 1  95  confidence interval  ci   2 0 to 8 7    2  patient blood loss exceeding 250ml  or  2 1  95  ci  1 2 to 3 7   and  3  being in the operating room longer than 1 hour  or  3 3  95  ci  1 6 to 7 1   of 110 blood contacts among surgeons  81  74   were potentially preventable by additional barrier precautions  such as face shields and fluid resistant gowns  twenty one  84   of 25 blood contacts among surgeons in procedures in which all three risk factors were present were potentially preventable by additional barriers  of 29 blood contacts among anesthesia and circulating personnel  20  69   would have been prevented by glove use  for surgical procedures in which operating room personnel are at increased risk of blood contact  reevaluation of surgical technique  use of appropriate barrier precautions  and development of puncture resistant glove materials are indicated  
class6	laparoscopic cholecystectomy laparoscopic cholecystectomy is a new endoscopic technique that has diffused throughout the surgical community with great rapidity  although the datta panelists considered the procedure appropriate with respect to both its safety and effectiveness  recognition was made that there are no comparative trials of this technique vs open cholecystectomy and virtually no literature on complication rates  the society of american gastrointestinal endoscopic surgeons has developed minimal credentialing criteria for determining competence in laparoscopic surgery  this includes completion of an approved residency training in general surgery  training in laparoscopic technique either by a surgeon experienced in this procedure or by completion of an approved course in the technique requiring hands on laboratory practice  and observation or proctoring of an actual surgical procedure  many of the datta panelists  35 of 40  87 5    reiterated the importance of requiring that the procedure be performed first with animals and that subsequent laparoscopic procedures on patients be done under the supervision of an expert in laparoscopic cholecystectomy  
class6	polyglucosan body disease  adult polyglucosan disease has been described in 15 cases  all had signs of peripheral neuropathy  upper motor neuron signs  and 12 of the 15 had sphincter problems  dementia was prominent in 8 of 15 cases  we reported 2 cases that contained these clinical features  electrophysiological studies showed axonal neuropathy  somatosensory evoked potentials on the second patient were abnormal  sural nerve biopsy showed clusters of polyglucosan bodies  although the presence of polyglucosan bodies in biopsy is nonspecific  the number as well as the clinical features are necessary to make the diagnosis  branching enzyme activity in muscle extracts of the muscles were normal  hence  a specific enzyme abnormality is not yet known  
class6	abnormal liver enzyme levels  evaluation in asymptomatic patients  chronic elevation of serum aminotransferase levels  even in the absence of symptoms  often reflects chronic hepatitis or other significant underlying liver disease  patients with persistently abnormal alkaline phosphatase levels may have extrahepatic biliary tract disease or a chronic cholestatic disorder  physicians can discover unsuspected liver disease without undue risk  expense  or inconvenience to the patient by means of the following  a carefully taken history and thorough physical examination  appropriate timing of follow up blood tests  and timely referral for percutaneous liver biopsy or endoscopic retrograde cholangiopancreatography  
class6	pancreatic pseudocysts  when to drain  when to wait  acute pain in the upper abdomen in a patient recovering from pancreatitis or abdominal trauma may herald a pancreatic pseudocyst  although small cysts resolve spontaneously  those larger than 6 cm across usually require treatment to prevent such complications as rupture into adjacent structures and infection  the authors describe operative and nonoperative treatment methods and the success reported with each  
class6	chilaiditi s syndrome  a diagnostic challenge  chilaiditi s syndrome should be considered in the differential diagnosis of abdominal and chest pain  although interposition of the right colon is a relatively common radiologic finding  there is a distinct paucity of information in the medical literature  chilaiditi s syndrome is usually asymptomatic  but when symptoms occur  conservative treatment is usually effective  recognition is important because this syndrome can be mistaken for more serious abnormalities  which may lead to unnecessary surgical intervention  
class6	peptic ulcer disease  how to treat it now  options for treatment of peptic ulcer disease are becoming more diverse  most new agents are effective yet offer no real advantage over more traditional therapy  however  omeprazole  prilosec  may be of benefit owing to its potent inhibition of acid secretion  but it is not yet approved for this purpose  whether treatment of helicobacter pylori infection will prove beneficial is not yet known  but the answer should be forthcoming  finally  as with any disease process  alleviation of risk factors is always important  appropriate counseling regarding use of nonsteroidal anti inflammatory drugs and cigarette smoking is a necessity  
class6	long term medical consequences of incest  rape  and molestation  one hundred thirty one patients who gave a history of childhood sexual abuse were seen in a general medical practice decades after the event and were compared with a control group  the subject patients were found to be distinct for chronic depression  morbid obesity  marital instability  high utilization of medical care  and certain psychosomatic symptoms  particularly chronic gastrointestinal distress and recurrent headaches  it is clear that these remote events can underlie difficult chronic medical problems  questions about childhood sexual abuse must become part of the practitioner s review of systems in these difficult cases  if not routinely  
class6	duodenal stricture  a complication of chronic fibrocalcific pancreatitis  over the past 10 years  one of us  m c a   has treated 92 patients who required operation for symptoms associated with alcohol induced chronic fibrocalcific pancreatitis  four of these patients had duodenal obstruction  all four had had lateral pancreaticojejunostomy to relieve pancreatic ductal obstruction and associated chronic abdominal pain  three of the four also required biliary diversion for stenosis of the intrapancreatic portion of the common bile duct  each duodenal stricture required reoperation and gastrojejunostomy to bypass the site of obstruction  a review of the english language literature revealed that duodenal obstruction in patients with chronic fibrocalcific pancreatitis is uncommon  only 58 previous cases having been reported  all of those patients had pancreatic ductal obstruction  and more than half had concomitant distal biliary stenosis  two thirds of the duodenal obstructions were treated by gastroenterostomy  and one third were resected  duodenal obstruction in patients with chronic pancreatitis and biliary stricture appears to reflect an advanced form of the disease  combined lateral pancreaticojejunostomy and biliary diversion has emerged as the preferred surgical procedure for this problem  careful preoperative assessment for evidence of duodenal stenosis also is needed in this group of patients  and gastroenterostomy is indicated in appropriate cases  
class6	postanginal sepsis with dysphagia  we have described a 10 year old girl who had dysphagia followed abruptly by arthritis  streptococcus pyogenes was identified as the pathogen by fasciotomy with bone biopsy  and a tonsillar fluid collection confirmed the diagnosis of postanginal sepsis  the patient was cured by a 6 week course of parenteral antibiotics  
class6	a complex ileovaginal fistula with associated obstructive uropathy in a patient with crohn s disease  technical considerations and review of the literature  a high index of suspicion of an ileogenital fistula should be aroused by a patient with crohn s disease  weight loss  malnutrition  and a persistent vaginal discharge  preoperative gastrointestinal and genitourinary evaluation should be used in an attempt to localize the fistulous origin as well as concomitant fistulae  the principles of surgical therapy include preoperative ureteral catheters  resection of the diseased bowel and fistulous segment of bowel  and interposition of healthy tissue  ie  omentum  between the bowel anastomosis and the vaginal cuff  
class6	spontaneous rupture of the stomach in an adult  we have reported a case of spontaneous rupture of the stomach in an adult  immediate onset of severe upper abdominal pain after overindulgence in food and drink along with radiographic evidence of pneumoperitoneum and the clinical findings of massive abdominal distention  epigastric tenderness  shock  and occasionally subcutaneous emphysema should suggest the possibility of gastric rupture  the treatment is simple  but mortality is high when surgical intervention is not rapid  
class6	gastric infarction  we have described a patient with an acute condition of the abdomen who had infarction of the stomach and the small intestine due to atheromatous thrombus of celiac and superior mesenteric arteries  we believe this unusual simultaneous occurrence of gastric and small intestinal infarction is coincidental  the outcome of gastric infarction is frequently fatal  
class6	late arterial hemorrhage secondary to a greenfield filter requiring operative intervention  retroperitoneal hematomas associated with greenfield filters have been described and are generally characterized as clinically insignificant  we report a retroperitoneal hematoma that was associated with a greenfield filter and that required operative intervention because of hemodynamic instability  at operation a lumbar arterial laceration apparently caused by a protruding filter prong was identified and ligated  the implications of this occurrence for filter placement indications are discussed  the potential life threatening severity of filter associated hematomas is emphasized  
class6	possible transmission of serum hepatitis in liver surgery with the ultrasonic dissector  when the ultrasonic dissector is used during liver surgery  the possibility exists of the transmission of virus to the attending hospital personnel because of unavoidable splashing of the irrigating solution  it becomes apparent from this study that the titer of hepatitis b surface antigen in the aspirated irrigating solution is almost the same level as that in the serum  we therefore strongly recommend that eye shields should be used in hepatic surgery when the ultrasonic dissector is in use  
class6	the role of cholecystokinin in the pathogenesis of acute pancreatitis in the isolated pancreas preparation  in a variety of animal models of acute pancreatitis  cholecystokinin receptor antagonists have ameliorated the injury response  these results suggest that cholecystokinin may play a primary role in the pathogenesis of pancreatitis initiated by multiple stimuli  in an effort to test this theory  a sensitive and high affinity cholecystokinin receptor antagonist l364 718 was administered to four different models of acute pancreatitis that were produced in the ex vivo perfused canine pancreas preparation  the four models of pancreatitis were initiated by cerulein infusion  partial duct obstruction with secretin stimulation  oleic acid infusion  and a 2 hour period of ischemia  in each model  pancreatitis was manifest by edema formation  weight gain  and hyperamylasemia during a 4 hour perfusion  in cerulein infusion induced pancreatitis l364 718 inhibited edema formation and weight gain  31     5 gm versus 7     6 gm  p less than 0 05  and significantly decreased plasma amylase activity  36 605     21 216 u dl versus 9421     5149 u dl  p less than 0 05   the acute pancreatitis induced by the other three stimuli was not ameliorated by l364 718 treatment  we conclude that in the ex vivo perfused canine pancreas preparation cerulein induced pancreatitis is mediated at least in part by the cholecystokinin receptor  early blockade of the cholecystokinin receptor was of no benefit in treating the other models of pancreatitis  suggesting that cholecystokinin is not involved in the early pathogenesis  
class6	cystic dilatation of the cystic duct  a new type of biliary cyst  a case of a patient with a congenital cyst that was localized solely to the cystic duct is presented  we propose including this anomaly in the biliary cyst classifications  which currently include choledochal and intrahepatic and extrahepatic biliary cysts  the diagnosis and management of this new type of cyst in addition to other types of biliary cysts are discussed  
class6	malignant melanoma of the biliary tract  a case report  a 58 year old man was seen with obstructive jaundice and discomfort in the upper abdomen  computed tomographic and ultrasound examinations revealed a soft tissue mass in the gallbladder  cholecystectomy and choledochotomy revealed a soft black mass in the gallbladder and a second one in the intrapancreatic portion of the common bile duct  each was diagnosed as malignant melanoma  subsequently  a whipple resection of the pancreas  duodenum  and distal bile duct revealed a melanoma circumferentially invading and obstructing the distal common duct  no lymph node or distant metastasis was identified  repetitive searches for another primary site have been negative  the tumor apparently originated in the biliary tract  the patient remains almost well 2 years after diagnosis  
class6	inflammatory pseudotumor of the liver  inflammatory pseudotumor of the liver is an extremely rare entity  because of its unusual clinical presentation and confusing histologic picture  a diagnosis of malignancy is frequently made  thus the surgeon is closely involved with the case and extensive procedures are not uncommon  however  this lesion is benign and will even regress spontaneously  making radical surgical procedures contraindicated  the difficulty lies in establishing an accurate diagnosis and the histologic pitfalls of this particular process  conservative therapy can then be applied  avoiding surgical morbidity  
class6	lymphoma of the gastric stump  report of a case  we report a case of primary lymphoma on a previously resected stomach in a 62 year old man  the patient was treated 22 years earlier with a partial gastrectomy and billroth ii reconstruction for a benign gastric ulcer  the rarity of this entity and its possible relationship with pseudolymphoma or lymphoid nodular hyperplasia is discussed  and the literature is reviewed  
class6	gastroesophageal reflux in infants  clinically significant gastroesophageal reflux occurs in one in 500 infants  symptoms resolve in 60 to 80 percent of infants by 18 months of age  thickened formula and position changes are often recommended  medication and surgical intervention may be needed in refractory cases  
class6	neuromuscular disease of the gastrointestinal tract  gastrointestinal motility is the function of gastrointestinal smooth muscle  it is controlled by both the intrinsic and extrinsic nerves of the gastrointestinal tract and  to a lesser degree  the gastrointestinal hormones  therefore  any abnormality of the above factors  theoretically  can cause gastrointestinal dysmotility  in a clinical situation  commonly seen is gastrointestinal dysmotility caused by either smooth muscle or intrinsic and extrinsic nerves dysfunction  diseases that cause smooth muscle dysfunction include familial visceral myopathies  nonfamilial visceral myopathies  collagen disease  muscular dystrophies  amyloidosis  thyroid disease  and so on  diseases that cause enteric nerve dysfunction include familial visceral neuropathies  nonfamilial visceral neuropathies  diabetes mellitus  chagas  disease  ganglioneuromatosis of the intestine  visceral neuropathy of carcinomatosis  parkinson s disease  and so on  the patients with neuromuscular disease of the gastrointestinal tract have a wide range of clinical manifestations regardless of the underlying cause  at one end of the spectrum  the patients may be asymptomatic  and at the other end of the spectrum  the patients may have functional obstruction of the gastrointestinal tract  plain abdominal x rays  upper gastrointestinal  ugi  and small bowel x rays  enteroclysis  barium enema  and manometric studies are useful for the work up of these patients  enteroclysis is especially helpful in ruling out mechanical obstruction of the small intestine in patients with chronic intestinal pseudo obstruction  treatment is mainly symptomatic and supportive  there is no effective drug to improve gastrointestinal motility  surgery may be helpful in selected cases of severe gastrointestinal dysmotility  
class6	evaluation of hepatocellular carcinoma aggressiveness by a panel of extracellular matrix antigens  invasion and metastasis requires a series of interactions between malignant cells and the extracellular matrix  ecm   antigen markers that relate to these interactions were evaluated for prognostic correlation in human hepatocellular carcinoma  basement membrane type iv collagen  civ   type iv collagenase  civase   laminin  and laminin receptors  lrs   all ecm antigens previously proposed to be modulated in association with tumor aggressiveness  were immunohistochemically investigated in 30 cases of hepatocellular carcinomas  hccs   the pattern of antigen expression was correlated with 1  36 months  clinical follow up and 2  the pathologic grade  as a means of estimating the proliferation fraction  an additional antigen  ki67  was also studied in this series  there were major differences in the distribution of civ and laminin  and in the quantity of civase   lr   and ki67 positive cells associated with grade and prognosis  a smaller quantity of civ and laminin and a higher number of civase   lr   and ki67 positive cells were detected in the poorly differentiated compared with the well differentiated hccs  the tumors with lower immunoreactivity for civ and laminin components accompanied by a higher number of civase   lr   and ki67 positive cells fall into a group with the poorest overall survival  p less than 0 006   the panel of antigens is proposed as a useful prognostic tool for evaluating hcc tumor aggressiveness  
class6	emergency laparoscopy  unnecessary abdominal explorations in severely injured patients can be reduced by employing emergent or urgent laparoscopy in blunt abdominal trauma and the obscured  acute abdominal cases  in 150 blunt abdominal trauma cases  a mini laparoscopy was used in the emergency room or the intensive care unit without major complications  in 56   the findings were negative  in 19   the laparoscopic findings were corroborated by surgery  in 25   a minimal to moderate hemoperitoneum was found and the laparoscopic impression dictated close observation  unnecessary exploration was avoided except in one case  in the elderly high risk patient with a poor history  abdominal examination can be noninformative  laparoscopy can detect acute appendicitis or organ perforation  in the young female  appendicitis can be differentiated from pelvic inflammatory disease  laparoscopy is more accurate and gives a larger latitude for decision making than lavage  it can also be useful in the obscured problematic abdominal case  
class6	laparoscopic cholecystectomy  with more than 500 000 cholecystectomies performed per year  great interest has developed in laparoscopic cholecystectomy  the procedure offers the patient reduced hospital stay  faster return to work  less pain  and improved cosmetic results  in september 1988  we developed a technique of performing laparoscopic cholecystectomy that we have now performed in more than 800 cases with good results  the technique allows the surgeon to fully evaluate the common duct via operative cholangiography and has allowed us to use a laparoscopic approach in all patients who were candidates for cholecystectomy  the technique offers a minimally invasive alternative to open cholecystectomy  
class6	a new technique of surgical treatment of chronic duodenal ulcer without laparotomy by videocoelioscopy  we performed truncal posterior right vagotomy with lesser curve anterior gastric myotomy by videocoelioscopy on 10 patients  5 men and 5 women  ranging in age from 19 and 54 years  with a mean age of 32 years   all had a long history of chronic duodenal ulcer with a mean duration of symptoms of 3 8 years  the mean length of the operation was 60 minutes  range  55 to 110 minutes   there was no morbidity  and all patients were discharged after 5 days  the acid secretion tests under basal conditions and under insulin stimulation preoperatively and 1 month postoperatively showed a mean decrease in the basal output of 79 3  and a mean decrease of 83 04  in the maximal output  the fibroscopic control at the second postoperative month showed a complete healing of the ulcer in nine patients and a residual ulcer scar in one  no patients had any abdominal complaints  right truncal vagotomy and anterior lesser curve seromyotomy by videocoelioscopy is an efficient and elegant method of treating chronic duodenal ulcer  but it needs thorough experimental practice  
class6	laparoscopic cholecystectomy using intracorporeal lithotripsy  over a 13 month period  november 1988 to december 1989   we performed our first 104 laparoscopic cholecystectomies using an intracorporeal ultrasonic lithotripsy technique  the procedure in three of these patients was converted to an open operation because of hemorrhage with unexpected findings of cirrhosis in two patients and dense subhepatic adhesions in a third  endoscopic retrograde cholangiopancreatography was successfully used in three other patients in whom common bile duct stones were identified  we encountered only three postoperative complications out of all the laparoscopic cholecystectomies performed  one complication was a biliary fistula that closed spontaneously 1 week after surgery  the remaining complications were attributable to abscesses  one subhepatic and one pelvic  which were aspirated and drained laparoscopically  there were no deaths  advantages of the laparoscopic approach included decreased perioperative pain  shortened hospitalization  absence of scar  and more rapid return to prehospitalization activities  
class6	safe performance of difficult laparoscopic cholecystectomies  laparoscopic cholecystectomy has been advocated for the treatment of uncomplicated symptomatic gallstone disease  but has not been widely advocated for the management of more complicated gallbladder disease such as acute cholecystitis  previous surgery  or common duct stones  during the last 9 months  360 patients underwent laparoscopic removal of their gallbladder  a total of 138 had a complicated presentation  making surgery more difficult  this article discusses the management of these patients with acute cholecystitis  previous surgery  or common duct disease  using the described techniques  there were no complications or mortality  laparoscopic management of difficult gallbladder problems is safe and effective  
class6	the los angeles experience with laparoscopic cholecystectomy  surgeons should be competent in diagnostic laparoscopy before performing laparoscopic cholecystectomy  lc   well structured and endorsed courses with experienced faculty are important  within 12 months  418 lcs were performed in our hospital  the number of open cholecystectomies decreased to one third of all cholecystectomies performed  cholangiography was attempted routinely and the duct was successfully cannulated in 90   inquiries were made at 6 other hospitals within a 5 mile radius where a total of 220 lcs were performed  the following gray areas need to be addressed  patients with slightly increased liver function tests but no jaundice  and unsuspected stones discovered by cholangiography  new projects are in progress to explore the common bile duct via the cystic duct or directly through the common bile duct with insertion of a t tube  the authors recommend proper training as well as caution and sound judgment before commencing with lc  
class6	the baltimore experience with laparoscopic management of acute cholecystitis  laparoscopic cholecystectomy has rapidly emerged as a popular alternative to traditional laparotomy and cholecystectomy  acute cholecystitis has been considered to be a relative or absolute contraindication to laparoscopic surgery  after gaining extensive experience in laparoscopic biliary tract surgery  this procedure was attempted in 15 patients with acute cholecystitis  all patients were operated on within 72 hours of admission  in five patients  the laparoscopic procedure was converted to an open laparotomy  in one patient  a localized abscess was found  and in the other four patients  extensive inflammation and edema precluded a safe dissection of the vascular and ductal structures  laparoscopic cholangiography was performed in 14 patients and proved valuable in demonstrating the ductal anatomy  patients were discharged an average of 2 7 days after the laparoscopic procedure  laparoscopic cholecystectomy may be safely performed by experienced surgeons in patients with acute cholecystitis  to ensure a low complication rate  a low threshold for converting the procedure to an open laparotomy must be maintained if the ductal and vascular anatomy cannot be safely demonstrated  
class6	training  credentialling  and granting of clinical privileges for laparoscopic general surgery  despite the lack of scientific data comparing it with traditional open operations  laparoscopic surgery has gained rapid acceptance and implementation by general surgeons  individual hospitals  which have the responsibility for developing their own privileging criteria  are searching for guidance as to the amount and type of additional training required to grant clinical privileges in laparoscopic general surgery  laparoscopic surgery involves techniques different from those learned during general surgery residency training  therefore  until such techniques are regularly included in general surgery residency programs  additional training for and granting of separate privileges in laparoscopic surgery are appropriate  adequate training for surgeons already experienced in abdominal and biliary tract surgery can be acquired through a preceptorship in diagnostic laparoscopy  attending a course in laparoscopic surgery that includes both didactic instruction and live animal experience  assisting with the procedures in humans  and being proctored and certified as competent by an experienced general surgeon  
class6	atracurium decay and the formation of laudanosine in humans  several groups of investigators have reported that the plasma concentrations of laudanosine  a metabolite of atracurium  are high immediately after administration of atracurium and thereafter decline  such a time profile of a metabolite in plasma is very unusual  the authors describe a model of atracurium decay and laudanosine disposition that satisfactorily explains these data  the model reveals the following  1  each atracurium molecule is degraded into two of laudanosine  2  the generation of laudanosine occurs through two processes  a rapid one  involving approximately 31  of the atracurium dose and proceeding with a half life of 0 25 min  and a slower one  involving the residual 69  and proceeding with a half life of 51 min  3  atracurium degradation by hofmann elimination proceeds in the central and the noncentral compartments  4  laudanosine formed from atracurium gains access to its central compartment and disappears from plasma in a biexponential pattern  5  in cirrhotic patients  only 18  of the atracurium dose is degraded rapidly and laudanosine is disposed of more slowly  the authors propose that the rapid degradation of atracurium in plasma proceeds through a nucleophilic substitution reaction  with plasma nucleophiles substituting for the laudanosine moiety in atracurium  because both laudanosine moieties in atracurium are required to establish and sustain plasma concentrations of laudanosine  excretion of atracurium or its degradation through pathways not generating laudanosine must be small  
class7	pulmonary metastases from ameloblastoma of the mandible treated with cisplatin  adriamycin  and cyclophosphamide  a case of delayed pulmonary metastases from an ameloblastoma of the mandible  which occurred 20 years after surgical resection of the primary tumor but with no recurrence at the primary site  is reported  combination chemotherapy using cisplatin  adriamycin  and cyclophosphamide has produced a very good clinical and radiologically documented response in this case  
class7	treatment of the retained permanent molar  the effect of five different treatments for retained permanent molars was evaluated in 59 patients to develop a rational guideline for adequate therapy  the results showed that a prosthetic buildup is the proper treatment if retention develops after the growth spurt  because in these cases the extent of infraocclusion is slight and relatively stable  if retention develops before the growth spurt  immediate removal of the retained molar followed by orthodontic treatment is the way to maximal success  when retention develops during the growth spurt  the tooth affected has to be observed at 6 month intervals  in such a case  no active treatment is indicated if the neighboring teeth show no tilting and the extent of infraocclusion is minor and stable  in all other cases  the teeth affected have to be removed  followed by orthodontic closure of the edentulous space  finally  all patients must be screened regularly  because in this investigation  new cases of retention were observed relatively frequently  
class7	morbidity associated with incompletely erupted third molars in the line of mandibular fractures  a retrospective analysis of 105 mandibular fractures associated with incompletely erupted third molars was undertaken  it was found that there was no difference in the rates of complication if the teeth were retained or extracted  or if an open or closed reduction was performed  the combination of tooth retention with open reduction  however  shows a trend toward being the treatment most prone to postoperative complications  
class7	invasive squamous cell carcinoma of the mandible presenting as a chronic osteomyelitis  report of a case  a case of invasive squamous cell carcinoma of the mandible initially thought to be chronic osteomyelitis is reviewed  discussion of the origin of the tumor and several imaging techniques used for differentiating maxillofacial infection from neoplasm are discussed  the difficulty of diagnosis of chronic painful maxillofacial lesions illustrates the need for a high degree of suspicion concerning any inflammatory lesion not responding to appropriate therapy  accurate diagnosis and treatment of such lesions most often necessitates microscopic examination  
class7	assessment of proplast teflon disc replacements  published erratum appears in j oral maxillofac surg 1991 feb 49 2  220  this retrospective study reports the findings in the follow up of 31 temporomandibular joints in which proplast teflon  vitek inc  houston  tx  replacements were used  among the problems noted were pain  malocclusion  restricted opening  and degenerative changes in the condyle and fossa  
class7	factors associated with soft  and hard tissue compromise of endosseous implants  this prospective analysis identifies factors associated with endosseous implant removal as well as factors associated with implant morbidity resulting in nonscheduled patient visits  treatment of the latter conditions is discussed  the most important factors identified for implant success were surgery without compromise in technique  placing implants into sound bone  avoiding thin bone or implant dehiscence at the time of implant placement  avoiding premature implant exposure during the healing period  establishing a balanced restoration  and insuring appropriate follow up hygiene care  in the posterior mandible  the presence of keratinized gingiva was strongly correlated with optimal soft  and hard tissue health  
class7	detection of human papillomavirus genomic dna in oral epithelial dysplasias  oral smokeless tobacco associated leukoplakias  and epithelial malignancies  human papillomavirus  hpv  is an infectious agent that is increasingly associated with mucosal cancers  in particular cancer of the cervix  the present investigation was undertaken in an attempt to determine whether hpv could be easily detected in biopsies of oral tissues  specifically oral squamous cell carcinomas  oral epithelial dysplasias  smokeless tobacco keratoses  verrucous hyperplasia  and verrucous carcinoma  in situ dna hybridization methods were used to isolate specific hpv genomes  among 100 instances of benign leukoplakia  only 4  of non tobacco related and 10  of smokeless tobacco related lesions harbored viral sequences  we were able to detect viral sequences in dysplastic lesions 3  of the time  alternatively  17  and 20  of the verrucous hyperplasias and verrucous carcinomas were positive for viral nucleic acids  six percent of the squamous cell carcinomas harbored hpv  on the basis of these findings  it is concluded that hpv of known genotype can be identified in oral premalignant and malignant neoplasms  
class7	contemporary management of a potentially lethal fetal anomaly  a successful perinatal approach to epignathus  prenatal diagnosis of epignathus  a teratoma originating in the oropharynx  has been reported previously  however  in many of these cases the neonates succumbed to acute respiratory distress secondary to airway obstruction at the time of birth  we describe a case of antepartum diagnosis of epignathus using ultrasonography and magnetic resonance imaging as complementary techniques  the ability to accurately define the fetal anomaly permitted us to plan a unique strategy for peripartum management  after cesarean delivery of the infant from the uterus  the umbilical cord was not clamped and the fetoplacental circulation was left undisturbed  a tracheostomy was then performed  after which the umbilical cord was clamped and the infant was stabilized  several hours later  a debulking procedure was performed in the operating room to remove the tumor from its attachment to the bony palate  both mother and infant did well postoperatively  the ability to plan and perform a controlled tracheostomy while the infant remained oxygenated and ventilated proved to be lifesaving in this case  
class7	capillary hemangioma of the maxilla  a report of two cases in which angiography and embolization were used  this article presents two clinical cases of capillary hemangiomas of the maxilla  such lesions are rare  as demonstrated by the review of the literature included in this article  the presentation  differential diagnosis  histopathology  management  and follow up for each case are discussed  our rationale for approaching these types of lesions  as well as our opinion that microembolization should be considered as a first line approach to treatment  is presented  
class7	dental extraction for patients on oral anticoagulant therapy  dental extraction in patients receiving long term oral anticoagulant therapy is a controversial issue  continuation of anticoagulation exposes the patient to serious hemorrhage  whereas cessation of therapy increases the risk of thromboembolism  forty patients treated by coumarin underwent 63 tooth extractions  without a change in the therapeutic protocol of anticoagulation  the biologic adhesive beriplast was used successfully to achieve local hemostasis at the site of the surgical wound  apart from one patient who had mild oozing  there were no incidences of postsurgical hemorrhage  
class7	oral squamous cell carcinoma arising in a patient with long standing lichen planus  a case report  the risk of malignant transformation of oral lichen planus remains a controversial point  many previous reports have been discounted on the basis of inadequate information or lack of histologic confirmation of lichen planus  we report a well documented case of long standing cutaneous and oral lichen planus in which squamous cell carcinoma of the dorsal portion of the tongue occurred  there is an apparent difference in the sites of oral carcinomas in patients with lichen planus compared with the general population  this suggests that lichen planus increases the risk of oral cancer in affected sites  
class7	premature alveolar bone loss in erdheim chester disease  erdheim chester disease is a rare histiocytosis also known as lipoid granulomatosis  oral findings have not been reported previously to our knowledge  this case report documents evidence of oral sequelae of erdheim chester disease  a patient whose course was followed for 10 years at the national institutes of health had premature alveolar bone resorption  he underwent full mouth extraction at age 29 years because of severe periodontitis  histopathologic evidence of erdheim chester disease was demonstrated in the periodontal soft tissues  in the ensuring years  accelerated resorption of the residual ridges precluded the use of conventional dentures  we recommend early preventive dental management for patients with erdheim chester disease  
class7	dental abnormalities associated with familial expansile osteolysis  a clinical and radiographic study  familial expansile osteolysis is a rare and possibly unique form of hereditary bone dysplasia with dental manifestations that has affected 42 members of a northern ireland family for five generations  twenty seven family members  aged 3 to 60 years  were examined clinically and radiographically  and it was found that cervical and or apical root resorption is an early manifestation of the dysplasia  of the 20 family members with skeletal manifestations of familial expansile osteolysis  16 showed root resorption  root resorption may therefore be a good prognosticator for later bone involvement  
class7	differences between florid osseous dysplasia and chronic diffuse sclerosing osteomyelitis  florid osseous dysplasia  fod  is confused in the literature with chronic diffuse sclerosing osteomyelitis  two cases of each condition are presented to demonstrate the differences between them  in fod  there are multiple lobulated sclerotic masses in several quadrants of the jaws  usually in black females  in some cases  the sclerotic masses are exposed to the oral cavity  resulting in a secondary osteomyelitis  periapical cemental dysplasia is often found in association with fod  chronic diffuse sclerosing osteomyelitis is a primary inflammatory condition of the mandible  patients have cyclic episodes of unilateral pain and swelling  the affected region of the mandible exhibits a diffuse opacity with poorly defined borders  although women are affected more often than men  black persons are not particularly susceptible  
class7	contiguous enlarged dental follicles with histologic features resembling the who type of odontogenic fibroma defective odontogenesis and or retarded eruption of teeth can be associated with histologic features akin to odontogenic fibroma in the dental follicles  unerupted mandibular premolar and molar teeth of a 24 year old man were surgically exposed  yet the teeth failed to erupt  about a year and a half later  radiographs indicated further enlargement of the follicle of the premolar  and both teeth were subsequently surgically removed  histologically  the follicles were composed of mature collagenous tissue among which epithelial islands and numerous clusters of calcified bodies were present  indirect immunofluorescence showed positive staining for type i and type iii collagen  which exhibited a sparse distribution  but not for the aminoterminal propeptide of type iii procollagen  the hamartomatous nature of the lesions is discussed with emphasis on their histologic resemblance to the who type of odontogenic fibroma  
class7	hyaline ring granuloma  a distinct oral entity  hyaline ring granuloma  hrg  is a distinct oral entity  in this study  64 cases from the literature are analyzed and two new cases are reported  the lesions could be classified by location as central hyaline ring granuloma  42   and peripheral hyaline ring granuloma  53    radiographically  a radiolucent area irregularly outlined by well formed trabeculae of bone was found in central hrg  and a poorly defined erosion at the crest of the alveolar ridge was often found in peripheral hrg  occasionally  the lesion occurred in the connective tissue wall of cysts  5    the etiology of this condition is controversial  but most lesions were in edentulous areas and most patients had a history of tooth extraction or other trauma  the majority of cases  83   occurred in the mandible  usually posterior to the premolar  the mean age of patients at diagnosis was 43 years  and the male female ratio was 1 9 1  pain was not a symptom  although local discomfort  such as recurrent swelling and tenderness  was noted in many cases  hyaline rings with giant cell inclusions are the significant features for histopathologic diagnosis  hrg is treated by curettage or surgical excision  care being taken to remove the entire lesion  the removal of a peripheral hrg in an edentulous jaw should be followed by careful smoothing of the bone surface  since the lesion tends to infiltrate and is not well demarcated  recurrence  probably due to incomplete excision  is uncommon  
class7	a dentist s dilemma  nonsurgical endodontic therapy or periapical surgery for teeth with apparent pulpal pathosis and an associated periapical radiolucent lesion  first presented is a brief review of nonsurgical versus surgical treatment of radicular cysts  this is followed by a consideration of the use of radiographs for differential diagnosis of periapical radiolucent lesions  some of the nonendodontic local and systemic lesions that can occur periapically are then presented  next examined are the fallibilities of pulp vitality testing methods  the need for histopathologic examination of periapical lesions is the subject of the next discussion  the dentist s dilemma is then examined  should teeth with apparent pulpal pathosis and an associated periapical radiolucent lesion have routine surgical treatment including biopsy or should they be treated nonsurgically and have periodic follow ups  a possible resolution of this dilemma is the final consideration  
class7	a clarification on endodontic flare ups  comment  in an article on endodontic flare ups by robert j  matusow  our research and publications are discussed  since we found what we consider to be distortions and misinterpretations of our work  it was decided to clarify the apparent discrepancies found in matusow s article  
class7	the radiologic morphology of asymptomatic temporomandibular joints  a high frequency of remodeling changes was demonstrated radiographically in a series of 200 female patients with asymptomatic temporomandibular joints  fewer than 10  of joints were completely radiologically  normal   generally  there was an increasing incidence of changes with increasing age and for edentulous patients  but these relationships were by no means direct or mutually exclusive  
class7	the radiologic morphology of painful temporomandibular joints  a high frequency of remodeling changes was demonstrated radiographically in a series of patients having pain in the temporomandibular joint region  radiologic morphologic differences between painful and asymptomatic temporomandibular joints were in frequency rather than type  caution should be taken not to overestimate the significance of radiologic abnormality in patients with pain in the temporomandibular joint region  
class7	a comparative study of temporomandibular symptoms following mandibular advancement by bilateral sagittal split osteotomies  rigid versus nonrigid fixation  rigid fixation to attach proximal and distal segments during bony healing of osteotomy sites has become increasingly popular  the effects of rigid fixation on the temporomandibular joints have been questioned  the purpose of this study was to evaluate the effects of rigid fixation after bilateral sagittal split osteotomies on temporomandibular dysfunction symptoms  forty patients who had mandibular advancement surgery were evaluated for temporomandibular joint dysfunction  twenty had received rigid fixation  and twenty had received nonrigid fixation  it was determined that there was no statistically significant difference in temporomandibular signs or symptoms between patients who were treated with rigid internal fixation for bilateral sagittal split osteotomies for mandibular advancement and those patients who were treated with nonrigid wire fixation  
class7	a retrospective evaluation of 301 tmj proplast teflon implants  a retrospective review of 301 meniscectomies with proplast teflon implants was performed  factors such as interincisal opening  occlusion  joint sounds  joint degeneration  and patient satisfaction were examined  the overall surgical success rate was 88 7   with an average follow up period of 33 months  although many patients demonstrated significant condylar degeneration at 1 year follow up  such change did not necessarily result in symptomatology or joint dysfunction  only 10  of implants resulted in removal  surgical and postoperative procedures are contrasted with those of other clinicians experiencing lower success rates  
class7	temporomandibular joint dysfunction and selected health parameters in the elderly  little research has focused on temporomandibular joint dysfunction  tmjd  in the elderly  the present study describes relationships between tmjd and selected health parameters in a population of 75  to 94 year old roman catholic sisters  nuns   mental  physical  and oral assessments made on 117 sisters identified 26 with tmjd  among all sisters  tmjd was not associated with age  education  mental impairments  hand coordination  handgrip strength  mobility  or use of walking aids  in 75  to 84 year old sisters  tmjd was positively associated with self reported arthritis  p   0 12   edentulism  p   0 09   and the presence of complete dentures  p   0 05   and negatively associated with the number of teeth present  p   0 05   especially the posterior teeth  these associations were weaker in 85  to 94 year old sisters  this study suggests that tmjd is associated with the presence of complete dentures and a low number of teeth  especially the posterior teeth  
class7	a dentofacial deformity associated with incontinentia pigmenti  report of a case  a case of ip in a 16 year old girl has been presented  this patient manifested classic ectodermal and mesodermal anomalies  we present this case to illustrate a rare etiologic factor in the development of dentofacial deformities that can be treated in the conventional manner  
class7	more unusual pigmentations of the gingiva  three unusual types of oral pigmentation are presented  the first is a brown orange pigmentation caused by the habit of using the bark of juglans regia for teeth cleaning  the second is a bright yellow pigmentation associated with the habit of chewing the seeds of cola nitida  the third is a generalized mousy brown pigmentation related to the habit of chewing the leaves of catha edulis  the purpose of this article is to describe the nature of these pigmentations and to present their clinical and histologic features  
class7	adult linear immunoglobulin a disease manifesting as desquamative gingivitis  desquamative gingivitis is a manifestation of various dermatoses  particularly lichen planus and mucous membrane pemphigoid  a rare example of adult linear immunoglobulin a disease manifesting as desquamative gingivitis is presented  although the initial clinical features were typical of desquamative gingivitis  the persistence of ulceration after dental extractions was unusual  and the management of the oral lesions proved difficult  the clinical  immunopathologic  and therapeutic aspects of linear immunoglobulin a dermatoses are reviewed  
class7	interferon activation of latent natural killer cells and alteration in kinetics of target cell lysis  clinical implications for oral precancerous lesions  reduced natural killer cell activity was observed in patients with oral leukoplakia and submucous fibrosis compared with normal control subjects  however  the number of target binding lymphocytes was found to be normal in these precancers  treatment of effector cells with interferon alpha resulted in highly elevated active killer cell activity  although no change was observed in target binding lymphocyte counts  this finding could imply that precytotoxic cells that are activated by interferon exist in peripheral blood or that direct recruitment of a new cell population takes place  in addition  altered target lysis kinetics was observed  with interferon activated killer cells demonstrating a tremendous lytic activation that is completed so quickly that a statistical kinetic analysis could not be accurately done  because natural killer cell activity is an important effector system in immunosurveillance against tumors  its modulation with interferon may be an exciting clinical possibility in the control of malignant transformation or oral precancers  
class7	immunohistochemical study of oral lesions of lichen planus  diagnostic and pathophysiologic aspects  the immunophenotype of lymphoid cells in the epithelium and lamina propria of the oral mucosa were examined in patients with lichen planus  nondysplastic leukoplakia  leukoplakia with lichen planus  and other unrelated lesions  in all groups t lymphocytes were predominant  however  the t4 t8 lymphocyte ratio was higher with lichen planus than with other groups  this may be of diagnostic value in the histologic evaluation of oral lesions not typical of lichen planus  finally  a higher percentage of langerhans cells were observed in lichen planus  an immunologic pathogenesis of lichen planus is proposed  
class7	progressive osseous destruction as a complication of hiv periodontitis  a pathologic condition is described  characterized by rampant necrosis of gingival mucosa  periodontium  and related osseous structures associated with systemic infection with the human immunodeficiency virus  hiv   it is believed that this condition is an extension beyond the normal clinical course of hiv periodontitis  hiv p  and manifests itself in three progressive stages   1  hiv associated gingivitis   2  hiv p  and  3  an extension of hiv p to osseous necrosis  two cases of osseous destruction attending hiv p are reported  one of which led to initial diagnosis of hiv infection  they represent the final stage of disease progression with localized necrosis of gingiva  periodontium  and alveolar bone  
class7	tyrosine rich crystalloids in a polymorphous low grade adenocarcinoma  a polymorphous low grade adenocarcinoma with tyrosine rich crystalloid deposits is reported  the literature is reviewed  and diagnostic and histogenetic implications of this finding are discussed  
class7	periapical lesions of mandibular bone  difficulties in early diagnostics  it is often difficult to establish a correct diagnosis on the basis of initial clinical and roentgenologic symptoms in mandibular bone disease  in this paper these problems are discussed  and some suggestions are made to overcome them  the discussion is based on cases of osteogenic sarcoma  histiocytic lymphoma  and chronic osteomyelitis  the patients were a boy and two middle aged women  all of them with primary clinical symptoms of pain and swelling  diffuse roentgenologic changes in mandibular bone  uncertain response to treatment  and an unusual progress of the disease  
class7	microleakage associated with retrofilling of the apical two thirds with amalgam  in this investigation the effect of increasing the thickness of amalgam retrofilling on its sealing ability was studied and compared with the sealing ability of the laterally condensed gutta percha with a sealer  the apical two thirds of the canals of 118 upper central incisors  filled with laterally condensed gutta percha  were sealed with amalgam  amalgam retrofills were also used to seal the apices of the roots of six teeth that had no other filling in their canals  the effectiveness of both techniques was determined by their ability to inhibit the penetration of methylene blue dye for the periods of 24 hours  1 week  and 1  3  and 6 months  at 24 hours both materials showed comparable sealing ability  however  the sealing ability of laterally condensed gutta percha was significantly better than that of amalgam from the 1 week period until the end of the study  the depth of marginal penetration around both materials increased with time  the amount of the dye penetration increased acutely around amalgam  whereas its increase around gutta percha was more uniform  at the end of the study  specimens retrofilled with amalgam exhibited total dye penetration that exceeded the full thickness of amalgam  6 mm  and spread into the root canal space  on the other hand  the mean value for marginal penetration of the dye around the laterally condensed gutta percha was 2 6 mm at the end of the study  the present investigation proved beyond doubt that the use of any thickness of retrograde amalgam to seal the apex  with no other filling within the canal  invites failure  
class7	fine detail panoramic radiography by free focus radiography  a clinical demonstration of diagnostic radiographs  previous comprehensive clinical studies have shown that free focus radiography  ffr  may be used to improve image detail and diagnostic value in panoramic radiography of the teeth and jaws  this study demonstrated the clinical image quality in fine detail panoramic ffr surveys relative to conventional surveys made by rotational panoramic or intraoral radiography  cases of particular diagnostic interest with respect to common dental disease and changes in the jaws were included  the radiographic area of diagnostic interest depicted in ffr surveys generally resembled that of conventional dental radiographic surveys with the use of intraoral films rather then those of conventional rotational panoramic surveys  
class7	the effects of tartar control toothpaste on the oral soft tissues  ninety two dental and dental hygiene students completed a double blind  controlled clinical trial  the purpose of the trial was to evaluate the effects of toothpastes  in varying concentrations of flavor and tartar control agents  four formulations of toothpastes were assessed   a  control low flavor with no tartar control   b  medium flavoring with medium tartar control   c  high flavoring with medium tartar control  and  d  medium flavoring with no tartar control  soft tissue reactions were assessed objectively and independently by three examiners  subjective perceptions about each toothpaste were gathered by a structured  open ended questionnaire  the  tartar control  toothpastes  b and c  resulted in statistically significant  p less than 0 005  higher rates of mucosal reactions  e g   ulceration  sloughing  erythema  migratory glossitis  than the  non tartar control  toothpastes a and d  when the oral mucosal reaction rates were adjusted for multiple clinical observations within each subject at the same point in time there was no statistically significant  p greater than 0 05  difference between male  0 25  and female  0 28  subjects  in this study population  the order of preference was observed as toothpaste a greater than d greater than b greater than c  the major reasons for disfavor were burning sensation in toothpastes c  2 4   and b  4    
class7	prevalence of shovel shaped incisors in saudi arabian dental patients  the prevalence of maxillary incisor shoveling was studied radiographically in 990 saudi patients  according to the radiomorphologic characteristics  a new classification was developed and shovel teeth were categorized  the findings of this study showed 9  shovel shaped incisors  among those  4  were central incisors and 5  were lateral incisors  frequency of dens invaginatus occurrence with the shovel shaped incisors was also investigated  eight percent of shovel shaped incisors showed presence of dens invaginatus  prevalence was found to be 4  in central shovel shaped incisors  whereas that in lateral shovel shaped incisors was 11   
class7	geometrical planning for the correction of orbital hypertelorism  orbital hypertelorism may be associated with a variety of deformities affecting several elements of the craniofacial skeleton  shortness of the central portion of the face represented by a wide  short nose and anterior open bite is frequently combined with the exaggerated interorbital distance  with the mobilization of the two halves of the face it is possible to approximate the orbits  simultaneously elongating the center of the face and normalizing the maxillary alveolar ridge  a technique is described to plan the operation geometrically in order to predict accurately the skeletal correction  the change of the inclination of the eye slant  and the modification of the axis of the teeth  
class7	one stage closure of the entire primary palate  timing of the closure of the anterior palate and alveolus is a subject of debate  late repair of this defect is complicated by high fistula formation and subjects the patient to the problems of palate fistula for extended periods of time  we have utilized a single procedure performed when the child is 3 months of age that completely closes the anterior hard palate and alveolus along with the cleft lip  our series consisted of 61 consecutive patients with unilateral clefts of the primary and secondary palate  mucosal turnover flaps from the vomer along with lateral nasal mucosal flaps provide the nasal lining  a buccal sulcus flap with a veau flap completes the oral repair  ninety five percent  58 of 61  of the patients had complete and stable closure of their anterior palate and alveolus after 1 year  the incidence of fistula formation in our series  3 of 61  is much lower than that reported with the utilization of other protocols  excellent exposure of the anterior palate and alveolar defect during lip repair  early restoration of anatomic relationships  establishment of a good nostril floor and sill  and very low fistula formation are among the benefits of this procedure  the increase in operative time is considered minimal in light of aforementioned advantages  
class7	congenital lateral cleft palate  a new anomaly  a case of atypical cleft palate abnormality that had not been identified before in a 9 year old girl is presented  the cleft was localized laterally and in an oblique position at the soft palate  the patient had cleft palate repair  finally  she had acceptable soft palate movements and speech  
class7	oral findings in hiv infected patients attending a department of internal medicine  the contribution of intraoral examination towards the clinical management of hiv disease the occurrence of oral mucosal lesions was studied in 70 consecutive human immunodeficiency virus  hiv  infected patients  including 35 patients with aids  who had been admitted to a department of internal medicine  lesions of the oral mucosa were observed in 52 patients  74 per cent   oral candidiasis  50 per cent   hairy leukoplakia  14 per cent   periodontal disease  13 per cent   and oral kaposi s sarcoma  4 per cent  were the most common lesions  oral mucosal lesions suggestive of hiv infection were present in ten of 12 patients of unknown hiv status in whom pneumocystis carinii pneumonia was suspected  close cooperation between the medical and dental professions is recommended since accurate intraoral examination can make a valuable contribution towards the clinical management of hiv infected patients and may influence the cdc classification of this disease  
class7	the surgical treatment of noma  noma is a gangrenous stomatitis affecting children from developing countries  it may leave dreadful mutilations around the mouth  with amputation of the lips  cheek  nose  lids  maxilla  palate  or mandibula  reconstruction should take into account the size of the defect  the presence of trismus or constriction of the mandible  the age of the child  and the child s general condition  during the last 3 years  eight patients were treated at the unit of plastic and reconstructive surgery of the hopital cantonal universitaire  except in one case  tracheostomy was avoided  thanks to intranasal intubation by fibroscopy  these children  aged 2 to 9 years  underwent 31 general anesthesias and complex reconstructive procedures  including latissimus dorsi musculocutaneous pedunculated and free flaps  cranial flaps with galea  cranial bone and skin grafts  and retroauricular temporal skin flaps  all patients were able to return to africa with dramatic functional and cosmetic improvements  however  satisfactory mouth opening and mandibular function were not always obtained  
class7	pharynx  value of oblique projections for radiographic examination  the utility of oblique views for augmenting standard posteroanterior and lateral double contrast radiography of the pharynx was examined  over an 8 month period  two oblique views were added to the standard posteroanterior and lateral views of the pharynx during routine upper gastrointestinal studies in 102 patients divided into two groups  group 1 consisted of 81 patients without suspected pharyngeal or esophageal disease who demonstrated what was considered to be normal anatomy on all radiographic views  group 2 consisted of 21 patients who were known or suspected to have pathologic abnormality of the pharynx  the members of this latter group each demonstrated various abnormal pharyngeal anatomy on the standard views  in just over half of these cases the oblique projection contributed significant information not obtained with conventional views  therefore  the authors conclude that oblique images are a beneficial addition to the diagnostic evaluation of patients highly suspected of having pharyngeal disease  
class7	immunogenicity and protective effect against oral colonization by streptococcus mutans of synthetic peptides of a streptococcal surface protein antigen  streptococcus mutans is known to be a major causative organism of human dental caries  a surface protein ag with a molecular mass of 190 kda of s  mutans  pac  is receiving attention as an anticaries vaccine  we have recently determined the complete nucleotide sequence of the gene for pac  in this study  four peptides were synthesized on the basis of amino acid sequence of pac  among these peptides  pac 301 319  corresponding to the alanine rich repeating amino acid region was the most strongly bound by polyclonal murine anti rpac antibodies  the peptide partially inhibited the binding of polyclonal anti rpac antibodies to rpac  the peptide induced the proliferation of t cells from balb c mice immunized with rpac  subcutaneous immunization with pac 301 319  or rpac emulsified in cfa ifa induced high serum igg responses to rpac and pac 301 319   in addition  serum igg responses to a surface protein ag with a molecular mass of 210 kda of streptococcus sobrinus were elicited in mice immunized by s c  injection with pac 301 319  or rpac  intranasal immunization with pac 301 319  coupled to cholera toxin b subunit  ctb  or with rpac and free ctb induced high serum igg responses to rpac  the immunization with pac 301 319  coupled to ctb or rpac and free ctb suppressed the colonization of murine teeth by s  mutans  these results suggest that intranasal immunization with the peptide or rpac may be effective for the prevention of dental caries  
class7	the human antibody response to streptococcal c5a peptidase  an elisa was developed to measure antibody  both igg and iga  against the streptococcal c5a peptidase  scp   in human sera and saliva  generally  sera and saliva from young  uninfected children lacked antibody to scp  in contrast  most sera and saliva specimens from healthy adults had measurable levels of anti scp igg and scp specific secretory iga  anti scp siga   paired acute and convalescent sera from patients with streptococcal pharyngitis possessed significantly higher levels of anti scp igg than did sera from healthy individuals  sera containing high concentrations of anti scp immunoglobulin were capable of neutralizing scp activity  a survey of healthy adults and children also showed that the latter were significantly less likely to have anti scp siga in their saliva  detection of this antibody in greater than 90  of the saliva specimens obtained from children who had recently experienced streptococcal pharyngitis demonstrated that children can produce a secretory response  this is thought to be the first report of a secretory iga response in humans to a somatic antigen of streptococcus pyogenes  
class7	facial pain  this article presents differential diagnosis and treatment of facial pain  facial pain is classified in accordance with the recent work of the headache classification committee of the international headache society  the two major divisions are facial pain associated with disorders of the head and neck  including their parts  and disorders of cranial nerves  including their central connections  special attention is paid to the controversial topics of temporomandibular joint dysfunction and atypical facial pain  
class7	maintenance of condyle proximal segment position in orthognathic surgery  twenty patients underwent bilateral sagittal ramus osteotomy for the correction of mandibular retrognathia  a condylar positioning device  cpd  was used intraoperatively in 10 patients to maintain preoperative condyle proximal segment position  while the cpd was not used in the other 10 patients  postoperatively  the condyle proximal segment positions in both groups were compared and evaluated for vertical  horizontal  and rotational changes  a significant improvement  p less than  05  was observed in the vertical and horizontal condylar position in the group in which the cpd was used  however  there was no significant difference in proximal segment rotation  
class7	central odontogenic fibroma  clinicopathologic features of 19 cases and review of the literature  the odontogenic fibroma is a benign neoplasm infrequently reported in the literature  20 cases   nineteen additional examples are reported  this lesion occurs most frequently in the maxilla anterior to the molars and displays a striking female predilection  on occasion  it may be associated with an unerupted mandibular third molar  histomorphologically  it is not encapsulated  a spectrum of fibrous connective tissue stroma is present  from myxoid to densely hyalinized and from relatively acellular to cellular  calcification may or may not be present  it is distinguished by the presence of sparse cords and islands of inactive odontogenic epithelium  enucleation or surgical curettage is appropriate therapy and recurrence is low  as there appears to be no correlation of histologic pattern with clinical behavior  it seems unnecessary to try to separate the tumor into two variants  
class7	dysgeusia  gustatory sweating  and crocodile tears syndrome induced by a cerebellopontine angle meningioma  facial nerve involvement in cerebellopontine angle tumors  both during their development and after excision  may be expressed in irreversible dysfunction of the parasympathetic pathways  the exact location of the lesion along the efferent nerve fibers can be established through evaluation of the functional level of those organs supplied by the cholinergic motor secretory components  this report deals with a female patient in whom peripheral facial palsy developed shortly after removal of a right cerebellopontine angle meningioma  she had slight facial asymmetry and deafness in the right ear and complained of prandial flush and sweating of the right malar area  occult ipsilateral hyposalivation and hypolacrimation were diagnosed  in patients with seventh and ninth cranial nerve pathoses  evaluation of the end organs that are supplied by their associated autonomous nerve fibers is mandatory to prevent late ocular and oral sequelae  
class7	lack of evidence for link between intradental lesions and chronic renal failure  in at least three publications  radiographic intradental changes have been mentioned in connection with end stage renal failure with and without renal osteodystrophy  the influence of immunosuppressive therapy has been suggested  in 63 patients with one or a combination of the above mentioned criteria  no evidence was found on intradental radiolucencies or of extreme narrowing  obliteration  of the dental pulp cavity  
class7	dexamethasone as an adjunct in oropharyngeal obstruction in a patient with leukemia  incipient airway obstruction due to fulminating bacterial infection of pharyngeal tissues requires prompt and definitive intervention  a case is presented in which dexamethasone was a key adjunct to antibiotic therapy in averting this problem in a severely neutropenic patient with acute leukemia  
class7	gingival and cutaneous xanthomatosis associated with primary biliary cirrhosis  report of a case  the first comprehensive case report of intraoral xanthomatosis associated with primary biliary cirrhosis is detailed  the lesions were present along the free gingival margin and labial vestibule  crevicular fluid was noted to be tinged yellow  generalized cutaneous eruptions were also seen  the xanthomas were attributed to the underlying hyperlipoproteinemia  advanced progression of the hepatic disease necessitated a liver transplant  disappearance of both oral and skin lesions were subsequently observed  
class7	oral melanotic macules in patients infected with human immunodeficiency virus  a group of 217 patients seropositive for human immunodeficiency virus  hiv  were studied for 2 years  during which time pigmented lesions of the oral mucosa developed in 14  6 4   of them  the lesions were well circumscribed in some cases and diffuse in others  in some patients the macules enlarged or recurred after surgical excision  in two patients the macules appeared during the administration of zidovudine  clinical and laboratory evidence of adrenal insufficiency was not detected in any of the patients examined  the histologic appearances were those of melanotic macules  no ultrastructural alterations of the melanocytes were observed  two of these macules also contained epstein barr virus  and in one case normal oral mucosa was examined and also contained epstein barr virus in the epithelial cells  as a control group we examined 180 health care workers who did not belong to any risk category  and 30 intravenous drug abusers who tested seronegative to hiv  oral melanotic pigmentation was found in eight of the control subjects  3 6    the difference was not statistically significant  p   0 3097   our study shows that oral macules do not occur more frequently in hiv infected patients  however  the clinical behavior of these lesions appears to be different during the course of hiv infection  in some hiv infected patients the cause of the macules might relate to the administration of zidovudine and antifungal or antibacterial drugs  in others the cause remains unknown and could be due to multiple factors  
class7	subacute necrotizing sialadenitis  twelve cases of a heretofore unreported minor salivary gland disease have been reported  although an infectious cause is suspected for this self limiting inflammatory process  the actual cause remains unknown  it typically presents as a unilateral  erythematous  nonuclerated but painful  solitary firm swelling of the posterior hard palate  patients are most often young white men who have spent several weeks in a new environment with a group of people living in close quarters such as military barracks  
class7	the potential of periodontal pocket formation associated with untreated accessory root canals  teeth that were to be extracted because of periodontic endodontic involvement  in six patients  were treated by hemisection or root amputation  the roots were processed histologically  all cases showed the presence of accessory root canals with remnants of pulpal tissue  bacteria  and necrotic debris  it was demonstrated in the cases studied that residual necrotic tissue in untreated root canals can result in periradicular pathosis  we may speculate that if the inflammatory process persists and drainage results via the sulcus  in time  plaque and then concretions may develop  
class7	reactions of rat odontogenic tissues to heat  twenty four wistar rats were anesthetized and 200 degrees c heat was applied for 4 minutes to each mandibular left first molar  eight of these rats were then killed at 2  8  and 14 weeks  the subject and control teeth were radiographed and compared  they were then prepared for histologic evaluation and scored for levels of inflammation in both the pulpal and periradicular tissues  furcal  interproximal  and apical radiographic changes were found at all three time intervals  these changes involved progressively larger percentages of teeth at 8 and 14 weeks  histologically  complete necrosis and or abscess formation were found in the coronal portions of all experimental pulps  with time  inflammatory changes increased in intensity and progressed through the radicular pulps  resulting in necrosis or calcific changes and  finally  inflammatory changes in the periradicular areas  the pathosis created by the application of heat was devoid of microorganisms as evaluated by the brown and brenn stain  
class7	a retrospective clinical study of endodontically treated mandibular incisors in a selected chinese population  clinical studies of incidences of the number of canals in human teeth should correlate with the percentages obtained in laboratory samples  in this study the incidence of two canals in the mandibular incisors was compared with figures obtained from in vitro extracted teeth  as well as from one clinical study  a very low percentage was obtained from the examination of clinical records  and this could be due to racial differences in the samples examined  
class7	cross sectional tomography  a diagnostic technique for determining the buccolingual relationship of impacted mandibular third molars and the inferior alveolar neurovascular bundle  twenty two patients with 31 impacted mandibular third molars were examined with a new  precise  cross sectional tomographic technique to assess the radiographic size  shape  branching pattern  location  and degree of cortication of the mandibular canal  and the inclination of impacted mandibular third molars in the buccolingual plane  the mandibular canal  including bifid canals  was accurately identified in 30 cases  96 8    the cross sectional appearance of the canal was an uncorticated  or partially corticated  radiolucent oval that measured on average      sd  2 9     0 7 x 2 5     0 6 mm in diameter  it was located more frequently  45 2   on the buccal aspect of the impacted mandibular third molar  about 60  of the mandibular canals notched the inner cortical plate of the mandible or the third molar root surface  cystic expansion and quantification of cortical bone destruction were readily assessed by this technique  it was concluded that diagnostic information obtained from cross sectional tomograms significantly aids the oral and maxillofacial surgeon during the preoperative diagnostic workup and that the radiation risks are comparable to those of other accepted localization techniques  
class7	spontaneous pneumomediastinum  an unusual cause of a sore throat  sore throat  usually related to pharyngitis  is a common presenting symptom in the primary care setting  drs frenkel and lyons describe a case showing that physicians need to be aware of another  puzzling cause  spontaneous pneumo mediastinum  
class7	potential role of beta carotene in prevention of oral cancer  recent data suggests that retinoids and carotenoids may be effective in reversing a putative  field cancerization  defect in the epithelium at risk for oral cancer  animal experiments have shown that these compounds can inhibit cancer formation  several clinical trials have demonstrated the ability of retinoids to reverse oral leukoplakia  however  toxicities associated with retinoids at the doses used in these studies limits their potential for chemoprevention  because of its lack of toxicity  beta carotene is a very attractive agent for chemoprevention  it suppresses micronuclei in exfoliated oral mucosal cells from subjects at risk for oral cancer and recently has been shown to be active in reversing leukoplakia  another area under investigation is the possibility of preventing second primary tumors in patients cured of their initial cancer who have an increased risk of developing new cancers of the upper acrodigestive tract  
class7	remission of precancerous lesions in the oral cavity of tobacco chewers and maintenance of the protective effect of beta carotene or vitamin a  participants in the intervention trials were fishermen  kerala  india   who chewed tobacco containing betel quids daily before and throughout the study period  frequency of oral leukoplakia  micronuclei in oral mucosal cells  and alterations in nuclear textures were used as endpoints  administration of vitamin a  60 mg wk  for 6 mo resulted in complete remission of leukoplakias in 57  and a reduction of micronucleated cells in 96  of tobacco chewers  beta carotene  2 2 mmol wk  induced remission of leukoplakia in 14 8  and reduction of micronucleated cells in 98   vitamin a completely suppressed and beta carotene suppressed by 50  formation of new leukoplakia within the 6 mo trial period  after withdrawal of vitamin a or beta carotene treatment  oral leukoplakias reappeared  frequency of micronuclei in oral mucosa increased  and nuclear textures reverted to those present before the administration of chemo preventive agents  the protective effect of the original treatment could be maintained for at least 8 additional months by administration of lower doses of vitamin a or beta carotene  
class7	undifferentiated carcinomas of salivary glands  undifferentiated carcinomas of salivary glands are those epithelial malignancies whose light optic histopathologic features are not sufficient to place them in other defined classes of carcinoma  they are ultrastructurally heterogeneous and can manifest neuroendocrine differentiation  with or without the latter  the carcinomas are biologically high grade and rank with salivary duct and high grade mucoepidermoid carcinomas in terms of morbidity and mortality  
class7	risk stratification of ambulatory patients suspected of pneumocystis pneumonia  to determine whether aspects of clinical history  physical examination  and laboratory studies improve the diagnostic accuracy of the chest roentgenogram in the diagnosis of pneumocystis carinii pneumonia  pcp   we followed up 302 consecutive patients with respiratory symptoms and risk factors for human immunodeficiency virus  of the 279 patients  92   with follow up information available  31  11   were diagnosed with pcp  only 68  of patients with pcp had typical chest roentgenograms  regression analysis identified four independent predictors of pcp  diffuse or perihilar infiltrates  presence of mouth lesions  lactate dehydrogenase level more than 220 u l  and erythrocyte sedimentation rate 50 mm h or more  using these four predictors  patients could be stratified into low   intermediate   and high risk groups for pcp  we suggest that examination of the mouth  chest roentgenogram  lactate dehydrogenase level  and erythrocyte sedimentation rate be part of the evaluation of ambulatory patients with respiratory symptoms at risk for human immunodeficiency virus  
class7	mediastinitis following nasal intubation in the emergency department  a patient who developed a retropharyngeal abscess and fatal mediastinitis following emergent nasal intubation is described  despite aggressive surgical therapy the patient died of mediastinitis  although mediastinitis as a complication of oral intubation has been described  mediastinitis following nasal intubation has not previously been reported  
class7	acinic cell carcinoma  clinicopathologic review  the authors reviewed 90 cases of acinic cell carcinoma treated at the mayo clinic to assess long term follow up and to study features predictive of disease progression  sixty three patients  55 females and 35 males  were seen for primary treatment  27 had recurrent disease when first evaluated  histologically  these tumors were composed of serous acinar cells and intercalated duct type cells  morphologic patterns included solid  microcystic  follicular  and papillary cystic  all patients were followed for at least 10 years or until death  of the primary treatment group  44  had local recurrence  19  had metastasis  and 25  died of disease  disease first recurred locally up to 30 years after presentation and resulted in death after as many as 38 years  poor prognostic features include pain or fixation  gross invasion  microscopic features of desmoplasia  atypia  or increased mitotic activity  and excision as initial treatment  neither morphologic pattern nor cell composition was a predictive feature  
class7	risk factors for cancer of the tongue in uruguay  from 1987 to 1989  a hospital based case control study of cancer of the tongue was conducted in montevideo  uruguay  as part of a large study to investigate a number of risk factors for cancer of the oral cavity  pharynx  and larynx  the study involved interviews with 57 cases and 353 controls and was restricted to men  relative risks  rr  associated with tobacco smoking  alcohol drinking  and selected dietary items were obtained by unconditional logistic regression analysis  users of black tobacco had a rr fourfold higher than users of blond tobacco  and heavy drinkers of alcohol had a rr of 11 6  infrequent consumption of vegetables was associated with a significant rr of 5 3  and heavy drinkers of the local infusion  mate  had a rr of 2 5  it was concluded that black tobacco smoking and alcohol drinking were the strongest risk factors for cancer of the tongue in uruguay  their effects combine according to a multiplicative model  also  infrequent vegetable intake and mate ingestion contribute to the risk of cancer of the tongue  
class7	an assessment of salivary function in healthy premenopausal and postmenopausal females  the elderly represent the most rapidly growing segment of the u s  population  and the majority of this group are females  the average woman can anticipate living about a third of her life beyond menopause  and many u s  women undergo hormonal replacement in an attempt to relieve menopausal symptoms  little is understood about the relationship between menopause  hormonal replacement therapy  and the oral structures  although oral discomfort  xerostomia  and salivary hypofunction have been associated with postmenopausal women  the effects of menopausal status and estrogen therapy on subjective reports of oral dryness and discomfort and objective measurements of major salivary gland output were assessed in 43 healthy premenopausal and postmenopausal females  no complaints of xerostomia or burning mouth and no alterations in the quantity of saliva occurred in this population  this study suggests that among healthy women salivary gland function is not significantly influenced by menopause or hormonal replacement therapy  
class7	uses and complications of uvulopalatopharyngoplasty  uvulopalatopharygoplasty has become widely performed for chronic snoring and for cases of obstructive sleep apnoea  unfortunately this operation is not without morbidity and complications  we report our results of a prospective series of 50 patients undergoing uvulopalatopharyngoplasty with a minimum follow up of one year  snoring was abolished in 18  36 per cent  and substantially reduced in the remainder  obstructive sleep apnoea syndrome  identified in 11 patients pre operatively  was reduced in severity in all but three  troublesome complications were seen in 18  36 per cent  patients  namely intermittent velopharyngeal incompetence in five  10 per cent   pharyngeal dryness in 11  22 per cent  and loss of taste in five  10 per cent   one patient had nasopharyngeal stenosis requiring correction  a cautious approach to this operation is required with rigorous case selection  the importance of full assessment and careful follow up should not be underestimated  
class7	marijuana smoking as a possible cause of tongue carcinoma in young patients  a case of t1n0m0 carcinoma of the tongue in a male 23 year old  regular  marijuana smoker is described  hemiglossectomy and complete bilateral neck dissection were carried out  no post operative radiotherapy was given as the resection margins were histologically negative  the tumour recurred one year later in the left cervical region involving the mandible and surgery was again performed  but after three months  neck disease was still evident  the case described case implies the introduction of marijuana as a possible new risk factor in the development of oral cavity tumours  resection of the primary lesion has to be as wide as possible even in t1 cases  due to the aggressive biological behaviour of such tumours in young subjects  
class7	randomized  double blind trial of mazindol in duchenne dystrophy  there is evidence that growth hormone may be related to the progression of weakness in duchenne dystrophy  we conducted a 12 month controlled trial of mazindol  a putative growth hormone secretion inhibitor  in 83 boys with duchenne dystrophy  muscle strength  contractures  functional ability and pulmonary function were tested at baseline  and 6 and 12 months after treatment with mazindol  3 mg d  or placebo  the study was designed to have a power of greater than 0 90 to detect a slowing to 25  of the expected rate of progression of weakness at p less than 0 05  mazindol did not benefit strength at any point in the study  side effects attributable to mazindol included decreased appetite  36    dry mouth  10    behavioral change  22    and gastrointestinal symptoms  18    mazindol dosage was reduced in 43  of patients  the effect of mazindol on gh secretion was estimated indirectly by comparing the postabsorptive igf i levels obtained following 3  6  9  and 12 months in the mazindol treated to those in the placebo groups  although mazindol treated patients gained less weight and height than placebo treated patients  no significant effect on igf i levels was observed  mazindol doses not slow the progression of weakness in duchenne dystrophy  
class7	sick building syndrome   sick building syndrome   sbs  is one of the more colorful terms describing an increasingly common pattern of symptoms found among workers in modern office buildings  core symptoms include lethargy  mucous membrane irritation  headache  eye irritation  and dry skin  to prompt a diagnosis of sbs  these otherwise common symptoms must be  excessively  reported and primarily  work related   the world health organization now estimates that 30  of new or remodeled office buildings show signs of sbs  and that between 10  and 30  of the occupants of these buildings are affected by sbs  despite such figures  sbs remains poorly researched and even more poorly understood  the following review provides the clinician an overview of sbs that will allow a more accurate differential diagnosis and will help to prevent the widespread suffering that can accrue when sbs is not quickly recognized  
class7	quincke s edema  revisited  angioneurotic edema involving the uvula is sometimes referred to as quincke s edema  the term angioneurotic edema describes several closely related diseases manifested by recurrent  acute edema of the skin or mucosa  we report a case of uvular edema secondary to food allergy  treated successfully with steroids  a short review of angioneurotic edema and its management is also presented  
class7	sjogren s syndrome and primary biliary cirrhosis  presence of autoantibodies to purified mitochondrial 2 oxo acid dehydrogenases  sjogren s syndrome is well known for the presence of antibodies directed at specific nuclear antigens  however  the presence of antibodies reacting with a variety of other self antigens  including antimitochondrial antibodies  has often been reported although their significance is unknown  moreover  patients with sjogren s syndrome have been occasionally reported to be concordant with primary biliary cirrhosis  to address this issue we studied in a group of 96 patients with sjogren s syndrome the presence of autoantibodies to the dihydrolipoamide acetyltransferases of both pyruvate dehydrogenase and branch chain ketoacid dehydrogenase and to alpha ketoglutarate dehydrogenase  these latter enzymes are the mitochondrial target antigens of primary biliary cirrhosis  we report that 7 of the 96 patients reacted with the mitochondrial antigens that are prominent in primary biliary cirrhosis  moreover  in those patients showing reactivity with mitochondrial antigens  the autoantibodies were directed at the same immunodominant epitopes that have been previously characterized in primary biliary cirrhosis  one of the 7 positive patients was known to have primary biliary cirrhosis  we hypothesize that the remaining 6 patients are at clinical risk for the development of primary biliary cirrhosis and or that abnormalities would be found on liver biopsy  
class7	vascularized full thickness parietal bone grafts in maxillofacial reconstruction  the role of the galea and superficial temporal vessels  reconstruction of bony structures of the face is always a problem as big as the defect and the function that must be replaced  everything from simple grafts to sophisticated distant bone flaps has been used  based on the studies of cutting et al   psillakis et al   and casanova et al   we have developed the full thickness galeoparietal bone flap  initially for mandibular reconstruction  but of great use for all maxillofacial reconstructions  from july of 1987 to december of 1988  14 patients have been operated on  the experience with this flap is shown in four patients as follows  primary reconstruction of a mandible as a result of ameloblastoma  secondary reconstruction of a mandible with associated old fractures and malalignment of segments  bilateral malar reconstruction in a patient with treacher collins syndrome  and severe sequelae of an already treated romberg case  small variations could be made to best accommodate the technique used to the defect we were treating  some technical details  the experience  the results  and possible sequelae or complications are also discussed  
class7	thalidomide  treatment of severe recurrent aphthous stomatitis in patients with aids  an increasing number of aids patients have been noted to suffer severe recurrent aphthous stomatitis  ras   a condition often associated with high morbidity that remains unresponsive to conventional therapeutic interventions  in two cases thalidomide was administered to successfully treat aids patients with ras  both patients experienced complete abatement of pain shortly after therapy was initiated  ulcerations that were present for months resolved after three or four weeks of thalidomide therapy without any adverse effects  thalidomide appears to be an effective agent for the treatment of severe ras unresponsive to traditional therapies  
class7	topical cyclosporine for oral mucosal disorders  topical cyclosporine may be effective in the treatment of various oral mucosal disorders  in three open trials and in one double blind study  a topical formulation of this drug produced significant improvement in oral lichen planus  cyclosporine blood levels were generally low in these studies and no abnormalities of laboratory values resulted during use  of six patients with oral bullous diseases treated with topical cyclosporine  four showed a decrease in erythema  partial healing of ulcerations  and a reduction in pain  three patients relapsed shortly after cyclosporine was discontinued  four of eight patients with persistent aphthous stomatitis remained virtually free of ulcers during 8 weeks of topical cyclosporine therapy  these results indicate that topical cyclosporine is beneficial as a therapy for oral lichen planus and possibly other mucosal diseases  
class7	sensitivity restored of class v abrasion erosion lesions  the effectiveness of restorative treatment in reducing sensitivity associated with the class v erosion abrasion lesion was evaluated and the efficacy of three tooth colored restorative materials in reducing sensitivity was compared  the 108 lesions were restored with either glass ionomer restorative material  composite resin with a dentin bonding agent  or composite resin with a dentin bonding agent and a glass ionomer liner  composite resin with glass ionomer liner restorations significantly reduced sensitivity to air and hot and cold water  glass ionomer restorations and restorations with composite resin and a dentin bonding agent significantly reduced sensitivity but were also associated with increased sensitivity to air and cold respectively in 20  to 30  of the lesions restored when evaluated at 6 months  
class7	reviewing the unicystic ameloblastoma  report of two cases  classification of ameloblastoma into solid  multicystic  unicystic  and peripheral types based on clinical appearance and effects has gained recent recognition  the unicystic ameloblastoma is a less encountered variant of the ameloblastoma  it appears more frequently in the second or third decade with no sexual or racial predilection  it is almost exclusively encountered asymptomatically in the posterior mandible  the following report of two cases discusses the pathophysiology  demographics  histology  and prognosis of the unicystic ameloblastoma  
class7	microleakage at gingival dentin margins of class v composite restorations lined with light cured glass ionomer cement  this study compared the microleakage of light cured and auto set glass ionomer liners used in class v composite laminated glass ionomer restorations by determining the amount of microleakage at the gingival cementum dentin margins  standardized nonundercut v shaped class v cavities with gingival margins below the cementoenamel junction were prepared on the mesial and distal surfaces of 40 molars  establishing a total of 80 cavities  which were randomly divided into four groups  each was lined with glass ionomers  group 1  ketac bond  espe premier   which served as the control  group 2  xr ionomer  kerr   group 3  xr ionomer with polyacrylic acid  paa  pretreatment  kerr   and group 4  vitrabond  3m   specimens were thermocycled for 300 cycles in 0 5  aqueous solution of basic fuchsin between 4 and 55 c with a 1 minute dwell time  and individually embedded in an epoxy resin  statistical analysis indicated no differences among groups using the light cured glass ionomer  groups 2 to 4   and they showed significantly less leakage than the control  group 1  at p less than 0 00001   removal of the smear layer using 10  polyacrylic acid solution did not influence microleakage in restorations with light cured glass ionomer liners  
class7	effect of endodontic access preparation on resistance to crown root fracture  this investigation involved the creation of coronal radicular fractures in vitro and compared the fracture resistance of intact human mandibular molars  with molars after varied tooth preparation  forty freshly extracted  non carious  nonrestored human mandibular molars were randomly divided into four treatment groups  the molars were subjected to constantly increasing occlusal load until coronal radicular fracture occurred  tooth preparations significantly diminished resistance to coronal radicular fracture  
class7	evaluating and influencing periodontal diagnostic and treatment behaviors in general practice  providers  periodontal diagnostic and treatment behaviors were assessed in 34 practices in two north carolina counties  regularly attending patients had a low prevalence of gingival pocketing on index teeth  moderate attachment loss  and fairly prevalent bleeding and calculus  treatment frequency and patient knowledge were generally adequate  but the notation of periodontal status in the patient record was insufficient  a continuing education intervention resulted in substantial and significant improvement in notation rates  changes in rates with which services were provided  and changes in patient periodontal status were smaller and mixed  the study shows that continuing education can be effective in helping some but not all providers adopt needed  appropriate behaviors  
class7	asymptomatic periapical radiolucent lesion found in an area of previous trauma  published erratum appears in j am dent assoc 1991 feb 122 2  18  the case of an anterior mandibular radiolucent area  which unexpectedly yielded salivary gland tissue  is described  salivary gland depressions in the posterior mandible are readily recognized because of their almost pathognomonic radiographic appearance  a salivary gland inclusion in the anterior mandible in the proximity of teeth may create a diagnostic dilemma where superimposed periapical pathosis is present  the clinical importance lies in the recognition and appropriate treatment of the lesion  for the anterior salivary gland inclusion  a biopsy and a microscopic examination provide the most reliable diagnosis  
class7	treatment of beta hemolytic streptococcal pharyngitis with cefaclor or penicillin  efficacy and interaction with beta lactamase producing organisms in the pharynx  the recommended treatment for group a beta hemolytic streptococcal pharyngitis has continued to be penicillin given in parenteral or oral form  treatment failures  as determined by the continued presence of the streptococcal organism in the pharynx  however  do occur in 6  to 25  of patients treated with penicillin  furthermore  beta lactamase produced by other bacteria in the pharynx could potentially inactivate the penicillin  resulting in increased treatment failures or infection relapses  a study was undertaken to compare the efficacy of cefaclor  which is relatively resistant to inactivation by beta lactamase  with penicillin for eradicating the group a beta hemolytic streptococcal organism from the throats of 93 patients with pharyngitis  additionally  extensive cultures for potential beta lactamase producing organisms were conducted on 37 patients  27  of these had one or more pharyngeal organisms that were producing beta lactamase  no statistically significant difference was found between the clinical responses or the bacteriological cure rates of those treated with cefaclor and those treated with penicillin when stratified by the presence or absence of beta lactamase producing organisms  the prevalence of beta lactamase producing organisms in the pharynx  however  was increased after treatment with penicillin  whereas no change was noted following treatment with cefaclor  
class7	extraoral parotid sialolithotomy  the extraoral approach to duct surgery for the removal of parotid stones can be a simple procedure once the stone is accurately located in relation to the skin surface  the combination of sialography and sonography can provide this information  a case report demonstrates the step by step approach to diagnosis  localization  and surgery for the management of such extraglandular sialoliths  
class7	indications for simultaneous orthognathic and septorhinoplastic surgery  orthognathic and rhinoplastic surgery can be combined successfully when certain guidelines are understood  relative indications and contraindications have been established that generally yield predictable results  tip position  rotation and projection  may be the most difficult aspect to predict and  therefore  is best avoided during simultaneous surgery  major deformities of the dorsum can be easily corrected in conjunction with maxillary surgery  three cases demonstrating these guidelines are presented and discussed  
class7	the relationship between the indications for the surgical removal of impacted third molars and the incidence of alveolar osteitis  six hundred forty two impacted third molars were surgically removed in 412 patients  before surgery  each patient was assessed clinically and radiographically  and the reason for the removal of each tooth was specifically recorded  one hundred eighty two of the impacted teeth were removed for prophylactic reasons and 460 for therapeutic reasons  as much as possible  standardization of the operating procedure and environment  and of the preoperative and postoperative regimens was observed  after surgery  each case was followed to determine the absence or presence of signs and symptoms of alveolar osteitis  it was found that several factors seem to contribute to the development of alveolar osteitis  however  the most significant related finding was that the reason for the extraction  that is  whether the extraction was undertaken for therapeutic or prophylactic reasons  
class7	evaluation of ultrasound in the diagnosis of pathologic processes in the parotid gland  the values of ultrasound in differentiation of pathologic processes in the parotid gland were studied in 61 patients  the ultrasound findings were compared with operative and histologic findings  in 28 patients with chronic inflammatory processes  the ultrasound findings were in complete correlation with the histologic findings  showing enlarged parotid glands  homogenous glandular epithelium  and small  multiple cysts  in 31 patients with a tumor of the parotid gland  ultrasound scanning detected the presence of the tumor  in determining the location of the tumor  the method is highly specific when it is localized in the superficial lobe  100    and it is less specific when it is localized in the deep lobe of the parotid gland  also  it is highly specific in determination of tumor size  96    in two cases with retention cysts  the ultrasound findings also correlated with the histologic and operative findings  the results obtained show that ultrasound is a reliable diagnostic method for detection of pathologic changes in the parotid gland  
class7	severe preeclampsia presenting as dysphonia secondary to uvular edema  a case report  in addition to hypertension and proteinuria  generalized edema is seen commonly in women with severe preeclampsia  a patient presented to us at term with the complaint of dysphonia  upon examination she appeared to be clearly preeclamptic and had a grossly edemetous uvula  which we think occurred secondary to generalized edema  this case might be the first reported one of preeclampsia presenting as dysphonia and of uvular edema in association with preeclampsia  
class7	pregnancy associated with gorlin s syndrome  a pregnant woman with gorlin s syndrome presented for the removal of malignant ovarian tumours  the main problem encountered by the anaesthetists was an unexpected increase in arterial blood pressure  this was most probably associated with surgical manipulation of the ovaries with an increase in prorenin renin production  
class7	right to left shunting through a patent foramen ovale caused by pulmonary hypertension associated with rheumatoid arthritis and sjogren s syndrome  a case report  this case report presents a fifty four year old woman with right to left shunt in the atrium  it seemed clinically at first that the shunt was due to atrial septal defect  however  she also had pulmonary disease associated with rheumatoid arthritis and sjogren s syndrome  at autopsy atrial septal defect was not evident  but a patent foramen ovale and pulmonary artery disease were observed  this case suggests that pulmonary hypertension secondary to rheumatoid arthritis and sjogren s syndrome could lead to right to left shunting through a patent foramen ovale  
class7	salivary gland involvement in wegener s granulomatosis  salivary gland involvement is a rare clinical feature of wegener s granulomatosis  we report a series of five cases in which submandibular or parotid gland swelling was part of the initial manifestation of the disease  all patients had limited forms of wegener s granulomatosis  the value of determination of serum anti neutrophil cytoplasmic autoantibodies is demonstrated in four of the cases  and its use as a new diagnostic adjunct and promising tool to monitor disease activity is discussed  the use of trimethoprim sulfamethoxazole as part of alternative treatment regimens for limited wegener s granulomatosis is advocated  
class7	patient controlled analgesic administration  a comparison of steady state morphine infusions with bolus doses  the authors have shown previously that bone marrow transplant  bmt  patients who self administered bolus doses of morphine gained equal oral mucositis pain relief while using less drug compared with similar patients receiving morphine by staff controlled continuous infusion  in a follow up study they compared the efficacy and side effects of morphine in two groups of marrow transplant patients who controlled their own analgesic administration either by conventional bolus dose  patient controlled analgesia  pca  or by adjusting the rate of continuous morphine infusion to increase or decrease their plasma morphine concentration  patients controlling their morphine infusion rates  pharmacokinetically based patient controlled analgesia  pkpca  group  obtained more relief from oral mucositis pain than did patients using conventional pca  patients in the pkpca group used more morphine than pca patients and achieved superior pain relief without significant increases in side effects  e g   nausea  mood changes  sedation   the authors conclude that pkpca improves the management of prolonged  severe pain in marrow transplant patients and that this approach to patient controlled analgesia may be useful in other types of persistent pain  
class7	combined chemotherapy and radiation therapy in advanced inoperable squamous cell carcinoma of the head and neck  the final report of a randomized trial  between 1983 and 1986  the national institute for cancer research in genoa and affiliated institutions conducted a randomized study to compare two different ways of combining chemotherapy  ct  and radiation therapy  rt   one hundred sixteen patients were randomized to receive neoadjuvant ct followed by definitive rt  treatment arm a  or alternating ct and rt  in treatment arm a  rt consisted of 70 gy to the involved areas and 50 gy to the uninvolved neck at 2 gy fraction  five fractions per week  in treatment arm b  rt consisted of 60 gy to involved areas and 50 gy to the uninvolved neck in three courses of 20 gy each  2 gy fraction  ten fractions 2 weeks alternated with four courses of ct  ct consisted of vinblastine 6 mg m2 intravenously followed 6 hours later by bleomycin 30 iu intramuscularly  day 1  methotrexate 200 mg intravenously  day 2  leucovorin rescue  day 3  ct was repeated every 2 weeks up to four courses  the same ct was used in both treatment arms of the study  fifty five patients were entered in treatment arm a and 61 in treatment arm b  complete responses were 7 48 and 19 57 in treatment arms a and b  respectively  p less than 0 03   four year progression free survival was 4  in treatment arm a and 12  in treatment arm b  p less than 0 02   and four year survival was 10  in a and 22  in b  p less than 0 02   mucosal tolerance was significantly worse in treatment arm b  p less than 0 00004   the subgroup analysis shows the major improvement of alternating ct and rt in patients with the worst prognostic characteristics  
class7	why aging leads to increased susceptibility to infection  the elderly are predisposed to various infections through a multitude of factors  although intrinsic  unalterable defects occur in the aging immune system and nonspecific host defenses  there are factors that physician and patient can concentrate on to reduce the risk of infection  for example  meticulous attention to skin care can reduce the risk of soft tissue infection  improvement in oral hygiene and relief of xerostomia might promote recolonization with normal oral flora  correction of urinary tract obstruction where possible  relying on the use of indwelling urinary catheters only when necessary  can significantly reduce the risk of utis  medications that impair cognitive function should be prescribed judiciously  since they can promote aspiration with subsequent pneumonia  xerostomia  and urinary retention  correction of protein malnutrition may improve cell mediated immunity and skin integrity  thereby reducing the risk of infection  the signs and symptoms of infection in the aged may be subtle  therefore  the primary care physician should approach this susceptible population with a heightened clinical suspicion  thus expediting possibly life saving early diagnosis and treatment  
class7	a new syndrome  hearing loss and familial salivary gland insensitivity to aldosterone in two brothers  two male siblings presented in infancy with hyponatremia  the levels of plasma renin activity and aldosterone were elevated  sodium supplement was necessary to maintain normal sodium balance  the salivary sodium concentrations were markedly elevated  with sweat sodium levels being in the upper normal range  urinary sodium concentration and renal epithelial exchange between sodium and potassium were normal  this was felt to be due to an autosomal recessive disorder  both siblings were later diagnosed as having a bilateral moderate to severe sensorineural hearing loss with intermittent conductive overlay due to middle ear fluid  the sensorineural loss was also felt to be autosomal recessive in origin  but the possibility of a disturbance of sodium balance in the inner ear has been questioned  
class7	mandibular involvement in oral cancer  it is difficult to predict the tumour invasion into the mandible by oral cancer pre operatively  and consequently the decision to preserve or sacrifice the mandible is largely individualistic  the present study of 44 cases analyses the reliability of pre operative parameters to assess mandibular involvement  clinical  radiological and scintigraphic features have been compared with the detailed histology of the bone  this study confirms the usefulness of superior marginal resections in lesions which are close to but not involving the mandible  as well as for superficial lesions which are actually seen to involve the mandible but their ct and bone scans are negative for tumour invasion  
class7	biotin deficiency per se is teratogenic in mice  we examined whether maternal biotin deficiency would potentiate the latent teratogenicity of relatively low doses of vitamin a in mice  the incidence and the type of gross congenital malformations  cleft palate  micrognathia  and micromelia  induced by biotin deficiency were similar among the groups given three different concentrations of vitamin a  4000  12 000 and 60 000 iu  in the diet  also  the type of these malformations was different from those  exencephaly  cleft palate and macroglossia  induced by a known teratogenic dose of vitamin a  1 200 000 iu   we conclude that in mice concentrations of vitamin a in the range of 4 10 times the level recommended by the national research council and biotin deficiency do not interfere with one another  also  biotin deficiency per se is teratogenic in mice  
class7	mucoepidermoid carcinoma of the salivary glands  a reappraisal of the influence of tumor differentiation on prognosis  thirty nine cases of mucoepidermoid carcinoma of the salivary glands were reviewed for a reappraisal of the influence of the grade of differentiation on the outcome of the disease  the age of the patients ranged between 7 and 84 years  fifteen patients were females and 24 males  the tumors were located at the parotid gland  n   30   the submaxillary gland  n   1   the soft palate  n   5  and the oral mucosa nos  n   3   at presentation 4 tumors were intraglandular and 35 extraglandular  three patients had lymph node metastases and one patient lung metastases  the grade of differentiation was assessed using the criteria of healey et al  twelve tumors were classified as grade i  17 as grade ii  and 10 as grade iii  follow up information was obtained with a duration of 5 144 months  mean 44 7 months   six cases recurred locally and 5 developed metastases  five years cumulative survival was 100  for grade i  70 1  for grade ii  and 47 2  for grade iii  the results point to the usefulness of the assessment of the grade of differentiation as a guide to anticipate the outcome of the disease  
class7	characterization of cytokines present in middle ear effusions  retention of inflammatory mediators and cells in the middle ear cleft during chronic otitis media with effusion  come   results in ongoing inflammation with the potential for pathologic changes and hearing loss  cytokines are glycoproteins produced by macrophages and other cells  activities of cytokines include fever production  osteoclast  fibroblast  phagocyte and cytotoxic cell activation  regulation of antibody formation  and inhibition of cartilage  bone and endothelial cell growth  using enzyme linked immunospecific assays we measured levels of six cytokines in middle ear effusions  mee  from children with come  significant levels of four cytokines  interleukin 1 beta  greater than 50 pg ml   interleukin 2  greater than 300 pg ml   tumor necrosis factor alpha  greater than 40 pg ml   and gamma interferon  greater than 6 25 pg ml  were found in 51   54   63   and 19  of mee  respectively  in contrast  levels of a fifth cytokine  granulocyte macrophage colony stimulating factor  and a sixth cytokine  interleukin 4  were undetectable  age was observed to have a significant effect on the levels of specific cytokines  interleukin 1  il 1  correlated inversely  p less than  02  with age such that the younger the child  the higher the level of il 1 in mee  tumor necrosis factor alpha  tnf  correlated directly  p less than  005  with age such that the older the child  the higher the level of tnf in mee  children undergoing tympanostomy on multiple occasions had average mee tnf levels  234 2     109 1 pg mg total protein  that were nearly 14 times higher  p less than  005  than those from children undergoing their first tympanostomy  16 9     3 0 pg mg total protein   thus il 1 correlated with the early stages of come  while tnf correlated with persistence of disease  the presence of these cytokines in mee may be responsible for the mucosal damage  bone erosion  fibrosis  and resulting hearing loss seen in some cases of come  
class7	aerobic and anaerobic microbiology of acute suppurative parotitis  aspirates of pus from acute suppurative parotitis were studied for aerobic and anaerobic bacteria  bacterial growth was present in 23 specimens  a total of 36 bacterial isolates  20 anaerobic and 16 aerobic and facultative  were recovered  accounting for 1 6 isolates per specimen  0 9 anaerobic and 0 7 aerobic and facultative   anaerobic bacteria only were present in 10  43   patients  aerobic and facultatives in 10  43    and mixed aerobic and anaerobic flora in 3  13    single bacterial isolates were recovered in 9 infections  6 of which were staphylococcus aureus and 3 were anaerobic bacteria  the predominant bacterial isolates were s  aureus  8 isolates   bacteroides sp   6 isolates  including 4 bacteroides melaninogenicus group   and peptostreptococcus sp   5   beta lactamase producing organisms were recovered from 11  73   of the 15 specimens tested  this study highlights the polymicrobial nature and importance of anaerobic bacteria in acute suppurative parotitis  
class7	granulomatous sialadenitis  granulomatous inflammation in salivary tissues is most often a response to liberated ductal contents  particularly mucin  in various degrees of obstructive sialadenopathy  far less often is a granulomatous sialadenitis the result of specific infective granulomas or systemic granuloma forming diseases  in these instances  the salivary parenchymal involvement is usually secondary to disease localization in regional lymph nodes  
class7	gross cystic disease fluid protein 15 in salivary gland tumors  gross cystic disease fluid protein 15  gcdfp 15  is a 15 kd glycoprotein that is expressed by normal apocrine epithelia and in a majority of breast carcinomas  however  recent studies have demonstrated that this substance is also present in tumors of the salivary glands  sweat glands  and prostate gland  to determine whether the expression of cgdfp 15 might aid in the differential diagnosis of salivary gland lesions  the anti gcdfp 15 monoclonal antibody d6 was applied to paraffin sections of 133 such neoplasms  benign tumors  76  reactive  were more often labeled than malignant lesions  28  reactive  by this antibody  overall  53  41   of 133 cases were positive for gcdfp 15  notably  the tubuloglandular components in 17  81   of 21 pleomorphic adenomas were reactive  but no example of either adenoid cystic carcinoma or polymorphous low grade adenocarcinoma were labeled  in contrast  24  of adenocarcinomas stained with this antibody  the apparent expression of gcdfp 15 by a spectrum of salivary gland tumors supports their biologic relationship to lesions of the cutaneous apocrine glands and breast  furthermore  the demonstration of this determinant may be of use in suggesting the salivary gland nature of poorly differentiated carcinomas of the head and neck  and it may facilitate the separation of pleomorphic adenoma from histologically similar malignant neoplasms in the salivary glands themselves  
class7	cyclic amp binding proteins in the head and neck  results are presented of a preliminary study in which camp binding activity was measured in 34 specimens from a variety of head and neck sites  a wide range of camp binding protein levels was detected in all tissues assessed  there appeared to be a subgroup of parotid adenomas with increased camp binding activity  the biological significance of these proteins remains to be determined and their relationship to tumour growth in the head and neck is likely to be complex  
class7	irritant and sensitizing potential of copper  mercury and tin salts in experimental contact stomatitis of rat oral mucosa  hgcl2  cuso4  sncl2  sncl4 or sodium lauryl sulphate  sls  were openly applied to rat oral mucosa for 1 min  followed 6 h later by histologic examination of the tissue response  granulocytes were the predominant inflammatory cells and no lymphocytic infiltration could be seen with any of the substances tested  irritant threshold levels were defined histologically for each of the substances  cuso4 was found to be non irritant at all concentrations  the addition of non irritant concentrations of sls lowered the threshold levels for hgcl2 and sncl2  but cuso4 sls was non irritant at all concentrations tested  preapplication to the mucosa of sls at non irritant concentrations gave results with hgcl2  sncl2 and cuso4 similar to those with sls added to the metal salt solutions  lesions of allergic contact type could not be induced in the oral mucosa to any of the metal salt preparations  
class7	clinical and biologic effects of granulocyte colony stimulating factor in the treatment of myelokathexis  successful treatment of a patient with myelokathexis  a rare form of chronic neutropenia associated with recurrent infections  is described  rapid mobilization of bone marrow neutrophils and improved myeloid morphologic features were observed after treatment with human granulocyte colony stimulating factor  transient thrombocytopenia and bone pain were observed during treatment  although neutrophil chemotaxis  superoxide production  and fcriii surface expression were reduced  the patient improved clinically after restoration of a normal neutrophil count  
class7	location of abnormalities in panoramic radiographs of edentulous patients  a series of 308 panoramic radiographs of edentulous patients was examined for the presence of pathoses to determine whether any predictive basis could be found for occurrence of abnormalities by sex  age  or location  radiolucencies  radiopacities  and retained roots and teeth were recorded by size and by anterior or posterior location in edentulous jaws  radiopacities were the most frequently found abnormality  18  of subjects   followed by retained roots  8    radiolucencies  3    and retained teeth  3    no significant correlation was found by chi square test between type or location of abnormality and sex of the patient  there was  however  a significant relationship between location and type of abnormality  radiopaque and radiolucent lesions were more frequently found in the mandible  and unerupted teeth and retained roots were more frequently seen in the posterior maxilla  selective radiographs to detect retained roots and unerupted teeth in the posterior maxilla may be most productive in terms of prosthodontic treatment outcome  otherwise  this study finds no basis for selection of intraoral sites for specific intraoral radiographs of asymptomatic edentulous patients  
class7	submandibular cystic hygroma resembling a plunging ranula in a neonate  review and report of a case  cystic hygromas are large lymphangiomas that are most often found in the posterior triangle of the neck and the axilla in children  they are most frequently found before age 2 and may be massive  after upper respiratory infection  they may become infected and enlarged  causing dysphagia and toxemia  the diagnosis can usually be made by history and physical examination and confirmed by biopsy  treatment is by surgical excision of small lesions and staged debulking excisions in more severe cases  a patient with a cystic hygroma having many clinical characteristics of a plunging ranula is presented  the cyst fluid was aspirated and analyzed for its amylase  sodium  potassium  chloride  urea nitrogen  glucose  and total protein content  the characteristics of the fluid were also compared with those of lymph and saliva  this report demonstrates the difficulty in determining the diagnosis of a tumor that has the clinical features of a cystic hygroma  as well as a plunging ranula  the necessity of a proper presurgical diagnosis is essential since the form of therapy for each is different and conflicting  a method that distinguishes between the cervical cystic hygroma and a plunging ranula by means of aspirated fluid is discussed  
class7	application of instat hemostat in the control of gingival hemorrhage in the patient with thrombocytopenia  a case report  gingival bleeding in the patient with thrombocytopenia can be a difficult management problem  primary therapy with platelet transfusions may not be sufficient to control the hemorrhage and adjunctive local therapy may be required  currently  few local management techniques can effectively control this problem  instat collagen absorbable hemostat can be used as a local adjunct with platelet transfusions and has certain application advantages over topical thrombin and microfibrillar collagen  two successful techniques of instat application to control gingival hemorrhage in a patient with severe thrombocytopenia in leukemic relapse are described  
class7	oral hairy leukoplakia in hiv infection  a diagnostic pitfall  twenty nine human immunodeficiency virus  hiv  infected patients with white  nonremovable lesions on the lateral border of the tongue  clinically suggestive of oral hairy leukoplakia  hl   were studied  in particular  the value of local antifungal therapy in establishing the diagnosis of hl was investigated  in 15 patients  52   the lesions could be ultimately attributed to a candidal infection of the tongue  in 10 of the remaining 14 patients  a biopsy was obtained from lesions persisting after local antifungal treatment  in all biopsy specimens  the diagnosis of hl was confirmed by histopathologic examination and the demonstration of epstein barr virus dna by polymerase chain reaction  southern blot hybridization  and dna in situ hybridization  the present data confirm that the diagnosis of hl in hiv infected patients cannot be reliably made on clinical criteria alone  but requires histopathologic confirmation including the demonstration of epstein barr virus dna  preferably by dna in situ hybridization  however  with regard to the differential diagnosis of white  nonremovable lesions on the lateral border of the tongue in hiv infected patients  the present study suggests that persistence of lesions after local antifungal therapy is highly suggestive of hl  
class7	hiv infection  clinical features and treatment of thirty three homosexual men with kaposi s sarcoma  the clinical findings of patients with oral kaposi s sarcoma are reviewed  these oral findings commonly included candidiasis  hairy leukoplakia  gingivitis associated with human immunodeficiency virus  hiv   periodontitis  and other symptoms  including xerostomia  the other common symptoms of hiv disease that may be of importance in leading to a diagnosis are reviewed in this patient group  treatment by local radiotherapy or by intralesional vinblastine of these oral kaposi s sarcomas resulted in successful palliation  with more than 50  regression of the lesions in 80  of the patients treated  
class7	gingival swelling as a manifestation of aplastic anemia  gingivitis in the preschool child is uncommon and is usually associated with underlying systemic disease such as leukemias  neutropenias  and other immunologic defects  this report describes gingival hyperplasia in a preschool child with aplastic anemia and highlights the need to exclude systemic disease in children with periodontal disease  
class7	melanocytic hyperplasia of the oral mucosa  lesions that exhibit melanocytic hyperplasia are uncommon in the oral mucosa  they are even more rare than the various morphologic types of nevomelanocytic lesions  this article reports the clinicopathologic features of oral lesions diagnosed as lentigo simplex  junctional lentigo   jentigo    atypical melanocytic hyperplasia  melanoma in situ   and melanocanthoma  the proper terminology for these lesions is also discussed  
class7	major aphthous like ulcers in patients with aids  this report describes persistent  painful oral ulcers that occurred in nine patients with the acquired immunodeficiency syndrome  aids   these ulcers resembled major aphthous ulcers in clinical appearance and response to therapy  they occurred less frequently in patients with aids than those caused by herpes simplex and were found in 4 of 346  1 1   patients with aids at one medical center  lesions were typically painful  identification and treatment with topical tetracycline and steroids led to resolution with relief of symptoms  further study is necessary to understand the etiology and pathogenesis of these ulcers  
class7	normal proprioceptive trigeminal afferents in patients with sjogren s syndrome and sensory neuronopathy  a pure sensory neuropathy due to neuronal damage in the gasserian and spinal ganglia has been described in patients with sjogren s syndrome  conventional electromyographic  emg  studies can demonstrate the selective involvement of the sensory pathways but they do not provide definite evidence for the site of the lesion  noting that the trigeminal sensory neurons carrying cutaneous and muscular afferents are differentially located in the gasserian and mesencephalic nuclei  respectively  we carried out an electrophysiological study of the trigeminofacial and trigeminotrigeminal reflexes in 5 patients with sjogren s syndrome and pure sensory neuropathy  in 10 patients with sensory motor neuropathies of other causes  and in 10 healthy subjects  our results show that patients with sjogren s syndrome and pure sensory neuropathy who exhibited abnormal blink reflexes and an abnormal  cutaneous induced masseter silent period had normal jaw jerks  whereas patients with sensory motor neuropathies who exhibited abnormal cutaneous responses had abnormal jaw jerks  these findings suggest that the lesion in pure sensory neuropathy involves damage to the neurons of the gasserian ganglia and not to the trigeminal axons  since an axonal lesion would be expected to involve the large axons from muscle spindle receptors  
class7	association of the complement allele c4aq0 with primary sjogren s syndrome in japanese patients  we studied allotypes of the fourth component of complement  c4  and factor b in 76 patients with sjogren s syndrome  ss  and in 63 normal subjects  c4a null  c4aq0  was found in 10 of 28 patients who had primary ss  compared with 1 of 63 control subjects  p less than 0 005   in contrast  no significant difference in the frequency of any c4 allotype was observed between patients with secondary ss and control subjects  an association of hla drw53 with primary ss in japanese patients has been reported  since there is no linkage disequilibrium between drw53 and c4aq0  it is possible that at least 2 genes in the major histocompatibility complex may determine susceptibility to the development of primary ss in the japanese population  
class7	pancreatic autoantibodies and pancreatic function in sjogren s syndrome  pancreatic autoantibodies were determined in 49 patients with sjogren s syndrome and related to functional parameters  pancreatic duct autoantibodies  pda  were detected in the sera of three patients  and all showed abnormal exocrine pancreatic function  islet cell antibodies  ica  were not detected in the sera of the 49 patients  including two individuals with diabetes mellitus  in conclusion  pda occur in patients with sjogren s syndrome  and may be associated with exocrine pancreatic dysfunction  
class7	the vascularized fibula graft in mandibular reconstruction  the use of a vascularized graft from the fibula for mandibular reconstruction is presented  the great strength  pliability  and long vascular pedicle that characterize such grafts make them particularly suitable for this type of repair  the results in six cases were highly satisfactory  masticatory function was well restored  without alteration of the facial contour  and with minimal sequelae at the donor site  
class7	fine needle aspiration biopsy of head and neck lesions  the case records of 213 fine needle aspiration biopsies  fnab  of head and neck masses performed on 209 patients over a 3 year period were reviewed to assess the diagnostic accuracy and safety of this technique in comparison with surgical histologic examination  cytologic diagnoses based on fnab were compared with histologic diagnoses in 110 patients who underwent surgery  based on cytology alone  40 3  of the lesions were reported as malignant  45 1  as benign  and 14 6  as indeterminant  a specific cytologic diagnosis was made in 85 5  of the cases  cytologic diagnoses concurred with surgical histologic diagnoses 90  of the time  fine needle aspiration biopsy was found to have a false positive rate of 0 5  and a false negative rate of 2 3   the sensitivity and specificity of fnab in determining a malignant diagnosis were 81 1  and 99   respectively  positive and negative predictive values were calculated at 98 9  and 82 8   respectively  diagnostic rate  sensitivity  and negative predictive value increased consistently throughout the study period  indicating that the diagnostic accuracy of fnab improved with experience  
class7	medical and dental implications of cocaine abuse  with the ever increasing supply of cocaine and use of  crack   the potent and smokeable form of cocaine  the dangers of cocaine abuse  with its high morbidity and mortality  have become recognized  oral and maxillofacial surgeons may frequently and unknowingly be treating patients who use cocaine  and  therefore  they must be educated about cocaine related problems and be prepared to deal with the complications  this article discusses the nature of cocaine  its pharmacology  systemic affects  the oral manifestations of cocaine abuse  and recommended clinical management of the patient  
class7	monocytoid b cell lymphoma  the clinical  light microscopic  ultrastructural  immunocytochemical and cytogenetic features of a case of monocytoid b cell lymphoma were investigated  the tumour initially affected the cervical and supraclavicular nodes  but 33 months later affected the left parotid salivary gland  the patient had subclinical sjogren s syndrome  the neoplastic cells showed characteristic morphological features and had peri  and interfollicular distribution in the node  immunocytochemically the tumour cells were l26  4kb5  mb2  cd19  cd20  cd22 and igm kappa positive  prominent plasmablastic plasmacytoid differentiation was present in the recurrent tumour  suggesting an origin from post follicular b cells  the lymphoma cells showed unusual cytogenetic abnormalities  
class7	dapsone is an effective therapy for the skin lesions of subacute cutaneous lupus erythematosus and urticarial vasculitis in a patient with c2 deficiency  the deficiency of second component of complement  c2d  is the most common hereditary complement deficiency  patients with c2 deficiency are frequently associated with an auto immune disease process  in particular  systemic lupus erythematosus  le  like syndrome and or vasculitic syndrome or bacterial infections  c2d has been associated with the le subset of subacute cutaneous le  scle   the presence of anti ro  ssa  antibodies  and the human leukocyte antigen  hla  types a10  b18  dr2  we describe the clinical  serologic and immunogenetic data in a patient with manifestations of sjogren s syndrome who developed urticarial vasculitis and photosensitive annular scle which were effectively treated with oral dapsone  our case illustrates the dynamic nature of le  
class7	prevention of dry socket  an overview  dentists  exodontists  oral surgeons  and now oral and maxillofacial surgeons have been plagued with a postextraction complication  commonly known as  dry socket   since the inception of our profession  other designations that have been attached to this malady over the years include alveolar osteitis  postextraction osteitis  osteomyelitic syndrome  alveolar sicca dolorosa  and  latterly  fibrinolytic alveolitis  myriad attempts to eliminate this painful condition have been made  to no avail  nonetheless  significant progress has been made in an endeavor to reduce its incidence  perhaps it is time to take an inventory of the proven methods that will assist the practitioner in reducing the incidence of this complication in his her practice  this article presents a review of past investigations that appear to have merit in this regard  with a summary of recommendations at the conclusion of the article  
class7	effects of removing inferior alveolar neurovascular structures on mandibular growth and the eruption of permanent dentition in puppies  investigation was performed on the effects of removing the inferior alveolar neurovascular structures on the permanent dentition and mandibular growth  five puppies with erupted deciduous teeth had the inferior alveolar neurovascular structures removed unilaterally  when the test animals were 28 weeks old  examination revealed that the deciduous teeth on the side operated had exfoliated but permanent teeth did not replace them  on the other hand  the permanent teeth on the side not operated on replaced the exfoliated deciduous teeth  after a second period of 28 weeks  the germs of the permanent teeth on the side operated on were still buried in the mandibular bone  and the permanent teeth on the side not operated on erupted normally  mandibular measurements demonstrated that translative and transformative growth and developmental processes were normal in both the sides operated on and the sides not operated on  
class7	orofacial odontogenic infections  review of microbiology and current treatment  orofacial odontogenic infections are common  current evidence indicates that anaerobes play a major role in these infections and that the most common microbial isolates are bacteroides  fusobacteria  peptococci  and peptostreptococci as well as some viridans streptococci  drainage must be established where possible  penicillin is still the drug of first choice for therapy  with metronidazole a good alternative  nevertheless  not all clinicians are aware of current views and  therefore  this article is a state of the art review for the practicing clinician of the microbiology and antimicrobial therapy of orofacial odontogenic infections  
class7	malignant melanoma of the oral cavity  a case report  the oral cavity is a rare location for the development of primary malignant melanoma  less than 2  of all malignant melanomas develop in the region  a case report is presented  illustrating the management in the site of the palate  together with a review of the relevant literature  
class7	oral lichen planus  the clinical  historical  and therapeutic features of 100 cases lichen planus is a chronic inflammatory epidermal and mucosal disease  the cause of which is poorly understood  we reviewed the clinical and historic features of 100 patients referred to our clinic for diagnosis and management of lichen planus  the age  gender  chief complaint  duration of the chief complaint  medical history  medications  and clinical findings were recorded  past therapeutic modalities were reviewed  of therapeutic significance  25 patients with oral lichen planus had a secondary oral candidiasis  management of symptomatic lichen planus with topical and systemic steroid is discussed  the pharmacology of topical and systemic steroid usage and the rationale for treatment are discussed  
class7	candidal infection in oral lichen planus  the prevalence of candidal infection in lichen planus  lp  and its possible association with ulceration were independently examined in two archived series of 108 and 77 cases derived from two separate populations  to ensure that similar material was being compared  each case was histopathologically reassessed and confirmed as lp or reclassified as nonspecific lichenoid stomatitis  nsls   lichenoid dysplasia  ld   or other  o   three further sections  cut at 25 microns intervals  were stained with periodic acid schiff reagent for the identification of intraepithelial candidal pseudohyphae  as control specimens  61 normal and 59 hyperkeratotic mucosal samples were similarly processed and examined  candidal infection was found in 17 4  and 16 4  of ulcerated and nonulcerated lp cases  respectively  and in 40 0  and 16 7  of ulcerated and nonulcerated nsls cases  respectively  one case of ld was infected  each control series contained one infected case  the results indicate that candidal infection occurs more readily in lp and nsls  with no apparent association with ulceration in lp  the comparatively marked increase in the infection prevalence of ulcerated nsls cannot be statistically confirmed  and its significance remains uncertain  
class7	a comparison of the signs of temporomandibular joint dysfunction and occlusal discrepancies in a symptom free population of men and women  to date  there has been no conclusive explanation for the predominance of female patients with temporomandibular joint  tmj  dysfunction  the purpose of this study was to survey a normal population without symptoms for the presence of certain putative signs of tmj dysfunction in association with certain signs of occlusal discrepancy and to determine the presence of any gender variation  the subjects  217 men and 217 women  were examined for the presence of three putative signs of tmj dysfunction  limited mandibular opening  under 37 mm   deviation on opening  and joint sounds  the subjects were also examined for the presence of four signs of occlusal discrepancy  an anterior slide from centric relation  cr  to centric occlusion  co   lateral slide from cr to co  nonworking occlusal contacts  and working disclusive contacts distal to the canines  cr is the mandibular position at which the condyles are in their most superior position on the posterior aspect of the articular tubercles  co is the mandibular position at which the mandibular and maxillary teeth are in maximum intercuspation  there were no significant differences in the prevalence of the putative signs of tmj dysfunction and occlusal discrepancy between men and women  it was concluded that factors other than the presence of these signs of tmj dysfunction and occlusal discrepancy are responsible for the high predominance of female patients with tmj dysfunction  
class7	grinspan s syndrome  a drug induced phenomenon  three cases of apparently drug induced grinspan s syndrome involving the triad of oral lichen planus  diabetes mellitus  and hypertension are reported  because drug therapy for diabetes mellitus and hypertension is capable of producing lichenoid reactions of the oral mucosa  the question arises as to whether grinspan s syndrome is an iatrogenically induced syndrome  
class7	adult t cell leukemia lymphoma of the tongue  a case of posterior tongue lymphoma associated with adult t cell leukemia  atl  that occurred as a lesion in the lingual dorsal portion is reported in a 64 year old woman  initially  a diagnosis of hodgkin s lymphoma was considered as no findings associated with atl except lymphadenopathy and serum anti atla antibodies were present  combined radiotherapy and chemotherapy were administered with favorable results  however  4 months later  pneumocystis carinii pneumonia developed  and 2 months later  generalized lymphadenopathy and hypercalcemia evolved  at this time  a diagnosis of atl was made  the patient died of renal dysfunction 6 months after the initial presentation  in suspected cases of atl and malignant diseases of t cell lineage  namely  malignant lymphoma and mycosis fungoides  the presence of htlv 1 infection should be confirmed by testing for anti atla antibodies  
class7	peripheral ameloblastoma with clear cell differentiation  this report details a case of mandibular peripheral ameloblastoma having a clear cell component  the latter consisted of ovoid cells with vacuolated or clear cytoplasm and vesicular or pyknotic nuclei that may be disposed as discrete clusters or show direct transition from typical acanthomatous areas  comparison of this lesion with other odontogenic and nonodontogenic tumors that contain clear cells is discussed in the context of the differential diagnosis  
class7	intracoronal radiolucencies within unerupted teeth  case report and review of literature  a panoramic radiograph obtained during orthodontic treatment revealed an intracoronal radiolucency within an unerupted permanent second molar  this unusual entity was successfully treated by surgical and endodontic intervention  followed by restorative and orthodontic treatment  these treatments enabled the tooth to maintain pulpal vitality  erupt  complete root formation  and function  this report will review the proposed etiologies for this condition  discuss the need for surgical intervention  and present the details of the case  
class7	a comparison of two temporary restorations  light cured resin versus a self polymerizing temporary restoration  temporary restorative materials are an important component of endodontic therapy  they must both adequately seal the access preparation between visits and protect the obturated canal s  from microleakage until a permanent restoration can be placed  the efficacy of cavit and t e r m   a new light cured composite product  was compared with the use of a carbon black coronal microleakage protocol  the teeth examined had previously received coronal restorations  after the teeth were accessed  restored with cavit or t e r m   and exposed to the dye  they were cleared  three dimensional assessment then revealed that cavit more consistently provided an effective seal  in addition  a great deal of microleakage was observed around the permanent restoration tooth interface  this indicates that perhaps leaking permanent restorations should be removed in their entirety before initiation of endodontic treatment  
class7	radiographic detection of recurrent carious lesions associated with composite restorations  the greatest potential problem associated with posterior composite restoration is secondary caries detection  it is essential that secondary caries is detected as early as possible to enhance the prognosis for a successful treatment outcome  this laboratory study evaluated the optimum level of radiopacity of composite materials for radiographic detection of secondary carious lesions associated with composite materials  results indicated that for the radiologic detection of secondary caries  it is sufficient for composite materials to have the same level of radiopacity as enamel  
class7	iliac versus cranial bone for secondary grafting of residual alveolar clefts  secondary bone grafting of the maxilla in the mixed transitional dentition stage has become a well accepted procedure in the surgical protocol for rehabilitation of patients with residual alveolar clefts  this retrospective study was undertaken to evaluate and compare the long term results obtained with iliac or cranial cancellous bone graft material in the area of alveolar clefts and was based on the independent experience of two plastic surgeons from the same center using exclusively cranial or iliac cancellous bone  respectively  the criteria for surgery were similar  the surgical technique  with the exception of the bone grafting material  also was similar  and all patients were treated by the same group of orthodontists  fifteen patients from each group  from a total of over 100 patients  were randomly selected and included in the study  all patients were followed up from 18 to 60 months  operative and perioperative parameters  donor site morbidity  and long term results were evaluated  compared  and analyzed  there were no significant differences between the two groups  and equally good results in terms of bone incorporation  tooth eruption  and appearance were obtained with both iliac and cranial bone grafts  we conclude from our study that successful bone grafting is primarily achieved by adherence to meticulous surgical technique  simultaneous closure of coexisting oronasal or palatal fistulae  use of cancellous bone particles only  and coverage of the grafts with well vascularized flaps  the source of bone graft does not seem to primarily influence the success of the outcome  
class7	radiographic manifestations of congenital anomalies affecting the airway  congenital anomalies of the airway are generally uncommon  but a vast array of possibilities exists  some present life threatening emergencies at birth  and others go undiagnosed for years  clinical symptoms are often nonspecific  and radiographic evaluation is frequently requested to localize and characterize the lesion before endoscopy  surgery  or medical management  the most common intrinsic congenital anomalies causing airway compromise in infants include choanal atresia  mandibular hypoplasia  laryngomalacia  vocal cord paralysis  and congenital subglottic stenosis  the radiologist must be on the alert for unsuspected additional anomalies involving the airway  lungs  and esophagus  which occur with relative frequency  numerous extrinsic congenital masses of the head  neck  and mediastinum may compromise the airway  hemangiomas  lymphangiomas  and teratomas are more likely to be noted at birth  whereas branchial cleft cysts  thyroglossal duct anomalies  and dermoid cysts frequently present later  mass location and radiographic characteristics usually allow accurate preoperative diagnosis  intracranial involvement by nasal or nasopharyngeal masses  intrathoracic involvement by lower neck mass  and intraspinal involvement by posterior neck mass must always be sought for radiographically  persistence of respiratory symptoms after removal of such masses is not uncommon because tracheal deformity and laxity may take months or years to resolve  recent advances in cine ct and mr imaging promise to improve imaging of the airway in general and in the pediatric population in particular  significant limitations in imaging of the pediatric larynx remain  as a result  endoscopy continues to be the primary diagnostic tool for airway anomalies of this region  
class7	primary sarcomas of the major salivary glands  sarcomas arising in the major salivary glands are rare  this article presents the clinicopathologic features of 11 patients with primary sarcomas of the parotid gland  eight men and three women aged 7 to 75 years  mean age  42 years   the 11 sarcomas were histologically typified as follows  three malignant fibrous histiocytomas and two each of neurosarcomas  rhabdomyosarcomas  fibrosarcomas  and osteosarcomas  four patients experienced disease recurrences  and seven patients developed metastases  seven patients died of their sarcomas  with a mean survival time of 30 months  four patients were alive from 5 to 12 years  one each with angiomatoid malignant fibrous histiocytoma  embryonal rhabdomyosarcoma  fibrosarcoma  and neurosarcoma   prognosis correlated with size of the neoplasm  type of sarcoma  and histologic grade  in this respect  salivary gland sarcomas behaved in identical fashion to their soft tissue counterparts  
class7	primary parotid malignancies  a clinical and pathologic review  one hundred ninety four patients with primary malignant tumors of the parotid gland who underwent surgery at the mayo clinic  1970 through 1987  are reviewed  survival patterns were analyzed using the kaplan meier product limit method that separated histologic results into three significantly different groups  survival rate was highest for patients with acinic cell  adenoid cystic  and low grade mucoepidermoid carcinomas  intermediate for patients with high grade mucoepidermoid carcinomas  and lowest for the remaining six histologic types encountered  cox multiple linear regression was used to identify patient and tumor characteristics with greatest prognostic significance  in order of decreasing strength  regional metastatic involvement  pain  male gender  grade  stage  and advancing age all demonstrated independent prognostic significance  fifty three percent of patients requiring facial nerve sacrifice were asymptomatic at presentation  a high positive correlation was observed between advancing grade and stage  
class7	further evaluation of radical surgery following radiotherapy for advanced parotid carcinoma  a series of 30 patients who have been treated for advanced carcinoma of the parotid gland using radiotherapy followed by radical surgery is presented  three patients deteriorated during preoperative radiotherapy and remained unfit for surgery  the remaining 27 underwent radical parotidectomy with block dissection of the neck  twelve patients received additional radiotherapy after operation  of those patients undergoing surgery  three have been lost to follow up  17 have died and seven remain alive  the period of follow up ranges from 3 to 133 months  fourteen patients remained free of recurrent disease at death or when last seen  and six patients developed a local recurrence at a medium period of 10 5  range 3 36  months after surgery  for all 30 patients  the cumulative proportion surviving for 5 years was 30 per cent  
class7	dry mouth  diagnosing and treating its multiple causes  dry mouth in the elderly is a common occurrence with multiple etiologies  it is not a normal phenomenon of aging and  therefore  an attempt at elucidating its cause should be made  sjogren s syndrome may occur  and it is diagnosed by labial biopsy  medications are also frequently associated with dry mouth  and dosages may need to be adjusted or the drug discontinued if symptoms are severe  strategies for management of dry mouth are explored  
class7	inhibition of fluorouracil induced stomatitis by oral cryotherapy  mucositis is a significant dose limiting toxicity associated with fluorouracil  5fu   particularly when it is combined with leucovorin  we hypothesized that oral cryotherapy would cause local vasoconstriction and would temporarily decrease blood flow to the oral mucous membranes  if cryotherapy were used during the time of peak serum 5fu levels  then the oral mucous membranes would have less exposure to 5fu and thus develop less mucositis  to test this hypothesis  95 patients scheduled to receive their first cycle of 5fu plus leucovorin were randomized to have oral cryotherapy at the time of chemotherapy administration or to serve as a control group  subsequent mucositis was significantly reduced in the group assigned to receive cryotherapy as judged by the attending physicians  p    0002  and by the patients themselves  p    0001   we now routinely recommend this cryotherapy procedure for our patients receiving daily bolus 5fu plus leucovorin  
class7	concurrent cisplatin  infusional fluorouracil  and conventionally fractionated radiation therapy in head and neck cancer  dose limiting mucosal toxicity  after a preliminary dose finding study involving 12 patients with advanced or locally recurrent head and neck cancer  27 patients were treated on a phase ii protocol  using fluorouracil 350 mg m2 d by continuous intravenous  iv  infusion over 5 days  followed on the sixth day by a 2 hour iv infusion of cisplatin 50 mg m2  administered during the first and fourth weeks of radiation therapy to total doses between 60 and 64 gy  using 2 gy daily fractions  eight of these 27 patients had american joint committee on cancer staging  ajcc  stage iii disease  and 12 had stage iv disease  four had recurrent disease after surgery  three year follow up is now available  twenty one  77 8   remitted completely following treatment  and 11 remain free of local and regional relapse at 3 years  four have developed systemic metastases  following successful salvage treatment in two cases  estimated determinate survival at 3 years is 64   acute toxicity was manageable with this regime  eleven instances of grade 3 radiation therapy oncology group european organization for research and treatment of cancer  rtog eortc  mucositis were observed  which caused interruptions to radiotherapy in only four cases  no late sequelae have so far been recorded  it is concluded that the protocol described is tolerable but probably did not cause a greater number of locoregional  cures  than would have been expected following conventional radiotherapy alone in this group of patients  the use of infusional fluorouracil with concurrent conventionally fractionated radiation therapy and cisplatin infusion results in mucositis that limits the dose of fluorouracil to levels that are probably subtherapeutic  
class7	apparent increase in the incidence of invasive group a beta hemolytic streptococcal disease in children  recently  among adults  an increase in the incidence of invasive disease caused by group a beta hemolytic streptococci  gabs  has been noted  as has the appearance of a severe illness called  toxic shock like syndrome   also caused by gabs  we now report an apparent increase beginning in 1987 in the incidence of invasive disease caused by gabs in children  among these patients the manifestations were varied  one child had signs and symptoms compatible with the streptococcal toxic shock like syndrome  among the gabs isolates from our patients  8  80   of 10 evaluated for m protein antigens were nontypeable  further studies will be necessary to determine the relationship between serotypes and virulence of gabs  physicians should be aware of the possibility of an increasing incidence of invasive gabs disease in children  as well as its manifestations  which may include toxic shock like syndrome  
class7	fine needle aspiration biopsy of salivary glands  between january 1  1973  and december 31  1988  the authors or their associates performed 552 fine needle aspiration biopsies on patients with clinically significant masses of the salivary glands  all patients presented at the medical college of virginia hospitals or clinics of virginia commonwealth university  they were followed for periods ranging from 1 to 16 years  when available  the fine needle aspiration diagnoses were correlated with histologic diagnoses and long term patient outcomes  the sensitivity for a neoplasm was 93 3   the specificity for the absence of a neoplasm was 99   diagnostic efficiency was 96 4   and predictive value of a positive aspiration for a neoplasm was 98 3   with fine needle aspiration  surgical excision of salivary gland masses is often unnecessary  in patients with primary and metastatic neoplasms involving the salivary glands  fine needle aspiration aids the surgeon in mapping the extent of the surgical procedure and in preoperatively preparing the patient  the procedure is cost effective  
class7	aerobic and anaerobic microbiology of peritonsillar abscess  thirty four aspirates of pus from peritonsillar abscesses that were studied for aerobic and anaerobic bacteria showed bacterial growth  a total 107 bacterial isolates  58 anaerobic and 49 aerobic and facultative  were recovered  accounting for 3 1 isolates per specimen  1 7 anaerobic and 1 4 aerobic and facultatives   anaerobic bacteria only were present in 6  18   patients  aerobic and facultatives in 2  6    and mixed aerobic and anaerobic flora in 26  76    single bacterial isolates were recovered in 4 infections  2 of which were streptococcus pyogenes and 2 were anaerobic bacteria  the predominant bacterial isolates were staphylococcus aureus  6 isolates   bacteroides sp  21 isolates  including 15 bacteroides melaninogenicus group   and peptostreptococcus sp  16  and s  pyogenes  10   beta lactamase producing organisms were recovered from 13  52   of 25 specimens tested  this retrospective study highlights the polymicrobial nature and importance of anaerobic bacteria in peritonsillar abscess  
class7	postanginal sepsis with dysphagia  we have described a 10 year old girl who had dysphagia followed abruptly by arthritis  streptococcus pyogenes was identified as the pathogen by fasciotomy with bone biopsy  and a tonsillar fluid collection confirmed the diagnosis of postanginal sepsis  the patient was cured by a 6 week course of parenteral antibiotics  
class7	nutritional supplementation and the development of linear enamel hypoplasias in children from tezonteopan  mexico  the purpose of this study was to compare the effect of nutritional intake during tooth crown formation on the subsequent development of linear enamel hypoplasias  lehs  in mexican nonsupplemented  control  adolescents  n   42  and adolescents who had received daily nutritional supplements since birth  n   42   the proportion of individuals with lehs was nearly two fold greater  74 4   95  ci 64 7 84 1   in the control than in the supplemented group  39 5   95  ci 28 6 50 4   chi 2   9 44  p   0 001   although the estimated peak age at formation  approximately 2 2 5 y  is similar in both groups  the proportion of early  before 1 5 y  and late  after 3 0 y  lehs was greater in the control group  leh was also more common in females and was associated with an increase in illness days and a decrease in growth velocity  results of this study suggest that mild to moderate undernutrition during enamel formation is causally linked to the formation of lehs  
class7	s 100 protein antibodies do not label normal salivary gland myoepithelium  histogenetic implications for salivary gland tumors  neoplastically modified myoepithelial cells have a key role in developing the histologic characteristics of some salivary gland tumors  s 100 protein expressed in certain of these tumors is suggested to support this role  as the principal component in the human salivary gland reported to be s 100 protein positive is myoepithelium  confirmation of such an important aspect is required  immunoperoxidase staining of parotid salivary gland shows considerably different patterns obtained with antibodies to s 100 protein  neuron specific enolase  and neurofilaments compared with those for muscle specific actin and cytokeratin 14  many more cells and their processes associated with acini and ducts are evident with the latter two antibodies  double immunofluorescent staining with antibodies to either s 100 protein or neuron specific enolase combined with muscle specific actin does not reveal colocalization of these antigens in myoepithelial cells  the former localize only to nerve fibers adjacent to  but separate from  acini  and the latter only to myoepithelial cells  it is apparent that s 100 protein staining of the rich network of unmyelinated nerves in the interstitial tissues  evident ultrastructurally  has been misinterpreted as myoepithelium  this result has important implications for histogenetic classifications of salivary gland tumors  
class8	hypercalcemia in infants presenting with apnea  to our knowledge apnea in infants has not been associated with hypercalcemia  we describe seven hypercalcemic infants aged 2 days to 3 months who had presented with apnea  six of the seven were otherwise healthy  the apneic attacks were brief  and normal breathing was restored spontaneously or after tactile stimulation  the attacks stopped and the apnea monitoring was discontinued when the children were 1 month to 2 years of age  the only abnormal finding common to all of the patients was hypercalcemia  idiopathic infantile hypercalcemia was diagnosed in six of the patients and familial benign hypercalcemia in one  our findings suggest that determination of the plasma calcium level be included in the investigation of apnea in infancy  
class8	cancer chemotherapy after solid organ transplantation  to assess how well chemotherapy is tolerated after solid organ transplantation  we reviewed our experience at the children s hospital of pittsburgh with five patients aged 1 to 12 years  four patients had a liver transplant  indications for which were hepatoblastoma in two patients  hepatic failure secondary to wilms  tumor chemoradiotherapy in one patient  and familial intrahepatic cholestasis in one patient  a fifth patient received a cardiac transplant for unresectable angiosarcoma of the right atrium  after transplant  chemotherapy was given for the treatment of the primary malignancy in four of the patients  the patient with familial intrahepatic cholestasis received chemotherapy for secondary lymphoproliferative disease that had not responded to the cessation of immunosuppression  all patients other than this patient were on immunosuppression with prednisone  0 5 to 2 mg kg daily  and cyclosporine  to maintain serum levels at 800 to 1000 ng ml radioimmunoassay  throughout the duration of chemotherapy  courses of chemotherapy included one or more of the following agents  adriamycin  adr  20 mg m2 daily  three patients   cyclophosphamide  ctx  1 gm m2  one patient   cisplatin  cddp  90 mg m2  one patient   vincristine  vcr  greater than 0 75 to 1 5 mg m2  three patients   actinomycin d  act d  7 5 micrograms kg  one patient   ifosfamide  i  1800 mg m2  one patient  and etoposide  vp 16  100 mg m2  one patient   all patients received greater than or equal to 3 courses  range  3 to 9  mean  5  of chemotherapy every 3 to 4 weeks  dose reductions were made because of neutropenia in three patients but none were greater than 50   severe rejection was seen in one patient who had  however  manifested evidence of rejection prior to his first postoperative course of chemotherapy  no nephro or cardiac toxicity was seen  this preliminary experience suggests that chemotherapy is well tolerated after solid organ transplantation  
class8	pulmonary metastases from ameloblastoma of the mandible treated with cisplatin  adriamycin  and cyclophosphamide  a case of delayed pulmonary metastases from an ameloblastoma of the mandible  which occurred 20 years after surgical resection of the primary tumor but with no recurrence at the primary site  is reported  combination chemotherapy using cisplatin  adriamycin  and cyclophosphamide has produced a very good clinical and radiologically documented response in this case  
class8	in vitro natural killer and lymphokine activated killer activity in patients with bronchogenic carcinoma  the authors examined peripheral blood mononuclear cells from 45 patients with bronchogenic carcinoma to determine natural killer  nk  and lymphokine activated killer  lak  activity after in vitro incubation with media alone or media plus interferon gamma  ifn  200 u ml  and or interleukin 2  il 2  100 u ml   our results show that lymphocytes from patients with bronchogenic carcinoma can acquire lak activity  but the level of activity acquired was significantly lower compared with lymphocytes from 25 control subjects when il 2 cultures were supplemented with 10  autologous human serum  ahs   15 6      2 1  specific release versus 26 0      2 9  specific release  p   0 004   the lak activity  defined as cytotoxicity of an nk resistant cell line  of the patients  lymphocytes was augmented when cells were cultured with both il 2 and ifn compared with il 2 alone  p   0 0001  paired t test   control subjects were unchanged  p   0 09   there was no significant difference between groups of patients with different histologic types of tumor or different stages of disease  the nk activity  defined as killing of nk sensitive k 562 target cells  of the patients  lymphocytes was not significantly different from that of the controls  lymphocytes  42 8      3 0  specific release versus 49 3      3 3  specific release  p   0 16   these studies indicate the feasibility of il 2 and ifn therapy in patients with bronchogenic carcinoma  
class8	tumor antigen 4  its immunohistochemical distribution and tissue and serum concentrations in squamous cell carcinoma of the lung and esophagus  the immunohistochemical distribution and concentrations of tumor antigen 4  ta 4  in tissues and serum were determined in patients with benign and malignant diseases  including 27 patients with squamous cell carcinoma  scc  15 in the lung and 12 in the esophagus   tumor antigen 4 immunoreactivity was present in the cytoplasm of many scc tissues  especially in the hyperparakeratotic region  and in the cytoplasm of differentiated squamous cells of the intermediate layer of normal epithelia of various organs  but not in those of other types of lung cancers or benign pulmonary diseases  consistent with the results of immunostaining  the ta 4 concentrations in scc tissues of the lung  esophagus  and normal squamous epithelia were much higher than in those of lung cancer other than scc  benign pulmonary diseases  normal lung  and submandibular gland tissues  the ta 4 concentration in scc tissue tended to increase with increasing grades of differentiation  serum ta 4 was elevated in 15 of 27 patients with scc but in no patients with other types of lung cancer or benign diseases  these results indicate that ta 4 is an antigen related to the differentiation of squamous cells and that tumor cells of scc can release a large amount of ta 4 into circulation whereas normal squamous epithelia cannot  
class8	postoperative active specific immunization in colorectal cancer patients with virus modified autologous tumor cell vaccine  first clinical results with tumor cell vaccines modified with live but avirulent newcastle disease virus  published erratum appears in cancer 1991 apr 15 67 8  2124  sixteen patients with colorectal carcinoma dukes  stage b2  c  or d were treated with an autologous virus modified tumor cell vaccine after potential curative tumor resection  r0 resection   an inoculum of 1 x 10 7  cells incubated with 32 hemagglutination units of nonirradiated newcastle disease virus  ndv  was given intracutaneously up to four times at 10 day intervals  the delayed type hypersensitivity  dth  skin reaction was measured  the vaccination was well tolerated  in 11 of 16 patients an increasing reactivity against the vaccine was observed during the vaccination procedure  a challenge test using autologous tumor cells without ndv after the vaccination cycle revealed a specific antitumor sensibilization in 12 patients  the dth response was not due to bacterial contamination or sensibility to the virus  histologic examination of the vaccination site showed a dense infiltration of predominantly helper t lymphocytes  we conclude that in most of the patients treated active  specific immunization led to a specific antitumor sensitivity  
class8	flow cytometric dna analysis of parathyroid tumors  implication of aneuploidy for pathologic and biologic classification  the previous cytometric studies on parathyroid tumors have provided conflicting data regarding the relationship between dna content and histopathology  resulting from differences in technical methods and data analysis  this study measured nuclear dna of parathyroid tumors by flow cytometry in fresh material and determined whether dna aneuploidy really assists in making a pathologic diagnosis of carcinoma or not  from may 1987 through april 1989  65 consecutive patients operated on for primary hyperparathyroidism had dna analysis of the freshly excised parathyroid tumors  three of the patients had metastatic lesions of parathyroid carcinoma in the lung  cervical lymph nodes  and lung and mediastinal lymph nodes  respectively  pathologic classifications of the lesions from the other 62 patients were 54 adenomas  four carcinomas  and four hyperplasias  in all the latter patients  hyperplasia was associated with a multiple endocrine neoplasia syndrome  unequivocal evidence of aneuploidy was found in all of the metastatic lesions and 60  of the primary lesions of the carcinomas  in 9  of the adenomas and in 50  of the hyperplasias  therefore  parathyroid carcinomas were more apt to be aneuploid than were adenomas  p   0 0015  both sided testing   in each of the cases of aneuploid hyperplasia  a small aneuploid peak was found  the high incidence of aneuploidy in patients with multiple endocrine neoplasia type 1 may indicate the presence of clonal heterogeneity of hyperplastic glands and the presence of an abnormal subset of cells that have malignant potential  cell distribution analysis did not provide any significant information beyond ploidy level  in conclusion  dna flow cytometric analysis of dna ploidy patterns is a valuable adjunct to the histopathologic diagnosis of parathyroid neoplasms  
class8	posttachycardia t wave changes  a 25 year old previously healthy man presented to the emergency department with a tachydysrhythmia  after pharmacological intervention  the patient s rhythm converted to normal sinus and symmetrically inverted t wave changes were noted  although asymptomatic after conversion  the patient was admitted to the hospital and monitored for two days to rule out cardiac ischemia correlating with the t wave changes  the patient was ultimately discharged in good health  a review of the emergency medical literature fails to reveal examples of post tachycardic t wave changes that may simulate myocardial ischemia but be of no clinical significance  
class8	elevated serum levels of soluble interleukin 2 receptors in small cell lung carcinoma  the presence of the soluble form of the interleukin 2 receptors  sil 2r  was evaluated in the serum of 21 patients with small cell lung carcinoma  sclc  and 37 patients with non small cell lung carcinoma  non sclc  by means of an enzyme linked immunosorbent assay  the sil 2r level was measured serially in patients with sclc both during and after therapy  the mean serum level of sil 2r in patients with sclc was 3 8 times higher than that of 47 healthy controls and was 1 9 times higher than in 37 patients with non sclc  six patients with sclc had very high levels of sil 2r  ranging from five to 52 times the mean level observed in normal controls  tumor cells in the pleural fluid of the patient with highest levels were positive with monoclonal antibodies to il 2r  cd25   nkh 1  okdr  and okt9  a longitudinal study in this patient showed a good correlation between tumor activity and sil 2r levels  also  the sil 2r levels decreased in patients responding to therapy  these results suggest that some sclcs secrete sil 2r and that the serial measurements of the serum sil 2r levels can be used as a noninvasive tumor marker in this disease  
class8	botulinum toxin treatment of cranial cervical dystonia  spasmodic dysphonia  other focal dystonias and hemifacial spasm  in the past five years  477 patients with various focal dystonias and hemifacial spasm received 3 806 injections of botulinum a toxin for relief of involuntary spasms  a definite improvement with a global rating greater than or equal to 2 on a 0 4 scale  was obtained in all 13 patients with spasmodic dysphonia  94  of 70 patients with blepharospasm  92  of 13 patients with hemifacial spasm  90  of 195 patients with cervical dystonia  77  of 22 patients with hand dystonia  73  of 45 patients with oromandibular dystonia  and in 90  of 21 patients with other focal dystonia who had adequate follow up  while the average duration of maximum improvement lasted about 11 weeks after an injection  range seven weeks in patients with hand dystonia to 15 weeks in patients with hemifacial spasm   some patients benefited for over a year  only 16  of the 941 treatment visits with follow up were not successful  except for transient focal weakness  there were very few complications or systemic effects attributed to the injections  this study supports the conclusion that botulinum toxin injections are a safe and effective therapy for patients with focal dystonia and hemifacial spasm  
class8	stiffman syndrome  a rare paraneoplastic disorder  an unusual case of the stiffman syndrome  associated with an oat cell carcinoma of the bronchus  is reported  pathological examination showed that it was due to an encephalomyelitis similar to that seen in paraneoplastic disorders  this suggests that atypical cases of the stiffman syndrome may occasionally be paraneoplastic  
class8	the use of risk factors in medical diagnosis  opportunities and cautions  we discuss in this paper the extent to which disease risk factors may assist in the diagnostic process  we caution that disease risk factors need not be very sensitive or specific  risk factor specificity and sensitivity may be further reduced if  in the former case  the risk factor is related to other illnesses having the same clinical presentation as the disease of interest  or if  in the latter case  the risk factor disappears with the onset of illness  we illustrate these points in a discussion of the utility of smoking as a diagnostic test for malignancy in two clinical situations  the patient with asymptomatic microscopic hematuria and the patient with a solitary pulmonary nodule  risk factors hold great promise as aids to medical diagnosis  as this information is readily available to clinicians at little or no cost  clinicians  however  should exercise caution when using risk factors of unproven diagnostic utility in medical diagnosis  as their presence may have little or no effect on disease probability  
class8	spirometric findings and mortality in never smokers  the relation of ventilatory function to overall mortality has been studied in 662 male and 2048 female never smokers who during the period 1976 1978 participated in the copenhagen city heart study  a prospective community study of more than 14 000 men and women randomly selected from the general population of the city of copenhagen  until the end of 1986  195 subjects who said they were never smokers died  mortality was analyzed using the proportional hazards model of cox  in addition to measures of ventilatory function  the mortality analysis included age  sex  body mass index  alcohol consumption  school education  diabetes mellitus  heart disease and bronchial asthma as confounding factors  forced expiratory volume in 1 second  fev1  as a percentage of that predicted  forced vital capacity  fvc  as a percentage of that predicted and the ratio of fev1 to fvc were significant risk factors for mortality among both sexes  the relative risk of death associated with a 50  decrease in fev1 and fvc as a percentage of a predicted value was 1 65 and 1 81  respectively  this study confirms that lowered ventilatory function is a strong risk factor for mortality among never smokers of both sexes  
class8	prolonged administration of oral etoposide in patients with relapsed or refractory small cell lung cancer  a phase ii trial  twenty two patients with recurrent small cell lung cancer  sclc  were treated with single agent etoposide 50 mg m2 d by mouth for 21 consecutive days  eleven patients had received previous chemotherapy with cyclophosphamide  doxorubicin  and vincristine  cav  or etoposide  cae  or both  cave   four of the latter patients also received salvage treatment with cisplatin and etoposide  ep   nine patients had been treated with ep as induction therapy  while two patients had received high dose cyclophosphamide  etoposide and cisplatin  hdcep   altogether  18 patients had received previous intravenous etoposide  the median time off chemotherapy was 4 5 months  range  1 to 28 9 months   ten patients  45 5   95  confidence interval  ci   27  to 65   achieved a complete or partial response  responses were most common in patients who had responded to previous chemotherapy and who had not received any treatment in the 90 days before initiation of oral etoposide  median response duration was 4 months  range  1 5 to 9 5 months  and median survival was 3 5  months  range  1 0 to 15  months   leukocyte and platelet nadirs were 1 800 microl and 160 000 microl  respectively  during cycle 1 of treatment and occurred between days 21 and 28  overall  total leukocyte count decreased to less than 1 000 microl during 10 of 56 cycles  18    five patients required six hospitalizations for neutropenia and fever  there were two toxic deaths due to sepsis  platelet counts less than 50 000 microl occurred in 14 cycles  25    alopecia developed in all patients  gastrointestinal toxicity was uncommon  this schedule of etoposide administration warrants further study in combination with other active agents in previously untreated patients with sclc  
class8	interleukin 2 therapy in patients with metastatic malignant melanoma  a phase ii study  forty seven patients with metastatic malignant melanoma were treated with two 5 day cycles of 100 000 u kg recombinant interleukin 2  il 2  intravenously  iv  every 4 hours separated by 1 week  this dose and schedule of il 2 were identical to those used in a previous combined il 2 and lymphokine activated killer  lak  cell phase ii clinical trial of the il 2 lak working group  patient eligibility criteria  and clinical management guidelines were similar to those used in the previous trial  forty six patients were assessable for response  objective responses were observed in 10 of 46 patients  two complete responses  crs   eight partial responses  prs   or 22  with responses occurring in lung and liver as well as lymph nodes and subcutaneous sites  the median response duration was 8 months  toxicity was significant  three patients developed myocardial infarction  and one patient died during therapy  overall the toxicity and response rate for single agent il 2 are similar to that observed with il 2 administered in combination with lak cells in the previous trial  these results suggest that single agent therapy with il 2 when administered in this schedule has significant antimelanoma activity in humans  and that lak cells generated from peripheral blood add little to the antimelanoma activity of this dose and schedule of il 2  
class8	adjunctive surgery after chemotherapy for nonseminomatous germ cell tumors  recommendations for patient selection  one hundred eighty five patients who underwent surgery within 6 months of completing chemotherapy were identified from 360 patients with nonseminomatous germ cell tumors  nsgct  treated with memorial hospital front line cisplatin  or carboplatin based combination chemotherapy protocols between 1979 and 1988  clinical  pathologic  and radiologic features were correlated with the pathologic findings at surgery  the size of a residual retroperitoneal mass  the degree of shrinkage that occurred with chemotherapy  and the presence of teratomatous elements in pretreatment pathology specimens were each correlated with the pathologic findings of retroperitoneal resections after chemotherapy  multivariable logistic regression analysis of those undergoing retroperitoneal resections identified the size and shrinkage of the residual mass and the prechemotherapy lactate dehydrogenase  ldh  and alphafetoprotein  afp  levels as the best predictors of finding only necrotic debris  no factors could be found  however  that could selectively exclude patients who had residual viable malignancy or teratoma in the retroperitoneum  of 39 patients with residual retroperitoneal masses measuring less than or equal to 1 5 cm in maximal diameter  three had residual malignancy and five had teratoma resected  no factors were identified for residual lung or mediastinal masses that could be used to select a group of patients who could safely avoid surgery  if serum markers have normalized after chemotherapy for nsgct  resection of all residual abnormalities on imaging studies of the retroperitoneum  lungs  and mediastinum is recommended  in addition  retroperitoneal lymph node dissection  rplnd  is recommended for all patients with initial bulky metastases  greater than or equal to 3 cm in diameter  in the retroperitoneum  irrespective of the findings of postchemotherapy computed tomography  ct   
class8	spinal cord arteriovenous malformation with an associated lymphatic anomaly  case report  spinal cord arteriovenous malformations  avm s   like other vascular anomalies of the central nervous system  can be associated with similar vascular lesions of the skin and viscera  a 7 year old girl  who presented with rapidly progressing paraplegia  was found to have a spinal cord avm  cutaneous angioma  and a chylous malformation of the lymphatic system  she had previously undergone treatment for a posterior thoracic cutaneous angioma  at surgery  upon incision of the paravertebral muscle fascia  viscous pale fluid was encountered emanating from a foramen in the thoracic lamina  the spinal avm was resected in spite of concern that the abnormality represented spinal osteomyelitis  postoperatively  there was full return of function in the lower extremities  along with recurrent episodes of chylothorax  which slowly came under control with dietary manipulation  a review of the anatomy of the thoracic duct and nontraumatic causes of chylothorax is presented  and the association of cutaneous and central angiomas is discussed  finally  the treatment of chylothorax is delineated  
class8	assessing clinical significance of apnea exceeding fifteen seconds with event recording  using event recording  we determined how often apnea exceeding 15 seconds in duration was associated with bradycardia and how often patients with apnea resumed breathing spontaneously  of 1306 documented apnea events exceeding 15 seconds  54 patients   926 lasted 16 to 20 seconds  262 lasted 21 to 25 seconds  and 118 exceeded 25 seconds  of these episodes  75 3  were isolated and 14 9  were associated with pulse deceleration  4 4  with irregular transthoracic impedance  and 5 4  with bradycardia  event recording provided data supporting discontinuation of monitoring in 50 of 54 patients  36 spontaneously resumed breathing before the auditory alarm and 14 had a decreased incidence of apnea with maturation  follow up of 51 patients  three not located  showed that none had subsequent apparent life threatening events or sudden infant death syndrome  our results in these older infants and children  median age 6 7 months  provide substantiation that such patients with apnea of less than 20 seconds without bradycardia do not require continued monitoring  further  these data suggest that in selected older infants  longer isolated apnea may be well tolerated  however  hemoglobin saturation during sleep and the ability to resume breathing after the apnea alarm delay is prolonged should be verified  our patient population had a wide age range and heterogeneity of diagnoses  and was typically free of symptoms  so these results should not be extrapolated uncritically to premature infants  infants with chronic lung disease  and patients with symptomatic apnea  
class8	the effect of sulindac on the abnormal cough reflex associated with dry cough  in order to determine the possible role of prostaglandins in the abnormal cough reflex in patients with dry cough  the effects of a cyclooxygenase inhibitor on cough symptoms were examined  this was measured by a cough symptom score and by the cough reflex sensitivity to inhaled capsaicin in a double blind  randomized  cross over study comparing the effects of placebo with sulindac  200 mg daily for 1 week  we studied six hypertensive patients with angiotensin converting enzyme inhibitor associated cough and six patients with an idiopathic  dry  unproductive cough  all of whom had an increase in the sensitivity of the cough reflex  there was no change in blood pressure control in the hypertensive patients during sulindac therapy  the patients with the angiotensin converting enzyme associated cough had a significant reduction in the cough symptom score and also a significant increase in the dose of capsaicin causing two or more coughs  threshold sensitivity  and that causing five or more coughs  near maximum response  during sulindac therapy as compared to placebo  in those patients with idiopathic  dry  unproductive cough  sulindac did not alter the symptom of cough or the cough reflex response to capsaicin  these results suggest that prostaglandins may be involved in cough associated with angiotensin converting enzyme inhibitor therapy  but are less likely to be important in the pathogenesis of more common dry coughs of unknown cause  
class8	predictive value of urethroscopy as compared to urodynamics in the diagnosis of genuine stress incontinence  a retrospective chart review was undertaken of 204 patients who underwent dynamic urethroscopy  ninety nine patients with a diagnosis of genuine stress incontinence were evaluated urodynamically and urethroscopically to determine the predictive accuracy of the sensitivity and specificity of each of these diagnostic modalities  the urodynamic cough profile was both highly reactive and specific for genuine stress incontinence  with sensitivity and specificity of 95  and 100   respectively  whereas dynamic urethroscopy yielded sensitivity and specificity of 60 2  and 79 1   respectively  dynamic urethroscopy is a relatively insensitive predictor of genuine stress incontinence  with many equivocal findings  11   as well  the urodynamic cough urethral pressure profile is recommended for diagnosing this condition  
class8	pyoderma gangrenosum complicating felty s syndrome  the case of a 54 year old woman with felty s syndrome whose course was complicated by mucocutaneous lesions clinically typical of pyoderma gangrenosum is described  necrotizing sinusitis and saddle nose deformity were distinctive clinical features  lymphocytic vasculitis and rheumatoid nodule formation observed within panniculus at the base of a cutaneous lesion and in a nasal mucosal lesion were unexpected histopathologic findings  
class8	pulmonary renal syndrome with  triad  involvement due to small vessel vasculitis  we describe the clinical course and morphologic findings of a 22 year old woman presenting with a systemic disease that included nasal ulceration  hemoptysis and rapidly progressive renal failure  biopsies of nasal septum and lung revealed small vessel leukocytoclastic angiitis while renal biopsy showed a diffuse crescentic glomerulonephritis  immunosuppressive therapy resulted in remission of clinical symptoms and resolution of glomerulonephritis as documented in a followup biopsy  although her clinical presentation with triad organ involvement strongly suggested wegener s granulomatosis  this case illustrates that other varieties of vasculitis may mimic wegener s granulomatosis  
class8	methionine dependency of malignant tumors  a possible approach for therapy when methionine  met   an essential amino acid  was substituted for by its precursor homocysteine  hcy  in the culture medium  normal cells such as fibroblasts proliferated normally  in contrast  many tumor cells failed to grow or grew at a lower rate  met dependency is acquired simultaneously with cell transformation  as observed with hbl 100  a human mammary epithelial cell line that acquired increased malignancy as a function of in vitro passage number  and nih 3t3  j10   a mouse fibroblast line transformed by transfection with the human hras oncogene  a relationship was observed between met dependency and metastatic potential of the rms 21  rms s4t  and rms j1 sublines derived from rms 0  a rat rhabdomyosarcoma cell line  the higher the metastatic potential of the cell line  the higher the concentration of met required to maintain its proliferation  met independent cells derived from the rms 0 line  obtained by a progressive decrease of met in the culture medium lost their tumorigenicity when injected into rats fed with met deprived diets  in addition  the in vitro motility of rms s4t tumor cells  a marker of metastatic capability  decreased in met free hcy complemented  met  hcy   medium  similarly  rms 0 tumor cells  preincubated in a met  hcy  culture medium for 24 hours  evidenced a decreased capacity to form lung colonies when injected into syngeneic rats  the median number of lung colonies was 27 and 3  p less than  05  for cells cultivated in met  hcy  and met  hcy  media  respectively  an amino acid defined mixture reproducing casein composition was used as a protein source in the diets fed to rms j1 tumor bearing rats  dietary substitution of hcy for met  i e   met deprivation  resulted in decreased tumor growth  from 44 4     1 0 to 40 6     1 4  p less than  05  and prevention of metastatic spread  from 37 to 0  p less than  05   in conclusion  exogenous met can be substituted for hcy to maintain the survival of normal cells but is essential for tumor cell growth in vivo as well as in vitro  therefore  this defect of cancerous versus normal cells could be used for a therapeutic purpose  
class8	the role of antibiotic therapy in the prevention of empyema in patients with an isolated chest injury  iss 9 10   a prospective study  the purpose of this study was to determine the impact of an antibiotic regimen on the incidence of empyema in patients admitted with isolated chest trauma  iss 9 10  and hemopneumothorax requiring tube thoracostomy  all patients with isolated chest trauma and hemopneumothorax  estimated iss 9 or 10  seen in our trauma center were considered eligible for this study  patients were excluded for the following reasons  age less than 18 years  presence of shock at the time of initial resuscitation  ongoing antibiotic therapy for unrelated disease  documented pre existing infection or documented abnormal immune status  ninety patients were randomized to two treatment limbs  antibiotics and tube thoracostomy or tube thoracostomy alone  all patients had the procedure performed in the trauma center in a standard fashion  wound care and tube care were identical  antibiotic therapy consisted of a first generation cephalosporin  cefazolin   one dose given just before the procedure and then q 6 h into the tube removal  injury severity scores were established as described by schwab after the manner of baker  statistical analysis was performed using fisher s exact test of binary outcome  in this study  antibiotics were able to reduce the incidence of empyema in patients with isolated chest trauma and for such patients antibiotic treatment appears justified  further work is required to determine the effect on patients with more severe injury and multisystem involvement  
class8	changes in quality of care for five diseases measured by implicit review  1981 to 1986 we measured quality of care before and after implementation of the prospective payment system  we developed a structured implicit review form and applied it to a sample of 1366 medicare patients with congestive heart failure  acute myocardial infarction  pneumonia  cerebrovascular accident  or hip fracture who were hospitalized in 1981 1982 or 1985 1986  very poor quality of care was associated with increased death rates 30 days after admission  17  with very good care died vs 30  with very poor care   the quality of medical care improved between 1981 1982 and 1985 1986  from 25  receiving poor or very poor care to 12    although more patients were judged to have been discharged too soon and in unstable condition  7  vs 4    except for discharge planning processes  the quality of hospital care has continued to improve for medicare patients despite  or because of  the introduction of the prospective payment system with its accompanying professional review organization review  
class8	prospective payment system and impairment at discharge  the  quicker and sicker  story revisited since the introduction of the prospective payment system  pps   anecdotal evidence has accumulated that patients are leaving the hospital  quicker and sicker   we developed valid measures of discharge impairment and measured these levels in a nationally representative sample of patients with one of five conditions prior to and following the pps implementation  instability at discharge  important clinical problems usually first occurring prior to discharge  predicted the likelihood of postdischarge deaths  at 90 days postdischarge  16  of patients discharged unstable were dead vs 10  of patients discharged stable  after the pps introduction  instability increased primarily among patients discharged home  prior to the pps  10  of patients discharged home were unstable  after the pps was implemented  15  were discharged unstable  a 43  relative change  efforts to monitor the effect of this increase in discharge instability on health should be implemented  
class8	intrapleural tetracycline for the prevention of recurrent spontaneous pneumothorax  results of a department of veterans affairs cooperative study this prospective  multicenter  randomized   unblinded   controlled clinical trial was designed to determine if the intrapleural instillation of 1500 mg of tetracycline hydrochloride would be effective in diminishing the ipsilateral rate of recurrence for spontaneous pneumothorax  during the 4 year enrollment period  113 patients were assigned to the tetracycline group  116 patients were assigned to the control group  during the 5 year study period  the recurrence rate in the tetracycline group  25   was significantly less than that in the control group  41    use of tetracycline seemed to reduce the recurrence rates for patients with either primary or secondary spontaneous pneumothorax and for patients with either an initial or a recurrent pneumothorax  we conclude that the intrapleural administration of tetracycline in patients with spontaneous pneumothorax significantly reduces the rate of ipsilateral recurrence but is associated with intense chest pain  intrapleural tetracycline therapy is indicated for patients with a spontaneous pneumothorax who are hospitalized and are treated with tube thoracostomy  
class8	immune reactivity in bronchogenic carcinoma and its relation to 5 year survival rate  we performed a prospective study on the correlation of various parameters of the immune response with the 5 year survival rate in patients with bronchogenic carcinoma  parameters were initially examined before starting treatment  delayed hypersensitivity skin tests  lymphoblastogenesis  natural killer  nk  cell activity  and interleukin 2  il 2  production were employed to assess immune competence  each reaction was classified into four or five grades in accordance with intensity  the 5 year survival rate of the patients showing each grade of the immune response was calculated  a correlation between response before treatment and the survival rate was most clearly noted for lymphoblastogenesis  the skin tests and the nk cell activity showed poorer correlations  and no exact correlation was noted between the il 2 production and the immune response  
class8	symptomatic pericardial effusion in lung cancer patients  the role of fluid cytology  during the years 1975 1988  twenty lung cancer patients with symptomatic pericardial effusion were treated conservatively at our center  echocardiography demonstrated small pericardial effusion in 2 patients  medium size effusion in 3 patients and large amount of fluid in 15 patients  fifteen patients developed cardiac tamponade  in three of these patients  this was the presenting manifestation of lung cancer  pericardiocentesis resulted in prompt  though temporary  symptomatic relief in all patients  fluid cytology demonstrated suspected malignant cells in 2 patients and malignant cells in 13 patients  based on cytology  the diagnosis of adenocarcinoma was established in six patients  small cell carcinoma in three patients  and epidermoid carcinoma in one patient  all patients were dead within 9 months from the time of diagnosis of pericardial effusion  17 died within less than 3 months  it is concluded that pericardial effusion in lung cancer is indicative of rapid tumor progression and short survival  fluid cytology provides an immediate and accurate means of diagnosis  
class8	cyclophosphamide and ifosfamide combination as neoadjuvant chemotherapy for locally advanced nonsmall cell lung cancer  a meta analytic review  twenty three patients with marginally resectable and unresectable non small cell lung cancer  stages iiia and iiib  were treated by neoadjuvant chemotherapy  all patients received three cycles of preoperative chemotherapy with two alkylating agents  cyclophosphamide 2 5 g m2 intravenously  i v   and ifosfamide 3 5 g m2 i v   mesna 12 g m2 was given additionally to prevent drug hematuria  six of 23 patients  26   had partial response  of the seven patients who underwent thoracotomy  two were completely resected  but with macroscopic residual disease  mean time to progression for the whole group was 7 months  fifteen patients had progression of disease  with local metastases only in six  and distant metastases in eight  after administering 52 chemotherapy cycles  cyclophosphamide ifosfamide doses were cut down  as eight of 16 patients required hospitalization for fever during neutropenia nadirs  this two alkylating  non cisplatin  regimen  unlike cisplatin based regimens  was ineffective  and further trials are not recommended  
class8	distinguishing malignant mesothelioma from pulmonary adenocarcinoma  an immuno histochemical approach using a panel of monoclonal antibodies  a panel of six monoclonal antibodies  mabs  was employed to evaluate antigen expression in pulmonary adenocarcinomas and mesotheliomas  monoclonal anti human milk fat globulin  hmfg 2   anti carcinoembryonic antigen  np 2   anti epithelial membrane antigen  ema   anti cytokeratin  pkk 1   anti tumor associated antigen 72  b72 3   and anti human myelomonocytic antigen  leu m 1  antibodies were used to localize their respective antigens in formalin fixed  paraffin embedded tumors by using the avidin biotin complex immunoperoxidase technique  in all  28 mesotheliomas obtained from ohio state university anatomic pathology files and from a southwest oncology group  swog  protocol were compared to 22 pulmonary adenocarcinomas by using this mab panel  none of the mesotheliomas demonstrated positive staining with mabs np 2  anti cea  or leu m 1  however  95   21 22  of adenocarcinomas stained with one of these two antibodies  although neither of these two mabs stained all adenocarcinomas  each antibody demonstrated positive immunostaining in more than 90  of the adenocarcinomas studied  therefore  mabs np 2 and leu m 1 are  individually  quite useful for distinguishing mesothelioma from adenocarcinoma  however  in our study  no single mab could be used to distinguish these two tumor types in every case  mab b72 3 stained 91   20 21  adenocarcinomas but also stained 7   2 28  of mesotheliomas  mab hmfg 2 reacted positively with 95  of adenocarcinomas  but also stained 39  of the mesotheliomas  usually in a membranous pattern  mabs ema and pkk 1 were not found useful in distinguishing mesothelioma from adenocarcinoma  we conclude that mabs leu m 1 and np 2 were both useful in distinguishing mesothelioma from pulmonary adenocarcinoma in that positive staining was demonstrated in adenocarcinomas and not mesotheliomas  
class8	development of a new surgical procedure for repairing tracheobronchomalacia  we have developed a new surgical method for repairing tracheobronchomalacia  in experiments on dogs we tried external fixation of marlex mesh  bard cardiosurgery division  bellerica  mass   on the trachea  we first made models of tracheomalacia by making fractures or resections in intrathoracic tracheal cartilages and then made an external fixation of marlex mesh on the malacic segments of the trachea  in 11 dogs marlex mesh was sutured onto the trachea with absorbable thread  the trachea was firmly supported after 2 to 6 months  compared with three controls in which no external fixation was made  however  mucosal defects associated with ischemia caused by the suture developed in four of the 11  in 13 more dogs marlex mesh was bonded to the trachea with fibrin glue  after 3 to 8 months the supporting strength of the trachea increased up to the level of the normal trachea  there was no evidence of inflammation or of mucosal defects  therefore marlex mesh was applied to a 44 year old man who had experienced frequent attacks of cough syncope  after the operation the attacks of cough syncope and collapsing of his airway disappeared completely  
class8	pleuroperitoneal shunt for persistent pleural drainage after fontan procedure  persistent effusions of chylous fluid may prolong the hospitalization period of many patients who have had a fontan procedure  herein we report the case histories of two patients in whom use of a pleuroperitoneal shunt to control the effusion shortened the hospital stay by several weeks  
class8	laryngeal mask airway and tracheal tube insertion by unskilled personnel after a short training programme 11 naval medical trainees inserted a laryngeal mask airway  lma  and a tracheal tube  ett  in random order in a total of 110 anaesthetised patients  they were allowed 40 s for each attempt  success was defined as the detection of expired carbon dioxide within 40 s of guedel airway removal which subsequently rose to an end tidal value of at least 4 kpa  together with satisfactory lung expansion and ventilation  without other airway intervention by the anaesthetist  104 lma insertions were successful compared with 56 of etts  p less than 0 01   all first attempts at lma insertion were successful  whereas satisfactory ett placement was progressive  insertion was also quicker with the lma  20 s  than with the ett  35 s   p less than 0 01   further studies are indicated to assess the value of the lma in emergencies  
class8	surgery for sinusitis and aspirin triad  an 11 year retrospective study was conducted to evaluate the surgical treatment of sinusitis in aspirin triad patients  twenty five patients were selected for surgery when their sinus disease and asthma progressed despite intense medical treatment  sixteen patients had radiographic evidence of severe ethmoid disease  and their initial surgical procedures were limited  i e   bilateral intranasal ethmoidectomies   of these 16 patients  6 required subsequent surgery for recurrent sinusitis  nine of the 25 patients had radiographic evidence of severe antral  as well as ethmoid  disease  their initial surgical procedures were radical  i e   bilateral caldwell luc operations with intranasal and transantral sphenoethmoidectomies  none of these 9 patients required further surgical treatment for control  this review indicates that if antral and sphenoid disease are detected in association with ethmoid involvement  a radical surgical approach is the operation of choice  
class8	olfactory neuroblastoma  clinicopathologic and immunohistochemical characterization of four representative cases  olfactory neuroblastomas are rare tumors whose clinical prognosis is not predictable by assessment of initial stage or grade  the pathologic diagnosis is often difficult because of the wide range of the patient s age and histologies  in this report  we document that the diagnosis of olfactory neuroblastoma can be clarified by immunohistochemical demonstration of a unique antigenic profile that can be obtained in routinely processed biopsies  we describe four cases of olfactory neuroblastoma diagnosed and treated from 1979 to 1989  each confirmed by immunohistology  one of our patients was misdiagnosed twice at an outside institution  first as having nasopharyngeal carcinoma and then as having small cell  undifferentiated  oat cell  carcinoma  despite accurate tumor diagnosis and appropriate therapy  we found that there was no apparent correlation of clinical outcome with kadish clinical stage or histologic grade of tumor  
class8	a new method of needle electrode placement in the posterior cricoarytenoid muscle for electromyography  in 1979 the authors developed a new method of needle electrode placement in the posterior cricoarytenoid muscle  pca  for electromyography  the pca muscle is easily reached by inserting a needle electrode through the cricothyroid membrane at the midline and penetrating the lamina of the cricoid cartilage in the subglottic cavity  access to the pca muscle for electrode insertion was best afforded by a percartilaginous approach  this report details the new technique used at our laboratory  to our knowledge  this is the first report of needle electrode placement in the pca muscle by a percartilaginous approach  this new electrode insertion technique has been applied to more than 100 dogs for research purposes and to 1200 patients with laryngeal motor disorders for clinical diagnosis  this is a simple technique requiring the usual skills  reliable electromyographic recordings have been obtained by this new method  no untoward effects  such as hematoma or infection from repeated placements were observed in approximately 3200 examinations performed to date  it is reasonable to assume that the percartilaginous route for electrode insertion in the pca muscle is feasible in man  techniques of electrode placement in the intrinsic laryngeal muscles are reviewed and compared  
class8	a randomized controlled trial of a reduced daily dose of zidovudine in patients with the acquired immunodeficiency syndrome  the aids clinical trials group  background  the initially tested dose of zidovudine for the treatment of patients with advanced disease caused by the human immunodeficiency virus type 1  hiv  was 1500 mg  although this dose is effective  it is associated with substantial toxicity  methods  to evaluate the efficacy and safety of a reduced dose  we conducted a randomized controlled trial in 524 subjects who had had a first episode of pneumocystis carinii pneumonia  the subjects were assigned to receive zidovudine in either a dose of 250 mg taken orally every four hours  the standard treatment group  n   262  or a dose of 200 mg taken orally every four hours for four weeks and thereafter 100 mg taken every four hours  the low dose group  n   262   results  the median length of follow up was 25 6 months  at 18 months the estimated survival rates were 52 percent for the standard treatment group and 63 percent for the low dose group  p   0 012 by the log rank test   at 24 months the estimated survival rates were 27 percent for the standard treatment group and 34 percent for the low dose group  p   0 033   in both groups  82 percent of the subjects had another opportunistic infection  and the length of time to that infection was similar in the two groups  p   0 56 by the log rank test   cd4 t lymphocyte counts improved transiently in both groups  and serum levels of hiv antigen decreased in the subjects with antigenemia  the hemoglobin level declined to less than 5 mmol per liter  80 g per liter  in 101 subjects in the standard treatment group and in 77 in the low dose group  39 vs  29 percent  p   0 0009 by the log rank test   the neutrophil count declined to less than 0 750 x 10 9  per liter in 134 subjects in the standard treatment group and in 96 in the low dose group  51 vs  37 percent  p   0 0001   conclusions  the reduced daily dose of zidovudine used in this study was at least as effective as the standard dose and was less toxic  however  with the use of a four week induction period with a high dose followed by low dose treatment  severe anemia and neutropenia were common complications of treatment with zidovudine  
class8	response of the lambert eaton myasthenic syndrome to treatment of associated small cell lung carcinoma  we evaluated the outcome in 16 patients with lambert eaton myasthenic syndrome  lems  associated with histologically verified small cell carcinoma  scc   thirteen patients received specific tumor therapy  chemotherapy  radiation therapy  or resection  and most also received pharmacologic and immunologic treatment for lems  seven of 11 patients surviving for more than 2 months after tumor therapy showed substantial neurologic improvement  1 patient being in complete remission at 7 years   in 3 of 11 improvement was transient  an emg index of disease severity  compound muscle action potential amplitude in abductor digiti minimi  was significantly increased at final follow up  p less than 0 01  n   11   a pretreatment amplitude greater than 3 0 mv was a good prognostic sign  we conclude that a combined treatment approach in scc lems usually results in neurologic improvement  
class8	aggravation of human and experimental myasthenia gravis by contrast media  after observing a 72 year old myasthenic patient develop an acute myasthenic exacerbation following the administration of routine diagnostic iv contrast material  an observation rarely described in the literature  we used the experimental autoimmune myasthenia gravis model in rabbits injected with a contrast agent to simulate the situation  there was significant worsening of the decremental response to 3 hz repetitive nerve stimulation from 40     29  to 55     27  following the iv administration of contrast agent at doses similar to those used in humans  iv calcium partially reversed this aggravation  caution is merited when myasthenic patients are administered contrast media  
class8	angiographic arterial embolization and computed tomography directed drainage for the management of hemorrhage and infection with abdominal pregnancy  hemorrhage during or after surgery  pelvic abscess  bowel obstruction  and prolonged febrile morbidity can complicate the puerperal course of the gravida after removal of an extrauterine fetus with nondisturbance of the extrauterine placenta  in this report we describe the successful angiographic arterial gelfoam embolization of the placental vascular bed to control heavy postoperative hemorrhage in a mother suffering adult respiratory distress syndrome after removal of the fetal portion of her abdominal pregnancy  six weeks later  computed tomography  ct  directed drainage by catheter of a placental abscess was performed  selective angiographic transcatheter embolization with gelfoam is a useful tool for the control of hemorrhage in the gravida who is an unfavorable operative candidate or who may present technical hemostasis problems peculiar to the placenta with abdominal pregnancy  later use of ct directed catheter drainage of the infected residual placental mass provided a nonoperative means of treatment  
class8	the modified superior based pharyngeal flap  part i  surgical technique  the superior based pharyngeal flap operation for the correction of velopharyngeal incompetence is perhaps the most commonly employed operation used today in a majority of cleft palate centers  however  inconsistent results with this operation are commonplace  this is believed by most to be due to poor control of the lateral portals  herein is a report of our approach to improve lateral portal control  
class8	the modified superior based pharyngeal flap  part iii  a retrospective study  a retrospective study of 31 patients who had diagnosed velopharyngeal incompetence and were surgically managed with the modified superior based pharyngeal flap was completed  the following were analyzed  age at time of operation  gender  physical status  diagnostic protocol  length of operation  length of total surgery  and length of superior based pharyngeal flap  length of postoperative hospital stay  length of total hospital stay  length of follow up  speech results  complications  patient care  and medication  the result showed that the optimal timing for correction of velopharyngeal incompetence was between 3 and 6 years of age  the mean length of total hospital stay was 2 7 days  postoperative complications were minimal  and speech results were generally good  
class8	open lung biopsy in the critically ill newborn  experience with 17 open lung biopsies in critically ill premature neonates was reviewed  despite their small size  prematurity  and near maximal ventilator requirements  the infants suffered no significant complications  in three cases  an infectious agent was identified  in one case end stage lung fibrosis associated with persistent  greater than 3 months   severe respiratory failure prompted termination of support  in the remainder of the cases  definitively ruling out infection allowed the confident trial of a course of steroids in an attempt to treat bronchopulmonary dysplasia  unlike older patients  the definitive diagnosis of no infection in the premature neonate is just as informative as the diagnosis of an infection  used judiciously  open lung biopsy can be performed in the premature infant with acceptable morbidity and mortality  
class8	serial munchausen syndrome by proxy  five cases of munchausen syndrome by proxy  msbp  are presented in which more than one child in the family was victimized  there was a high incidence of maternal psychiatric histories  marital difficulties  and munchhausen syndrome in the mothers themselves  seventy one percent of the children in the families were known to be victims of msbp  four of these children  31   died  multiple child msbp may reflect more significant maternal psychopathology than found in other cases of msbp  or it may indicate the deteriorating consequences to the mother and other children in the family if this syndrome is not identified with the first child and effective interventions made  
class8	acute respiratory infections during the first three months of life  clinical  radiologic and physiologic predictors of etiology  the usefulness of clinical  radiologic  and physiologic characteristics to identify pathogens was assessed in 90 infants aged two through 12 weeks  presenting to an outpatient clinic with an acute respiratory infection  eighty four cases had cultures or rapid diagnostic tests for rsv  of which 25 were positive  eighty two infants had cultures or rapid diagnostic tests for chlamydia  of which 16 were positive  additional respiratory pathogens identified included parainfluenza  6 cases   rhinovirus  3 cases   pertussis  2 cases   and cmv  1 case   multiple pathogens were identified in four cases  chlamydia and rsv  2 cases   chlamydia and parainfluenza  1 case   and chlamydia and cmv  1 case   clinical characteristics other than the need for hospitalization were not useful predictors of specific pathogens  x rays were obtained in 20  80   of the rsv infections  13  81   of the chlamydia infections  six of the parainfluenza infections  two pertussis infections  and 25 cases without identification of the pathogen  x ray findings could not distinguish between patients with or without a pathogen or between the pathogens  severe findings were present in 28   11 40  of cases with a pathogen identified  compared to 12   3 26  of cases without a pathogen identified  ns   moderate findings were present in 58   23 40  of cases with a pathogen identified compared to 62   16 26  of cases without a pathogen identified  slight negative findings were present in 15   6 40  of cases with a pathogen identified  compared to 27   7 26  of cases without a pathogen identified  pulse oximetry was done in 30 cases  22 of which had a pathogen identified  rsv 14  chlamydia 7  pertussis 1   
class8	chest pain in teenagers  when is it significant  chest pain in teenagers often has no obvious organic cause  onset of symptoms with an emotionally stressful situation may indicate psychogenic chest pain  the differential diagnosis also includes cardiac  musculoskeletal  gastrointestinal  and respiratory disorders  routine testing generally does not help to establish a diagnosis and may even do harm by reinforcing a patient s unspoken fear of serious illness  most teenagers with chest pain have no such illness  and symptoms usually resolve without therapy  an important role for primary care physicians is to provide support during evaluation and follow up  
class8	understanding dizziness  how to decipher this nonspecific symptom  dizziness is a common but often nonspecific symptom  through careful history taking and physical examination  primary care physicians can usually determine the type of sensation  vertigo or light headedness  and its source  although most causes of dizziness are benign  disorders of the central nervous system tend to be ominous and require immediate referral to a specialist  
class8	initial management of trauma  the first 5 minutes  trauma is the leading cause of death in young americans and is responsible for the loss of more productive years of life than heart disease and cancer combined  initial management of trauma consists of the establishment or maintenance of a patent airway  ensurance of adequate breathing  and resuscitation of the circulation  all of these are accomplished simultaneously with a cursory survey to identify immediately life threatening injuries and to prevent permanent disability  
class8	a clinicopathological study of the paraneoplastic neuromuscular syndromes associated with lung cancer  the highest incidence of remote neuromuscular disorders in cancer has previously been reported in lung carcinoma  the clinical incidence of neuromuscular disorder was estimated and correlated with muscle histology and the histological type of lung tumour in 100 patients with lung carcinoma who were studied prospectively  thirty five patients had small cell carcinoma and 65 patients non small cell lung cancer  clinically  33 patients had a polymyopathy  of whom 18 had a cachectic myopathy and 15 had a proximal myopathy  two patients had lambert eaton myasthenic syndrome  one presented with dermatomyositis and one had evidence of ectopic acth production   cachexia was more common in non small cell cancer  proximal myopathy was more common in small cell cancer  ninety nine patients had abnormal muscle histology  74 had type ii atrophy  12 had type i and ii atrophy  one had type i atrophy and 12 had necrosis  the majority of patients were affected sub clinically and the clinical entities of cachectic and proximal myopathy did not correspond to previous pathological classifications  atrophy was not related to the duration of tumour symptoms  ageing  clinical type of myopathy or histological type of lung tumour  and was statistically different from that seen in controls  qualitatively  the presence of weight loss  muscle wasting and metastatic disease were not factors in the development of atrophy  similarly  necrosis was not related to the type of lung tumour  the presence of metastases  ageing  weight loss  muscle wasting  duration of tumour symptoms or the clinical form of myopathy  this study demonstrates that lung carcinoma has a direct effect on the motor unit  including atrophy  a necrobiotic myopathy and lambert eaton myasthenic syndrome  clinical assessment does not accurately assess the  remote  neuromuscular effects of cancer on the motor unit  
class8	oral findings in hiv infected patients attending a department of internal medicine  the contribution of intraoral examination towards the clinical management of hiv disease the occurrence of oral mucosal lesions was studied in 70 consecutive human immunodeficiency virus  hiv  infected patients  including 35 patients with aids  who had been admitted to a department of internal medicine  lesions of the oral mucosa were observed in 52 patients  74 per cent   oral candidiasis  50 per cent   hairy leukoplakia  14 per cent   periodontal disease  13 per cent   and oral kaposi s sarcoma  4 per cent  were the most common lesions  oral mucosal lesions suggestive of hiv infection were present in ten of 12 patients of unknown hiv status in whom pneumocystis carinii pneumonia was suspected  close cooperation between the medical and dental professions is recommended since accurate intraoral examination can make a valuable contribution towards the clinical management of hiv infected patients and may influence the cdc classification of this disease  
class8	double blind randomized study of prolonged higher dose oral amoxycillin in purulent bronchiectasis  thirty eight patients with bronchiectasis and daily expectoration of purulent sputum despite conventional antibiotic courses were randomly allocated to receive a sachet of amoxycillin  3 g  or matched placebo twice daily for 32 weeks in a double blind study  nine patients  four amoxycillin  five placebo  were withdrawn from the study treatment  the response of the two patients  both on amoxycillin  withdrawn within the first six weeks was not assessed  the pretreatment characteristics of the two groups were similar  independent assessment of overall response based on patients  diary cards showed that a higher proportion improved in the amoxycillin group  11 of 17  than in the placebo group  four of 19  p   0 02   patients in the amoxycillin group spent significantly less time confined to bed and away from work during treatment  the frequency of exacerbations during the study treatment phase was similar in the two groups but they were less severe than before study treatment in the amoxycillin group  there was a greater reduction in purulent sputum volume between exacerbations during the study treatment in the amoxycillin group to 20 per cent of pretreatment volume than in the placebo group  88 per cent of pretreatment volume  p   0 008   although the concentrations of haemophilus spp  in sputum between exacerbations was similar in the two groups  adverse effects experienced were minor except in one patient  amoxycillin  withdrawn after developing a rash and in six patients  three amoxycillin  three placebo  who had diarrhoea lasting more than one week necessitating withdrawal of two patients  one amoxycillin  one placebo  from study treatment  sputum and stool cultures collected regularly during the study showed no important changes in the bacterial flora in either group  prolonged higher dose antibiotic therapy in these patients with severe purulent bronchiectasis significantly reduced the host  patient  inflammatory response to colonizing microorganisms and reduced morbidity  
class8	pulmonary neoplastic and lymphoproliferative disease in aids  a review  kaposi sarcoma and lymphoma are the most common forms of neoplastic disease encountered in patients with acquired immunodeficiency syndrome  aids   pulmonary involvement is fairly common with kaposi sarcoma  while lymphoma only rarely involves the lungs  there has been a significant increase in the number of aids patients who develop kaposi sarcoma  especially male homosexuals  there has also been an increase in the incidence of high grade  aggressive  lymphoma in male homosexuals  and young men in general   lymphoid interstitial pneumonia is a chronic condition that primarily affects adults and is becoming more common in patients with aids  when present in children less than 13 years old  lymphoid interstitial pneumonia is considered to be an indication of aids  bronchus associated lymphoid tissue and a condition resembling angioimmunoblastic lymphadenopathy are also being found in children with aids  a review of the literature on neoplastic and lymphoproliferative disease in aids suggests that a variety of lymphoproliferative disorders in aids can be expected in the future  
class8	hemoptysis  ct bronchoscopic correlations in 58 cases  computed tomographic  ct  and chest radiographic findings were retrospectively correlated with those found at fiberoptic bronchoscopy  fob  in 58 patients presenting with hemoptysis  abnormalities involving the airways were depicted by ct in a total of 28 cases  48    in 18 of these  31  of the total group of 58   focal abnormalities involving the central airways were identified  17 were subsequently proved to be malignant  and in 10  17  of the total   ct showed bronchiectasis  focal airway abnormality was shown by fob in 18 cases  31    all of these were depicted with ct  malignancy was diagnosed in 24 patients  including three in whom results of fob were normal but malignant cells were identified at transbronchial biopsy  ct abnormalities were identified in all cases of malignancy  in 10 of 21 cases  48   of non small cell lung cancer  ct allowed definitive staging by documenting either direct mediastinal invasion and or metastatic disease  while fob allowed definitive staging in only three cases  ct studies provided no false negative results  it is concluded that when carefully performed  ct may be an effective modality for evaluating patients presenting with hemoptysis  
class8	coal worker s pneumoconiosis  ct assessment in exposed workers and correlation with radiographic findings  to study the signs of coal worker s pneumoconiosis  cwp  at computed tomography  ct   the authors obtained thoracic ct scans in 170 coal dust exposed workers who were concomitantly evaluated with conventional posteroanterior and lateral radiography  the profusion and extent of disease was assessed by means of ct in two groups of miners  group 1  n   86   miners with worker s compensation and radiographic evidence of cwp  and group 2 n   84   miners who had applied for compensation without radiographic evidence of cwp  the ct signs of cwp consisted of micronodules  nodules  and progressive massive fibrosis  the comparative analysis demonstrates the superiority of an optimal ct technique over chest radiography in the evaluation of simple silicosis  with improved sensitivity in the detection of small parenchymal opacities  ct provides additional information on the stage of the disease but also clarifies some ambiguities of the ilo classification of small opacities  ct was equivalent to radiography for complicated silicosis  except in the identification of necrosis  ct evaluations are complementary to plain radiography in the assessment of cwp  and the addition of high resolution ct is useful in achieving a more accurate evaluation of the small parenchymal opacities  
class8	hamman rich syndrome revisited in this article  we retrospectively review 29 cases of hamman rich syndrome  as in some other recent reports  we have used the term  acute interstitial pneumonia  to emphasize the clinical and pathologic features of these cases and to distinguish them from the more common chronic interstitial pneumonias  particularly idiopathic pulmonary fibrosis  of the 29 patients  12 survived  some after a long and complicated hospitalization  the histologic features were those of organizing diffuse alveolar damage  and some patients  including survivors  had extensive fibroblastic distortion of lung parenchyma  the overall survival among these patients was not appreciably different from the survival of patients with the adult respiratory distress syndrome in general  
class8	haemophilus influenzae  an important cause of maternal and neonatal infections  although haemophilus influenzae is recognized as a major pathogen of infants  its role in maternal and neonatal infections is not as well appreciated  we analyzed the records of all mothers and neonates infected with h influenzae over a 10 year period  twenty eight mother neonate sets were identified in which at least one had documented infection with h influenzae  of the 18 mothers with documented infection  13 had chorioamnionitis  endometritis  or both  and two of these mothers were bacteremic with h influenzae  of the 23 infected neonates  15 presented with early sepsis and or pneumonia and nine had conjunctivitis  during the period of the study  only group b streptococci and escherichia coli were more common as causes of early neonatal bacteremia  under the conditions of this retrospective study  maternal infection predicted neonatal infection  however  prospective studies in which asymptomatic patients are cultured will be required to determine how well maternal colonization infection with h influenzae predicts neonatal infection  
class8	cross sectional physiology of the lung  it is well known that gravity influences the physiology of the lung and thereby affects the intrapulmonary localization of disease processes  less well known are the anatomic and physiologic differences in the axial or cross sectional plane  which also affect the distribution of disease  physiologic gradients in ventilation  perfusion  and lymph flow and stresses in the lung are present in the axial plane  anatomic difference in branching patterns  interstitial design  and development of the secondary pulmonary lobules are also found  these regional disparities in anatomy and physiology can be applied to an old concept  the corticomedullary organization of the lung  and are used to consider why some diseases exhibit a propensity for the central or peripheral portions of the lung  the same analysis is applied to the anatomy and physiology in the secondary pulmonary lobule  
class8	hepatocellular carcinoma within siderotic regenerative nodules  appearance as a nodule within a nodule on mr images  large regenerative nodules in cirrhotic livers may accumulate iron and develop internal iron poor foci of hyperplasia or malignancy  magnetic resonance examinations were performed on 23 patients with biopsy proved cirrhosis  a  nodule within nodule  appearance was noted in two patients  this appearance consisted of markedly low intensity of a large nodule on gradient echo images  with one or two internal foci that were isointense to the liver  each of the large nodules was 2 cm in diameter  and each of the internal foci was less than 1 cm  serum alpha fetoprotein levels were normal in both patients  aspiration biopsy performed in one patient failed to show malignancy  but histologic confirmation of hepatocellular carcinoma was obtained eventually in both cases  the nodule within nodule sign  which reflects the unique histopathology of hepatocellular carcinoma in large siderotic regenerative nodules  is strongly suggestive of early hepatocellular carcinoma  even if serologic markers and biopsy results do not support this diagnosis  
class8	sphenochoanal polyps  evaluation with ct and mr imaging  a sphenochoanal polyp is a solitary mass of low attenuation on computed tomographic  ct  scans that arises from the sphenoid sinus and extends through the sphenoid ostium  across the sphenoethmoid recess  and into the choana  the boundary between the nasal cavity and nasopharynx   more often  however  a choanal polyp is an antrochoanal polyp  which arises from the maxillary antrum  protrudes through the middle meatus  extends into the nasal cavity  and continues back to the choana  contiguous axial or coronal magnetic resonance and ct images help clearly differentiate the rare sphenochoanal polyp from the more common antrochoanal polyp  the sinus of origin is important to identify  as the surgical approach depends on the target sinus  
class8	inferior hilar window  the authors undertook a study to determine the ability to detect mass or adenopathy in the  inferior hilar window   a normally avascular region inferior to the shadow of the right pulmonary artery and vein and anterior to the descending left pulmonary artery on lateral chest radiographs  fifty patients with normal results of thoracic computed tomography  ct  and 25 with unilateral or bilateral hilar masses or adenopathy  defined as opacity greater than 10 mm in diameter  were selected retrospectively  patients with concomitant pulmonary masses or consolidation at ct that might be confused with or obscure an inferior hilar mass or adenopathy were excluded from study  the 75 corresponding lateral chest radiographs were then evaluated blindly  forty seven of the 50 normal cases were correctly interpreted  specificity   94    the anterior walls of the right and left lower lobe bronchi were seen in 36  and 84  of normal cases  respectively  the average thickness was 2 mm  of the 25 patients with inferior hilar masses  22 were recognized as having abnormalities  sensitivity   88    two of the three patients with false negative results had right hilar masses  overall accuracy was 92   for only eight  32   of the 25 patients was the laterality of abnormality correctly diagnosed  evaluation of the inferior hilar window on lateral chest radiographs is accurate in assessing the presence or absence of inferior hilar mass or adenopathy  
class8	mediastinal abnormalities  detection with storage phosphor digital radiography  conventional film radiography  fr  and six postprocessing algorithms of isodose storage phosphor digital radiography  sr   0 2 mm x 10 bit pixel matrix  were compared in the evaluation of 40 mediastinal and 30 pulmonary lesions in 60 patients who underwent computed tomography of the chest  the six sr algorithms varied among each other in only one image parameter  one algorithm approximated conventional image characteristics  the other five algorithms were designed to optimize imaging of the mediastinum and tested the effects of gray scale reversal  adjustment of optical density  a linear instead of a sigmoid gradation curve  and moderate edge enhancement of high and medium spatial frequencies  performance was evaluated by calculating the average area under the receiver operating characteristic curve  az  of 5 040 observations by six readers  post processing with high frequency edge enhancement and density optimization for the mediastinum significantly improved performance of sr over fr in the detection of mediastinal lesions  az    80      02 vs  73      01  respectively   gray scale reversal significantly decreased performance  az    64      03   all sr algorithms that were postprocessed to optimize imaging of the mediastinum were significantly inferior to fr in the detection of pulmonary lesions  
class8	data compression  effect on diagnostic accuracy in digital chest radiography  high resolution digital images make up very large data sets that are relatively slow to transmit and expensive to store  data compression techniques are being developed to address this problem  but significant image deterioration can occur at high compression ratios  in this study  the authors evaluated a form of adaptive block cosine transform coding  a new compression technique that allows considerable compression of digital radiographs with minimal degradation of image quality  to determine the effect of data compression on diagnostic accuracy  observer tests were performed with 60 digitized chest radiographs  2 048 x 2 048 matrix  1 024 shades of gray  containing subtle examples of pneumothorax  interstitial infiltrate  nodules  and bone lesions  radiographs with no compression  with 25 1 compression  and with 50 1 compression ratios were presented in randomized order to 12 radiologists  the results suggest that  with this compression scheme  compression ratios as high as 25 1 may be acceptable for primary diagnosis in chest radiology  
class8	airway evaluation in children with use of ultrafast ct  pitfalls and recommendations  ultrafast computed tomographic  ct  evaluation of the airway can be performed with either 50 msec low resolution images  cine ct  or 100 msec high resolution images  high resolution ct   to determine the best imaging strategy for ultrafast ct of the pediatric airway  the authors prospectively compared ultrafast ct and endoscopy in 20 children  both studies were performed in 11 patients  cine ct alone was performed in six and high resolution ct alone in three  six patients had normal anatomy  six patients had focal tracheal stenoses  four had tracheomalacia or laryngomalacia  one had a laryngoesophageal cleft  one had irregularity and narrowing in the subglottic area  one had laryngeal papillomas  and one had focal stenosis with stoma granuloma  cine ct results agreed with those of endoscopy in 10 of 17 cases  in five cases focal stenosis was misinterpreted with cine ct as tracheomalacia  high resolution ct results agreed with those of endoscopy in 10 of 14 cases  the results of a technique that combined high resolution ct for the entire airway and cine ct at selected areas agreed with those of endoscopy in 10 of 11 cases  only a tracheoesophageal cleft was missed with the combined technique  for the greatest diagnostic accuracy with ultrafast ct in evaluation of the pediatric airway  both cine and high resolution modes should be used  
class8	management of post tuberculous complex aspergilloma of the lung  role of surgical resection  of 14 patients with complex aspergilloma complicating healed tuberculosis  12 underwent lobectomy or pneumonectomy for recurrent haemoptysis  no deaths occurred  though one patient needed re exploration for bleeding  there was no postoperative worsening of dyspnoea despite a mean forced vital capacity  fvc  of 60  predicted for the patients undergoing surgery and of 20  predicted for two patients with severe restrictive defects  perhaps owing to the fact that there was little or no function in the resected part of the lung  as shown by preoperative isotope ventilation perfusion scanning  and that patients were under the age of 50 and generally fit  there has been no recurrence of haemoptysis during follow up  which has been from 12 to 33 months  surgical resection  provided that cases are carefully selected  offers the best chance of cure with low mortality and morbidity  
class8	a general practice based survey of bronchial hyperresponsiveness and its relation to symptoms  sex  age  atopy  and smoking  the prevalence and associations of bronchial hyperresponsiveness were investigated in a general practice population  the sample was obtained by using every 12th patient on the practice age sex register  replacing non responders with corresponding age and sex matched individuals from up to two further 1 in 12 samples  the response rate was 43   366 patients were studied  doubling concentrations of methacholine were given to a maximum of 32 mg ml or until a 20  fall in forced expiratory volume in one second  fev1  occurred  provocation concentration  pc20fev1   bronchial hyperresponsiveness was defined arbitrarily as a pc20fev1 of 2 mg ml or less  or 11 mumol cumulative dose  pd20fev1   the prevalence of bronchial hyperresponsiveness was 23   bronchial hyperresponsiveness was not associated with age but was more prevalent in women than men  31  13    it was also more common in those who had ever wheezed  39   and in those who had had an attack of rhinitis in the preceding month  45   p less than 0 1   in atopic individuals  30    and in smokers  32    but it was not associated with cough or dyspnoea  there was a positive correlation between pc20fev1 and resting fev1  r   0 288  and a negative correlation between pc20fev1 and mean daily peak flow variability  r    0 356   stepwise binary logistic regression analysis showed significant independent effects on pc20fev1 for mean daily peak flow variability  gender  number of positive skin test responses  resting fev1  and mean histamine skin weal area  but no relation with smoking or mean allergen weal area  the prevalence of bronchial hyperresponsiveness was much higher than the prevalence of diagnosed asthma in the practice in 1984  4 9    analysis of case notes of 169 individuals showed that those with bronchial hyperresponsiveness had not attended the practice more frequently for respiratory complaints during the previous five years  
class8	a simple method for correcting single breath total lung capacity for underestimation  the single breath method underestimates total lung capacity by comparison with the multiple breath method  tlcmb  because of inhomogeneity of ventilation distribution  this study proposes a simple correction for the single breath tlc  tlcsb   using inert gas phase iii slope to account for the effects of uneven ventilation distribution  a model of a non uniform lung ventilation was designed  composed of a serial dead space and two alveolar compartments arranged in parallel  whose relative ventilations were determined from the phase iii plateau  before correction tlcsb was 104 44  of tlcmb in 64 subjects  17 with diffuse interstitial disease  42 with chronic obstructive pulmonary disease  and five healthy subjects   the limit of acceptability for the correction  tlccorr  was determined from the 95  confidence interval of tlcsb tlcmb in the healthy subjects  the correction resulted in a significant increase in tlcsb  p less than 0 004   tlccorr remained under the limit of acceptability for only 12 patients with emphysema  and all 12 showed a large improvement in the tlc estimate  the presence of poorly ventilated zones during a single breath in these patients may explain this partial correction  
class8	lung fibrosis induced by thorotrast  a 63 year old woman developed progressive shortness of breath  pulmonary hypertension  and respiratory failure and died from pulmonary fibrosis 45 years after thoracic fistulography with thorotrast  bouts of acute respiratory failure occurred with features of noncardiogenic pulmonary oedema  lung tissue obtained by biopsy and at necropsy showed abundant radioactive particles of thorium dioxide in the lungs  the particles were congregated in the walls of blood vessels and in perivascular fibrous zones  consistent with a causal role of thorotrast in the development of lung fibrosis  it is suggested that the fibrosis was due to the combined effects of alpha radiation on the interstitial perivascular zones and of recurrent pulmonary oedema due to endothelial damage  
class8	adult respiratory distress syndrome after limited resection of adenocarcinoma of the lung  two cases of the adult respiratory distress syndrome developed after limited resection for lung carcinoma  no other known precipitants were evident  the adult respiratory distress syndrome is a clinical expression of acute lung injury that may arise from various insults and include air and blood borne factors  tumour related blood borne factors may have contributed to lung injury in these cases  
class8	diffuse alveolar haemorrhage associated with progressive systemic sclerosis  a 41 year old man with an eight year history of progressive systemic sclerosis developed severe diffuse alveolar haemorrhage and died  the importance of diffuse alveolar haemorrhage as a rare but potentially serious complication of connective tissue disease should not be overlooked  
class8	eosinophilic granuloma of the lung presenting as a solitary pulmonary nodule  a symptomless 58 year old man had an eosinophilic granuloma of the lung that presented as a solitary pulmonary nodule rather than the usual diffuse reticulonodular shadow on the chest radiograph  only one previous case presenting in this way has been described  
class8	effect of obesity on safe duration of apnea in anesthetized humans  obese patients have a decreased functional residual capacity and  hence  a reduced oxygen supply during periods of apnea  to determine whether obese patients are at greater risk of developing hypoxemia during induction of anesthesia than patients of normal weight  24 patients undergoing elective surgical procedures were studied  group 1  normal  were within 20  of their ideal body weight  group 2  obese  were more than 20  but less than 45 5 kg over ideal body weight  group 3  morbidly obese  were more than 45 5 kg over ideal body weight  patients were preoxygenated for 5 min or until expired nitrogen was less than 5   after induction of anesthesia and muscle relaxation the patients were allowed to remain apneic until arterial saturation as measured by pulse oximetry reached 90   the time taken for oxygen saturation to decrease to 90  was 364     24 s in group 1  247     21 s in group 2  and 163     15 s in group 3  these times are significantly different at p less than 0 05 between groups  regression analysis of the data demonstrated a significant negative linear correlation  r    0 83  between time to desaturation and increasing obesity  these results show that obese patients are at an increased risk of developing hypoxemia when apneic  
class8	effect of sulfurous  thermal  water on t lymphocyte proliferative response  we studied the effect of sulfurous water thermal therapy on the phenotype and the proliferative response of peripheral lymphoid cells from ten subjects affected by chronic upper respiratory disease and from six suffering from articular and periarticular disorders  sulfurous water  s h2o  therapy did not modify the phenotype and function of peripheral blood mononuclear cells  pbmc  nor did it modify systemic immunologic reactivity  a different result was obtained by analyzing the response to mitogens of peripheral blood mononuclear cells in cell cultures containing graduated amounts of s h2o  these  in vitro  studies have shown an important dose dependent inhibitory effect of s h2o on mitogen induced t lymphocyte proliferation and on il2 production  h2s present in s h2o seems to be the primary component responsible for inhibition  our results are consistent with a local immunosuppressive role of s h2o  which may explain part of the observed therapeutic effect of inhalation therapy on upper respiratory allergic disorders  
class8	respiratory health of plywood workers occupationally exposed to formaldehyde  this study was undertaken to enlarge our understanding of the adverse health effects of formaldehyde exposure in the workplace and community environment  the respiratory health status of 186 male plywood workers was evaluated by spirometric tests  respiratory questionnaires  and chest x rays  area concentrations of formaldehyde were measured in the work environment and found to range from 0 28 to 3 48 ppm  the average personal exposure was to 1 13 ppm of formaldehyde  exposure to formaldehyde was associated with decrements in the baseline spirometric values  i e   forced expiratory volume in 1 sec  fev1 0   forced expiratory volume forced vital capacity  fev fvc   and fef25  75   and with several respiratory symptoms and diseases  including cough  phlegm  asthma  chronic bronchitis  and chest colds  the results of the study support the hypothesis that chronic exposure to formaldehyde induces symptoms and signs of chronic obstructive lung disease  
class8	involvement of thromboxane and neutrophils in multiple system organ edema with interleukin 2  interleukin 2  il 2  produces toxicity characterized by generalized edema within 24 hours  this study tests whether the rate of il 2 administration modulates the onset of edema and examines thromboxane  tx  and neutrophils as possible mediators of this event  recombinant human il 2  10 5  u  n   7   10 6  u  n   9   or vehicle  n   8  were given to anesthetized rats intravenously during a period of 1 hour  at 6 hours edema  as measured by increase in wet to dry weight  w d  ratio  was present in the heart  liver  and kidney  with 10 5  u il 2 and in the lung  heart  liver and kidney  with 10 6  u il 2  relative to values with vehicle infused controls  all p less than 0 05   with a 1 hour infusion of 10 6  u il 2  there was an increase in plasma thromboxane  tx b2 level to 1290     245 pg ml  higher than 481     93 pg ml in control rats  p less than 0 05   lung polymorphonuclear leukocyte  pmn  sequestration of 53     7 pmn 10 higher power fields  hpf  relative to 23     2 pmn 10 hpf in controls  p less than 0 05   and increased bronchoalveolar lavage  bal  fluid protein concentration of 1970     210 micrograms ml relative to 460 micrograms ml in controls  p less than 0 05   when 10 6  u il 2 was given as a 1 minute intravenous bolus  n   9   edema was not demonstrated  plasma txb2 levels were similar to controls  there was no leukosequestration  and bal protein levels were normal  these data indicate that a constant infusion but not the rapid bolus administration of il 2 produces in rats multiple system organ edema  increased plasma txb2  sequestration of pmns  and microvascular permeability  these findings may explain the early toxicity seen in patients given high dose il 2 in cancer treatment  
class8	normalization of ventilation perfusion relationships after liver transplantation in patients with decompensated cirrhosis  evidence for a hepatopulmonary syndrome  to examine the effect of liver transplantation on the respiratory and cardiovascular functions  ventilation perfusion relationships were determined by multiple inert gas elimination technique in six patients with end stage liver disease 1 to 19 mo before and 2 to 6 mo after liver transplantation  cardiac output and pulmonary vascular pressures were measured after catheterization of the pulmonary artery  all patients had normal spirometry and chest x ray films before transplantation  pao2 before transplantation was 78 8     7 4 mm hg  range   51 8 to 102 8 mm hg   all patients had perfusion of poorly ventilated lung regions  low ventilation perfusion relationships  varying from 3  to 19  of cardiac output  mean   8 5      2 4  of cardiac output  and two patients had intrapulmonary shunting  3  and 20  of cardiac output   measured and calculated pao2 agreed closely  indicating absence of pulmonary diffusion abnormality  as well as of extrapulmonary shunting  after transplantation  pao2 normalized in all patients  and both shunting and low ventilation perfusion relationships disappeared  cardiac output decreased from 9 1     1 4 to 6 6     0 5 l min  p less than 0 05   and the pulmonary vascular resistance increased from 0 69     0 14 to 1 64     0 43 mm hg l min  p less than 0 05   the systemic vascular resistance also increased  before   8 7     1 0  after   15 3     1 1 mm hg l min  p less than 0 001   normalization of respiratory and cardiovascular alterations  after liver transplantation  in patients with end stage liver disease indicates that these changes have a direct functional relationship to the diseased liver  it is hypothesized that this is part of a  hepatopulmonary syndrome   which in similarity to the hepatorenal syndrome disappears with improved liver function  
class8	role of histamine in natural killer cell mediated resistance against tumor cells  the formation of lung metastases by i v  injected b16 melanoma  f1 and f10 strain  cells in swiss albino  c57bl 6  and balb c mice was reduced by a single dose of histamine given 24 h before tumor cell inoculation  the antimetastatic effect of histamine was specifically mediated by histamine h2 receptors  h2r   it was blocked by the h2r antagonist ranitidine and mimicked by dimaprit  a specific h2r agonist but not by an h2r inactive structural analog of this compound  nor dimaprit  or the h1r agonist 2 thiazolyl ethylamide  a single dose of any of the h2r antagonists ranitidine  tiotidine  famotidine  or cimetidine drastically augmented metastasis  effects of h2r interactive compounds on b16 metastasis required intact nk cells  as judged by the inability of histamine or ranitidine to affect b16 metastasis after nk cell depletion in vivo using antibodies to asialo gm1  nk cell mediated lysis of yac 1 lymphoma cells in vivo was enhanced by histamine and reduced by ranitidine within 4 h after inoculation of tumor cells  the antimetastatic effect of il 2 was potentiated by histamine  in some experiments  combined treatment with a low dose of il 2  6000 u kg  and histamine completely eliminated metastasis  whereas concomitant treatment with ranitidine abrogated antimetastatic effects of il 2  animals treated with ranitidine and il 2 displayed the same level of enhanced metastasis as those treated with ranitidine alone  the presented data are suggestive of an earlier unrecognized role for histamine in nk cell mediated resistance against metastatic tumor cells  
class8	mediastinitis following coronary artery bypass surgery  a 3 year review  twenty cases of mediastinitis after coronary artery bypass graft operations in 1985 1987 were reviewed to determine risk factors  two distinct clusters with a methicillin resistant staphylococcus aureus  mrsa  strain occurred in 1986  one resident was exposed to six cases but to only 5 of 24 controls  p less than  008   cultures of his nares in january and november 1986 revealed the same mrsa strain as that of the cases  an attempt to eradicate the resident s nasal carriage of mrsa in january 1986 failed  eradication of his carrier state was achieved only after treatment with mupirocin  in a case control study examining patients exposed to the resident  a prolonged duration of surgery  p less than  05  and a preoperative albumin level of less than 3 0 g dl  p less than  009  were associated with mediastinitis with this mrsa  for the other 14 mediastinitis patients  who were not exposed to the resident  a preoperative albumin level of less than 3 0 g dl was also a risk factor  8 14 cases vs  8 43 controls  p less than  009   thus  this study suggests that it is important to follow mrsa disseminators and to recognize that preoperative serum albumin levels are a risk factor for mediastinitis  
class8	human serologic response to envelope associated proteins and adenylate cyclase toxin of bordetella pertussis  the human serologic response to several envelope associated proteins and adenylate cyclase toxin of bordetella pertussis was examined using immunoblot techniques  antigens recognized by sera from individuals with culture confirmed pertussis and by sera from infants immunized with three doses of conventional whole cell pertussis vaccine included a 63 000 da protein that was shown to be antigenically related to a mycobacterial heat shock protein  a 29 000 da protein reacted with sera from convalescent individuals  whereas a 91 000 da protein reacted with sera from vaccinated individuals  antibodies to adenylate cyclase toxin were common in sera from individuals diagnosed with pertussis  b  pertussis lipooligosaccharide was also recognized by antibodies in some of these sera  these data suggest that some of these antigens may play a role in immunity to pertussis  
class8	pharmacokinetics of intravenous pentamidine in patients with normal renal function or receiving hemodialysis  the pharmacokinetics of intravenous pentamidine were studied in 10 patients with normal renal function  group 1   9 volunteer subjects without pneumocystis carinii pneumonia who were receiving maintenance hemodialysis  group 2   and 5 patients with normal or mildly abnormal renal function  group 3  after the last dose of therapy  the concentration time data were best represented by a three compartment model  the peak plasma concentration  plasma clearance  and elimination half life ranged from 249     80 to 227     110 ng ml  268     70 to 329     58 l h  and 29     25 to 118     119 h  respectively  in groups 1 and 2  in group 1  trough concentration increased progressively  linear regression  y   4 4x  r    91  p    001  without achieving steady state  and the renal clearance to plasma clearance ratio was 2 1      0 01   in group 3  the elimination half life after the last dose was 12 0     2 3 days  the elimination half life of pentamidine was long and accumulation occurred with daily dosing even in patients with normal renal function  dose adjustment is not recommended for renal impairment as renal clearance accounts for a small fraction  2 1   of plasma clearance  
class8	effects of tromethamine and hyperventilation on brain injury in the cat  the metabolic brain acidosis after trauma has been thought to be harmful and to contribute to neurological deterioration  amelioration of the brain acidosis either by systemic buffering agents or by hyperventilation has been proposed as a method of treatment  the objective of this study was to explore with magnetic resonance  mr  spectroscopy the metabolic changes in brain that occur with the use of hyperventilation  tham  tromethamine  tris hydroxymethyl aminomethane   and a combination  tham and hyperventilation  therapy in experimental fluid percussion injury  brain lactate  brain ph  inorganic phosphate  pi   and adenosine triphosphate levels were measured by 1h and 31p mr spectroscopy  arterial and cerebrovenous lactate and water content in brain tissue was determined in 29 cats using the specific gravimetric technique  following injury  the phosphocreatine  pcr  pi ratio  which is an index of cerebral energy depletion  decreased to 76  in four untreated animals  to 79  in 11 tham treated animals  to 68  in seven animals receiving hyperventilation  and to 66  in seven animals with combination tham and hyperventilation therapy  the pcr pi ratio returned to a normal level in 8 hours in animals treated with tham and tham in combination with hyperventilation  the brain lactate index increased to 157  in the hyperventilation group after trauma  in cats receiving tham plus hyperventilation  the brain lactate index was reduced to 142   while the minimum rise of 126  was associated with treatment of tham alone  in the tham treatment and combination treatment groups  the water content of the white and gray matter was significantly decreased compared with that in untreated cat brains  prolonged hyperventilation provided relative ischemia in brain tissue and promoted more production of brain lactate  no recovery of the pcr pi ratio  and no decrease in brain edema  on the other hand  administration of tham decreased production of brain lactate and brain edema and promoted the recovery of cerebral energy dysfunction  it was found that tham ameliorates the deleterious effects of hyperventilation by minimizing energy disturbance and that it also decreases brain edema  the authors conclude that tham may be effective in reducing brain tissue acidosis and helpful as a metabolic stabilizing agent following severe head injury  
class8	the management of flail chest injury  factors affecting outcome  the records of 57 patients presenting with flail chest injury from 1981 through 1987 were reviewed to determine factors affecting morbidity and mortality  fifteen patients  26   had 8  rib fractures with a unilateral flail and seven  12   had multiple rib fractures with a bilateral flail  thirty two  56   had moderate severe pulmonary contusions and 44  77   required chest tubes for hemo pneumothorax  ventilatory assistance was used in 36  63    the major factors determining the need for ventilatory assistance were  an iss greater than or equal to 23  blood transfusions in the first 24 hours  moderate severe associated injuries  fractures  head injuries or truncal organs requiring operation   and shock on admission  p less than 0 001   an adverse outcome occurred in 15  28    nine required ventilatory assistance greater than or equal to 14 days and six died of sepsis with pneumonia  the main factors associated with an adverse outcome were  an iss greater than or equal to 31  p less than 0 001   moderate severe associated injuries  p less than 0 001   and blood transfusions  p less than 0 005   although the primary determinants of an adverse outcome were the associated injuries and blood loss  a bilateral flail  p less than 0 01  and age greater than or equal to 50 years  p less than 0 02  were contributing factors  
class8	molecular pathologic study of human papillomavirus infection in inverted papilloma and squamous cell carcinoma of the nasal cavities and paranasal sinuses  nasal inverted papilloma is a rare benign tumor occasionally associated with squamous cell carcinoma  to determine the etiological role of human papillomavirus in inverted papilloma  and to clarify the relationship between human papillomavirus and malignant transformation of this benign tumor  we retrospectively analyzed inverted papillomas from 26 patients  7 of whom had squamous cell carcinoma  we used an immunohistochemical method and molecular pathologic techniques  or dot blot hybridization of dna extracted from paraffin embedded tissues  in situ hybridization  and polymerase chain reaction  human papillomavirus was detected in 5 of 26 patients  19    3 patients with human papillomavirus 11 and 2 patients with human papillomavirus 16  the latter 2 patients had inverted papillomas associated with squamous cell carcinoma  we speculate that human papillomavirus may be related to the malignant transformation of inverted papillomas  
class8	esthesioneuroblastoma with intracranial extension  the authors present five cases of olfactory neuroblastoma with intracranial extension operated on in the department of neurosurgery in collaboration with otorhinolaryngologists  this tumor is most frequently reported as growing inside the nasal cavities  and it can extend to the paranasal sinuses  cases presenting initially as intracranial tumors have been infrequently reported  at present  histological diagnosis of this tumor is aided by the use of electron microscopy and immunocytochemistry  total resection combined with radiation therapy remains the most satisfactory treatment  
class8	surfactant treatment of full term newborns with respiratory failure  surfactant inactivation has been shown to be a significant factor in animal models of lung injury and may also be important in some forms of respiratory failure in full term newborns  fourteen full term newborns with respiratory failure associated with pneumonia  7 patients  and meconium aspiration syndrome  7 patients  were treated with 90 mg kg of a calf lung surfactant extract  given intratracheally up to every 6 hours for a maximum of four doses  the group mean fraction of inspired oxygen  fi02  before treatment was 0 99     0 01 sem  and the mean airway pressure  map  was 14 6     1 0 cm h2o  patients showed significant improvement in oxygenation after initial surfactant treatment  with the arterial alveolar oxygenation ratio  a a ratio  rising from 0 09     0 01 before surfactant treatment to 0 22     0 05 by 15 minutes  p    03  and remaining improved for 6 hours  the oxygenation index  incorporating map as well as oxygen variables  also improved significantly from 26 2     3 1 to 11 2     1 7 at 15 minutes  p less than  001   with improvement sustained for more than 6 hours  chest radiographs were blindly scored from 0  normal  to 5  severe opacification   and these improved with marginal significance after initial surfactant treatment  from 2 9     0 2 to 2 5     0 2  p    05   
class8	risk of respiratory illness associated with day care attendance  a nationwide study  the risk of respiratory and other illnesses in children  age groups  6 weeks through 17 months  18 through 35 months  and 36 through 59 months  in various types of day care facilities was studied  children considered exposed to day care were those who were enrolled in day care with at least one unrelated child for at least 10 hours per week in each of the 4 weeks before the interview  unexposed children were not enrolled in any regular child care with unrelated children and did not have siblings younger than 5 years of age receiving regular care with unrelated children  although an increased risk of respiratory illness was associated with attending day care for children in all three age groups  this risk was statistically significant only for children 6 weeks through 17 months of age  odds ratio   1 6  95  confidence interval   1 1 to 2 4  and children 18 through 35 months of age who had no older siblings  odds ratio   3 4  95  confidence interval   2 0 to 6 0   in contrast  day care attendance was not associated with an increased risk of respiratory illness in children 18 through 35 months of age with older siblings  odds ratio   1 0   for children aged 6 weeks through 17 months  the exposure to older siblings was associated with an increased risk of respiratory illness  however  for children aged 36 through 59 months  older siblings were protective against respiratory illness  in addition  for the children in each age group currently in day care  increased duration of past exposure to day care was associated with a decreased risk of respiratory illness  
class8	greenfield filter as primary therapy for deep venous thrombosis and or pulmonary embolism in patients with cancer  in 1985  as a result of the high complication rate associated with anticoagulants in patients who have cancer and deep venous thrombosis  dvt  and or pulmonary embolism  pe   we established a policy of placing greenfield filters  gfs  as primary therapy instead of anticoagulation  since 1985 we have been asked to consult in the treatment of 18 patients with cancer and with dvt and or pe  and we have placed a gf in each of these patients  this represented 34   18 53  of the filters placed during that same period  over the same 4 year period  11 patients with cancer and dvt and or pe underwent anticoagulation therapy  the purpose of this study was to compare the results of anticoagulation versus gf insertion in these two groups of patients  a significantly higher number of major complications  n   4  occurred in the anticoagulation group  p less than 0 05  fisher s exact test  than in the gf group  n   0   the four complications that occurred in the anticoagulation group included three bleeding episodes  tumor bleeding  gastrointestinal bleeding  and hip hematoma  and one pe  despite adequate anticoagulation  two patients died as a direct result of these complications  pe and gastrointestinal bleeding   the three patients with bleeding complications each required a transfusion of more than 3 units of blood  all four of the patients with complications had metastatic disease  pancreatic carcinoma  chronic lymphocytic leukemia  prostate carcinoma  and uterine carcinoma   although this is a small  nonrandomized  nonprospective study  the data seem to indicate that gf placement is safer than anticoagulation for dvt or pe in patients with cancer and particularly in patients with metastatic disease  we conclude that gf insertions may be a better primary treatment than anticoagulation  
class8	adult respiratory distress syndrome during pregnancy and immediately postpartum  from 1976 to 1983  the adult respiratory distress syndrome occurred in 14 patients during pregnancy or within a month postpartum  there were 8 survivors  giving a 43  mortality  all but 2 patients had obstetric related precipitating events  labor problems  infections  eclampsia toxemia  and obstetric hemorrhages  during emergency cesarean sections  3 patients had respiratory problems that may have caused their respiratory distress syndrome  the average duration of mechanical ventilatory support was 16 days  six patients had barotrauma with 1 patient sustaining an irreversible anoxic central nervous system injury  infections were documented in 8 patients  6 of whom had obstetric foci  there is a lack of information regarding the adult respiratory distress syndrome in this patient group  though uncommon  it can cause substantial mortality and morbidity  
class8	intravenous streptomycin  streptomycin is an effective drug for the treatment of tuberculosis  it is currently recommended for use only by the intramuscular route  this method of drug delivery is accompanied by considerable pain which is unacceptable to many patients  with the advent of many improvements in intravenous therapy that have occurred in the past 40 years  reevaluation of the intravenous use of this drug is warranted  we describe the short term use of intravenous streptomycin in four patients with pulmonary tuberculosis  
class8	central pulmonary embolism with normal ventilation perfusion scan diagnosis by nuclear pulmonary artery flow studies  pulmonary embolism  although uncommon in children  occurs in as many as 104 per 100 000 pediatric patients  undiagnosed and untreated pulmonary embolism has a high mortality rate  thus  a high index of clinical suspicion and reliable diagnostic modalities are necessary to ensure prompt and accurate diagnosis  we report the case of a patient with severe central pulmonary embolism with a normal ventilation perfusion scan  the embolus was identified by a nuclear pulmonary flow study using dynamic imaging  which obviated the need for contrast pulmonary angiography  the traditional ventilation perfusion scan may appear normal despite severe central pulmonary embolism  in this situation  early dynamic imaging is necessary to detect severe obstruction of the central pulmonary arteries  this approach may obviate the need for contrast pulmonary angiography in hemodynamically stable patients  
class8	oral corticosteroid therapy for patients with stable chronic obstructive pulmonary disease  a meta analysis purpose  to evaluate the effectiveness of oral corticosteroid therapy in patients with stable chronic obstructive pulmonary disease  data identification  an english language literature search using medline  1966 to 1989  and a bibliographic review of all retrieved articles identified 33 original studies of oral corticosteroid use in chronic obstructive pulmonary disease published since 1951  study selection  we submitted a photocopy of each study s  methods  section to three nonstudy physician investigators who used nine explicit criteria to independently assess study quality  ten studies met all criteria and five studies met some of the criteria  data extraction  to compare outcomes across all qualifying studies  we defined response to therapy as a 20  or greater increase in the baseline forced expiratory volume in 1 second  fev1   we defined the treatment effect size for each study as the proportion of patients who responded to corticosteroid therapy minus the proportion of patients who responded to placebo  potential confounding variables as related to eligibility criteria and treatment protocols were also assessed for each study  results of data synthesis  among ten studies that met all nine criteria  we found no significant differences in eligibility criteria  treatment protocol  or study design  no association was found between treatment effect size and publication date  study size  mean patient age  or fev1  these studies had reported effect sizes ranging from 0  to 56   we calculated a weighted mean effect size of 10   95  ci  2  to 18    when studies meeting only some of the criteria were included in the calculation  the weighted mean effect size was 11   95  ci  4  to 18    conclusions  patients with stable chronic obstructive pulmonary disease receiving oral corticosteroid therapy have a 20  or greater improvement in baseline fev1 approximately 10  more often than similar patients receiving placebo  
class8	respiratory failure and unilateral caudal brainstem infarction  we report clinicotopographic correlations in 2 patients with central hypoventilation and unilateral infarct in the caudal brainstem  one patient had nearly complete loss of ventilation involving both automatic and voluntary components  he showed no ventilator response during a co2 retention test  paco2 62 mm hg  pao2 82 mm hg   while consciousness was preserved until death  the infarct involved the reticular formation  nucleus tractus solitarius  nucleus ambiguus  and nucleus retroambiguus on the right but spared the dorsal motor nucleus of the tenth cranial nerve  and sensory and corticospinal tracts  the second patient showed hypoventilation more selectively involving automatic responses  ondine s curse   the infarct involved the medullary reticular formation and nucleus ambiguus but spared the nucleus tractus solitarius  we suggest that unilateral involvement of pontomedullary reticular formation and nucleus ambiguus is sufficient for generating loss of automatic respiration  while associated lesion of the nucleus tractus solitarius may lead to more severe respiratory failure involving both automatic and voluntary responses  
class8	pneumocystis carinii pneumonia treated with eflornithine in aids patients resistant to conventional therapy  eflornithine  dfmo  was used to treat 31 aids patients with confirmed pneumocystis carinii pneumonia who had clinically failed treatment with pentamidine  sulphamethoxazole trimethoprim or both agents as their first line therapy  twenty one of 31  68   responded to second line treatment with 400mg kg per day of eflornithine  five patients discontinued treatment because of bone marrow toxicity  eflornithine appears to be a useful salvage therapy in patients failing first line treatments  
class8	extrapulmonary and disseminated tuberculosis in hiv 1 seropositive patients presenting to the acute medical services in nairobi  we studied 506 consecutive adult acute medical admissions to hospital in nairobi  95  18 8   were seropositive for hiv 1  and 43 new cases of active tuberculosis  tb  were identified  tb was clearly associated with hiv infection  occurring in 17 9  of seropositive patients compared with 6 3  of seronegatives  odds ratio  or  3 2  95  confidence limits  cl  1 6 6 5   extrapulmonary disease was more common in seropositive than seronegative tb patients  nine out of 17 versus five out of 26  or 4 7  95  cl 1 01 23 6   this accounted for most of the excess cases of tb seen in seropositive patients  mycobacteraemia was demonstrated in two of eight seropositive tb patients but in none of 11 seronegative tb patients  no atypical mycobacteria were isolated  the world health organization  who  clinical case definition for african aids did not discriminate well between seropositive and seronegative tb cases  five out of seven seropositive women with active tuberculosis had delivered children in the preceding 6 months and were lactating  compared with only one out of eight seronegative tuberculous women  an association between recent childbirth  hiv immunosuppression and the development of tb is suggested  
class8	mechanism of bronchodilator effect in chronic airflow limitation  objective  to examine the mechanisms through which two bronchodilators  theophylline and salbutamol  influence dyspnea during daily activities  methods  twenty four patients with chronic airflow limitation participated in a multiple crossover  randomized  placebo controlled trial  the effect of theophylline and salbutamol  alone or combined  on pulmonary function and dyspnea during daily activities was examined  correlations of changes in forced expiratory volume in 1 second  fev1  and maximum expiratory pressures  mips   independent variables  and changes in dyspnea score during daily activities  dependent variable  were also examined  results  the two drugs proved to be beneficial the effects in general were additive rather than synergistic  the drugs improved the fev1  theophylline significantly improved the mips  the correlation between the changes in fev1 and those in dyspnea score  after adjustment for the changes in mips  was 0 55  p less than 0 001   the correlation between the changes in mips and those in dyspnea score  after adjustment for the changes in fev1  was 0 39  p less than 0 001   conclusions  changes in airway calibre and in respiratory muscle strength play an independent and important role in dyspnea during daily activities in patients with chronic airflow limitation  changes in airway calibre may be of greater importance  
class8	current status of etoposide in the management of small cell lung cancer  etoposide is a schedule dependent drug with excellent activity against small cell lung cancer  sclc   single agent etoposide achieves overall response rates ranging from 15  to 84   depending on the schedule of drug administration and the characteristics of the treated population  the route of etoposide administration  intravenous versus oral  has little impact on response rate  provided appropriate dose adjustments are made for oral therapy  in combination with other active agents  etoposide has proven particularly effective in the management of sclc  etoposide can be substituted for doxorubicin or vincristine in the cyclophosphamide  doxorubicin  and vincristine  cav  regimen without loss of efficacy  the etoposide and cisplatin  ep  combination is thought to be synergistic and has proven to be an effective salvage regimen for cav failures  a regimen that alternates cav and ep has been found by some investigators to be modestly more effective against sclc than cav alone  however  ep alone may be as useful as an alternating regimen  most studies to date have demonstrated that ep induction is at least as effective as any other standard induction regimen  however  ep has the potential advantage of being more easily integrated with thoracic radiation therapy  rt   this is particularly important in limited disease patients  two recent pilot studies employing ep induction with hyperfractionated thoracic rt yielded 2 year survival rates of greater than 50   these promising results are being evaluated further in an ongoing phase iii trial in the united states  the available data indicate that etoposide is one of the most active agents against sclc and therefore should be included as a component of induction therapy in all patients  new schedules of etoposide administration warrant further study  
class8	a randomized trial to compare intravenous and oral etoposide in combination with cisplatin for the treatment of small cell lung cancer  in a randomized multi center study  83 patients with small cell lung cancer were randomly assigned to treatment with cisplatin 100 mg m2 intravenously  iv  day 1 and etoposide 120 mg m2 iv days 1  2  and 3 or cisplatin 100 mg m2 iv day 1 and etoposide 120 mg m2 iv day 1 and 240 mg m2 orally days 2 and 3  both regimens were repeated every 4 weeks  prior to randomization  patients were stratified by extent of disease  performance status  and gender  a total of 41 patients were randomly assigned to the parenteral treatment only regimen  and 42 patients received cisplatin and iv oral etoposide therapy  both treatment arms were comparable regarding patient characteristics  limited disease  ld  patients constituted 52  and 49  of the patient population for the oral and iv etoposide regimens  respectively  the overall complete response  cr  and partial response  pr  rate was 50   95  confidence interval  ci  35  to 65   for the oral etoposide regimen and 59   95  ci 44  to 74   for the iv etoposide regimen  p   0 438   for both regimens  55  of the ld patients achieved either cr or pr  time to progression and survival were comparable for both treatment arms  hematologic toxicity was comparable in both treatment arms  with 80  of patients experiencing grade 3 or 4 neutropenia or thrombocytopenia  moderate to severe anemia and weight loss were more predominant with the iv than with the oral regimen  
class8	etoposide in the management of non small cell lung cancer  etoposide is a phase specific  schedule dependent derivative of podophyllotoxin that appears to act by inhibiting dna topoisomerase ii  early preclinical work demonstrated sharp activity in mouse leukemias and possible synergy with cisplatin  as a single agent  either orally or intravenously   it demonstrated limited benefit in non small cell lung cancer  nsclc   with response rates around 10   in combination with cisplatin  it has become a mainstay of chemotherapeutic efforts  either as primary therapy or in conjunction with radiation  response rates in advanced disease average around 30   climbing to more than 50  in patients with stage iiia or iiib disease  more recent work suggests that the issue of the true synergy of etoposide with cisplatin in nsclc needs reassessment  the relative roles of etoposide and cisplatin in the combination are unclear  as several studies conflict  pharmacokinetic data suggest that multiple daily fractions of etoposide are superior to prolonged infusions  warranting several future trials  the current major role for etoposide plus cisplatin would appear to be in multimodality therapy where the combination can be readily combined with radiation and or surgery  several other agents have been studied with etoposide or etoposide plus cisplatin  mitomycin  vindesine  doxorubicin  cyclophosphamide  ifosfamide  and carboplatin   but it is unclear whether the addition of any of them offers any response or survival advantage  
class8	recent advances in etoposide therapy for non small cell lung cancer  non small cell lung cancer  nsclc  continues to be a major health problem in the us  in 1990  approximately 120 000 new cases will be diagnosed  and the majority of these patients will have either unresectable disease or resected disease that has a relatively low chance of being cured  a variety of chemotherapy treatments have been evaluated in patients with advanced nsclc  the objective of this review is to summarize the results of the chemotherapy trials in stage iii and iv nsclc patients  
class8	pulmonary metastases and bone sarcomas  surgical removal of lesions appearing after adjuvant chemotherapy  pulmonary metastasis is the leading cause of death in pediatric patients with bone tumors  multiple thoracotomies for surgical removal of individual lesions are performed at many centers  to explore the efficacy of this procedure and establish guidelines for an appropriate choice of patients  the experience with 43 thoracotomies in 24 children was reviewed  the appearance of first metastasis later than one year after diagnosis  presence of fewer than five nodules  and completeness of surgical resection were favorable predictors of postthoractomy survival  early or multiple metastases  unresectable disease  and hilar  nodal  or pleural lesions conferred an unfavorable prognosis  with careful patient selection  pulmonary metastecotomy is a safe procedure that has few operative or long term complications  it must be emphasized that although surgical removal of pulmonary metastases prolongs survival with good quality of life  the majority of patients with bone sarcomas ultimately succumb to their disease after thoracotomy  follow up time of greater than eight years is necessary to adequately assess the effectiveness of pulmonary resection in eradicating all disease in these patients  
class8	pulmonary surveillance using bronchoscopy and bronchoalveolar lavage during high dose antineoplastic therapy  pulmonary failure is a major contributor to morbidity and mortality during marrow aplasia following high dose antineoplastic therapy  for this reason  we initiated a pulmonary surveillance program for patients undergoing high dose chemotherapy for leukemia or bone marrow transplantation  as part of this program  bronchoscopy with bal was performed prior to therapy and at the onset of granulocytopenia  thirty three of the first 57 patients managed in this program developed some evidence of pulmonary complications  twelve patients died in aplasia  all had pulmonary failure  forty patients had clinically significant abnormalities on the bronchoscopy before treatment including 12 of 19 patients who had normal findings on chest x ray films  physical examination  and pulmonary function testing  and no fever  twenty seven patients had clinically significant abnormal bronchoscopy or bal at the onset of granulocytopenia  thirteen patients required additional bronchoscopy  no patient required an open lung biopsy  pulmonary surveillance using bronchoscopy with bal is useful in the detection of pulmonary disease prior to the initiation of and following high dose antineoplastic therapy  
class8	the chest roentgenogram in pulmonary tuberculosis patients seropositive for human immunodeficiency virus type 1  to determine the impact that co infection with hiv has on the radiographic presentation of pulmonary tuberculosis  we examined the chest roentgenograms obtained before treatment in 225 hiv tested adult haitians with bacillary  smear or culture or both  positive pulmonary tuberculosis  there were 67 hiv seropositive and 158 hiv seronegative patients  intrathoracic adenopathy alone was more common and parenchymal infiltrates less common in hiv seropositive patients  p less than 0 05   although a parenchymal infiltrate was less likely to be cavitating in the hiv seropositive group  p less than 0 05  when cavitary parenchymal disease was present  hiv seropositivity did not affect the number of cavities  single or multiple  or the size of the largest cavity  patients with aids were significantly more likely to have a chest radiographic pattern consistent with primary tuberculosis  80 percent  than hiv seropositive patients without aids  30 percent   and the latter were significantly more likely to have such a pattern than hiv seronegative patients  11 percent   p less than 0 05   the hiv seropositive patients were equally infectious  regardless of the pattern of disease  primary vs postprimary   even though pulmonary tuberculosis in an hiv seropositive adult probably results from reactivation of dormant foci or reinfection  the pattern on the chest roentgenogram often suggests primary disease  especially if the patient has aids  
class8	target flow inspiratory muscle training during pulmonary rehabilitation in patients with copd  the effects of additional target flow inspiratory muscle training  tf imt  on the performance of the inspiratory muscles  on general exercise capacity  and on psychologic parameters during a pulmonary rehabilitation program  pr  were studied in 40 patients with copd selected for ventilatory limitation during exercise  the mean age of the patients was 59 years  and the mean fev1 was approximately 50 percent of predicted  all patients participated in a ten week pr program  they were randomized to receive either additional tf imt  pr   imt  or not  pr   the tf imt was performed by means of a target flow resistive device  the generated mouth pressure and the duration of inspiration and of the respiratory cycle were imposed  after the training period  maximal inspiratory mouth pressure and emg fatigability of the diaphragm were significantly better in the pr   imt group than in the pr group  maximal work load and psychologic symptoms increased to the same extent in both groups  the 12 minute walking distance also increased in both groups  but it increased significantly more in the pr   imt group than in the pr group  we believe that additional tf imt during pr in a selected group of patients with copd who have ventilatory limitation has an extra beneficial effect on the performance of the inspiratory muscles and on exercise performance  
class8	99mtc anti cea radioimmunoscintigraphy of lung adenocarcinoma  anti carcinoembryonic antigen radioimmunoscintigraphy  anti cea ris  in colorectal adenocarcinoma has been reported to allow a better estimation of the local tumor extension than other radiologic methods  this study evaluated the clinical feasibility of a 99mtc labeled anti cea monoclonal antibody  bw 431 26  behring institute  frg  in 11 patients for staging of primary adenocarcinoma of the lung  the primary tumor size ranged from 3 to 8 cm with a mean of 4 cm  mediastinal and hilar nodes were present in four patients  intrapulmonary metastases were present in two patients  and pleural and liver metastases were present in one patient each  the cea levels were in the range of 2 to 265 ng ml and elevated  greater than 5 ng ml  in six patients  planar scintigraphy was performed at 6 h and 24 h post injection  pi   analog and digitized images were interpreted by two observers  one patient was imaged twice and experienced serum sickness due to human anti mouse antibodies  hama  after the second study  which showed marked unspecific tracer uptake in liver  spleen  and bone marrow  but no specific uptake by the tumor and was excluded from further analysis  visual interpretation identified the primary tumor clearly in seven patients  no tumor imaging was observed in two patients  two patients were classified as having questionable imaging due to a poor separation of tumor uptake from mediastinal blood pool  the primary tumor could be clearly delineated in both patients after comparison with the chest radiograph  thus  the overall sensitivity for imaging of the primary tumor was 82 percent  the average target background ratio was 1 31     0 17 1 at 6 h pi  and 1 30     0 16 1 at 24 h pi  hilar and mediastinal nodes were correctly suspected in three patients  but the cardiac blood pool hampered a clear interpretation  intrapulmonary and pleural metastases were diagnosed in all cases  the single liver metastasis was missed because of the high unspecific tracer uptake  planar anti cea ris with 99mtc bw 431 26 was superior to computed tomography  ct  in one case with subtotal tumor resection  we summarize that at present  planar anti cea ris with 99mtc bw 431 26 cannot be advised as a routine staging procedure in adenocarcinoma of the lung  but it may be helpful in the detection of residual or recurrent tumor tissue  
class8	pulmonary complications of combination therapy with cyclophosphamide and prednisone  oral cyclophosphamide and prednisone are standard treatment for some neoplasms and necrotizing systemic vasculitis and are advocated with increasing frequency for idiopathic interstitial lung disease  during a 15 month period  we observed four cases of acute respiratory failure from pneumocystis carinii pneumonia  pcp  in patients treated with oral cyclophosphamide and prednisone  one patient each had polyarteritis nodosa  wegener s granulomatosis  bronchiolitis obliterans with organizing pneumonia  and chronic lymphocytic leukemia with red blood cell aplasia  hypoalbuminemia  serum albumin level less than 3 0 g dl  and daily therapy were associated with increased risk for development of pcp  p less than 0 05   none of the patients had leukopenia  less than 3 500 cu mm  or neutropenia  less than 1 000 cumm  at diagnosis  all were negative for the human immunodeficiency virus  patients receiving oral cyclophosphamide and prednisone may be at higher or increasing risk for pcp  a high index of suspicion and aggressive evaluation for opportunistic infection are needed in these patients  consideration for trimethoprim sulfamethoxazole prophylaxis and development of more quantitative measures of immunosuppression are needed  
class8	combined thermodilution and two dimensional echocardiographic evaluation of right ventricular function during respiratory support with peep  in ten patients requiring respiratory support for an episode of acute respiratory failure  arf   the best therapeutic level of peep was determined by measurement of changes in lung and chest wall compliance  ct  during a peep challenge from 0 to 20 cm h2o  during this challenge  hemodynamic monitoring combined with thermodilution measurement of right ventricular  rv  ejection fraction  ef  and two dimensional echocardiographic measurement of rv size permitted assessment of the effects of increasing levels of peep on rv function  rv preload  as reflected by rv end diastolic volume  edv  and two dimensional rv end diastolic area  eda   remained unchanged and rv diastolic compliance progressively decreased  on the other hand  rv systolic function  as assessed by rvef and two dimensional rv fractional area contraction  fac   was progressively depressed  substantial deleterious effects of peep were noted at high levels of peep including reduced ct and augmented pulmonary vascular resistance  inadequate increase in rv preload to compensate for increased rv afterload resulted in depressed rv systolic function and contributed to the reduction in cardiac output  finally  two dimensional echocardiography proved to be more sensitive than fast response thermodilution to evaluate change in rv function  
class8	respiratory failure and death following acute inhalation of mercury vapor  a clinical and histologic perspective  a family of four was exposed to toxic levels of mercury vapor while attempting to extract silver from mercury amalgam  all four suffered respiratory failure and subsequent death despite chelation therapy with dimercaprol  histologic findings at autopsy were similar in all four cases demonstrating a progression of acute lung injury that appeared related to postexposure day survival  there were no clinical signs of extrapulmonary manifestations despite toxic serum mercury levels  although serum mercury levels decreased in response to the mercury chelating agent dimercaprol  serum levels remained in the toxic range and no clinical response was observed  acute inhalational exposure to high concentrations of mercury vapor causes pneumonitis that can lead to respiratory failure and death  this continues to be a health hazard in both the workplace and the home environment  
class8	a longitudinal study of respiratory symptoms in a community population sample  correlations with smoking  allergen skin test reactivity  and serum ige chronic cough and or phlegm  wheeze in the absence of colds  and rhinitis attributed to allergies are three of the most common respiratory symptoms encountered in community populations  in this study  we have determined the prevalence of these complaints in a random population sample  n   1 109  using standardized questionnaires at two points in time  eight years apart  cross sectional prevalence and changes in symptom occurrence have been correlated with smoking status  allergen skin test reactivity  and total serum ige levels  our objective was to determine the individual and combined influence of these three variables on symptom prevalence  initially  19 2 percent of the population admitted to wheeze  17 9 percent to cough  and 44 1 percent to allergic rhinitis  cough and wheeze prevalence changed little over the eight year period  while rhinitis increased 11 percent by the second survey  the occurrence of chronic cough was strongly correlated with smoking  and was not further influenced by either allergen skin reactivity or ige level  conversely  rhinitis prevalence was related to skin test reactivity with no additional association with smoking or ige level  the occurrence of wheeze in the absence of colds was associated with both smoking and allergen skin reactivity  among smokers  the prevalence was over 30 percent and was similar in both skin test positive  stp  and skin test negative  stn  individuals  however  on both surveys  stp ex smokers and nonsmokers had significantly more wheeze than those who were stn  while the prevalence of wheeze in stn nonsmokers was low  6 8 percent   an ige wheeze relationship was also suggested on the second survey  in addition to these cross sectional symptom relationships  changes in either smoking status or allergen skin reactivity during the study period were associated with changes in the prevalence of each symptom  
class8	natural killer cell activity in a rat model of amiodarone induced interstitial lung disease  the role of lymphocytes in the pathogenesis of amiodarone induced lung disease is controversial  increases in the percentages of lymphocytes in bronchoalveolar fluid of both patients and animals with amiodarone pulmonary toxicity have been reported  to assess whether these lymphocytes are functionally activated  we measured natural killer cell activity in the lungs and blood of rats with amiodarone induced pulmonary toxicity  amiodarone treated rats exhibited pathologic evidence of amiodarone induced lung disease after one week of treatment and this injury was sustained and more extensive during the remainder of the study period  control rats had histologically normal lungs  blood nk activity was equally present in both amiodarone treated and control groups and was not significantly different over the course of the study  16     3 percent and 13     2 percent  respectively  p greater than 0 05   thus  nk cells were activated only in the lungs of rats treated with amiodarone  suggesting a local immune response in the lung  these data support the concept that lymphocytes play an important role in the pathogenesis of amiodarone induced lung disease  
class8	minute squamous cell carcinoma arising in the wall of a congenital lung cyst  a case of minute squamous cell carcinoma arising in a congenital lung cyst is reported  two aspects of this case were notable  first  we were able to make the diagnosis of squamous cell carcinoma by bronchial lavage at an early stage  second  to our knowledge  this is the first case of probable de novo origin of squamous cell carcinoma in a congenital lung cyst  
class8	pulmonary reactions caused by welding induced decomposed trichloroethylene this is the report of a welder who performed argon shielded electric arc welding in an atmosphere containing trichloroethylene  he developed immediate respiratory symptoms  pulmonary edema 12 hours after exposure  and recurring dyspnea ten days after exposure  these pulmonary reactions might be explained by inhalation of decomposition products of trichloroethylene such as dichloroacetyl chloride and phosgene  
class8	lightning injury with lung bleeding in a tracheotomized patient  a 68 year old man  who had undergone laryngectomy six months earlier  was struck by lightning and developed pulmonary hemorrhage  this was attributed to pulmonary barotrauma due to a lightning blast via his tracheostoma  
class8	obliterative bronchiolitis  virus induced  this report describes a 28 year old patient with an acute onset of respiratory symptoms associated with clinical and roentgenographic features of an interstitial lung disease which proved fatal  the entity of bronchiolitis obliterans  which was diagnosed on transbronchial biopsy  is discussed  with particular emphasis on the postinfectious type  
class8	tension pneumothorax secondary to a gastropleural fistula in a traumatic diaphragmatic hernia  we report a case of tension pneumothorax due to a gastropleural fistula resulting from perforation of the stomach in a traumatic diaphragmatic hernia  awareness of perforation of strangulated stomach or bowel in a diaphragmatic hernia as a cause of pneumothorax  with or without tension physiology  in a patient with a history of trauma is important so that surgical repair can be undertaken without delay  
class8	pneumocystis carinii pneumonia  rare cause of hemoptysis  pneumocystis carinii pneumonia is a frequent manifestation of the acquired immunodeficiency syndrome  aids   it commonly presents with nonproductive cough  fever  and dyspnea  we report this case of p carinii pneumonia presenting with hemoptysis  since to the best of our knowledge  hemoptysis has not been reported to be a presenting manifestation of p carinii pneumonia  autopsy revealed multiple lung cavities  
class8	noncardiogenic pulmonary edema complicating massive diltiazem overdose  non cardiogenic pulmonary edema has not been previously described in calcium channel blocker overdose  we describe a case of non cardiogenic pulmonary edema occurring during the course of therapy for massive diltiazem overdose in a young patient with anorexia nervosa  review of the current literature suggests that major and minor pulmonary complications occur with some frequency in the setting of calcium channel blocker overdose although their exact incidence remains unclear  
class8	cough in hot pepper workers  study objective  to determine whether there is an effect on the prevalence of respiratory symptoms  an alteration in lung function  or an increase in the cough threshold to capsaicin among workers chronically exposed to hot chili  capsicum  peppers  design  cross sectional study of responses to a structured questionnaire  lung function assessed by spirometry and cough threshold to inhalation of capsaicin aerosol in a group of occupationally exposed capsicum workers as compared to non exposed employees of the same work site  setting  spice manufacturing facility  participants  twenty two capsicum exposed and 19 nonexposed workers  measurements and main results  when evaluated by questionnaire  13  59 percent  of the capsicum exposed workers reported cough as compared to 4  21 percent  of the nonexposed workers  p less than 0 05   baseline fev1 and fvc did not differ between the two groups  cough threshold  as assessed by the lowest concentration of inhaled capsaicin eliciting cough  was related to workplace exposure  p   0 05   displaying a bimodal pattern of higher and lower cough thresholds among the capsicum workers as compared to a unimodal distribution among the nonexposed workers  within the exposed group  a higher cough threshold was significantly related to male gender  p   0 03  and was associated to a lesser extent with dietary preference for hot food  p   0 09  and cumulative cigarette smoking  p   0 07   conclusion  chronic occupational exposure to chili peppers is associated with complaints of cough but does not alone lead to decreased responsiveness of capsaicin sensitive nerves when assessed by cough threshold  the cough response to capsaicin inhalation may be modified by the effects of multiple  potentially interactive factors  
class8	fiberoptic bronchoscopy for refractory cough  fiberoptic bronchoscopy  fb  has a low yield in the diagnosis of chronic cough  greater than 3 weeks  in unselected patients  we assessed the yield of fb for cough during a four year period in patients with nonlocalizing chest roentgenograms who were refractory to diagnostic efforts and empiric bronchodilator or antitussive therapy  seven  28 percent  of 25 patients undergoing fb for cough  of greater than 1 500 bronchoscopies  had diagnostic findings  broncholithiasis  two  tracheobronchopathia osteochondroplastica  two  and tuberculous bronchostenosis  laryngeal dyskinesia  and arytenoid polyp  one each   no tracheobronchial neoplasms were detected  age greater than 50 years and female sex independently predicted positive results  p   0 02 fisher s exact test   while duration of cough  two to 240 months   airflow  and smoking status did not  when patients with prior pulmonary or extrathoracic neoplasms were excluded  seven  35 percent  of 20 studies were diagnostic  diagnoses potentially could have been made by thoracic computed tomographic scanning in four patients and indirect laryngoscopy in two  fiberoptic bronchoscopy has a respectable yield for diagnosis of refractory chronic cough and is a reasonable procedure in carefully selected patients  
class8	angiotensin converting enzyme inhibitors and cough  prevalence in an outpatient medical clinic population  to determine the frequency of ace inhibitor cough in an outpatient medical clinic population  a cross sectional epidemiologic survey using mailed questionnaires was done  patients were randomly selected from a computerized hospital pharmacy data base  the overall prevalence of cough was 19 percent in the ace inhibitor groups compared with 9 percent in the hydrochlorothiazide treated group  the observed odds ratio for cough among ace inhibitor users was 2 3  95 percent ci  1 02 to 5 00   this study is the first systematic investigation of frequency and characteristics of ace inhibitor cough that includes a control group  our results suggest that cough may more frequently accompany treatment with ace inhibitors than has been previously reported  we recommend that physicians specifically inquire about cough in patients taking an ace inhibitor  recognition of this side effect may prevent unnecessary testing and treatment of patients receiving ace inhibitors  
class8	comparison of incentive spirometry and intermittent positive pressure breathing after coronary artery bypass graft  fifty two patients were randomized to receive either incentive spirometry  is  or intermittent positive pressure breathing  ippb  in addition to conventional chest physical therapy following coronary artery bypass grafting  slow vital capacity and peak expiratory flow readings decreased rapidly and to an equal extent in both groups after surgery  and partly recovered by the sixth postoperative day  pop   arterial po2 values were similar for the groups on the first three pops  on the pops 2  3  and 6  the number of chest films showing atelectases as well as the number of individual patients having atelectases revealed no statistically significant differences between the two groups  based on the three variables studied  we consider both devices equal in efficiency after coronary surgery  
class8	metered dose inhalers for bronchodilator delivery in intubated  mechanically ventilated patients  we determined the relative efficacy of two bronchodilator aerosol delivery methods in 18 intubated mechanically ventilated patients with airways obstruction  two treatment arms  consisting of albuterol 270 micrograms  three puffs  from a metered dose inhaler and albuterol 2 5 mg from a saline solution nebulized with an updraft inhaler  were compared in a single blind  randomized crossover design  pulmonary function was evaluated using an interrupter technique  changes in passive expiratory flow at respiratory system recoil pressures between 6 and 10 cm h2o provided the therapeutic endpoints  paired measurements were made before and 30 minutes after drug delivery  the mdi and neb resulted in similar improvements in iso recoil flow  mean increase for both groups   0 1 l s   treatment sequence  severity of obstruction  and bronchodilator responsiveness had no effect on relative efficacy  albuterol caused a small but significant increase in heart rate that was similar following both delivery methods  we conclude that bronchodilator aerosol delivery with metered dose inhalers provides a viable alternative to nebulizer therapy in intubated mechanically ventilated patients and may result in a cost savings to hospitals and patients  
class8	complications of general anesthesia for nd yag laser resection of endobronchial tumors  we studied the incidence and mechanisms of cardiovascular complications and postoperative respiratory insufficiency associated with ga and nd yag laser endobronchial tumor resection  the records of 73 patients undergoing 87 procedures were reviewed  preoperative status  anesthetic methods and perioperative complications were analyzed by multiple regression to determine predictors of outcome  twenty three percent of patients had greater than 90 percent mainstem bronchus obstruction  longer serum elimination half life of relaxant drug was significantly correlated with longer duration of mechanical ventilation after neuromuscular blockade reversal  cardiovascular complications were noted in 24 procedures and often required therapeutic intervention  variables predicting cardiovascular complications included longer duration of ga and increasing age  perioperative respiratory and cardiovascular complications are common after ga for nd  yag laser resection  short acting neuromuscular relaxants  careful assessment prior to postoperative extubation  limiting duration of ga and cardiovascular monitoring are recommended when implementing ga for nd  yag laser resection of endobronchial tumors  
class8	acute eosinophilic pulmonary disease associated with the ingestion of l tryptophan containing products  a series of four patients with pulmonary infiltrates  pleural effusions  hypoxemia  peripheral eosinophilia  and symptoms of dyspnea  fatigue  and weakness is reported  lung tissue obtained in three patients revealed interstitial pneumonitis  small to medium vessel mixed cell vasculitis  and alveolar exudate of histiocytes and eosinophils  all patients reported ingestion of l tryptophan containing products at a time when an association between l tryptophan and the eosinophilia myalgia syndrome was established  this clinical pattern of pulmonary involvement may be part of the continuum of the eosinophilia myalgia syndrome  the pathophysiology of this syndrome and the relationship with the ingestion of l tryptophan containing products have not yet been identified  
class8	the diagnostic utility of the antibody coated bacteria test in intubated patients  purpose  pilot study to determine if the presence of antibody coated bacteria  acb  in sputum specimens obtained from endotracheal tube suctioning would aid in the diagnosis of lower respiratory tract infection  lrti   patients and methods  all endotracheally intubated and mechanically ventilated patients for a two month period were recruited for study  the diagnosis of lrti was based on a clinical suspicion sufficient enough to start or change antibiotic therapy  specimens were obtained by blind endotracheal tube suctioning  after processing  sputum smears were stained with fluorescein labelled antibody to the fc portion of igg  igm  and iga  more than five fluorescein labelled bacteria per oil immersion field were considered positive smears  results  seventy one specimens were obtained from 36 patients  eighteen specimens were positive in 12 patients  all of whom had lrti  no specimen was positive in patients not diagnosed as having lrti  the acb test was positive in 12 of 25 patients with lrti  patients with lrti but negative acb were more likely to have received prior antibiotic therapy  p less than 0 001   acb was positive prior to the clinical diagnosis of lrti in seven of nine patients  av 4 1 days  range 2 6 days  and converted to negative in three specimens obtained seven or more days after starting appropriate antibiotics  while in three specimens it remained positive three six days post treatment initiation  conclusions  the acb test appears to be highly specific for the presence of lrti in intubated patients  sensitivity of the test may be adversely affected by prior antibiotic therapy  a positive acb test may predict the subsequent development of lrti  further study is warranted  
class8	proximal esophageal ph metry in patients with  reflux laryngitis   fiberoptic laryngoscopic examinations were performed on 40 patients with gastroesophageal reflux disease  25 of whom had persistent laryngeal symptoms  dysphonia  cough  globus sensation  frequent throat clearing  or sore throat  and 15 without laryngeal symptoms who served as disease controls  ten patients with laryngeal symptoms but none of the controls had laryngoscopic findings consistent with reflux laryngitis  dual site ambulatory ph recordings were obtained with the ph electrodes spaced 15 cm apart and with the proximal sensor positioned just distal to the upper esophageal sphincter  patients in the three groups  disease controls  group 1  patients with symptoms but without laryngoscopic findings  group 2  and patients with both laryngeal symptoms and findings  group 3  were comparable in terms of age  smoking habit  the presence of esophagitis  and distal esophageal acid exposure  proximal esophageal acid exposure was  however  significantly increased in groups 2 and 3  and nocturnal proximal esophageal acidification occurred in over half of these patients but in none of the group 1 patients  we conclude that the subset of reflux patients who experience laryngeal symptoms show significantly more proximal esophageal acid exposure  especially nocturnally  and often have laryngoscopic findings of posterior laryngitis not observed in control reflux patients  
class8	managing lung disease in late life  a new approach  advanced pulmonary disease  apd   a progressive  incurable condition  ultimately leading to death  is associated with significant  distressing symptoms  this paper reviews how the hospice approach to care  with its emphasis on treating those symptoms causing the patient the most distress  might be used by physicians in the outpatient setting to improve the patient s quality of life  important aspects of care include management of hypoxia  malnutrition  osteoporosis  adverse drug reactions  and  especially  the symptomatic relief of dyspnea  relief of emotional symptoms  depression  anxiety  panic  is also discussed  
class8	effects of changes in level and pattern of breathing on the sensation of dyspnea  breathing during hypercapnia is determined by reflex mechanisms but may also be influenced by respiratory sensations  the present study examined the effects of voluntary changes in level and pattern of breathing on the sensation of dyspnea at a constant level of chemical drive  studies were carried out in 15 normal male subjects during steady state hypercapnia at an end tidal pco2 of 50 torr  the intensity of dyspnea was rated on a borg category scale  in one experiment  n   8   the level of ventilation was increased or decreased from the spontaneously adopted level  vspont   in another experiment  n   9   the minute ventilation was maintained at the level spontaneously adopted at pco2 of 50 torr and breathing frequency was increased or decreased from the spontaneously adopted level  fspont  with reciprocal changes in tidal volume  the intensity of dyspnea  expressed as percentage of the spontaneous breathing level  correlated with ventilation    vspont  negatively at levels below vspont  r    0 70  p less than 0 001  and positively above vspont  r   0 80  p less than 0 001   at a constant level of ventilation  the intensity of dyspnea correlated with breathing frequency    fspont  negatively at levels below fspont  r    0 69  p less than 0 001  and positively at levels above fspont  r   0 75  p less than 0 001   these results indicate that dyspnea intensifies when the level or pattern of breathing is voluntarily changed from the spontaneously adopted level  this is consistent with the possibility that ventilatory responses to changes in chemical drive may be regulated in part to minimize the sensations of respiratory effort and discomfort  
class8	compensation of respiratory alkalosis induced after acclimation to simulated altitude  conscious intact rats previously acclimated for 3 wk to barometric pressure of 370 380 torr  3whx  were made alkalotic for 3 h by a decrease in inspired o2 fraction from 0 10 to 0 075 at ambient barometric pressure  730 740 torr   controls were normoxic littermates  nx  in which inspired o2 fraction was lowered from approximately 0 21 to 0 10 for 3 h  arterial pco2 decreased progressively and similarly in both groups  65 70  of control at 15 min   initially  arterial ph increased less in 3whx  0 09     0 004 vs  0 15     0 008   as hypocapnia continued  delta hco3   delta ph  mmol l 1 ph  became more negative in nx  from  15 2     2 5 at 15 min to  37 0     2 9 at 3 h  indicating nonrespiratory compensation of alkalosis  in 3whx  delta hco3   delta ph did not change during alkalosis  cumulative renal excretion of base  mueq 100 g  during alkalosis increased by 73 2     11 1 in nx and 25 4     7 3 in 3whx  this difference was mainly due to a larger increase in hco3  excretion in nx  the data suggest that the smaller compensation of hypocapnic alkalosis in 3whx is partly due to the smaller increase in renal base excretion  because base availability limits renal base excretion  the smaller renal response of 3whx may be secondary to the low plasma hco3  concentration that accompanies altitude acclimation  
class8	role of dopamine and arterial chemoreceptors in thermal tachypnea in conscious cats  in mammals submitted to a warm environment  intracerebral injection of dopamine  da  produces no change or an increase in body temperature accompanied by an increase in metabolic heat production  but its effect on heat loss mechanisms such as vasodilation and tachypnea is not clear  because the principal mechanism of heat loss in the conscious cat is thermal tachypnea  we studied the influence of da on thermal tachypnea in response to heat stress  ambient temperature   33 36 degrees c  in five conscious cats  we first studied the steady state response to a da agonist  apomorphine  which crosses the blood brain barrier  intravenous injection of apomorphine greatly reduced thermal tachypnea by decreasing respiratory frequency  from 94 9 to 52 5 breaths min  and increasing tidal volume  from 13 2 to 20 4 ml   the subsequent injection of the da antagonist haloperidol  which also crosses the blood brain barrier  restored the initial tachypnea  to further investigate the mechanism involved in thermal tachypnea  we studied the influence of peripheral chemoreceptors by transiently stimulating or inhibiting carotid body  cb  activity during tachypneic breathing  cb stimulation by intravenous injection of nacn or domperidone reduced thermal tachypnea mainly by decreasing the respiratory frequency  whereas cb inhibition by da tended to increase frequency and thus tachypnea  it is concluded that 1  in a warm environment  central da receptors are also greatly involved in heat loss mechanisms  2  arterial chemoreceptor input appears to counteract this tachypneic breathing  and 3  thermal and hypoxic tachypnea may be controlled by the same mechanism in which a da like system has a key role  
class8	effects of ligation and embolization on kf and multiple tracer measurements in dog lungs  in isolated blood perfused dog lungs  the capillary filtration coefficient  kf  and the permeability surface area product of urea  ps  were measured to determine their responses to two different methods of altering filtration area  lobe ligation  ll  n   5  and glass bead embolization  gbe  n   4  during constant perfusion rates  700     45 ml min   when two of three lobes were ligated  kf decreased  1 36     0 13 to 0 58     0 23 g min 1 cmh2o 1  p less than 0 05   but ps did not change  2 02     0 4 to 1 71     0 3 ml s   kf per gram of perfused blood free dry lung weight was unchanged by ll  0 051     0 17 to 0 052     0 18 g min 1 cmh2o 1   indicating that surface area per gram measured by kf remained the same  however  ps per gram dry lung doubled  0 07     0 016 to 0 146     0 06 ml s  p less than 0 05  after ll  suggesting that recruitment occurred in the remaining lobe  when three lobes were embolized with 200 microns glass beads  0 48     0 01 g beads kg body wt   ps decreased  2 1     0 22 to 0 94     0 09 ml s  p less than 0 05   but kf was not altered  1 01     0 17 to 1 04     0 18 g min 1 cmh2o 1   the constancy of kf after gbe implies that the vascular pressure increase during the kf measurement was transmitted to both blocked and flowing vessels and thereby measured the same filtration area before and after gbe  ps decreased significantly after gbe because of a loss of perfused surface area by the beads blocking flow in small arterial vessels  
class8	airflow obstruction after substance p aerosol  contribution of airway and pulmonary edema  we have studied the effects of aerosolized substance p  sp  in guinea pigs with reference to lung resistance and dynamic compliance changes and their recovery after hyperinflation  in addition  we have examined the concomitant formation of airway microvascular leakage and lung edema  increasing breaths of sp  1 5 mg ml  1 1 mm   methacholine  0 15 mg ml  0 76 mm   or 0 9  saline were administered to tracheostomized and mechanically ventilated guinea pigs  lung resistance  rl  increased dose dependently with a maximum effect of 963     85  of baseline values  mean     se  after sp  60 breaths  and 1 388     357  after methacholine  60 breaths   after repeated hyperinflations  methacholine treated animals returned to baseline  but after sp  mean rl was still raised  292     37   p less than 0 005   airway microvascular leakage  measured by extravasation of evans blue dye  occurred in the brain bronchi and intrapulmonary airways after sp but not after methacholine  there was a significant correlation between rl after hyperinflation and evans blue dye extravasation in intrapulmonary airways  distal  r   0 89  p less than 0 005  proximal  r   0 85  p less than 0 01   examination of frozen sections for peribronchial and perivascular cuffs of edema and for alveolar flooding showed significant degrees of pulmonary edema for animals treated with sp compared with those treated with methacholine or saline  we conclude that the inability of hyperinflation to fully reverse changes in rl after sp may be due to the formation of both airway and pulmonary edema  which may also contribute to the deterioration in rl  
class8	effect of acute hypercapnia on limb muscle contractility in humans  the effect of acute hypercapnia on skeletal muscle contractility and relaxation rate was investigated  the contractile force of fresh and fatigued quadriceps femoris  qf  and adductor pollicis  ap  was studied in normal humans by use of electrical stimulation  maximum relaxation rate from stimulated contractions was measured for both muscles  acute hypercapnia led to a rapid substantial reduction of contraction force  the respiratory acidosis after 9  co2 was breathed for 20 min  mean venous blood ph 7 26 and end tidal pco2  petco2  65 1 torr  reduced 20  and 100 hz stimulated contractions of qf to 72 8     4 4 and 80 0     5 1  of control values  respectively  after 8 and 9  co2 were breathed for 12 min  ap forces at 20  and 50 hz stimulation were also reduced  twitch tension of ap was reduced by a mean of 25 5  when subjects breathed 9  co2 for 12 min  mean arterialized venous blood ph  phav  7 25 and petco2 66 torr   over the range of 5   phav 7 38 and petco2 47 torr  to 9  co2  there was a linear relationship between twitch tension loss and phav  arterialized venous blood pco2  and petco2  acute respiratory acidosis  mean petco2 61 torr  increased the severity of low frequency fatigue after intermittent voluntary contractions of ap  at 20 min of recovery  twitch tension was 63 2     13 4 and 46 8     16 4  of control value after exercise breathing air and 8  co2  respectively  acute hypercapnia  mean petco2 65 1 and 60 5 torr  did not alter the maximum relaxation rate from tetanic contractions of fresh qf and from twitch tensions of ap  
class8	effect of synchronous increase in intrathoracic pressure on cardiac performance during acute endotoxemia  in the anesthetized closed chest canine model of gram negative endotoxemia  n   10   we tested the hypothesis that the effect of cardiac cycle specific intrathoracic pressure pulses delivered by a heart rate  hr  synchronized high frequency jet ventilator  sync hfjv  on systolic ventricular performance is dependent on the level of preload  to control for hfjv frequency  hemodynamic responses were also measured at fixed frequency within 15  of hr  async hfjv   biventricular stroke volumes  sv  were measured by electromagnetic flow probes  measurements were made before  baseline  and 30 min after infusion of 1 mg kg escherichia coli endotoxin  serotype 055 b5  and then after 2 mg kg propranolol at both low  less than 10 mmhg  left ventricular filling pressure  lvfp  and high  greater than 10 mmhg  lvfp  ventricular function curves  aortic pressure flow  p q  relationships  and venous return  vr  curves were analyzed  we found that endotoxin did not alter vr curves but shifted the aortic p q curves to the left with pressure on the x axis  p less than 0 05   volume loading increased sv  p less than 0 01  because of a rightward shift of the vr curve  no specific differences occurred with either sync or async hfjv during endotoxin  presumably because of preserved vr and shifted aortic p q  the lack of cardiac cycle specific effects of itp appears to be due to the selective endotoxin induced changes in peripheral vasomotor tone that counterbalance any depressed myocardial contractility  
class8	time course of changes in lung permeability and edema in the rat exposed to 100  oxygen  rats were exposed to 100  oxygen for up to 60 h to determine early changes in lung permeability leading to the development of pulmonary edema  the time course of development of increased solute flux was assessed by the clearance of 99mtc labeled diethylenetriamine pentaacetate  99mtc dtpa  from the lung and the accumulation of 125i labeled albumin  125i albumin  in the lung  these end points were related to the development of pulmonary edema by the measurement of the wet to dry weight ratio of the lung and the weight of fluid in the pleural cavity  no significant changes occurred until 48 h of hyperoxia  when sharp increases in both indexes of lung permeability and wet to dry weight ratio occurred  by 60 h of exposure  pleural effusions had developed  the volume of this effusion was significantly correlated to both 99mtc dtpa clearance and 125i albumin flux  
class8	stimulation of rat endothelial cell transforming growth factor beta production by bleomycin  this study examines the hypothesis that mediators from lung endothelial cells could promote lung collagen synthesis in pulmonary fibrosis  since bleomycin induces pulmonary fibrosis in humans and animals  the effects of this drug on endothelial cells were examined  endothelial cell conditioned media were prepared in the presence of various doses of bleomycin  and tested for their ability to stimulate lung fibroblast collagen synthesis  the results show a dose dependent stimulation of endothelial cell secretion of collagen synthesis stimulatory activity by bleomycin  which peaked at a dose greater than or equal to 100 ng ml  stimulation was selective for collagenous protein synthesis  gel filtration analysis showed most of the activity to reside in fractions with an estimated molecular mass range of 10 27 kd  the activity was inhibited by anti transforming growth factor beta  tgf beta antibody  but not by nonimmune control igg  the presence of tgf beta was confirmed using the mink lung epithelial cell assay  northern blotting revealed significant increases in tgf beta mrna in bleomycin stimulated endothelial cells  thus in vitro stimulation of endothelial cells by bleomycin upregulates tgf beta production  presumably by increased transcription  in view of the chemotactic and matrix synthesis stimulatory properties of this cytokine  such an increase in tgf beta production may play an important role in bleomycin induced pulmonary fibrosis  
class8	purification and characterization of a major human pneumocystis carinii surface antigen  previous studies of pneumocystis carinii have identified the major surface antigen of rat and human isolates as proteins of 116 000 and 95 000 mol wt  respectively  that are antigenically not identical  in this study both rat and human p  carinii proteins were purified by solubilization with zymolyase followed by molecular sieve and ion exchange chromatography  the native proteins had an apparent mol wt of 290 000 or greater  based on molecular sieve studies as well as cross linking studies  both proteins were glycoproteins  treatment with endoglycosidase h resulted in a 9  decrease in mol wt  the carbohydrate composition of the rat p  carinii glycoprotein was distinct from the human isolate  glucose  mannose  galactose  and glucosamine occurred in approximately equimolar ratios in the human p  carinii protein  whereas glucose and mannose were the predominant sugars of the rat p  carinii protein  to evaluate humoral immune responses to the human p  carinii protein  an enzyme linked immunosorbent assay using purified protein was developed  some  but not all  patients who subsequently developed p  carinii pneumonia demonstrated a serum antibody response to the surface antigen  nearly all subjects without a history of p  carinii pneumonia had no detectable antibodies  purified p  carinii proteins will greatly facilitate the investigation of host p  carinii interactions  
class8	mohs micrographic surgery fixed tissue technique for melanoma of the nose  mohs micrographic surgery  fixed tissue technique  for excision of nasal melanoma provides three important benefits  1  assurance of eradication of the main mass along with its  silent  contiguous outgrowths  2  safe management of non contiguous satellites too small to be visible initially  and 3  safe sparing of maximal amounts of surrounding normal tissues  these benefits are achieved because all incisions are through chemically fixed  killed  tissue  eliminating the danger of disseminating the highly transplantable melanoma cells and permitting the excision of successive layers for microscopic scanning of their undersurfaces by the systematic use of frozen sections  the process is continued to the termination of each ramification  there is no need to remove a wide margin of normal tissue as is customary with conventional surgery  clinically invisible satellites are not moved or disturbed and can be removed safely by the same method if they appear  the reliability of the method is manifested by the 62 5  5 year cure in a series of 10 consecutive patients  all of whom had no local recurrence after micrographic surgery  
class8	elevated serum concentrations of ige antibodies to environmental antigens in hiv seropositive male homosexuals  forty five homosexual male subjects with human immunodeficiency virus  hiv  infection  who received care during a 4 month period in an ambulatory center for acquired immunodeficiency syndrome  aids   were classified according to their principal presentation with characteristic secondary infections  cdc group iv c  n   28   cancers  iv d  n   10   or limited or no symptoms  groups ii  iii  iv a  or iv b  n   7   the incidence of allergic rhinitis and conjunctivitis increased after hiv seroconversion by approximately twofold in patients of groups iv c and iv d  the mean serum concentration of ige was significantly higher for group iv c than for the other hiv seropositive groups and for a control group of 45 hiv seronegative homosexual male subjects from the same community who were studied concurrently  more patients in groups iv c and iv d had positive rasts for a panel of environmental antigens than patients in the other hiv seropositive groups and the hiv seronegative control group  patients with aids presenting with typical secondary infections thus have a high frequency of some clinical and laboratory manifestations of allergic diseases  
class8	comparison of the effects of inhaled corticosteroids on the airway response to histamine  methacholine  hyperventilation  and sulfur dioxide in subjects with asthma  to investigate whether inhaled steroids modulate the airway response to different bronchoconstrictive stimuli  we studied 25 subjects with mild asthma with a double blind  noncrossover design to compare the effect of a 3 week treatment with salbutamol  0 2 mg  four times a day  q i d    and placebo  n   11  to the effect of salbutamol  0 2 mg q i d   and inhaled beclomethasone dipropionate  bdp  0 5 mg q i d    n   14   airway response to histamine and methacholine was assessed as the provocative concentration  in milligrams per milliliter  necessary to increase the specific airway resistance  sraw   in centimeters of h2o times second  by 100   pc100 sraw   airway response to hyperventilation of air and to hyperventilation of 0 75 ppm of sulfur dioxide  so2  was determined as the provocative ventilation  in liters per minute  necessary to increase sraw by 75   pv75 sraw   challenges were performed on separate days before and after treatment  and salbutamol inhalation was withheld at least 6 hours before each challenge  salbutamol and placebo did not change perchallenge baseline sraw nor did they have any significant effect on the airway response to the stimuli  salbutamol and bdp decreased the mean prechallenge baseline sraw  sem  from 7 7  0 37  to 5 9  0 28   p less than 0 01  and significantly  p less than 0 01  increased geometric mean  sem  pc100 sraw for histamine from 0 5  1 42  to 0 9  1 53  mg ml  for methacholine  from 0 2  1 47  to 0 5  1 51  mg ml  and mean  sem  pv75 sraw for hyperventilation of air from 51 8  2 32  to 58 4  1 86  l min  in contrast  the change of pv75 sraw during hyperventilation of so2 from 26 2  2 29  to 31 4  3 30  l min was not significant  
class8	physiologic responses to intranasal dose response challenges with histamine  methacholine  bradykinin  and prostaglandin in adult volunteers with and without nasal allergy  the dose response  dose  0 01  0 05  0 1  0 5  1  and 5 mg  profiles of 10 atopic and 10 nonatopic subjects were determined for nasal patency  secretion weight  pulmonary function  eustachian tube function  middle ear function  and symptoms after intranasal inhalation challenges with histamine  bradykinin  methacholine  prostaglandin d2  and prostaglandin f2 alpha  pgf2 alpha   results demonstrated that challenge with pgf2 alpha increased nasal patency  whereas challenge with all other substances decreased patency  the relationship between substances in eliciting a nasal congestive response was prostaglandin d2 greater than histamine greater than bradykinin greater than methacholine  a similar effect ordering was noted for the postchallenge development of eustachian tube dysfunction  secretion weights were significantly greater after challenge with histamine compared to all other substances  a decrease in pulmonary function was observed only after challenge with pgf2 alpha  although the effect was not statistically significant  no changes in middle ear pressure were observed for challenges with any of the substances  only histamine challenge provoked sneezing  whereas challenge with either of the prostaglandins provoked cough  with the exception of methacholine  all substances caused symptoms of rhinorrhea  congestion  and sore throat  bradykinin was particularly effective in provoking  pain pressure  related symptoms  with the exception of secretion weight  the differences between responses of atopic and nonatopic subjects were not statistically significant  these results document mediator specificity in the physiologic and symptomatic responses to intranasal challenge  
class8	a double blind comparison of intranasal budesonide with placebo for nasal polyposis  intranasal budesonide  400 micrograms two times a day  was evaluated in 36 patients referred for treatment of nasal polyposis  the age range was 20 to 68 years  polypectomy was done 5 6  mean  times previously  after a 5 week  treatment free  baseline period  patients were treated in a double blind fashion with either budesonide or placebo during 4 weeks  after this treatment period  placebo treated patients started receiving budesonide in an open trial for an additional 4 weeks  the patients rated their nasal symptoms daily  nasal examinations and nasal inspiratory flow rate  ifr  measurements were done at clinic visits  after 3 and 4 weeks of treatment  the response to budesonide was significantly greater than response to placebo  the greater reduction in nasal blockage caused by polyps  observed on physical examination  p   0 005  was mirrored by an increase in nasal ifr  p   0 0001   patient rating of the severity and frequency of nasal blockage were reduced more by budesonide than by placebo  p less than or equal to 0 0005   switching placebo treated patients to budesonide treatment resulted in a reduction of nasal blockage  p less than 0 001  and an increase in nasal ifr  p less than 0 001   the results demonstrate that topical nasal budesonide  400 micrograms two times a day  is an effective treatment of nasal polyps  
class8	cytotoxic chemotherapy induces cell differentiation in small cell lung carcinoma  despite the high response rates resulting from chemotherapy  the majority of small cell lung cancer  sclc  patients relapse with chemoresistant tumors  to analyze the phenotypic changes that are precursors of chemoresistant status  and to investigate the role of chemotherapy in these changes  tumor samples from 20 patients  taken before chemotherapy  etoposide  doxorubicin  and cyclophosphamide  and again at the onset of chemoresistance  after at least three courses of chemotherapy   were compared  the histologic changes were minor in 10 of 20 patients  as shown by an increase in cell size  they were major in 10 of 20 patients  with the appearance of mixed composite tumors in which neuroendocrine  ne   epidermoid  and glandular components were mixed  major changes correlated with a good response to chemotherapy  p    001   ultrastructural studies showed an increase in neurosecretory granules and desmosomes  and a high frequency of multidirectional differentiation  45   when comparison was made with pretherapy samples  10    p less than  01   immunohistochemical  ih  analysis showed an increase in cytokeratin  ck  expression in treated patients  with a different labeling pattern and the expression of higher molecular weight ck  the expression of ne lineage markers  leu 19  sy 38  sl 11 14  remained stable  while that of ne differentiation markers  leu 7  chromogranin  increased in the treated patients  the neuron specific enolase  nse  activity remained stable in treated sclc  large cells with a more differentiated phenotype and proliferative capacity  as shown by ki 67 labeling   appeared to be characteristic of treated and secondary chemoresistant sclc  the acquisition of a more complex phenotype  which correlates with primary response to therapy  implies a drug induced differentiation in sclc  
class8	nosocomial pneumonia in adult patients undergoing bone marrow transplantation  a 9 year study  two hundred seventy five consecutive patients treated with bone marrow transplantation  bmt  during a 9 year interval were analyzed for the incidence and etiology of nosocomial pneumonia  cases included adults who acquired pneumonia during the first hospitalization period within 100 days of the transplant  fifty five  20   of the 275 patients developed nosocomial pneumonia  and the crude mortality during the hospitalization period was 74 5   an etiology was established in 67 3   37 of 55  of episodes  thirty six percent  20 of 55  of the cases were caused by aspergillus species  either as the sole agent  15 patients  or in association with others  the crude mortality for patients with aspergillus pneumonia was 95   elimination of 90  of aspergillus cases in our unit would have the effect of reducing the overall attack rate of nosocomial pneumonia to 13 4  and the associated crude mortality to 43 4   
class8	effect of dietary alpha linolenic acid on growth  metastasis  fatty acid profile and prostaglandin production of two murine mammary adenocarcinomas  the purpose of this study was to determine whether dietary  n 3  fatty acids would affect mammary tumor growth and metastasis  weanling female balb c mice were fed diets that contained 10  corn oil  co   linseed oil  lo  or a fish oil corn oil mix  fo  for 3 8 wk prior to receiving subcutaneous injections of one of two syngeneic mammary tumor cell types  410 and 410 4   tumor growth was assessed by monitoring mean tumor diameter and tumor weight upon removal  feeding lo  but not fo  reduced the growth  p less than 0 05  of 410 4 mammary tumors compared with growth in those fed co  metastasis data paralleled the tumor growth rate  feeding lo and fo enhanced  p less than 0 005  incorporation of  n 3  fatty acids into tumors  tumor prostaglandin e  pge  production was reduced  p less than 0 005  by lo and fo  compared with co  fo feeding reduced 410 4 tumor pge synthesis more  p less than 0 05  than lo feeding  yet tumor growth was only inhibited by lo  these data suggest an inhibitory effect of dietary linolenic acid  i e   18 3  n 3   on mammary tumor growth and metastasis  however  this effect did not directly correlate with diet induced changes in pge synthesis  
class8	the cholecystokinin receptor antagonist devazepide enhances morphine induced analgesia but not morphine induced respiratory depression in the squirrel monkey  the effects of the cholecystokinin antagonist devazepide on analgesia and respiratory depression induced by morphine in squirrel monkeys were examined  pain thresholds were determined using the tail withdrawal procedure  in which monkeys restrained in chairs kept their tails in cool  35 degrees c  water for at least 20 sec  but withdrew them from warm  55 degrees c  water in less than 4 sec  morphine produced a dose related increase in tail withdrawal latencies from warm water  devazepide  injected i p  or p o   had no effect on tail withdrawal latencies when given alone but enhanced the analgesic effects of morphine  the devazepide dose response curve for morphine enhancement was bell shaped with doses of 3  10  30 and 100 micrograms kg injected i p  increasing morphine analgesia whereas higher and lower dose did not  in a separate group of monkeys  morphine produced dose dependent decreases in respiratory rate and oxygen tension and increases in carbon dioxide tension  in contrast to its effects on morphine analgesia  devazepide had no effect on the various indices of morphine induced respiratory depression  these data suggest that devazepide may have therapeutic utility as an adjuvant to morphine analgesia allowing lower dose of the opiate to be used to relieve pain and reducing the risk of opiate induced respiratory depression  
class8	phase ii trial of whole cell pertussis vaccine vs an acellular vaccine containing agglutinogens  an acellular pertussis vaccine containing agglutinogens 2 and 3  pertussis toxin  and filamentous haemagglutinin was developed by the centre for applied microbiology and research in the uk  188 infants were entered into a randomised blind trial and received either the acellular or a whole cell vaccine  combined with diphtheria and tetanus toxoids  in a 3  5  and 8 10 month schedule  local reactions were similar in the two groups but significantly fewer infants had systemic symptoms after the acellular vaccine  mean log antibody titres to the agglutinogen and toxin components were higher with the acellular than with the whole cell vaccine  persistence of antibodies one year after the third dose was also better in the acellular group  
class8	dexamethasone as an adjunct in oropharyngeal obstruction in a patient with leukemia  incipient airway obstruction due to fulminating bacterial infection of pharyngeal tissues requires prompt and definitive intervention  a case is presented in which dexamethasone was a key adjunct to antibiotic therapy in averting this problem in a severely neutropenic patient with acute leukemia  
class8	short course chemotherapy for childhood tuberculosis a prospective study  with an attempted 24 month post treatment follow up  of children with tuberculosis  tb  treated with short course chemotherapy  scc  for 6 months was carried out because published experience of scc in childhood tb was limited  all children in port moresby diagnosed as having tb between november  1984  and november  1986  entered the trial  of the 639 children 165  26   were younger than 2 years old  of these  227  35   had extrapulmonary tb  peripheral lymph node  110  central nervous system  43  abdominal  27  miliary  16  bone and joint  11  pleural  11  polyserositis  9   clinical response to scc was rapid  adverse drug reactions occurred in 15  2    mainly to streptomycin  twelve  2   died  38  6   transferred out and 145  28  of the 518 who did not die  transfer or live too far from a treatment centre  defaulted  three hundred seventy three  58   completed a 2 month course of daily rifampin  isoniazid  pyrazinamide and streptomycin followed by a 4 month course of twice weekly rifampin and isoniazid  a further 71  11   had their treatment modified because of their distance from a treatment center  only 70  19   of the 373 children available for post treatment follow up attended the every 3 month follow up visits for 24 months  although 223  60   attended one or more of the follow up visits  seven of the 373 children relapsed  mostly within 3 months  five of these children had been irregular with their treatment  scc for childhood tb is safe and effective for pulmonary and extrapulmonary disease  
class8	a randomized trial of fully intermittent vs  daily followed by intermittent short course chemotherapy for childhood tuberculosis fully intermittent short course chemotherapy regimens have been used successfully in adults but not in children  we report the results on 76 children with tuberculosis  excluding central nervous system tuberculosis and primary pulmonary complex  isoniazid  rifampin and pyrazinamide were used for treatment  they were randomly allocated to regimen a  52 doses  and regimen b  94 doses   overall efficacy of both schedules was greater than 95  in 27 children with lymphatic  43 with pulmonary and 6 with disseminated tuberculosis  compliance in 10 children after 2 to 4 months of therapy was poor because rapid improvement was mistaken by parents for cure  two children died  probably of underlying lung disease  follow up for up to 2 years did not reveal any case of relapse or recurrence of the disease  therapy for 6 months involving administration of only 52 or 94 doses of drugs was found to be economical  effective and safe for treating children with tuberculosis  
class8	spontaneous pneumomediastinum  an unusual cause of a sore throat  sore throat  usually related to pharyngitis  is a common presenting symptom in the primary care setting  drs frenkel and lyons describe a case showing that physicians need to be aware of another  puzzling cause  spontaneous pneumo mediastinum  
class8	expression of neurophysin related precursor in cell membranes of a small cell lung carcinoma  a monoclonal antibody  mab l6  to a small cell lung carcinoma surface antigen recognizes a common epitope of vasopressin neurophysin and oxytocin neurophysin in hypothalamic nuclei  we now report on the identification of a neurophysin like precursor in human lung carcinoma  lx 1  cell membrane  mab l6 immunoaffinity chromatography of solubilized membranes resulted in a single band of approximately 45 kda  western blot analysis demonstrated immunoreactivity of this band with mab l6  anti vasopressin  and an antibody to the vasopressin precursor  pro pressophysin  n terminal sequencing of this band demonstrated a 21 amino acid homology with the n terminus of human pro pressophysin  and substitution of a cys33 residue in the tumor antigen with arg33  absence of immunoreactivity with the antibodies described above in cytosolic extracts and culture medium suggests nonsecretion of processed or intact pro pressophysin like peptide  northern analysis of lx 1 mrna with a 30 mer to the c terminus of rat pro pressophysin resulted in a band of approximately 1000 base pairs  250 base pairs larger than hypothalamic message  in situ hybridization of lx 1 tumor bearing nude rat brain with the same probe demonstrated specific hybridization in rat hypothalamus and xenografted tumor  these findings suggest expression of a pro pressophysin like protein in this tumor cell line that is preferentially targeted to the cell membrane  
class8	efficacy of doxazosin in specific hypertensive patient groups  in practice  some of the major problems for the physician who treats hypertension are patients who are resistant to treatment or who have other complicating risk syndromes  therefore the overall efficacy of an antihypertensive agent must include an assessment of effect in patients with serious ancillary problems  in this article  doxazosin is reviewed for its efficacy in the treatment of severe essential hypertension and specific complications or conditions of mild or moderate essential hypertension  namely  left ventricular hypertrophy  hyperlipidemia  noninsulin dependent diabetes mellitus  renal insufficiency  pheochromocytoma  chronic obstructive pulmonary disease  peripheral vascular disease  and smoking  doxazosin is particularly efficacious in many specific subgroups of patients with hypertension  and the results of relevant studies are discussed  
class8	beta carotene and cancer prevention  the basel study  in 1971 1973 at the third examination of the basel study started in 1959  the major antioxidant vitamins and carotene were measured in the plasma of 2974 men  a subsample and their families were reinvestigated in 1977 79  during the 12 y observation period  1973 85  553 men died  204 of cancer  lung cancer 68  stomach cancer 20  colon cancer 17  all other malignancies 99   we found significantly lower mean carotene levels for all cancer  bronchus cancer  and stomach cancer  all p less than 0 01  compared with the 2421 survivors  the relative risk of subjects with low carotene  less than 0 23 mumol l  was significantly elevated  p less than 0 05  for lung cancer  cox s model   higher risks were noted for all cancer  p less than 0 01  if both carotene and retinol were low  low plasma carotene which is known to reflect carotene intake is in our study associated with increased cancer risk  
class8	studies evaluating antioxidants and beta carotene as chemopreventives  cancer chemoprevention research takes leads from epidemiologic and laboratory research and develops them through in vitro and in vivo preclinical research and initial human studies into randomized controlled clinical trials  at present  the chemoprevention program is sponsoring 21 human efficacy studies  these trials are testing the potential of agents  beta carotene  folic acid  13 cis retinoic acid  4 hydroxyphenyl retinamide  vitamins c and e  and minerals  as inhibitors of a variety of cancers in humans  colon  lung  esophagus  cervix  bladder  and skin   endpoints in these studies include overall incidence of cancer  incidence of specific cancers  rate of regression or progression of preneoplastic changes  and changes in cellular or biochemical parameters  study participants include volunteers from the general population  populations at high risk for cancer because of occupation  lifestyle  or place of residence  persons with previously treated cancers  and persons with preneoplastic lesions  study designs include single agent randomization  combination of agents and complete factorial designs  
class8	surfactant replacement therapy in respiratory distress syndrome  meta analysis of clinical trials of single dose surfactant extracts  replacement therapy with surfactant extracts in premature infants with respiratory distress syndrome has been evaluated in several clinical trials  the results of individual trials do not provide conclusive evidence that administration of a single dose of surfactant improves morbidity or mortality  meta analysis is a statistical method to combine the results of such clinical trials  and combined analysis provides a means to overcome the problem of not being able to detect significant small differences in individual trials due to these small sample sizes  seven clinical trials  277 patients treated with nonhuman surfactant extract and 263 controls  met the criteria for analysis  five outcome measurements  mortality  patent ductus arteriosus  pneumothorax  intraventricular hemorrhage  and bronchopulmonary dysplasia  were selected to estimate the treatment effect  the meta analysis showed that a single dose of surfactant administered before the first breath or within 15 hours of birth significantly decreased the mortality rate  95  confidence interval    0 19 to  0 03  and the risk of developing pneumothorax  95  confidence interval    0 28 to 0 14  in infants with respiratory distress syndrome  further clinical trials are needed to evaluate other aspects of surfactant replacement therapy in premature infants because inconsistent results were observed among the seven analyzed studies  
class8	differences in expression of cystic fibrosis in blacks and whites  the recent identification of the cystic fibrosis  cf  gene confirms that genetic heterogeneity occurs in cf  a three base pair deletion in exon 10 resulting in a loss of the phenylalanine residue at amino acid position 508 of the gene product  termed the cf conductance regulator protein  accounts for 70  of cases of cf in white subjects  however  this gene defect occurs in only 37  of affected blacks  analysis of cf genes from american blacks has revealed a number of mutations  most of which are unique to that population  we therefore searched for potential differences in expression of cf between 24 black and 48 white patients with cf matched for birth date and gender  black patients more frequently presented with only respiratory symptoms  38  vs 10    black patients had fewer hospitalizations for pulmonary exacerbations  2 vs 6 9   a better mean forced vital capacity  77  vs 62  of predicted   and higher chest roentgenogram scores  18 2 vs 14 4  than white patients  complication rates were similar except for a higher incidence of hyponatremic dehydration  21  vs 2   and peptic ulcer disease  13  vs 0   in blacks  survival time appeared to be longer in blacks  but the difference was not statistically significant  we conclude that phenotypic differences exist between black and white patients with cf  which may be due to the genetic heterogeneity between these two populations  
class8	recurrent laryngeal nerve avulsion for treatment of spastic dysphonia  treatment of spastic dysphonia by recurrent laryngeal nerve section has resulted in reproducibly good results in the early postoperative period in most patients  however  critical long term follow up has shown a high recurrence rate of adductor spasms by the third year after initial nerve section  a patient who developed recurring adductor spasms 1 year after nerve section was reexplored  with identification of neural regrowth into the distal segment of the recurrent laryngeal nerve  the technique of neural avulsion removing the distal nerve up to its insertion into the laryngeal muscles is described  neural regrowth  which is just one of the possible mechanisms for recurrence of spastic dysphonia  should be prevented by this surgical modification  twelve patients who have undergone neural avulsion primarily for spastic dysphonia are being followed up without recurrence of symptoms thus far  although these results appear promising  this short follow up that averages 1 5 years must be extended to firmly support these concepts  
class8	laryngeal changes during exercise and exercise induced asthma  exercise induced asthma is defined as bronchospasm within the distal airways initiated by exercise  whether the larynx responds to produce an exacerbation or alleviation of symptoms during an attack has never been evaluated  thirty subjects were tested  including 15 normals and 15 with exercise induced asthma  laryngeal response to exercise was determined by measuring the area of the glottic aperture before  during  and after exercise  the glottis was visualized with a flexible laryngoscope and video images were recorded during monitoring of respirations  asthma was induced in subjects by having them exercise on an ergometer for 10 minutes while breathing dry air at 10 degrees c  measurements were subsequently made from recorded images and relative glottic areas were compared between groups  our data quantify the normal physiologic response of the larynx to exercise and demonstrate a substantial laryngeal contribution to asthma induced by exercise  
class8	congenital tracheal stenosis with unilateral pulmonary agenesis  cogenital tracheal stenosis with unilateral pulmonary agenesis is a rate and frequent fetal combination  in an 8 year period  5 infants  ages 2 to 6 months  with these anomalies were treated  the presenting signs and symptoms consisted of wheezing  stridor  and tachypnea and included frank respiratory failure requiring emergency therapy in several patients  the operative repair consisted of segmental resection and anastomosis in one patient  and rib cartilage tracheoplasty in the other four  two infants died  one of cerebral hypoxia  and the other of aortotracheal fistula  long term follow up in the three survivors is satisfactory  
class8	rupture of a benign mediastinal teratoma into the right pleural cavity  a 27 year old woman with a ruptured mediastinal cystic teratoma had high levels of amylase and carcinoembryonic antigen in cystic fluid  the activity of the amylase is thought to be the most likely cause of the rupture  high levels of carcinoembryonic antigen in pleural fluid are not necessarily indicative of a malignant lesion but may suggest the presence of a ruptured teratoma in patients with mediastinal tumors  
class8	tracheoesophageal anastomosis for intractable aspiration pneumonia  permanent tracheostomy and tracheoesophageal anastomosis were performed as a means of surgical intervention for the treatment of intractable aspiration pneumonia  conventional methods of tracheoesophageal anastomosis have entailed various problems  the improved method devised by us uses the special histological features and enables safe and reliable anastomosis  by this method  the tracheal perichondrium is retained and the strength of the anastomosed portion of the trachea is maintained  the failure of sutures due to tension on the anastomotic site being prevented  also  reanastomosis can be performed after the cure of primary disease  
class8	multiple primary bronchogenic carcinomas  treatment and follow up  a second primary bronchogenic carcinoma subsequently developed 8 to 156 months later in 19 patients who underwent curative resection of primary bronchogenic carcinomas  the second primary tumor was treated by surgical resection in 9 patients  3 patients  tumors were considered unresectable  and the remaining 7 patients  despite having potentially resectable tumors  did not undergo resection because of insufficient pulmonary reserve or unwillingness to undergo resection  actuarial life table analysis of survival for the 9 patients who underwent resection showed a median survival time of 110 3 months compared with 19 months for the group with unresected but resectable tumors and 10 5 months for the group with unresectable tumors  there was no operative mortality in the group with resected tumors  we conclude that in patients in whom a second primary carcinoma of the lung develops  surgical resection prolongs survival and can be performed with a low operative mortality  
class8	altered cellular immune function in the atelectatic lung  pulmonary atelectasis is common and may predispose the lung to infection  we have previously shown that atelectasis impairs alveolar macrophage antibacterial function  this study examines the effect of atelectasis on the cytotoxic function of lymphocytes harvested from the bronchoalveolar space of atelectatic lung segments by bronchoalveolar lavage  specifically  we studied natural killer and lectin dependent cell mediated cytotoxicity in peripheral blood and bronchoalveolar lavage lymphocytes from the atelectatic lower lobes and contralateral normal lobes in a group of 8 dogs  we observed a decline of natural killer and lectin dependent cell mediated cytotoxicity to 62 7  and 61 5   respectively  of preatelectasis control values in the affected lung lobes  p less than 0 01   simultaneous measurements of cytotoxic activity of bronchoalveolar lavage lymphocytes harvested from the unaffected contralateral normal lungs were comparable with control values  on the other hand  natural killer and lectin dependent cell mediated cytotoxicity activities in peripheral blood lymphocytes were significantly increased in animals having right lower lobe atelectasis  166 7  and 154 7  of pretreated normal control  respectively  p less than 0 01   atelectasis was also associated with an influx of polymorphonuclear leukocytes into the bronchoalveolar compartment  these findings confirm the presence of natural killer cells and cytotoxic lymphocytes in the bronchoalveolar compartment and demonstrate an atelectasis induced impairment of local bronchoalveolar lymphocyte function  such a dysfunction of local lung cellular host defenses may render the atelectatic lung susceptible to infection  
class8	risk stratification of ambulatory patients suspected of pneumocystis pneumonia  to determine whether aspects of clinical history  physical examination  and laboratory studies improve the diagnostic accuracy of the chest roentgenogram in the diagnosis of pneumocystis carinii pneumonia  pcp   we followed up 302 consecutive patients with respiratory symptoms and risk factors for human immunodeficiency virus  of the 279 patients  92   with follow up information available  31  11   were diagnosed with pcp  only 68  of patients with pcp had typical chest roentgenograms  regression analysis identified four independent predictors of pcp  diffuse or perihilar infiltrates  presence of mouth lesions  lactate dehydrogenase level more than 220 u l  and erythrocyte sedimentation rate 50 mm h or more  using these four predictors  patients could be stratified into low   intermediate   and high risk groups for pcp  we suggest that examination of the mouth  chest roentgenogram  lactate dehydrogenase level  and erythrocyte sedimentation rate be part of the evaluation of ambulatory patients with respiratory symptoms at risk for human immunodeficiency virus  
class8	hemoptysis  indications for bronchoscopy  indications for bronchoscopy in patients with hemoptysis and a normal or nonlocalizing chest roentgenogram continue to be controversial  we reviewed the records for 119 bronchoscopies performed for hemoptysis in patients with a normal  n   75  or nonlocalizing  n   44  chest roentgenogram  bronchogenic carcinoma was identified in 2 5  of the bronchoscopies  additional neoplasms were found in another 2 5   the presence of nonlocalizing abnormalities was not associated with an increase in either the rate of bronchogenic carcinoma or in the diagnostic yield  specific anatomic diagnosis or bleeding site identified  at bronchoscopy when compared with patients with normal chest roentgenograms  the factors of male sex  age more than 40 years  and a more than 40 pack year smoking history appear useful in identifying patients in whom the yield of bronchoscopy is likely to be high  
class8	the ventilator dependent child  issues in diagnosis and management  infants  children  and adolescents with chronic respiratory failure are surviving in increasing numbers and  thereby  producing a significant population of ventilator dependent pediatric patients  chronic respiratory failure can occur as a complication of a wide variety of disease states  in pathophysiologic terms  it generally results from either decreased central nervous system output or inadequate force generated by the respiratory pump  its laboratory hallmark is hypercapnia with or without hypoxemia  stabilization of the patient with mechanical ventilatory support may permit long term survival  management of the ventilator dependent pediatric patient is a complex task that must begin with an accurate prognostication of each patient s survival and quality of life  once a decision is made concerning the practicality and appropriateness of long term ventilatory support  informed choices must be made with respect to need for an artificial airway  mode of ventilation  and location of care  many younger patients  especially those with intrinsic lung disease  like bronchopulmonary dysplasia   may require a hospital setting for long term care  whereas others with neuromuscular or central disorders may benefit from being discharged to home  the patient s family must be thoroughly educated in the child s care  and they must be involved in decision making  a multidisciplinary team of physicians  therapists  nurses  and other professionals is required to deliver optimal care  outcome is good for most patients who are carefully selected  
class8	adult respiratory distress syndrome from organophosphate poisoning  a 46 year old man after an accidental exposure to organophosphates developed florid adult respiratory distress syndrome  ards   a markedly suppressed level of pseudocholinesterase and red blood cell cholinesterase with profuse salivation and sweating confirmed the diagnosis of organophosphate poisoning  within 48 hours  patient developed respiratory distress needing intubation  despite maximum ventilatory support and positive end expiratory pressure  hypoxia persisted  swan ganz  baxter healthcare inc  irvine  ca  pressures showed low pulmonary capillary wedge pressure and patient died on the third hospital day  an autopsy confirmed the picture of ards  other potential causes of ards were excluded  although rare  organophosphate poisoning should be added to the list of toxins causing ards  
class8	mediastinitis following nasal intubation in the emergency department  a patient who developed a retropharyngeal abscess and fatal mediastinitis following emergent nasal intubation is described  despite aggressive surgical therapy the patient died of mediastinitis  although mediastinitis as a complication of oral intubation has been described  mediastinitis following nasal intubation has not previously been reported  
class8	ultrasound assessment of the position of the tongue during induction of anaesthesia  tongue position was assessed in 15 female patients at induction of anaesthesia with either thiopentone or propofol  a video recording of a midline sagittal section of the tongue was made using an ultrasound transducer placed below the chin  and representative figures analysed by an observer who was not aware of the patient s state  in 11 satisfactory recordings  the tongue movement was inconsistent in direction and not more than 8 mm in the anterior tongue and 6 mm in the posterior tongue  the movements detected did not suggest that the tongue is likely to be an important cause of airway obstruction on induction of anaesthesia  
class8	factor analysis in difficult tracheal intubation  laryngoscopy induced airway obstruction  we have studied eight patients with a history of difficult tracheal intubation  using x ray laryngoscopy and local anaesthesia  a curved macintosh blade and a standard intubating position  the view obtained was better than recorded previously during general anaesthesia in two patients  and in a third the x ray showed that positioning the blade tip beneath the epiglottis would have improved vision  suggesting that reproducibility of the assessment may not be consistent  the  ease of intubation  and  complementary  angles may be helpful in the assessment of such patients  a  peardrop  effect is described whereby during laryngoscopy  the epiglottis became pressed against the posterior pharyngeal wall as a result of tongue compression  in the absence of muscle paralysis  removal of the blade caused immediate correction  however  during anaesthesia with neuromuscular block it is suggested that this not only occurs more readily but  may not correct when the blade is removed  iatrogenic airway obstruction during moderately difficult tracheal intubation may be common and should be anticipated  
class8	the cancer experience in the framingham heart study cohort  the almost 40 year records of the framingham heart study  fhs  cohort were reviewed to establish the cancer experience of this noninstitutionalized group of white subjects  diagnoses were confirmed from pathology and laboratory reports and clinical notes  age specific incidence rates were compared with connecticut surveillance  epidemiology  and end results  seer  data  among the 5209 subjects  1201 malignancies were confirmed  median age at diagnosis was 69 for men and 65 for women  lung  prostate  skin  and colon accounted for more than half of men s cancers  breast  colon  and skin made up half of the women s  fhs and connecticut seer rates matched closely  with the same primary tumor sites appearing commonly in both groups  thus  the fhs cohort should provide a fair database for analysis of risk factors in cancer incidence  as it has done in cardiovascular diseases  
class8	evaluation of serum ca 125 as a tumor marker in non small cell lung cancer  serum ca 125 levels were evaluated in 130 healthy subjects and 133 patients with untreated pulmonary lesions  these were 33 patients with benign pulmonary conditions and 100 with lung cancer  the mean concentration of ca 125 was higher in patients with lung cancer  37     81 u ml  than in those with nonmalignant disease  4 2     5 7 u ml   p less than 0 01   in the healthy control group ca 125 concentrations were significantly lower  0 63     1 5 u ml   p less than 0 001   in patients with lung cancer the concentration of this tumor marker was related to the tumor node metastasis  tnm  stage  at a cut off value of 15 u ml  ca 125 had a sensitivity of 44   specificity of 100   positive predictive value of 100   and negative predictive value of 65  with respect to healthy subjects  in patients with benign pulmonary conditions  these values were 44   94   94   and 31   respectively  at this cut off value  a correlation between the respectability prognosis and the likelihood of survival 24 months posttreatment was observed  these findings suggest that ca 125 can be used as an adjunctive test in the management of patients with lung cancer patients  
class8	diagnostic sensitivity of different techniques in the diagnosis of lung tumors with the flexible fiberoptic bronchoscope  comparison of brush biopsy  imprint cytology of forceps biopsy  and histology of forceps biopsy  brush and forceps biopsies were done consecutively in 186 cases of pulmonary neoplasia with a flexible fiberoptic bronchoscope guided by x ray television fluoroscopy  imprint and histologic sections were prepared from all forceps biopsy specimens  the three techniques were compared for their diagnostic sensitivity  as a result 84 9  of all imprints  80 6  of brush biopsy specimens  and 62 9  of histologic sections were positive for malignancy  the sensitivity of brush biopsy specimens was independent of the location and morphology of the tumors  but the sensitivity of forceps biopsy specimens was lower in neoplasms unidentified by bronchoscopy  the sensitivity of the diagnostic accuracy when all three methods were used jointly was 97 3   and the specificity was 100   agreement in the final morphologic tumor type was found in 130 of 150 cases  86 7   by positive brush biopsy specimens  in 136 of 158 cases  86 1   by positive imprint cytology  and in 104 of 117 cases  88 9   by positive histology from forceps biopsy specimens  for routine bronchoscopy  all three methods should be used in combination to obtain the highest diagnostic yield  
class8	surgical management of pericardial effusion in patients with malignancies  comparison of subxiphoid window versus pericardiectomy  there is a lack of consensus regarding optimal surgical management of symptomatic pericardial effusions in patients with malignancies  subxiphoid pericardial window formation  subxiphoid pericardial drainage  has been considered a safe and effective method for diagnostic and therapeutic purposes  to ensure adequate drainage  many surgeons prefer the formation of a larger pericardial window by performing either an anterior thoracotomy or a partial total pericardiectomy  to evaluate the efficacy of these methods for palliation of symptomatic pericardial effusion in patients with malignancy  28 consecutive pericardial surgery cases involving patients with malignancy were retrospectively analyzed  ten patients  group 1  had subxiphoid window formation  whereas 18 patients  group 2  had partial or total pericardiectomy or pericardial window formation by anterior thoracotomy  there was no statistically significant difference  p   0 22  in the survival rates between these two groups  a median survival time of 2 67 months  range  0 43 to 26 6 months  was observed in group 1 versus 1 23 months  range  0 03 to 10 83 months  in group 2  however  a statistically significant difference  p less than or equal to 0 02  in postoperative morbidity was observed between the two groups  67  in group 2 versus 10  in group 1  because of lower morbidity  subxiphoid pericardial window formation is recommended by this study as the preferred surgical method for palliation of symptomatic pericardial effusion in patients with malignancy  
class8	prolonged venous infusion of cisplatin and concurrent radiation therapy for lung carcinoma  a feasibility study  fifty patients with non resectable and or inoperable bronchogenic carcinoma were entered into a feasibility study of cisplatin  cddp  given in continuous infusion with concurrent radiation therapy  the radiation therapy regimen consisted of 2 gy given 5 days a week in the first 3 and last 2 weeks of a 7 week split course  50 gy of total dose   the cddp  daily dose of 4 to 6 mg m2  was administered to cover the days of radiation treatment by means of a central venous catheter and a portable pump  less than 1  of predicted duration of infusion was lost due to complications related to venous access and pump  toxicity was moderate  the overall probability of a locoregional major response  complete   partial  within 1 month after treatment completion was 86   twenty three patients underwent resection  the 1 year actuarial probability of survival was 64   the high response and survival rates warrant further studies on concurrent cddp continuous infusion and radiation therapy in inoperable lung carcinoma  
class8	malignant fibrous histiocytoma of soft tissue  a population based epidemiologic and prognostic study of 137 patients  epidemiology and prognosis were analyzed in a consecutive  population based series of 137 patients with malignant fibrous histiocytoma of soft tissue in the extremities and trunk wall  with a complete follow up of minimum 3 years  all but one patient were treated by surgery in 28 cases combined with adjuvant radiotherapy or chemotherapy  the annual incidence was 0 42 10 5   the ratio men to women was 1 1  the median age was 64 years  range  22 to 87 years   the thigh was the most common location  the median size was 6 cm  superficial tumors constituted 43  and were smaller than deep seated tumors  eighty three tumors were storiform pleomorphic  53 were myxoid  and one was of inflammatory type  the myxoid tumors were smaller and more often superficial  the cumulative 5 year survival rate for all patients was 0 7  but differed markedly between the histologic types  it was 1 0 in patients with myxoid tumors and 0 5 in patients with storiform pleomorphic tumors  in the 77 patients with storiform pleomorphic tumors without metastases at presentation  only tumor size larger than 10 cm and tumor necrosis independently impaired survival  the 23 patients who had none of these risk factors had a 5 year survival rate of 0 8  
class8	life threatening airway obstruction at the presentation of hodgkin s disease  mediastinal involvement from hodgkin s disease is common  significant symptoms resulting from disease at this site are less common and only rarely does severe airway obstruction occur  the authors report six cases of hodgkin s disease in which life threatening airway obstruction was a major feature of the clinical presentation and early clinical course  the literature describing this complication is reviewed  general anesthesia with endobronchial intubation should be avoided if at all possible in patients with airway obstruction and alternative methods of diagnosis and management are discussed  
class8	a pilot study of intermediate dose methotrexate and cytosine arabinoside   spread out  or  up front   in continuation therapy for childhood non t  non b acute lymphoblastic leukemia  a pediatric oncology group study  one hundred six children with newly diagnosed non t   non b cell acute lymphoblastic leukemia  all  were treated in a pediatric oncology group  pog  pilot study in which six courses of intermediate dose methotrexate  mtx  and cytosine arabinoside  ara c   1 g m2 each  were added to a  backbone  of standard continuation therapy  the dose and sequence of mtx ara c administration were based on a preclinical model that demonstrated synergism between mtx and ara c  poor risk patients  n   49  were assigned to  up front  therapy  in which the mtx ara c courses were administered during the initial 15 weeks of remission  standard risk patients  n   57  were assigned to  spread out  therapy  in which the mtx ara c courses were interspersed at 12 week intervals within continuation treatment  toxicity after intermediate dose mtx ara c  principally neutropenia and fever  was judged significant but manageable  unexpectedly  the incidence of fever and neutropenia less than 500 mm3 was greater after  spread out  therapy  38   than after  up front  therapy  6    at 4 years  the kaplan meier estimate of event free survival  efs  is 71       7   for standard risk patients and 53       8   for poor risk patients  the results of this pilot study support the use of intermediate dose mtx ara c in additional studies  
class8	clinical characteristics of high grade lymphomas with immune genes in germline configuration  in a prospective study of 42 high grade lymphomas which were categorized according to the kiel classification  the clinical significance of immune genotyping was studied  immunoglobulin  ig  and t cell receptor  tcr  gene rearrangements were investigated  in 33 cases the immune genotype confirmed the phenotype  in one case with equivocal phenotype a tcr beta chain rearrangement proved the t cell origin of the lymphoma  none of the cases showed a bigenotype  there were eight lymphomas with immunoglobulin and tcr beta chain and gamma chain genes in germline configuration  which were divided into a group of immature lymphomas and a group of lymphomas with a more mature phenotype  the immature lymphomas had widespread disease  rapid progression  and favorable prognosis after intensive chemotherapy  the group of t cell and ki 1 lymphomas with null cell genotype was clinically heterogeneous  three of four cases were secondary lymphomas after lymphomatoid papulosis  lymphomatoid granulomatosis  or hodgkin s disease  all cases presented with extranodal involvement  only one of these patients is in continuous remission  in conclusion  the lack of immunoglobulin and tcr beta chain and gamma chain gene rearrangements does not exclude the diagnosis of high grade malignant lymphoma  especially in cases with unusual extranodal involvement  however  the dna analysis identifies a null cell genotype subset of high grade lymphomas which may have clinical significance  
class8	immunosuppressive acidic protein in malignant diseases  clinical relevance  the immunosuppressive acidic protein  iap  has been described as a tumor associated marker in some solid tumors and hematologic diseases  to define the clinical relevance the authors determined the serum iap levels in 194 patients with malignancies before initiation of therapy  14 patients with idiopathic thrombocytopenic purpura  itp   28 patients with bacterial pneumonia  and 23 healthy volunteers  immunosuppressive acidic protein was measured by radial immunodiffusion  the mean value of our controls was 405     48 micrograms ml  this is consistent with published data  the mean values for patients with malignancies varied from 554 micrograms ml to 698 micrograms ml  these are only marginally higher than those observed for the controls  in contrast patients with bacterial pneumonia demonstrated significantly elevated values  1038     261 micrograms ml   the authors conclude that iap cannot be used as a diagnostic marker for the malignant diseases examined in this study  
class8	novel antigens characteristic of neuroendocrine malignancies  the authors describe the immunochemical detection  biochemical characterization  and tissue distribution of neuroendocrine antigens recognized by three newly developed monoclonal antibodies  moab  obtained after immunization of mice with the variant small cell lung cancer  sclc  cell line nci h82  rnl 1 was reactive with neuroendocrine tissues similar to the sclc cluster 1 moab  known to recognize n cam  antibodies rnl 2 and rnl 3 are directed against different epitopes on the same proteinaceous complex  both moab recognize an intracellularly located  water soluble antigen which has a subunit composition with a protein triplet ranging in molecular weight between 44 and 45 kilodaltons  kd  next to a component of approximately 30 kd  the antibodies rnl 2 and rnl 3 reacted with a subset of neuroendocrine tissues and neuroendocrine neoplasms  in lung cancer both antibodies reacted only with some sclc and carcinoids and not with nonneuroendocrine lung carcinomas  the potential diagnostic applicability of antibodies rnl 1  rnl 2  and rnl 3 is discussed  
class8	clinicopathologic characteristics of adenosquamous carcinoma of the lung  fifty six cases of surgically resected adenosquamous carcinoma of the lung were studied clinicopathologically  and their outcome was compared with that of adenocarcinomas and squamous cell carcinomas of the lung  the frequency rate of adenosquamous carcinoma was 2 6  of 2160 primary lung cancers resected in the national cancer center hospital  tokyo  japan   the survival curves of patients with adenosquamous carcinomas  adenocarcinomas  and squamous cell carcinomas indicated that the outcome of adenosquamous carcinoma was poorer than that of adenocarcinomas and squamous cell carcinomas  particularly in stages i and ii  the amount of adenocarcinoma component did not affect the survival rate  although the histologic features of metastatic lymph nodes was somewhat influenced by the histologic type of the primary tumors  the histologic subtype of adenosquamous carcinoma was one of the independent prognostic determinants  
class8	immunohistochemical evaluation of seven monoclonal antibodies for differentiation of pleural mesothelioma from lung adenocarcinoma  a panel of seven monoclonal antibodies including anti vimentin  anti keratin markers ae1 ae3 and eab902  human milk fat globule  hmfg 2   b72 3  anti carcinoembryonic antigen  cea   and anti leu m1 were used for an immunoperoxidase staining assay to determine their value in the differentiation of pleural mesothelioma from lung adenocarcinoma  anti vimentin positively identified 86  of the mesotheliomas and none of the adenocarcinomas  ae1 ae3  eab902  and b72 3 reacted with a high percentage of both mesothelioma and adenocarcinoma specimens  with hmfg 2  both membrane and cytoplasmic staining was observed in 92  of the adenocarcinomas and in 14  of the mesotheliomas  whereas 26  of the mesotheliomas only exhibited membrane staining  eighty percent of the adenocarcinomas and 8  of the mesothelioma tissues stained with anti leu m1  anti cea did not react with any of the 50 mesotheliomas tested but did react with 95  of the lung adenocarcinomas tested  from this study  it was concluded that anti cea and anti leu m1 were the most effective of the seven tumor markers evaluated  and that 100  of the pleural mesothelioma tissues could be correctly differentiated from lung adenocarcinomas using a panel consisting of anti vimentin  hmfg 2  anti cea and anti leu m1 monoclonal antibodies  
class8	nonseminomatous germ cell tumor with very high serum human chorionic gonadotropin  most patients with disseminated nonseminomatous germ cell tumor  nsgct  have an excellent prognosis with modern chemotherapy  although certain subgroups with a worse prognosis have been described  one such subgroup includes patients with high serum levels of the tumor marker  human chorionic gonadotropin  hcg   sixteen patients of 104 treated for nsgct at the crc wessex medical oncology unit  southampton  uk  presented with serum hcg greater than 25 000  most of these patients exhibited features of the  choriocarcinoma syndrome  with bulky  rapidly progressive disease  frequent pulmonary  hepatic  and central nervous system complications  and a generally poorer response to standard nsgct chemotherapy  histologic identification of trophoblastic tumor was not made in all patients and is not essential for the diagnosis of the syndrome  indeed  closed biopsy may be contradicted in some circumstances because of the risk of hemorrhage  the nsgct patients with poor prognosis  including patients with the choriocarcinoma syndrome  must be clearly identified in order to improve management and  eventually  cure rates  
class8	recurrent renal cell carcinoma arising in wilms  tumor  a 19 month old black girl had a radical nephrectomy for a wilms  tumor that contained areas of epithelium indistinguishable from renal cell carcinoma  she was treated with chemotherapy but subsequently had pulmonary metastases develop and massive abdominal recurrence  the recurrent tumor was histologically renal cell carcinoma with no identifiable wilms  tumor elements  the child died with recurrent and metastatic tumor 13 months after nephrectomy  pathologic  immunoperoxidase  and flow cytometric studies of this unusual case are presented  
class8	acute respiratory failure and pulmonary thrombosis in leukemic children  acute respiratory failure  arf  in an 11 year old child with pre t acute lymphoblastic leukemia  all  at the beginning of induction therapy was observed  connected with a pulmonary thrombosis and not with an infective origin  a systematic search for this pathology identified six other children with the same pulmonary complication  five of whom where in the early phase of acute nonlymphoblastic leukemia  anll  and one in induction therapy for all in marrow relapse  at the beginning of the symptomatology  all children presented severe hypoxia and hypercapnia  with no or minimal chest radiograph abnormalities and no clear hemodynamic involvement  in all patients the arteriography and nuclear imaging studies confirmed the diagnosis  the causes of the thrombi could be connected with neoplastic emboli after cell lysis and or with the vascular damage resulting from antiblastic therapy  intravenous urokinase treatment and respiratory assistance had been successfully carried out in six of seven children  
class8	comparative epidemiology of cancer between the united states and japan  a second look  vital statistics were examined for the years 1955 through 1985 for japanese natives and united states whites to elucidate changes in cancer mortality and related antecedent patterns of life style in these two populations  results show that lung cancer rates are rapidly accelerating among japanese males as a consequence of their prior history of heavy cigarette smoking  oropharyngeal cancer rates are also rising in japan paralleling increases in alcohol and tobacco utilization  as the japanese life style and diet continue to become more  westernized   the rates of malignancies of the breast  ovary  corpus uteri  prostate  pancreas  and colon also continue to rise  nevertheless  the mortality patterns of certain malignancies  viz   laryngeal  esophageal  and urinary bladder cancer  are discrepant with their established risk factor associations  suggesting the existence of other differences in risk factor exposure between the two countries  epidemiologists and health educators need to develop innovative international programs of investigation and health promotion with preventive impact on common malignancies associated with risk factors of life style  
class8	once daily intramuscular ceftriaxone in the outpatient treatment of severe community acquired pneumonia in children  published erratum appears in clin pediatr  phila  1991 may 30 5  326  ceftriaxone  a broad spectrum third generation cephalosporin with a half life of six to eight hours  was evaluated prospectively in 147 children with severe community acquired bacterial pneumonia during the period 11 15 88 5 15 89  thirty nine of the children had been unsuccessfully treated with vanous oral antibiotics prior to admission  corrected   all the patients were initially hospitalized and started on once a day intramuscular ceftriaxone  mean duration of ceftriaxone therapy was five days  pathogens were recovered from blood cultures of 17  11 6   patients and included s  pneumoniae  13 patients   h  influenzae  three  all resistant to ampicillin  and s  viridans  1   corrected   all isolates were sensitive to ceftriaxone  an additional patient had l  pneumophila diagnosed by serology  cure was achieved in 142  96 6   patients  improvement was usually observed within 24 48 hours  after 48 hours  121  82 2   children could be discharged and continued the therapy on ambulatory basis  based on previous experience we estimated that 383 hospitalization days were saved  no serious side effects were observed  five patients were considered therapeutic failures  two of them developed empyema and one of them required repeated drainage procedures  a third patient experienced a relapse of pneumonia shortly after completion of therapy  the other two remained febrile for more than seven days  their subsequent improvement was unrelated to the antibiotic therapy  suggesting a viral or mycoplasmal syndrome  our data suggest that once daily intramuscular ceftriaxone can be successfully used for the outpatient treatment of most community acquired severe bacterial pneumonias in children  in our opinion it represents the treatment of choice for patients who failed treatment with other antimicrobials and are clinically stable enough not to require hospitalization  
class8	bronchopulmonary involvement in ulcerative colitis  we report two cases of pulmonary involvement in ulcerative colitis  the first patient  a 37 year old woman  had bilateral basal bronchiectasis full of mucopurulent secretion  with a marked improvement of pulmonary function and roentgenographic appearance after a conservative approach  the second patient had severe pulmonary fibrosis of autoimmune nature and died owing to a pulmonary infection  in the second patient  a sulfasalazine reaction as an etiologic factor was excluded  while in the first this possibility seemed unlikely  therefore  we take these two cases as examples of the extraintestinal manifestations of ulcerative colitis  
class8	vocal fold sulcus  vocal fold sulcus is a cause of dysphonia which has not been recognized until recently  awareness of its existence combined with use of laryngostroboscopy would enhance the management of this group of patients  five such cases were treated initially by voice therapy and subsequently combined with microlaryngeal teflon injections of the vocal cord  representative photomicrographs and the end results of treatment are presented  a good voice  subjectively and objectively  was obtained in three patients  with satisfactory improvement in the other two  
class8	tracheostomy closure in restrictive respiratory insufficiency  a retrospective study is presented of 31 patients who required ventilatory support via a tracheostomy for periods of one month to 27 years whilst in a tertiary referral centre for the care of patients with restrictive respiratory insufficiency  all patients underwent closure of a long standing tracheostomy  post operative follow up periods of up to 16 years are documented  the indications for and the complications of tracheostomy closure in patients with severe chronic restrictive respiratory insufficiency requiring long term respiratory support are discussed  it is concluded that the benefits of operative tracheostomy closure outweigh the disadvantages in this unusual type of patient  
class8	cartilaginous metaplasia of the epiglottis  metaplastic elastic cartilaginous tissue has been described in the vocal cord  vestibular fold and ventricle of the larynx  this report documents a case in which cartilaginous metaplasia developed in the soft tissue of the epiglottis following an episode of epiglottitis  
class8	fulminant monophasic multiple sclerosis  marburg s type  the clinical  neuroradiological and necropsy findings are described in a 49 year old woman with long standing idiopathic pulmonary haemosiderosis and acute monophasic multiple sclerosis  marburg s type   progression of the demyelinating process produced blindness and paraplegia over three weeks  at five weeks  magnetic reasonance imaging  mri  studies showed lesions in the pons and left occipital lobe  the patient died 10 weeks after onset of symptoms  necropsy examination revealed acute plaques in the optic chiasm  and the white matter around the lateral and fourth ventricle and spinal cord  similarities between this and previously described cases of marburg s disease are discussed  
class8	clustering of cancer in families of patients with primary lung cancer  we have previously shown that patients with a positive family history of lung cancer did not exhibit characteristics expected if the familial association was a surrogate for a genetic mechanism which was absent in those without such a history  in this study  we examine the incidence of cancer  all sites  in two groups of families   a  those ascertained through a patient with primary lung cancer  n   359 families  and  b  through a community control subject  n   234   the index subjects were excluded from all incidence data analyses  most families  62 vs 57   reported at least one member with a history of neoplastic disease  patients  families were more likely to have 2 or more affected members  p less than 0 05   to exhibit a multigenerational pattern  33 vs 24   and to have a higher risk of multiple tumours  or   1 5  in the same individual  however  most of the sites with the highest odds ratios  males  vocal cord esophagus 8 3  colon rectum 2 3  lung 1 96  females  pancreas 4 8  vocal cord esophagus 4 1  lung 1 8  are smoking associated although these were not necessarily the most frequently affected sites  in conclusion  these data support an ecogenetic etiology of cancer within families  
class8	differential diagnosis of lung tumor with positron emission tomography  a prospective study  to predict the nature of non calcifying lung tumors  we performed a prospective study of 46 cases with l  methyl 11c methionine  met  24 cases  and 18f fluorodeoxyglucose  fdg  22 cases  using positron emission tomography  pet   mean tumor muscle radioactivity ratios are 5 3     2 0  n   14  for malignant and 1 9     0 9  n   10  for benign with met  p less than 0 001   and 4 4     2 2  n   12  and 1 5     0 3  n   10   respectively  with fdg  p less than 0 001   the ratios indicate that malignant tumors have higher metabolic demand than benign lesions  tumors less than 1 cm in diameter were difficult to accurately evaluate due to pet resolution  compared to the diagnosis at pathology  the met study showed a sensitivity of 93   13 14   a specificity of 60   6 10   and an accuracy of 79   19 24   the fdg study showed 83   10 12   90   9 10   86   19 22   respectively  no significant differences were observed between the two tracers  this study suggests that pet studies using either met or fdg may be very useful for the differential diagnosis of lung tumors  
class8	spect quantitation of iodine 131 concentration in phantoms and human tumors  the validity of spect measurement of iodine 131  131i  concentration was tested in vitro in phantoms and in vivo by measuring bladder urine concentrations  phantom studies comparing known and spect measured concentrations showed a good correlation for 131i  r   0 98  s e e    20 94 counts voxel  for phantoms of 25 to 127 cc and concentrations of 0 13 to 9 5 microci cc  the in vivo  in vitro correlation of 131i concentrations in the urine was also good  r   0 98  s e e    0 677 microci cc   quantitative spect was used to calculate the effective half life and dosimetry of radioiodine in 12 sites of thyroid carcinoma in seven patients  spect was also used to determine the dosimetry of  131i mibg  metaiodobenzylguanidine  in two patients with carcinoid  two with neuroblastoma  and one with pheochromocytoma  the radiation dose for thyroid carcinoma metastases varied between 6 3 and 276 9 rad mci  the dose from mibg varied between 13 4 and 57 8 rad mci  these results indicate the validity of quantitative spect for in vivo measurement of 131i and the need to measure the concentration of 131i in individual human tumor sites  
class8	effectiveness of an antihistamine decongestant combination for young children with the common cold  a randomized  controlled clinical trial  we tested the hypothesis that antihistamine decongestant combinations cause no clinically significant relief of the symptoms of upper respiratory tract infections in young children by randomly assigning 96 children to one of three treatment groups  antihistamine decongestant  placebo  and no treatment  there were no differences among the three study groups in the proportion of children considered  better  overall by the parent 48 hours after the initial assessment  drug  67   placebo  71   no treatment  57   p   0 53   there were no differences among groups in individual or composite symptom score changes  two thirds of parents whose children were eligible for the drug trial believed that their child needed medicine for cold symptoms  in the proportion of parents believing that their child needed medicine  there was no difference between those who consented to participate and those who refused  parents who wanted medicine at the initial visit reported more improvement at follow up  regardless of whether the child received drug  placebo  or no treatment  we conclude that there is no clinically significant improvement in symptoms of upper respiratory tract infection  including no significant placebo effect  in young children for whom an antihistamine decongestant is prescribed  
class8	treatment of childhood angiomatous diseases with recombinant interferon alfa 2a  a heterogeneous group of five patients with progressive  invasive angiomatous diseases including pulmonary hemangiomatosis  angiosarcoma  or massive hemangioma with associated consumptive coagulopathy were treated with interferon alfa 2a for periods of 17 to 33 months  one patient with a large thoracic hemangioma  cardiorespiratory failure  and consumptive coagulopathy died after less than 2 months of treatment  the remaining four patients have shown beneficial responses  including  1  regression of abnormal vessels on pulmonary angiogram and improved exercise tolerance in pulmonary hemangiomatosis  two patients    2  decreased corticosteroid and or platelet transfusion requirements in consumptive coagulopathy  two patients   and  3  decreased size and number of tumor nodules in the one patient with angiosarcoma arising in preexisting angiomatous lesions  responses occurred during periods of 2 to 20 months of treatment  there was no measurable progression of angiomatous lesions in any patient receiving interferon at the therapeutic dose  except possibly in the one who died  each of the four surviving patients had improved linear growth and weight gain during interferon treatment  
class8	postoperative adjuvant chemotherapy in non small cell lung cancer  prognostic value of dna ploidy and post recurrent survival  eighty six patients with non small cell lung cancer who underwent curative operations were postoperatively randomized to control and adjuvant chemotherapy groups  in the adjuvant chemotherapy group  patients received cisplatin based combination chemotherapy 3 or 4 weeks after operation and the average cycle of chemotherapy was 2 3  from 1 to 6 cycles   in this trial  no evidence of improved survival or delayed recurrence was seen in the treated patients  in multivariate analysis of prognostic variables  the most important factor was the pathological stage of the disease and  second  dna ploidy of the primary tumor  although histology  squamous vs  non squamous cell carcinoma  had a trend to influence the survival  it was not a significant factor  a total of 33 patients had recurrences  17 and 16 patients were in control and adjuvant chemotherapy groups  respectively  postrecurrent survival in the adjuvant chemotherapy group was significantly shorter than that in the control group  as determined by the generalized wilcoxon and log rank tests  median survival time after recurrence in the control and adjuvant therapy groups was 18 5 and 7 5 months  respectively  these results suggest that dna ploidy of primary tumors should be considered as a prognostic factor in future trials of adjuvant therapy  furthermore  analysis of postrecurrent survival in the adjuvant chemotherapy trial  as well as that of overall and disease free survivals should be done  
class8	adjuvant  specific  active immunotherapy for resectable squamous cell lung carcinoma  a 5 year survival analysis  in 1976 stewart et al   annals of the new york academy of sciences 277 436 466  reported the effectiveness of adjuvant specific active immunotherapy of lung carcinoma in improving the postoperative survival of stage i lung carcinoma patients in a phase ii study using lung carcinoma associated antigen  taa  and complete freund s adjuvant  cfa   a phase iii study was then designed by the authors to see the effects of specific active immunotherapy compared to the conventional management  no treatment  and to nonspecific immunotherapy  from 1976 to 1981  85 patients with resectable  stages i and ii  squamous cell lung carcinoma were entered into a randomized study  1  control group  2  specific immunotherapy group  three monthly doses of 500 micrograms of taa emulsified with cfa  3  nonspecific immunotherapy group  three monthly doses of cfa emulsified in saline  all the patients in the study received skin tests with 100 micrograms of the same taa used for the immunotherapy  recently  a 5 year follow up of all the patients became available  the life table 5 year survival of group 1 was 34   of group 2 was 75   and of group 3 was 53   the median survivals for the three groups were group 1  38 months  group 2  106 months  and group 3  71 months  the difference was significant at p    007  cox mantel test   
class8	antimicrobial resistance of pneumococci in children with acute lower respiratory tract infection in pakistan 87 strains of streptococcus pneumoniae isolated during three winter seasons  1986 89  from the blood of children with acute lower respiratory tract infection  alri  in pakistan were serotyped and tested for susceptibility to a range of antimicrobial agents  97  of isolates were resistant to at least one antimicrobial drug  62  had decreased susceptibility to co trimoxazole  trimethoprim sulphamethoxazole   31  were fully resistant  and 39  were resistant to chloramphenicol  all isolates were susceptible to erythromycin  cefaclor  cephalothin  ceftriaxone  cefuroxime  rifampicin  vancomycin  and clindamycin  29  of isolates were neither vaccine types nor vaccine related types  serotype distribution and antimicrobial susceptibility varied significantly during the three winter seasons  no single serotype was found in all three winters  the findings highlight the need for surveillance of antimicrobial resistance and serotype distribution of s pneumoniae in developing countries as a guide both to the choice of agent for treatment of pneumococcal infections  especially alri  and to the formulation of new pneumococcal conjugate vaccines for use in young children  
class8	measurement of d dimer in plasma as diagnostic aid in suspected pulmonary embolism the potential of plasma measurement of d dimer  dd   a specific derivative of crosslinked fibrin  for diagnosis or exclusion of pulmonary embolism was investigated in a prospective series of 171 consecutive patients who attended an emergency department with suspected pulmonary embolism  the diagnosis was made or excluded by means of a clinical decision making process which included clinical evaluation  ventilation perfusion  vq  lung scan  and  as indicated  pulmonary angiography  venography  or non invasive examination of the leg veins  pulmonary embolism was diagnosed by this process in 55  32   of 170 patients with sufficient data  all but 1 of these 55 patients had a dd concentration of 500 micrograms l or above  the sensitivity and specificity of this cutoff concentration for the presence of pulmonary embolism were 98  and 39   respectively  which give positive and negative predictive values of 44  and 98   among the 115 patients  68   who had inconclusive vq scans  31 were diagnosed as having pulmonary embolism  29 of the remaining 84 patients without pulmonary embolism had dd concentrations below 500 micrograms l  which means that further diagnostic procedures could have been avoided in a quarter of the patients with inconclusive vq scans  the sensitivity of the plasma measurement of dd remained high even 3 and 7 days after presentation  96  and 93    plasma measurement of dd therefore has a definite place in the diagnostic procedure for suspected acute pulmonary embolism in attenders at emergency departments  a concentration below 500 micrograms l rules out the diagnosis  
class8	respiratory arrest in near fatal asthma background and methods  the majority of asthma related deaths occur outside the hospital  and therefore the exact factors leading to the terminal event are difficult to ascertain  to examine the mechanisms by which patients might die during acute exacerbations of asthma  we studied 10 such patients who arrived at the hospital in respiratory arrest or in whom it developed soon  within 20 minutes  after admission  results  the characteristics of the group were similar to those associated in the literature with a high risk of death from asthma  including a long history of the disease in young to middle aged patients  previous life threatening attacks or hospitalizations  delay in obtaining medical aid  and sudden onset of a rapidly progressive crisis  extreme hypercapnia  mean      sd  partial pressure of arterial carbon dioxide  97 1     31 1 mm hg  and acidosis  mean      sd  ph  7 01     0 11  were found before mechanical ventilation was begun  and four patients had hypokalemia on admission  despite the severe respiratory acidosis  no patient had a serious cardiac arrhythmia during the resuscitation maneuvers or during hospitalization  we observed systemic hypertension and sinus tachycardia in eight patients  atrial fibrillation in one  and sinus bradycardia in another  in both patients with arrhythmia the heart reverted to sinus rhythm immediately after manual ventilation with 100 percent oxygen was begun  the median duration of mechanical ventilation was 12 hours  and all patients had normocapnia on discharge from the hospital  conclusions  we conclude that at least in this group of patients  the near fatal nature of the exacerbations was the result of severe asphyxia rather than cardiac arrhythmias  these results suggest that undertreatment rather than overtreatment may contribute to an increase in mortality from asthma  
class8	polymyositis  pulmonary fibrosis and autoantibodies to aminoacyl trna synthetase enzymes  the clinical and laboratory features of 29 patients who had one of three anti aminoacyl trna synthetase autoantibodies  anti jo1  histidyl trna synthetase   anti pl12  alanyl trna synthetase  or anti pl7  threonyl trna synthetase  were analysed and compared with the findings of other published reports  these autoantibodies were found to be associated with a syndrome delineated by inflammatory myositis  24 patients  and pulmonary fibrosis  23 of 29   but also including inflammatory arthritis  26 29   keratoconjunctivitis sicca  17 29   sclerodactyly  21 29   raynaud s phenomenon  27 29   hepatitis  8 29  and subcutaneous calcinosis  7 29   the most important clinical determinant of outcome in this group of patients was the severity of the interstitial pulmonary disease  no patient fulfilled the classification criteria for systemic lupus erythematosus  although 10 had autoantibodies to extractable nuclear antigens including ro  la  rnp  and sm  and two patients had anti dsdna antibodies  although it seems unlikely that anti aminoacyl trna synthetase antibodies are directly responsible for causing disease  they may provide an important clue to the aetiology of this unusual syndrome  
class8	mycobacterial infection after renal transplantation  report of 14 cases and review of the literature  during a nine year period  14 cases of mycobacterial infection  tuberculosis  developed in 403 renal transplant recipients at the king faisal specialist hospital and research centre in riyadh  saudi arabia  an incidence of 3 5 per cent  the annual incidence of tuberculosis was about 50 times higher than that in the general population  infection was disseminated in nine  64 3 per cent   pulmonary in four  28 6 per cent   and genitourinary in 1  7 1 per cent   in one patient tuberculosis was transmitted by the donor s kidney  the clinical manifestations were often ill defined and not different from that in the normal host  cultures from all patients grew mycobacterium tuberculosis  concomitant infection with other organisms was present in five patients  35 7 per cent   two of 18 patients  group 1  with positive pretransplant tuberculin skin test developed tuberculosis after transplantation  11 per cent   and neither received isoniazid prophylaxis  three of 70 patients  group 2  with negative skin tests developed tuberculosis after transplantation  4 3 per cent   the difference between the two groups was not statistically significant  review of all published cases of mycobacterial infections in renal transplant recipients revealed 130 cases  tuberculosis was disseminated in 38 7 per cent  pulmonary in 40 2 per cent  cutaneous in 12 per cent  and miscellaneous in 9 4 per cent  atypical mycobacteria were responsible for 29 per cent of disseminated infections  8 per cent of pulmonary infections and all cases of cutaneous and articular tuberculosis  invasive procedures were needed to establish the diagnosis in 21 of 33 disseminated cases but in only three of 47 cases of pulmonary tuberculosis  p less than 0 0001   the mortality rate from disseminated disease was 37 per cent and from all other forms of tuberculosis was 11 per cent  p less than 0 005   these findings  1  confirm the higher incidence of tuberculosis in renal transplant recipients  compared to the general population   2  suggest that pretransplant skin testing probably has little value in identifying patients at risk   3  show that disseminated tuberculosis is common after renal transplantation and requires invasive procedures for diagnosis   4  confirm that the donor kidney may be an important source of infection  and  5  indicate that concomitant infection with other organisms is common  
class8	nosocomial infections due to xanthomonas maltophilia  pseudomonas maltophilia  in patients with cancer  from december 1985 to may 1986  xanthomonas maltophilia  formerly known as pseudomonas maltophilia  was isolated at an increased rate at our institution  52 isolates of x  maltophilia were obtained in cultures of clinical specimens from 38 patients during that time  the records of 35 of these patients form the basis of this study  twelve  71   of the 17 infected and nine  50   of the 18 colonized patients had received or were receiving antimicrobial therapy  eleven of 17 patients  three of seven with septicemia  three of five with pneumonia  three with urinary tract infection  and two with wound infection  responded to antimicrobial therapy  microbiologic studies of the potential environmental sources revealed growth of x  maltophilia in two water faucets and in one water sample from the medical intensive care unit  x  maltophilia is emerging as an important nosocomial pathogen in immunocompromised patients  especially those receiving broad spectrum antimicrobial therapy  
class8	eosinophilic pneumonia associated with reaction to radiographic contrast medium  we have described what we believe to be the first published case of a reaction to radiographic contrast medium followed by a diffuse eosinophilic pneumonia  this association seems to confirm what is know about the immunologic mechanisms of such reactions  and though further verification of causation is needed  we found it to be the most plausible explanation  
class8	rheumatoid arthritis of the larynx  the importance of early diagnosis and corticosteroid therapy  rheumatoid arthritis is a destructive systemic disorder characterized by remissions and exacerbations  the larynx is involved in approximately 25  of these patients  the importance of early detection of laryngeal involvement by this disease and treatment with corticosteroids has not been adequately addressed in the literature  we have described five patients who had early diagnosis and successful treatment with systemic corticosteroids and or corticosteroid injection of the cricoarytenoid joint  
class8	ultrasonographic findings of testicular microlithiasis associated with intratubular germ cell neoplasia  testicular microlithiasis is an uncommon condition in which calcified concretions fill the lumina of seminiferous tubules  we report the case of a twenty three year old white man with a metastatic germ cell tumor and normal findings on testicular physical examination  but abnormal ultrasonography of the right testis  orchiectomy revealed intratubular germ cell neoplasia with testicular microlithiasis  multiple circular echogenic foci on ultrasound correlated with the histologic finding of testicular microlithiasis  further studies are indicated for assessing ultrasonography as an adjunct for screening the population at risk for intratubular germ cell neoplasia  
class8	perinatal transmission of human papillomavirus  human papillomavirus infection is probably the most prevalent sexually transmitted disease in the united states  in adults  it is associated with condylomata acuminata and with neoplastic changes ranging from dysplasia to carcinoma  infected mothers may transmit human papillomavirus during the perinatal period  affected children face prolonged  difficult treatment for respiratory papillomatosis  prevention of infection remains the best approach  since diagnostic and therapeutic methods are suboptimal  
class8	chronic upper lobe cavitary lung disease  chronic upper lobe cavitary lung disease may be caused by infections  emphysema  cystic fibrosis  lung cancer  sarcoidosis and rheumatologic syndromes  the diagnostic evaluation includes a complete history  a physical examination  a chest radiograph  and sputum examination and culture  in some cases  computed tomographic scanning and biopsy are required  
class8	prevalence of unsuspected mitral regurgitation and left ventricular diastolic dysfunction in patients with coronary artery disease and acute pulmonary edema associated with normal or depressed left ventricular systolic function  to define the prevalence and role of left ventricular  lv  systolic dysfunction  lv diastolic dysfunction and mitral regurgitation  mr  in patients with acute pulmonary edema  40 patients with coronary artery disease and acute pulmonary edema were prospectively evaluated within 36 hours of presentation  lv ejection fraction and 3 parameters of lv diastolic function were measured with radionuclide ventriculography  whereas mr was assessed with doppler echocardiography  lv ejection fraction was normal in 11  27   and depressed in 29  73   patients  moderate or severe mr without lv diastolic dysfunction was common and equally prevalent in patients with and without lv systolic dysfunction  33 vs 38   difference not significant   diastolic dysfunction without mr was less frequent but equally prevalent in patients with and without systolic dysfunction  17 vs 27   difference not significant   two  18   of 11 patients without and 12  33   of 36 patients with lv systolic dysfunction had both mr and lv diastolic dysfunction  furthermore  mr was clinically silent and unsuspected in two thirds of all patients with mr  regardless of a normal or depressed systolic function  these data show that there is a high prevalence of unrecognized moderate to severe mr in patients with acute pulmonary edema  regardless of the presence or absence of lv systolic dysfunction  furthermore  the prevalence of lv diastolic dysfunction without mr is relatively low even in patients with normal lv systolic function and pulmonary edema  thus  unrecognized mr may be an important contributor to the syndrome of acute pulmonary edema in patients with normal or depressed lv systolic function  
class8	disseminated pneumocystis carinii infection with hepatic involvement in a patient with the acquired immune deficiency syndrome  extrapulmonary infection with pneumocystis carinii  p  carinii  in aids patients is uncommon  and is often described only at postmortem examination  although most antemortem cases involve spread to the bone marrow or spleen  p  carinii involvement of other organs has only recently been described  despite the frequency of liver enzyme abnormalities in aids patients with a history of p  carinii pneumonia  p  carinii has been observed only rarely in the liver  we present a well documented case of p  carinii involving the liver in an aids patient with p  carinii pneumonia and progressive liver enzyme abnormalities  we suggest that p  carinii infection should be considered in the differential diagnosis of aids related liver disease  
class8	pharmacokinetics of ganciclovir in a patient undergoing hemodialysis  the pharmacokinetics and effect of hemodialysis on the clearance of ganciclovir were evaluated in a patient with cytomegalovirus  cmv  retinitis and pneumonitis requiring dialytic support  a dose of 300 mg ganciclovir  5 mg kg  was administered by intravenous infusion over a 60 minute period  blood samples were obtained over the next 10 hours and used to assess plasma ganciclovir concentrations  the patient underwent hemodialysis the following day during which paired arterial and venous blood samples were obtained to determine dialyzer clearance of this antiviral agent  high performance liquid chromatography was used to quantify ganciclovir plasma concentrations  ganciclovir levels declined in a monoexponential manner following infusion and prior to dialysis  the patient s peak ganciclovir concentration was markedly elevated  20 micrograms ml  compared with previously reported peak concentrations in patients with normal renal function  similarly  the elimination half life  t1 2  was increased  6 3 hours  in this patient compared with values reported in patients with normal renal function  the volume of distribution  0 21 l kg  and total body clearance prior to hemodialysis  35 5 ml min  were diminished in this patient  hemodialysis reduced ganciclovir levels by approximately 62  with an extraction coefficient of 0 29 resulting in a dialyzer clearance of 48 3 ml min  this supports supplementation of ganciclovir in patients receiving this antiviral agent when they are undergoing hemodialysis  additionally  close monitoring of ganciclovir concentrations in patients with abnormal renal function is necessary in order to make appropriate dosage adjustments  
class8	body position changes redistribute lung computed tomographic density in patients with acute respiratory failure  ten patients with parenchymal acute respiratory failure  arf  underwent computed tomography  ct  scans while in the supine and prone positions  at equal levels of positive end expiratory pressure  the authors measured the changes of ct density in dorsal and ventral basilar lung regions induced by the change of position as well as alterations of gas exchange  the level of venous admixture did not change with body position  the ct scan image of each lung was fractionated into ten levels from dorsal to ventral  each constituting 10  of the lung height  after measuring each lung fraction  the volume  the average ct number  its frequency distribution  and the expected normal value  we computed the lung tissue mass  the excess tissue mass  and the fraction of normally inflated tissue  excess tissue mass   amount of  tissue   which includes edema  cells  and blood in excess of the expected normal value   we also estimated the superimposed hydrostatic pressure on each lung region  we found that the excess lung tissue mass is independent of position  however  in patients in the supine position  lung ct density increased and regional inflation decreased from ventral to dorsal  suggesting progressive deflation of gas containing alveoli along the gravity gradient  a similar ventral dorsal deflation pattern occurred within 10 min in patients in the prone position  we conclude that the lung in patients with arf behaves like an elastic body with a diffusely increased mass  dependent lung regions are compressed by the pressure of overlying structures  
class8	bronchial responsiveness is not increased by bronchoalveolar and bronchial lavage performed after allergen challenge  nonspecific bronchial responsiveness was studied in 23 allergic patients with a history of rhinitis and or bronchial asthma who underwent fiberoptic bronchoscopy with bronchoalveolar and bronchial lavage  bal bl  4h  group a  or 24 h  group b  after an allergen inhalation challenge  in all patients  the dose of methacholine causing an fev1 fall of 15   pd15  was determined at baseline  24 h before allergen challenge  methacholine bronchial challenge was repeated 1 h before bal bl in patients of both groups and again 12 to 14 h after bal bl in group a and 24 h after bal bl in group b  in patients of group a  the values of methacholine pd15 after bal bl were not significantly different from those determined before bal bl  this was also the case in patients in whom bronchial responsiveness was increased after allergen challenge  in patients of group b  methacholine pd15 was significantly decreased after allergen challenge  and this decrease was correlated with the occurrence and the severity of the late asthmatic reaction  even in patients who showed dual asthmatic reactions and an increased responsiveness after allergen challenge  methacholine pd15 was not further decreased after bal bl  these data support the safety of a procedure combining bronchial allergen challenge with bal bl  which can be used for studies on the pathophysiology of bronchial asthma  
class8	bronchiolar inflammation and fibrosis associated with smoking  a morphologic cross sectional population analysis  the lungs of 42 smokers and 13 nonsmoking males of various ages who died suddenly and unexpectedly were examined grossly using gough wentworth whole lung sections and by microscopic planimetry to assess the severity and prevalence of emphysema  the bronchioles in representative histologic sections were evaluated for inflammation and epithelial metaplasia as well as for fibrosis and muscular hypertrophy  postmortem interviews with next of kin established a history of cigarette smoking and excluded possible occupational exposures to toxic or particulate inhalants  emphysematous changes were not prominent in members of the study group  but they tended to be more severe in smokers  p   0 059  and increased in severity with age  p less than 0 001   inflammatory changes  so called smoker s bronchiolitis  were evident in smokers of all ages  although they were significantly less prominent in the lungs of older smokers  on the other hand  respiratory and membranous bronchiolar wall fibrosis was increasingly evident in older smokers  p less than 0 05   muscular hypertrophy in the bronchiolar walls was significantly greater in smokers  but a change with age was not observed  these findings strongly suggest that bronchiolar fibrosis is associated with chronic cigarette use  these lesions occur independently of emphysema and may account for some of the subtle physiologic alterations observed in smokers  
class8	a positron emission tomographic comparison of pulmonary vascular permeability during the adult respiratory distress syndrome and pneumonia  we measured extravascular density  evd  and the pulmonary transcapillary escape rate  ptcer  for 68ga transferrin using positron emission tomography in 14 normal volunteers and 29 patients with radiographic infiltrates  including six patients with congestive heart failure  chf   eight patients with the adult respiratory distress syndrome  ards   and 15 patients with focal pneumonia  contralateral  radiographically normal regions were also evaluated in the patients with focal pneumonia  mean evd was elevated in the patients with chf  ards  and pneumonia in regions of radiographic infiltrate compared with values from normal subjects  p less than 0 05   but it was not significantly different among the three patient groups  ptcer in normal subjects and in patients with chf was not significantly different  21     11 versus 44     16 x 10  4  min 1  respectively  p   ns   ptcer was elevated in regions of infiltrate because of either pneumonia  173     99  or ards  170     79   ptcer was also elevated in regions contralateral to those with focal infiltrate during pneumonia  even though these regions were radiographically normal and had normal evd values  these results suggest that ptcer is a sensitive but nonspecific index of abnormal pulmonary vascular permeability  which may be useful for classifying patients in clinical studies of pulmonary edema  
class8	sepsis induced lung injury and the effects of ibuprofen pretreatment  analysis of early alveolar events via repetitive bronchoalveolar lavage  current knowledge of alveolar pathophysiology during early sepsis induced acute lung injury  ali  and the role of resident alveolar macrophages  am  in mediating alveolar inflammatory events during sepsis is limited  further  the effects of ibuprofen pretreatment upon alveolar pathophysiology and am function during early sepsis induced ali is unclear  utilizing repetitive bronchoalveolar lavage  bal  in a porcine model of sepsis induced ali  we studied changes in alveolar cellular constituents  bal protein content and molecular composition  and am superoxide anion  o2    generation during early sepsis  the neutrophil percentage of recovered alveolar cells  17     8   t   300 min versus 2     1   t   0  p   0 06  and the bronchoalveolar lavage total protein content  493     110 micrograms ml  t   300 min versus 109     18 micrograms ml  t   0  p less than 0 05  increased in septic animals  increases in bal fluid total protein were primarily due to low molecular weight plasma protein  indicating relative preservation of alveolar capillary membrane size selectivity  alveolar macrophages harvested following 300 min of sepsis generated significantly less o2   following phorbol myristate acetate  pma  stimulation compared to am harvested at baseline  ibuprofen pretreatment of septic animals completely blocked leakage of plasma proteins into the alveoli and attenuated neutrophil migration but did not prevent downregulation of am o2   generation  increased alveolar capillary membrane permeability  neutrophil migration into the alveoli  and downregulation of am oxidant generation occur within hours of the onset of sepsis  ibuprofen pretreatment significantly attenuates early sepsis induced ali without altering sepsis induced am dysfunction  
class8	sweet s syndrome with lung involvement  severe dyspnea and pulmonary infiltrates were associated with recurrent episodes of sweet s syndrome  acute febrile neutrophilic dermatosis  in a 54 yr old woman with myelodysplasia  lung and skin biopsies revealed a sterile infiltration of the interstitial tissues by mature neutrophils  corticosteroid therapy resulted in rapid clinical improvement  however  recurrent episodes were increasingly resistant to therapy  and she ultimately died from respiratory failure  sweet s syndrome involving the lung is rare  with only two previously reported cases documented by lung biopsy  prompt recognition of sweet s syndrome with lung involvement is important because of the potential for severe respiratory compromise  
class8	prognosis of idiopathic pulmonary fibrosis in patients with mucous hypersecretion  in order to determine the prognosis of patients with chronic idiopathic pulmonary fibrosis  ipf   we evaluated clinical  laboratory  and bronchoalveolar lavage  bal  data at the onset of ipf in 25 patients who survived beyond 1 yr  nine women and 16 men  59     3 yr of age  mean     se   when the patients were divided into two groups according to whether they had or did not have mucous hypersecretion  11 patients with hypersecretion  group a  had a poorer survival rate  6 yr  than did 14 patients without hypersecretion  group b   10 yr   p less than 0 01   further  there was a significant negative correlation between sputum volume and the duration of survival in 25 patients  r    0 55  p less than 0 01   before glucocorticoid treatment  we also found significantly larger numbers of neutrophils  17   and eosinophils  5   in differential cell counts of bronchoalveolar lavage fluid  balf  in group a than in group b  neutrophils  1   eosinophils  0 6    p less than 0 05 each   chest radiographic findings and other laboratory data including pulmonary function tests did not correlate with the survival rate  these findings suggest that mucous hypersecretion as well as neutrophils and eosinophils in balf are among the determinants of prognosis in patients with chronic ipf  
class8	the influence of human immunodeficiency virus infection on tuberculosis in kampala  uganda  the clinical  radiographic  and microbiologic features of 59 patients with pulmonary tuberculosis in kampala  uganda were studied and correlated with the serologic reactivity to the human immunodeficiency virus  hiv  of these patients  two thirds of the patients with tuberculosis were hiv seropositive  histories of fever and weight loss were more prominent in hiv seropositive patients  and perihilar and basilar infiltrative diseases were more frequently seen in hiv seropositive patients  although all patients responded similarly to drug therapy  cutaneous drug reactions were seen in nearly one third of hiv seropositive patients receiving thiacetazone  
class8	serum and lavage lactate dehydrogenase isoenzymes in pulmonary alveolar proteinosis  pulmonary alveolar proteinosis  pap  is a rare disease characterized by the accumulation of lipoproteinaceous material in the alveolar space  serum lactate dehydrogenase  ldh  has been noted to be elevated in patients with pap in previous studies  we sought to extend this observation in a series of patients with pap by looking at total serum ldh concentrations and ldh isoenzyme fractions measured before and after whole lung lavage  total ldh and ldh isoenzymes were also determined in the lavage effluent  total serum ldh was elevated before lavage in 10 of 16 patients  prelavage serum ldh and prelavage alveolar arterial o2 gradient showed a significant correlation  r   0 62  p less than 0 05   a decrease in serum ldh was found after lavage in all patients in whom postlavage data was available  paired t test  p less than 0 01  n   11   although the magnitude of this decrease varied considerably  the isoenzyme pattern before lavage was isomorphic  and this pattern was unchanged after whole lung lavage  this was in marked contrast to the ldh isoenzyme pattern observed in the lavage effluent  which showed a lower percent ldh1 and ldh2 and a higher percent ldh3  ldh4  and ldh5 when compared with the corresponding prelavage isoenzyme percentages for serum  unpaired t test  p less than 0 001   there was no correlation between the total serum ldh concentration and the total lavage ldh concentration  these data confirm that elevated serum ldh is a common finding in pap  furthermore  the ldh elevation found consistently in the alveolar fluid points to this as the source of the serum ldh  
class8	lung health consequences of reported accidental chlorine gas exposures among pulpmill workers  the long term consequences of accidental chlorine gas exposure have been investigated  mainly in the community setting  among persons exposed as a result of a nearby chlorine spill  this circumstance is not analogous to the more frequent chlorine or chlorine dioxide gas overexposures that occur commonly in pulpmills over a background of a low level of gas exposure  to investigate the respiratory health consequences of these accidental exposures   chlorine gassing   in the industrial setting  we carried out a cross sectional respiratory health survey among workers at a british columbia coastal pulpmill and a nearby rail maintenance yard  a greater proportion of pulpmill workers were unavailable for study because of illness  10 5  versus 2 4  in the railyard  p less than 0 01   procedures involved simple spirometry  respiratory symptom assessment  and measurement of average levels of air contaminants  average chlorine levels in the pulpmill were below 1 ppm  however  60  of the pulpmill workers reported one or more accidental  chlorine gassing  incidents  pulpmill workers who reported being  gassed  were significantly more likely to report wheezing on occasion than were other pulpmill workers and railyard workers  rate for these three groups  nonsmokers  8  2  1   ex smokers  17  11  7   current smokers  42  21  19   p less than 0 05   no significant lung function differences were found between the overall pulpmill group and the railyard workers  however  nonsmoking and formerly smoking pulpmill workers who reported being  gassed  had significantly lower average midmaximal flow rate and fev1 fvc ratio than did their counterparts in the remainder of the pulpmill population  p less than 0 05   
class8	silicosis  chronic airflow limitation  and chronic bronchitis in south african gold miners  in a cross sectional study of a working population of black south african gold miners  1 197 men were studied with respiratory and occupational questionnaires  lung function tests  and chest radiographs  the study was designed to examine the effects of silicosis on respiratory symptoms and lung function  a total of 857 men with chronic  simple silicosis and 340 men without silicosis were included in the sample  other determinants of lung disease including the duration and intensity of underground dust exposure and tobacco smoking were also examined  three distinct pulmonary disorders could be discerned  silicosis associated pulmonary dysfunction with dyspnea on effort  chronic airflow limitation  which was related to the duration of underground exposure  and a chronic bronchitic symptom complex  which reflected the intensity of dust exposure in the workplace  chronic  uncomplicated silicosis was found to be associated with significant loss of lung function  and all of the measured indices  fvc  fev1  fev1 fvc   maximal midexpiratory flow rate  mmef   and lung diffusion for carbon monoxide measured by the single breath method  dlco  were reduced  when comparing men with category 3 3 nodule profusion with men without silicosis  reductions of fvc of 351 ml  fev1 of 447 ml  mmef of 1 04 l s  and dlco of 4 7 ml min mm hg  p   0 0001  were detected after controlling for age  height  the direct effects of the underground environment  and tobacco smoking  dyspnea on effort was more common in the men with silicosis  p less than 0 001   
class8	reductions in exercise lactic acidosis and ventilation as a result of exercise training in patients with obstructive lung disease  though exercise training is part of most pulmonary rehabilitation programs  whether there is a physiologic basis for increased exercise tolerance is unclear  we sought to determine whether patients with chronic obstructive pulmonary disease  copd  are capable of obtaining a physiologic training effect  as manifested by a reduction in blood lactate and ventilation  ve  at a given level of exercise  we also sought to determine whether training work rate determines the size of the training effect  nineteen participants with copd of predominantly moderate severity in an inpatient rehabilitation program performed two cycle ergometer exercise tests at a low and a high work rate for 15 min or to tolerance and also an incremental exercise test to tolerance  arterial blood was sampled for blood gas and lactate analyses  identical tests were performed before and after 5 day per week cycle ergometer training for 8 wk either for 45 min day at a high work rate  average  71 w  or for a proportionally longer time at a low work rate  average  30 w   average fev1 was 56     12  predicted and did not change with training  peak exercise lactate  average  6 5 meq l  was not correlated with fev1  for the high work rate training group  identical work rates engendered less lactate  4 5 versus 7 2 meq l  and less ve  48 versus 55 l min  after training  the low work rate training group had significantly less lactate and ve decrease  p less than 0 01   further  endurance time for the high constant work rate increased 73  in the high work rate training group but only 9  in the low work rate training group  at identical work rates  ve decrease average 2 5 l min per meq l decrease in lactate  r   0 75   we conclude that most copd subjects studied increased blood lactate at low work rates  many of these patients were able to achieve a physiologic training effect  though total work was the same  training at a high work rate was more effective than was training at a low work rate  the lower ve requirement to perform exercise was in proportion to the lower lactate level  but the ve decrease for a given decrease in lactate was smaller than that seen in normal subjects  7 2 l min meq l   apparently because patients with copd fall to hyperventilate in response to lactic acidosis  paco2 does not drop   these findings provide a physiologic rationale for exercise training of patients with copd  
class8	endoscopic ethmoidectomy and maxillary antrostomy in immunodeficient patients  the efficacy of endoscopic sinus surgery was evaluated in 11 patients with diverse types of primary immunodeficiency disease and symptoms of chronic sinusitis  the postoperative symptoms and ability to eliminate antibiotics were used as outcome parameters  in two patients  the follow up time was too short to assess therapeutic effectiveness  five of the remaining nine patients had total or significant resolution of symptoms  patients with transient immunodeficiency had the best resolution of symptoms  eight of the total 11 patients were treated with intravenous immunoglobulin preoperatively  and in five patients  the treatment was continued postoperatively  the ability to terminate gamma globulin reflects not the success of the surgery  but the transient nature of some of the immunodeficiencies  
class8	hyponatremia and hyperreninemic hypoaldosteronism in a critically ill patient  combination of insensitivity to angiotensin ii and tubular unresponsiveness to mineralocorticoid  a 62 year old man with pneumonia and left flank pain had a clinical syndrome of hyponatremia  hypotension  dehydration  and high urinary sodium excretion in the presence of a normal glomerular filtration rate  the plasma level of antidiuretic hormone was relatively high despite decreased serum osmolality  thyroid function and excretion of glucocorticoid and sex steroids were normal  the serum aldosterone level was very low despite elevated plasma renin activity  angiotensin ii failed to stimulate any secretion of aldosterone  despite the occurrence of a progressive rise in blood pressure  on the other hand  rapid acth administration increased both serum aldosterone and cortisol  the patient showed no effective response to increased salt intake  but large doses of mineralocorticoid resulted in a normal serum sodium level without dehydration  subsequently  he suffered cardiac arrest secondary to ventricular tachycardia  postmortem examination showed well differentiated adenocarcinoma in the left pleura and an intact  histologically normal adrenal zona glomerulosa and kidney  this is the first reported case of a critically ill patient with hyponatremia caused by hyperreninemic hypoaldosteronism possibly due to angiotensin ii insensitivity and tubular unresponsiveness to mineralocorticoid  
class8	increased extravascular lung water in patients with low pulmonary artery occlusion pressure after acute myocardial infarction  objective  to evaluate the clinical characteristics of increased extravascular lung water  evlw  in patients with low pulmonary artery occlusion pressure  paop  in the early phase of acute myocardial infarction  design  consecutive sample for descriptions of the clinical features of medical disorders  setting  a general medicine group practice in a university hospital  patients  sixteen patients with low paop  less than 18 mm hg  on the initial measurement obtained within 12 hr of chest pain onset  measurements and main results  evlw was measured by the thermal indocyanine green dye double indicator dilution method  qrs score was obtained on hospital day 7 from the selvester s qrs scoring system  eleven  69   patients had increased evlw greater than 7 ml kg despite low paop  evlw had no significant correlation with paop and the difference between plasma colloid osmotic pressure and paop  but did have a significant correlation with pulmonary vascular resistance index  r2    31  p less than  05   and qrs score  r2    45  p less than  005   conclusions  larger infarcts led to increased evlw even with low paop  and the accumulation of increased evlw around the small arterioles might have led to increased pulmonary vascular resistance  
class8	breathing circuit respiratory work in infants recovering from respiratory failure  objective  to compare cardiopulmonary function during spontaneous breathing with three continuous flow breathing circuits  the major difference between these circuits was the degree of flow resistance offered by the exhalation valve  design  randomized crossover trial  patients  twelve infants less than 12 months of age recovering from respiratory failure of variable etiology  only patients weighing 3 to 10 kg were studied  interventions  the patients were connected to each respiratory circuit in a random sequence  with 15 min allowed for equilibration before assessment of cardiopulmonary function  airway pressure  paw  and fio2 were maintained unchanged  measurements and main results  ventilation  gas exchange  or circulatory function were not altered significantly by changing the breathing circuit  however  paw and esophageal pressure fluctuations were altered and were largest during breathing with the circuit that had an exhalation valve with high flow resistance  the paw fluctuation recorded while the patient was breathing with the flow resistor circuit increased with weight and exceeded 2 cm h2o in all patients weighing greater than 4 5 kg  paw fluctuation could be decreased by greater than 2 cm h2o in ten of 12 patients by using the threshold resistor circuit  conclusions  the results indicate a need for evaluating the characteristics of respiratory circuits used for spontaneous breathing in infants and children  to avoid unnecessary equipment related increase in respiratory work  
class8	single versus double indicator dilution measurements of extravascular lung water  objective  to compare a simplified method of measuring extravascular lung water  evlw  using only a single indicator  evlw si  with the standard double indicator dilution technique  evlw di   design  direct comparison of evlw si with evlw di in 18 critically ill patients  setting  a general medical icu in a university affiliated hospital  patients  nine men and nine women  ages 19 to 80 yr  six patients were in shock  four from septic shock   and 11 were in respiratory failure  interventions  evlw di and cardiac output were measured in triplicate during injection of cold indocyanine green dye  cardiac output was calculated both from pulmonary artery  copa  and femoral artery  cofem di  thermal dilution signals  evlw si and cofem si were also measured during three additional injections of cold saline using only thermal signals from the pulmonary and femoral arteries  order of measurements was random  evlw si was measured in ten patients while blood was withdrawn through the femoral catheter and in ten patients without blood drawn through the femoral catheter  measurements and main results  a total of 84 comparisons were made  although the overall correlations were good  r2    86   evlw si systematically overestimated evlw di  p less than  05   this difference was greater when evlw si was measured without blood withdrawal through the femoral catheter  in this subgroup  mean values for evlw by the two methods were within 20  of one another in only two of ten patients  in contrast to the results in six of eight patients in which blood was withdrawn through the catheter  cofem si and cofem di also overestimated copa  conclusions  theoretically  neither injection of green dye nor blood withdrawal should be necessary during measurements of evlw si  making it a simpler technique for bedside use than evlw di  however  significant discrepancies exist between the two techniques  some of this difference is apparently due to technical factors related to catheter design  in any case  we cannot recommend use of the single indicator dilution technique at present to estimate evlw  
class8	young s syndrome  obstructive azoospermia and chronic sinobronchial infection   a quantitative study of axonemal ultrastructure and function  the ultrastructure and function of nasal cilia and sperm tails were examined in 23 men with young s syndrome and compared with data previously collected from 10 normal subjects  quantitative electron microscopic assessment showed that sperm tails from patients with young s syndrome contained significantly fewer central pair microtubules  radial spokes  and inner dynein arms  and their cilia contained less inner dynein arms than normal subjects  the young s syndrome patients had normal in vitro ciliary beat frequency  11 4     0 9 hz   and 12 of the 23 had normal nasal mucociliary clearance  15 0     5 0 minutes   however  the remaining 11 had markedly abnormal nasal mucociliary clearance in vivo  in these patients  the deficiency of ciliary inner dynein arms did not appear to affect ciliary function in vitro but may under mucus loading lead to abnormal in vivo ciliary function  the consistent abnormalities shown in cilia and sperm tails  though apparently minor  constitute a common factor in both the reproductive and respiratory tracts which may  in combination with abnormalities in the in vivo environment  lead to the features of young s syndrome  
class8	exposure to an aeroallergen as a possible precipitating factor in respiratory arrest in young patients with asthma background  exposure to airborne spores of the common mold alternaria alternata has been implicated in asthma attacks  such exposure is particularly frequent in the midwest during the summer and fall months  to determine the role of a  alternata in triggering severe asthma attacks  we investigated the cases of 11 patients with asthma who had sudden respiratory arrest and determined the frequency of sensitivity to this allergen in these patients  methods  the 11 patients  age range  11 to 25 years  with initial episodes of respiratory arrest  which was fatal in 2 patients  were identified in the course of their care in our pediatric and adult clinical allergy practice and by a retrospective review of all mayo clinic records of patients with severe asthma cared for between 1980 and 1989  skin test reactivity to a  alternata and levels of ige antibody against this mold in the 11 patients were compared with those in 99 matched controls with asthma who had no history of respiratory arrest  results  all the patients came from the upper midwest  and the episodes of respiratory arrest occurred in the summer or early fall  ten of the 11 patients with asthma who had respiratory arrest  91 percent  had positive skin puncture tests for sensitivity to alternaria  as compared with 31 percent of the controls  p less than 0 001   and the serum levels of ige antibodies to alternaria were elevated in all 9 patients tested  among the covariates we examined  age  sex  and distance from the mayo clinic   only age was a significant confounder  after adjustment for age  alternaria skin test reactivity was found to be associated with an increase of approximately 200 fold in the risk of respiratory arrest  adjusted odds ratio  189 5  95 percent confidence interval  6 5 to 5535 8   conclusions  exposure to the aeroallergen a  alternata is a risk factor for respiratory arrest in children and young adults with asthma  
class8	pneumocystis carinii infections in hiv infected children  since 1981  1200 children with acquired immunodeficiency syndrome have been reported to the centers for disease control  among these children  pneumocystis carinii has been the leading cause of serious morbidity and mortality  this review discusses the epidemiology  diagnosis  and treatment of p  carinii  
class8	lymphocytic interstitial pneumonia  lymphocytic interstitial pneumonia is at present a pathologic diagnosis  in the setting of a chronic interstitial pneumonia in a child with lymphocytosis  hyperglobulinemia  and lymphadenopathy or parotid enlargement  the diagnosis is often clinically presumed  at present the diagnosis can be established firmly only by lung biopsy  models of pathogenesis include nonspecific stimulation of the immune system  hiv specific stimulation  or synergy between ebv and hiv  treatment includes oxygen and bronchodilators as needed  the role of zidovudine and of steroids in the management of lip remains to be determined  
class8	upper respiratory tract infections in young children  duration of and frequency of complications  this study was performed to determine the usual duration of community acquired viral upper respiratory tract infections and the incidence of complications  otitis media sinusitis  of these respiratory tract infections in infancy and early childhood  children in various forms of child care arrangements  home care  group care  and day care  were enrolled at birth and observed for 3 years  families were telephoned every 2 weeks to record on a standardized form the type and severity of illnesses experienced during the previous interval  only children remaining in their original child care group for the entire study period were compared  the mean duration of an upper respiratory tract infection varied between 6 6 days  for 1  to 2 year old children in home care  and 8 9 days  for children younger than 1 year in day care   the percentage of apparently simple upper respiratory tract infections that lasted more than 15 days ranged from 6 5   for 1  to 3 year old children in home care  to 13 1   for 2  to 3 year old children in day care   children in day care were more likely than children in home care to have protracted respiratory symptoms  of 2741 respiratory tract infections recorded for the 3 year period  801  29 2   were complicated by otitis media  during the first 2 years of life  children in any type of day care were more likely than children in home care to have otitis media as a complication of upper respiratory tract infection  in year 3  the risk of otitis media was similar in all types of child care  
class8	sudden infant death syndrome and small airway occlusion  facts and a hypothesis  respiratory failure is almost certainly the cause of death in the majority of cases of sudden infant death syndrome  sids   but the mechanisms leading to it have not been elucidated  sids shares many environmental and socioeconomic risk factors with severe forms of bronchiolitis  and the age distribution of incident cases is similar  present knowledge of lung and airway development during infancy  determinants of peripheral airway patency  changes in lung surface activity in infants with sids  and fluid film dynamics in small airways are reviewed  it is hypothesized that many cases of sids may be due to a final episode of progressive peripheral bronchial occlusion in infants with preceding critically diminished conductance of the smaller airways  
class8	the reliability of magnitude estimation for dyspnea measurement  the reliability of magnitude estimation with an open scale was evaluated in a physiologically stable population of adults with chronic respiratory disease who experienced chronic dyspnea  magnitude estimation was used to measure one dimension of dyspnea  perceptual sensitivity  the relationship between external inspiratory resistive loads  stimuli  and numbers that reflected the perceived intensity of the breathing effort  response  as expressed by a power function was measured on three visits 3 to 5 days apart  the correlations of the exponent of the power function between visits were high and stable  
class8	lung abscess  ct guided drainage  lung abscesses were drained by means of catheters guided by computed tomography  ct  in 19 patients who still had sepsis despite standard medical therapy  all patients had received antibiotics for at least 5 days  and 11 of the 19 patients had undergone bronchoscopy  the abscess was cured  by clinical and radiographic criteria  in all 19 patients  100    and surgery was avoided in 16 of the 19 patients  84    three patients underwent surgery for removal of organized tissue or decortication after the lung abscess was evacuated  complications included a hemothorax that required a chest tube in one patient and three minor complications  a clogged catheter in two patients and transient elevation of intracerebral pressure in one patient   the hemothorax occurred in one of two patients in whom the catheter traversed normal lung  the percutaneous drainage catheters traversed juxtaposed abnormal pleura on route to the abscess in 17 of the patients  ct guided drainage of lung abscess is an effective method to treat lung abscesses that are refractory to conventional therapy  the procedure should obviate major operation in most patients  a catheter route through abscess pleural syndesis is preferable  and ct is useful for planning this route  
class8	malignancy associated with chronic empyema  radiologic assessment  radiologic findings of six cases of malignancy associated with chronic empyema 5 39 years in duration were reviewed  pathologic examination confirmed three b cell non hodgkin lymphomas  one round cell sarcoma  one mesothelioma  and one adenocarcinoma  retrospective findings on plain chest radiographs suggested the occurrence of malignancy  increased radiopacity in the thoracic cavity  soft tissue bulgings and or unsharpness of fat planes in the chest walls  destruction of bone near the empyema  and extensive medial deviation of the calcified pleurae  computed tomography delineated masses with soft tissue attenuation more clearly than radiography in all cases  magnetic resonance images of three cases were informative because empyema cavities were surrounded by low intensity rims  and two of them showed a signal intensity different from that of necrotic tumors  scintigraphy revealed increased uptake of gallium in all cases  ultrasonography was useful for biopsy guidance  every radiologist should know this entity in observation of chest radiographs obtained in patients with chronic empyema  and further radiologic assessment and aggressive biopsy are recommended if malignancy is suspected  
class8	detection of streptococcus pneumoniae and haemophilus influenzae type b antigens in the serum and urine of patients with pneumonia in papua new guinea  comparison of latex agglutination and counterimmunoelectrophoresis  latex agglutination  la  was compared with counterimmunoelectrophoresis  cie  for the diagnosis of pneumonia due to streptococcus pneumoniae or haemophilus influenzae type b in children less than 6 years old in papua new guinea  neither la nor cie was sufficiently sensitive for the detection of pneumococcal antigens  cie was superior to la but had a sensitivity of only 60   six of 10  in concentrated urine and a specificity of 90   54 of 60   la for the detection of h  influenzae type b had a sensitivity of 100   eight of eight  relative to that of blood culture and a specificity of 99   112 of 113  when urine diluted fivefold was tested  as compared with a sensitivity of 100   nine of nine  and a specificity of 92   56 of 61  in undiluted urine  undiluted and concentrated urine specimens were unsuitable for la because of the many false positive reactions that resulted from nasal carriage of h  influenzae type b and nasal carriage of the cross reactive s  pneumoniae type 6  cie for the detection of h  influenzae type b had a sensitivity of only 44   four of nine  in concentrated urine  
class8	bacterial colonization of the upper respiratory tract and its association with acute lower respiratory tract infections in highland children of papua new guinea  acute lower respiratory tract infection  alri  is the major cause of death among children in papua new guinea  this longitudinal study reports the bacteriologic findings for children observed in their hamlets  a total of 1 449 nasal swab specimens from 158 children less than 5 years of age who were studied intensively for 18 months were examined  non serotypable strains of haemophilus influenzae were isolated from 91  of specimens  and serotypable strains were isolated from 35   8  h  influenzae type b  of specimens  all children had acquired streptococcus pneumoniae by the age of 3 months  the most frequently occurring serotypes of s  pneumoniae were 6  19  and 23  children more frequently carried invasive pneumococci during an episode of alri than when they were healthy  also  children more frequently carried serotypable strains of h  influenzae during the 2 weeks preceding an episode of alri than when they were healthy  between children analyses showed that children who were susceptible to attacks of alri and those who were not susceptible had similar rates of carriage of bacteria  
class8	diversity of outer membrane protein profiles of nontypable haemophilus influenzae from children from papua new guinea and the philippines  we determined capsular serotypes and  with use of sds page  patterns of outer membrane proteins  omp  of haemophilus influenzae isolates from specimens of blood  lung  or csf from children with acute respiratory tract infections or meningitis who were hospitalized in papua new guinea or the philippines  among 72 isolates from papua new guinea  72  were type b  14  were other encapsulated serotypes  and 14  were nontypable  the respective frequencies among 43 isolates from the philippines were 56   7   and 37   the type b isolates could be subdivided into at least eight outer membrane subtypes  most of which have been described previously  in contrast  omp profiles of the nontypable h  influenzae isolates from children in both countries were highly heterogeneous  these results differ markedly from those previously found for isolates from children with acute respiratory tract infections in pakistan  for which encapsulated h  influenzae strains other than serotype b were not observed  95  of type b isolates were of a single omp subtype  and nontypable isolates showed evidence of clonal restriction  candidate vaccines for use in developing countries as protection against disease caused by h  influenzae will need to include both capsular and noncapsular antigens and investigators must take into consideration regional differences among strains  
class8	epidemiologic risk factors for children with acute lower respiratory tract infection in buenos aires  argentina  a matched case control study  the risk factors that predisposed 516 hospitalized and 154 ambulatory patients to acute lower respiratory tract infection  alri  are examined in a matched case control study  the control group was selected from children attending immunization and well baby clinics at the same institution that was treating the children with alri  sex  age  nutritional status  socioeconomic level  as well as season and place of residence were used as matching criteria  because of their distinct profiles  hospitalized and outpatient groups were analyzed separately  however  the four variables with the highest odds ratios  incidence ratios or relative risk  were found to be the same for both groups  these variables were related to the host s condition  bronchial hyperreactivity  presence of persistent symptoms of the upper respiratory tract   family  presence of acute respiratory tract disease in household members   and environment  indoor contaminants   
class8	epidemiology of acute respiratory tract infections among guatemalan ambulatory preschool children  acute respiratory tract infections  ari  were studied during a 2 year period in 521 preschool children living in a marginal area of guatemala city  there were 3 646 episodes of ari detected during 26 329 child weeks at risk  for an incidence of 14 per 100 child weeks or 7 2 episodes per child per year  the median duration of ari episodes was 11 days  the highest incidence of ari was observed in children 6 23 months old  boys had more respiratory tract illnesses than did girls  the presence of a cigarette smoker in the household was associated with higher morbidity  acute lower respiratory tract illnesses  alri  were more common among younger infants 0 5 months old  with nutritional status having no apparent effect  parental formal education and crowding in households were found to be directly related to the incidence of alri  in general  ari morbidity interfered with appropriate physical growth  
class8	epidemiology of acute respiratory tract infections among young children in kenya  the epidemiology of acute respiratory tract infection  ari  was investigated in a rural community 80 km north of nairobi  kenya  this research was conducted prospectively on 250 families with 470 children less than 5 years of age who were contacted every 8 days during the 3 year study  the yearly incidence of respiratory tract infections decreased from 5 2 to 3 4 during the study  less than 5  of these infections involved the lower respiratory tract  the incidence was inversely related to age  and the illnesses were generally mild and brief in length  fifteen children died during the study period  the precise causes of death are unknown  but respiratory infections possibly played a role in most cases  this study emphasizes the importance of determining the risk factors responsible for unusually severe morbidity and high mortality in children with ari in developing countries  
class8	child care practices with respect to acute respiratory tract infection in a poor  urban community in nigeria  a longitudinal study conducted over a 3 year period in a poor  urban community in nigeria  a developing country  found that acute respiratory tract infection  ari  was common  in particular among infants and boys  between 81  and 95  of the children treated for ari over the 3 year period were brought to the clinic by their mothers  about 32  of these children had been treated with cough medicines  42  with antipyretics  5  with antibiotics  and 10  with hematinics before they were brought to the clinic  the source of such medications included medicines left over from previous prescriptions and those bought from chemists  shops and street vendors  up to 64  of the children treated for ari had been force fed local herbal teas by their mothers  herbal teas were used for both preventive and curative purposes  
class8	acute respiratory tract infection in children in idikan community  ibadan  nigeria  severity  risk factors  and frequency of occurrence  a longitudinal  community based study of the epidemiology of acute respiratory tract infection  ari  in children less than 5 years old was carried out in a community of low socioeconomic level in ibadan  nigeria  the annual incidence of ari ranged from 6 1 to 8 1 episodes per child per year  the incidence was highest in the first 2 years of life and decreased with increasing age  the incidence was higher in boys than in girls  ari occurred in all seasons of the year  the most common symptoms were cough  nasal discharge  and fever  while the most common signs referable to the respiratory tract were abnormal breathing sounds  tachypnea  and chest retraction  
class8	malnutrition and acute respiratory tract infections in filipino children  the impact of malnutrition on morbidity and mortality associated with acute respiratory tract infection  ari  was studied in filipino children less than 5 years old  malnutrition measured by weight for age z scores of less than  3 sd and less than  2 sd from the national center for health statistics median reference population was associated with the following significant relative risks of morbidity  1 24  95  confidence interval  ci    1 14  1 34  and 1 14  95  ci   1 08  1 19   respectively  for ari  and 1 9  95  ci   1 46  2 39  and 1 2  95  ci   1 03  1 47   respectively  for acute lower respiratory tract infection  alri   these risk ratios remained significant when adjusted for age  crowding  and parental smoking  malnourished children with severe alri also had a mortality risk two to three times higher than that of healthy children  this risk remained significant even when adjusted for significant predictors of mortality  including clinical complications  concurrent measles  severe infections  and female gender  and for clinical factors  including extent of pneumonic infiltrates  dehydration  and hepatic enlargement  these findings underscore the importance of nutritional intervention in the control of morbidity and mortality among patients with ari  
class8	clinicopathologic studies of children who die of acute lower respiratory tract infections  mechanisms of death  clinicopathologic correlations for 71 cases of fatal pneumonia in children were determined  the mechanism of death for these patients was multifactorial  severe pneumonia alone accounted for 11 deaths  15 5    pneumonia associated with sepsis occurred in 42 children  59 2    heart failure  8 5    hypovolemia  4 2    and nosocomial infection  12 6   were also seen in children with fatal acute lower respiratory tract infection  extensive consolidation  squamous metaplasia  and hyaline membranes were present in the lungs of these children  patients with severe disease must receive  in addition to antibiotics for acute episodes  individualized intensive respiratory and supportive care  since these types of care are not available in poor communities  vaccination against measles and vitamin a supplementation for malnourished children may ameliorate the conditions that appear to predispose these children to severe or fatal disease  
class8	etiologic  clinical  and pathologic analysis of 31 fatal cases of acute respiratory tract infection in argentinian children under 5 years of age  during a 3 year survey of 805 children with acute lower respiratory tract infection  alri  who were admitted to three hospitals in buenos aires  31 fatal cases were recorded  a fatality rate of 3 8   of the 31 children who died  77  were less than 1 year of age  48  were boys  58  were malnourished  29  had previous respiratory disease  and 22  had previous congenital disease  all children who died had clinical diagnoses of pneumonia  71   or bronchiolitis  29    autopsies were performed in 14 of the cases  viral etiology was determined by both cell culture and indirect immunofluorescence  iif  assay of either nasopharyngeal aspirates  npa  or lung tissue and bacterial etiology was determined by isolation of organisms from blood  lung tissue  and or pleural fluid  npa was examined for bordetella pertussis by iif  pathogens were identified in 65  of fatal cases  seven cases were bacterial  seven cases were viral  and six cases resulted from mixed infections  lung tissue yielded positive etiologic results in 10 of 13 cases  histopathologic examination performed on specimens from the 14 autopsied children revealed necrotizing bronchiolitis with intranuclear inclusions  n   5  and multifocal pneumonia  n   9   
class8	respiratory rate greater than 50 per minute as a clinical indicator of pneumonia in filipino children with cough  the diagnosis and epidemiology of acute respiratory tract infection  ari  in 199 children less than 5 years old were investigated in manila  as part of this study  children who were treated at one of two outpatient clinics for cough of less than 3 weeks  duration were studied to test the validity of the use of a respiratory rate  rr  of greater than 50 minute for identifying ari of a severity necessitating treatment with antibiotics  in the first population  in which 69  of the children had radiologically confirmed pneumonia  the sensitivity of a rr of greater than 50 minute was 54   the specificity was 84   the false positive rate was 16   and the false negative rate was 46   in the second population  in which 29  of the children had pneumonia  the sensitivity and positive predictive values were low  the validity of a rr of greater than 50 minute may vary in populations with different prevalences of ari  
class8	the epidemiology of acute respiratory tract infection in young children  comparison of findings from several developing countries  coordinated data group of bostid researchers  investigators from 10 countries studied the epidemiology of acute respiratory tract infection  ari  among children 0 59 months old  data on incidence rates  by age  gender  and season  on pathogenic agents  on case fatality rates  and on selected risk factor findings are presented  incidence rates from six of the community based studies ranged from 12 7 to 16 8 new episodes of ari per 100 child weeks at risk  and rates of lower respiratory tract infection  lri  ranged from 0 2 to 3 4 new episodes per 100 child weeks at risk  children spend from 21 7  to 40 1  of observed weeks with ari and from 1  to 14 4  of observed weeks with lri  the incidence rates for ari are highest in younger children  viruses  especially respiratory syncytial virus  are isolated more frequently than bacteria from children with episodes of lri  risk factors exhibited different patterns of association with ari in different studies  interventions could have great impact on high risk levels common in the study populations  these studies provide interesting and useful data on the epidemiologic dynamics of ari  
class8	etiologic and clinical evaluation of acute lower respiratory tract infections in young argentinian children  an overview  this paper summarizes the first study on clinical  etiologic  and epidemiologic features of acute lower respiratory tract infection  alri  in children in argentina  a total of 1 003 children less than 5 years of age  805 inpatients and 198 outpatients  presenting with alri were studied during a 40 month period  nasopharyngeal aspirate  npa   blood  urine  and throat swab samples were collected when each child was first seen for care  virologic studies were performed on the npa by means of indirect immunofluorescence and isolation of virus in cell culture  bacteriologic studies primarily were done by means of culture of blood or pleural fluid  when available   bordetella pertussis and mycoplasma pneumoniae  however  were searched for by the use of immunofluorescence and complement fixation testing  respectively  in paired sera  respiratory syncytial virus was the most commonly isolated virus  followed by adenovirus  parainfluenza virus  and influenza virus  streptococcus pneumoniae was the most frequently isolated bacterium  followed by b  pertussis and haemophilus influenzae type b  overall  the patient fatality rate was 3 8  among inpatients with pneumonia or bronchiolitis  
class8	acute lower respiratory tract infections in hospitalized patients with diarrhea in dhaka  bangladesh  this study focused on 401 children less than 5 years old who were hospitalized with acute lower respiratory tract infection  alri  and diarrhea in dhaka  bangladesh  and who were investigated for the presence of both bacterial and viral respiratory tract pathogens as well as for selected diarrheal pathogens  the most common manifestations of alri were pneumonia  374 cases   bronchiolitis  12 cases   and tracheobronchitis  11 cases   the majority  77   of the illnesses were in children less than 2 years of age  and 88  of the children were malnourished  a respiratory tract pathogen was identified in 30  of the patients  and a diarrheal pathogen was identified in 34   the overall case fatality rate in children with alri and diarrhea was 8   the case fatality rate was 14  in children with bacterial pneumonia and diarrhea  3  in those with viral pneumonia and diarrhea  and 14  in malnourished children with shigellosis and alri  the most common respiratory tract pathogens were respiratory syncytial virus  streptococcus pneumoniae  influenza viruses  and haemophilus influenzae type b  
class8	diagnoses of acute lower respiratory tract infections in children in rawalpindi and islamabad  pakistan  a hospital based inpatient and outpatient study of 1 492 cases of acute lower respiratory tract infection  alri  was conducted from november 1986 to march 1988 in two hospitals in rawalpindi and islamabad  pakistan  specimens of nasopharyngeal aspirate were processed for viral studies in all cases  blood cultures were performed in 1 331 cases  and urine was obtained for detection of bacterial antigen in 378 cases  but 227 of these samples had bacterial contamination and were discarded  respiratory syncytial virus was identified in 33  of cases  and haemophilus influenzae and streptococcus pneumoniae were identified in 9 6  and 9 9  of cases  respectively  nonencapsulated h  influenzae accounted for 32  of the haemophilus isolates  and type b was the only encapsulated h  influenzae strain identified  of the s  pneumoniae serotypes isolated  31  are not included in the currently available polyvalent pneumococcal vaccine  no clinical characteristic was demonstrated to be a reliable indicator for bacterial alri  
class8	microbial agents associated with pneumonia in children from uruguay  the etiology of severe pneumonia  not frequently encountered in a community based study  was determined in 204 hospitalized children less than 5 years of age  potential pathogens were identified in 41  of episodes  viruses were isolated or antigen was detected in 36 3  of cases  82 4  of these cases were due to respiratory syncytial virus  bacteria or bacterial antigens were identified in 13 2  of cases  streptococcus pneumoniae and haemophilus influenzae were the most frequently identified bacterial pathogens isolated from blood and or pleural effusions  mixed infections were identified in 4 9  of the episodes  among the 17 patients with pleural effusion whose pleural space was drained  the etiology was suggested for 10  58 8    a clear cut seasonal variation was seen  with the highest prevalence between may and october  viral infections were more common in the first 6 months of life  although viral and bacterial infections were distributed throughout the first 5 years of life  
class8	etiology of acute lower respiratory tract infection in children from alabang  metro manila  the etiology of acute lower respiratory tract infection  alri  was identified in 235  43 8   of 537 hospitalized children less than 5 years of age  clinical evidence of measles was found in 258  48 0   patients  of whom 59 had a second viral infection  a viral agent was identified in an additional 121 patients  so that a total of 379  70 6   had viral infections  after measles  respiratory syncytial virus was the most common respiratory virus  bacteremia was noted in 72 children  13 4    occurring as frequently in children with measles  14 8   as in those without  12 1    haemophilus influenzae and salmonella typhi were predominant in the former  and h  influenzae  staphylococcus aureus  and streptococcus pneumoniae were prominent in the latter  the presence of bacterial antigen in urine was not helpful in identifying bacterial infection  extrapulmonary and intrapleural complications  concomitant measles  complicated alri  female gender  and malnutrition were associated with increased mortality among children with alri  the importance of measles immunization  vitamin a supplementation for alleviation of defects associated with malnutrition  and timely antimicrobial therapy is emphasized  
class8	patterns of acute respiratory tract infection in children  a longitudinal study in a depressed community in metro manila  the incidences of acute respiratory tract infection  ari  and acute lower respiratory infection  alri  were 6 1 and 0 5 per child year  respectively  in children less than 5 years old in a depressed urban community in manila  the peak age specific incidence occurred in those children 6 23 months old for ari and 6 11 months old for alri  age less than 2 years  malnutrition  household crowding  and parental smoking were associated with a statistically significant  though modest  increase in ari morbidity  the crude mortality rate was 14 3 per 1 000 children 0 4 years old  with a corresponding ari specific mortality rate of 8 9 per 1 000  the prevalence of viral infection was 32 8 and that of bacteremic alri was 6 7 per 1 000 children with moderate alri  respiratory syncytial virus was the predominant viral pathogen  while streptococcus pneumoniae  haemophilus influenzae  and staphylococcus aureus were the most frequently isolated bacterial pathogens  transmission of respiratory pathogens in depressed communities  facilitated by inadequate housing  inaccessible health services  and prevalent malnutrition  will continue unless meaningful socioeconomic improvement is realized  
class8	acute respiratory tract infections among a birth cohort of children from cali  colombia  who were studied through 17 months of age  for this study  340 children less than 18 months old from a low income  urban neighborhood in cali  colombia  were observed from birth by means of weekly home visits to detect cases of acute respiratory tract infection  all suspected cases were confirmed by trained doctors in a special clinic  information on symptoms  signs  and potential risk factors was documented prospectively  etiologic agents were identified in cases of lower respiratory tract infection  lri   the overall incidence of acute respiratory tract infection was 6 6 cases per child year at risk  the incidence of upper respiratory tract infection was 4 9 cases per child year at risk and that of lri was 1 7 cases per child year at risk  crowding in the home was found to be significantly associated with an increased incidence of lri  respiratory syncytial virus was the viral agent most frequently isolated from cultures of nasopharyngeal aspirates of children with lri  staphylococcus aureus was the bacterial agent most frequently isolated from the blood of patients with lri  
class8	a community based study of acute respiratory tract infection in thai children  a 2 year longitudinal study was conducted among the population of a socioeconomically depressed urban community in bangkok  thailand  from january 1986 through december 1987 to determine the incidence  etiologic agents  and risk factors associated with acute respiratory tract infection  ari  in children less than 5 years of age  data were obtained for a total of 674 children  who were visited twice weekly for detection of signs and symptoms of ari  during the first year of the study  throat swab specimens were obtained for bacterial culture from both ill and healthy children and a nasal wash was performed on mildly ill children for detection of virus  during both years of the study  nasopharyngeal aspiration for identification of virus was performed for children with more severe infection  the overall incidence of ari was 11 2 episodes per child year  the highest  14 9  and lowest  8 8  rates per child year occurred in age groups 6 11 months and 48 59 months  respectively  respiratory syncytial virus  parainfluenza virus  adenovirus  streptococcus pneumoniae  and haemophilus influenzae were the prevalent pathogenic agents identified  factors associated with higher risk of ari were low family income  working mothers  mothers with allergies  chronic malnutrition  and crowding in the home  
class8	a community based study of acute respiratory tract infections in children in uruguay  acute respiratory tract infection  ari  was investigated in children less than 5 years old in a longitudinal community based study of 166 families living in a socioeconomically depressed area in montevideo  uruguay  pediatricians made home visits every 10 days from may 1985 to december 1987  and symptoms and signs of ari were recorded  the incidence of ari was 5 8 episodes per child year during the first 12 months of life and decreased with increasing age of the index children  the rate was highest in children 1 5 months old  children observed from birth were ill during 21  of the visits  according to the definitions of the study  the incidence of lower respiratory tract infection was 11 6  higher than the incidence of upper respiratory tract infections  the rates of ari were higher during the colder months  most risk factors for ari were only marginally statistically significant  
class8	isolation and identification of viral agents in argentinian children with acute lower respiratory tract infection  from a total population of 1 002 children with acute lower respiratory infection  alri   identification of virus was achieved in 304 cases  in this survey  1 000 nasopharyngeal aspirate and 13 lung tissue samples were tested in four cell lines  hep 2  mrc 5  mdck  and llc mk2  and by indirect immunofluorescence  iif   while 242 paired sera were studied by complement fixation  respiratory syncytial virus  rsv  was the most frequently detected agent  n   183   followed by adenovirus  n   28   parainfluenza  n   5  and 3  n   16  viruses  and influenza a  n   10  and b  n   4  viruses  the sensitivity and specificity of iif identification vs  isolation in cell culture were high for rsv  91 5  and 94 9   respectively   however  iif proved poorly sensitive for detection of adenovirus  sensitivity  23 8   specificity  100    the complement fixation test proved the least effective  with a sensitivity of only 41 5   therefore  on the basis of our experience  it appears that the yield for positive diagnosis of virus is increased if both isolation in multiple cell lines and identification by means of iif are used  our survey provides for the first time reliable data on the viral etiology of alri in argentina  as determined by three different methods  
class8	acute lower respiratory tract infection due to virus among hospitalized children in dhaka  bangladesh  the nature of acute lower respiratory tract infection  alri  in hospitalized children and of the associated viral agents was assessed in a study of 601 children less than 5 years old over a 24 month period  of these children  80  were less than 24 months of age and the ratio of boys to girls was 1 7 1  pneumonia  86 5  of cases  was the most frequently observed clinical manifestation  shedding of virus was detected in 21 1  of the children  the highest rate occurred in infants 0 5 months old  27   as compared with a rate of only 12 5  in children 25 60 months old  virus was detected in 33 3   32 8   21 2   and 20  of the cases of tracheobronchitis  bronchiolitis  pneumonia  and croup  respectively  among the viruses detected  78  were respiratory syncytial virus  rsv   91  of infections with this virus occurred in children less than 2 years old  and 14 4  were influenza virus types a and b  of the rsv infections  61  occurred in infants less than 1 year old  the case fatality rate was 6 8  overall and was 4 8  in virus associated cases  no consistent pattern of seasonal occurrence of viral infections was discerned  rsv was detected throughout the year  with increased prevalence from january to april  
class8	a hospital based study of acute viral infections of the respiratory tract in thai children  with emphasis on laboratory diagnosis  the hospital based study described here examined the viruses found in 738 children less than 5 years old who presented at ramathibodi hospital  bangkok  thailand  from january 1986 to december 1987 with acute respiratory tract infections  three methods for detection of viral infection are compared  direct examination of epithelial cells of the respiratory tract with the use of fluorescent antibody staining  isolation of virus  and measurement of antibody in acute  and convalescent phase sera  viral infections were found in 44 7  of the study population  diagnosis by the examination of epithelial cells with the fluorescent antibody staining procedure was found to have several deficiencies  however  this technique was the most sensitive for diagnosis of infection due to respiratory syncytial virus  isolation of virus was the best method for identification of adenoviruses  parainfluenza 1 and 3 viruses  and influenza b virus  problems associated with serodiagnosis included failure to obtain specimens of convalescent phase blood in 24 5  of cases and insensitivity of serodiagnosis for young children except for the identification of antibody to influenza a virus  the combination of all three tests yielded the best rate of detection of virus  
class8	identification of viruses in a study of acute respiratory tract infection in children from uruguay  for the purpose of identifying viral agents associated with acute respiratory tract infections  ari  in children less than 5 years old  a longitudinal community study was undertaken in montevideo  uruguay  from may 1985 to december 1987  this report includes results obtained by cell culture and immunofluorescence techniques for detection of respiratory syncytial virus  rsv   influenza a and b viruses  parainfluenza 1 and 3 viruses  and adenovirus  two populations were studied  children visited at home by pediatricians  group 1  and children with an ari episode who attended an outpatient clinic  group 2   nasopharyngeal aspirates were obtained at the time of an ari episode  858 from group 1 and 488 from group 2  viruses were identified in 15 3  of group 1 specimens and in 17 6  of group 2 specimens  rsv was the most frequently recovered agent  accounting for 67 9  and 58 1   respectively  of all viruses detected  the sensitivity and specificity of rsv isolation by cell culture are compared with detection by indirect immunofluorescence  
class8	aspiration pneumonitis  risk factors and management of the critically ill patient  pulmonary aspiration of gastric contents is a significant source of patient morbidity  mortality  and increased healthcare costs  prevention by identifying patients at risk for aspiration and initiating prophylaxis is the most effective method of reducing complications associated with aspiration pneumonitis  h2 receptor antagonists are among the best prophylactic agents because of their efficacy in reducing gastric acidity and their convenience of administration  
class8	pathophysiology  monitoring  and management of the ventilator dependent patient  considerations for drug therapy  emphasis on stress ulcer prophylaxis  adult respiratory distress syndrome  ards   or noncardiac pulmonary edema  is a form of acute hypoxemic respiratory failure  the goals of treatment for patients with ards are to provide supportive therapy  to reverse the underlying etiology or pathology  and to prevent subsequent complications  supportive therapy consists of supplemental oxygen  positive end expiratory pressure  and  often  mechanical ventilation  the reversal of the underlying pathology varies according to the etiologic origin of ards  complications from ards include stress ulcers  which occur when gastric aggressive and defensive functions become unbalanced  antacids and cytoprotective agents are used for stress ulcer prophylaxis  but histamine h2 receptor antagonists are now regarded as the standard of care  because all the marketed h2 receptor antagonists are efficacious  choice of the agent is based on the adverse effect profile and drug interactions  no definitive data currently exist linking stress ulcer prophylaxis regimens that raise intragastric ph to a significant risk for nosocomial pneumonia  
class8	diagnostic value of dna analysis in effusions by flow cytometry and image analysis  a prospective study on 102 patients as compared with cytologic examination one hundred twenty six effusion samples from 102 patients were examined by cytology and flow cytometry  fcm   overall  there was an 84  correlation between cytologic and fcm results  of the 36 malignant cases determined by cytologic examination  fcm revealed an aneuploid peak in 20  56    image analysis  ia  performed on the malignant cytologic cases with a diploid flow pattern detected two additional aneuploid peaks  in addition  fcm indicated three aneuploid cases in which cytologic characteristics were initially interpreted as benign  false negative   aneuploidy was therefore detected in 64  of the malignant effusion specimens by fcm and ia  twenty three of the total of 24 aneuploid cases detected by fcm were associated with malignancy  predictive value   96    the one nonmalignant case was that of hemorrhagic pancreatitis with infected pseudocyst  fcm is an excellent tool when moderate to large numbers of tumor cells are present  whereas use of ia is advantageous for specimens containing smaller numbers of malignant cells because these can be directly analyzed  when an aneuploid peak is present  a diagnosis of malignancy must be suspected  and  if the initial cytologic screen is negative  a critical review of the cytology slides is justified  in those cases with an equivocal atypical cytology report and an abnormal cytometric histogram  additional investigation is warranted  in some malignancies the tumor cells will be diploid  in this study 36   and neither fcm nor ia will add to tumor detection  leaving cytologic examination as the definitive technique  
class8	widespread dissemination of pneumocystis carinii infection in a patient with acquired immune deficiency syndrome receiving long term treatment with aerosolized pentamidine  patients with acquired immune deficiency syndrome  aids  may be infected with many opportunistic pathogens  the most common of which is pneumocystis carinii  p  carinii infection typically presents as a subacute pneumonia  however  rare cases of localized  extrapulmonary  and disseminated disease have been described  standard therapy for p  carinii is systemically administered trimethoprim sulfamethoxazole or pentamidine  these agents  however  frequently are associated with serious adverse effects  more recently  aerosolized pentamidine has been proposed as an alternative treatment for those who cannot tolerate standard therapy and as primary and secondary prophylaxis  inhaled pentamidine is effective  but it is not without hazards  the authors describe a patient with aids who received long term treatment with aerosolized pentamidine and yet died as a result of widely disseminated p  carinii infection  
class8	assessment of nasal patency by rhinoscopic measurement of cross sectional nasal airway area  correlation with subjective nasal symptoms  assessment of nasal patency by the recording of nasal symptom scores was compared with an objective method of determining nasal airway area using a fiberoptic rhinoscope  sixty patients with active allergic rhinitis and nasal congestion requiring treatment were studied  nasal symptoms were recorded and nasal airway area was measured before and at fixed time intervals after administration of either pseudoephedrine or oxymetazoline  both methods detected a decongestant response to both drugs  and the symptom of congestion correlated with the measured nasal airway area  rhinoscopic measurement of cross sectional nasal airway area is an objective method that may be used to complement other methods for evaluation of nasal patency  
class8	thoracoscopy for the diagnosis of pleural disease  objective  to assess the accuracy and safety of thoracoscopy for the evaluation of pleural disease  design  prospective evaluation of patients referred for thoracoscopy  setting  university hospital specializing in chest diseases  patients  we studied 102 patients with pleural disease  the cause of which had not been determined after initial investigation  including thoracentesis and needle biopsy  eighty six patients had pleural effusion  11 had pleural mass  and 5 had pleural effusion in association with a known primary lung carcinoma  intervention  all patients had thoracoscopy under local anesthesia with mild sedation  visually directed biopsies were done of parietal pleura  measurements  we recorded clinical characteristics  laboratory data  findings and duration of thoracoscopy  and any complications associated with the procedure  hospital and clinic follow up records were reviewed  and patients were contacted by telephone 12 and 24 months after thoracoscopy to assess their health status  main results  one hundred and four thoracoscopies were done in 102 patients  a definitive diagnosis was established in 95 patients  42 had malignant pleural disease and 53 had benign pleural disease  a diagnosis of benign pleural disease using thoracoscopy could not be confirmed in the remaining 7 patients because of insufficient follow up information  overall  thoracoscopy was 96  accurate with a sensitivity of 91   a specificity of 100  and a negative predictive value of 93  for the diagnosis of pleural malignancy  thoracoscopy was well tolerated under local anesthesia and entailed hospitalization for less than 24 hours in most cases  no deaths occurred  although 1 9  of patients had major complications  and 5 5  had minor complications  conclusions  among patients with pleural disease remaining undiagnosed after usual initial investigation  thoracoscopy done under local anesthesia is a rapid  safe  and well tolerated procedure with an excellent diagnostic yield that is equivalent to that of thoracotomy  
class8	diagnosing pulmonary embolism  new facts and strategies purpose  to provide a clinical approach to the diagnosis of pulmonary embolism  data identification  an english language literature search using medline  1982 to 1990  and bibliographic reviews of textbooks and review articles  study selection  in addition to several reviews  studies that evaluated the diagnostic technology of pulmonary embolism were selected  preference was given to studies with a prospective design  particularly those done within the past decade  data extraction  studies were assessed independently by three unblinded observers  data were chosen to describe the efficacy of diagnostic technology on the basis of disease prevalence  sensitivity and specificity  and predictive value  results of data analysis  a normal lung scan or pulmonary angiogram rules out the diagnosis of clinically important pulmonary embolism with at least 95  certainty  lung scan interpretations indicating high or low probability have approximately a 15  error in diagnosing or ruling out pulmonary embolism  the accuracy of either scan result improves when the clinical suspicion of pulmonary embolism matches the lung scan result  serial impedance plethysmography of the lower extremities may exclude thromboembolism with 95  certainty in patients without high probability lung scan results or cardiopulmonary disease  conclusions  the combination of clinical suspicion and the results of the lung scan and impedance plethysmography appear to offer acceptable diagnostic accuracy in evaluating many patients suspected of having pulmonary embolism  the usefulness of this approach for patients with cardiopulmonary disease is still unknown  
class8	increasing asthma prevalence in a rural new zealand adolescent population  1975 89  a survey of asthma symptoms and spirometry in 435 adolescent schoolchildren was undertaken in 1989 in a rural  largely maori population  the survey questionnaires were identical to those used in a 1975 survey at the same school  the prevalence of reported asthma or wheeze significantly increased from 26 2  to 34 0   this increase occurred in groups reporting asthma  and also those reporting wheeze unassociated with colds  but without a previous diagnosis of asthma  there was a tendency for a rise in reported wheeze in europeans  24 3  to 27 4   and a significant rise in maoris  27 1  to 36 2    the reclassification of other respiratory problems did not account for the increase  data from this study provides evidence that there has been a rise in the prevalence of asthma in this new zealand population over a time period of 14 years  
class8	diagnosis of pneumocystis carinii pneumonia from non invasive sampling of respiratory secretions  an infant infected with hiv presented with fever  tachypnoea  hypoxia  and radiological evidence of bilateral pneumonitis  fluorescent antibody technique identified pneumocystis carinii within 24 hours from secretions obtained by nasopharyngeal aspiration  this rapid  non invasive method should be the first line investigation of suspected p carinii pneumonia in immunocompromised patients  
class8	air pollution and fatal lung disease in three utah counties  a unique situation found in two utah counties has made it possible to estimate the fraction of respiratory cancer and nonmalignant respiratory disease  nmrd  deaths  which are attributable to community air pollution  cap  in one county  the two counties were very similar in many ways  including low smoking rates  until a steel mill constructed during ww ii caused substantial cap in one of them  subsequent differences in mortality rates from both respiratory cancer and nmrd are striking  a third county  similar to many counties outside utah  was included in the analysis for comparison  in one county  30 40  of the respiratory cancer and nmrd deaths were attributable to cap  in this county  nmrd deaths  but not respiratory cancer deaths  were slightly more frequent than in salt lake county where smoking rates were twice as high  
class8	health effects of volcanic ash  a repeat study  the mount sakurajima volcano in kyushu  japan  is proximal to a large residential area  and it emits an enormous amount of volcanic ash during frequent eruptions  in our previous study  we investigated  for the first time  respiratory effects of chronic exposure to volcanic ash  the study demonstrated a low prevalence of respiratory symptoms  even in the area of highest exposure  only a slight excess prevalence of symptoms appeared to be associated with exposure to volcanic ash  to confirm the findings of our previous study  the prevalence study of chronic respiratory symptoms for residents was repeated in kanoya and tashiro  which are located 25 and 50 km  respectively  from the crater of mt  sakurajima  the concentration of suspended particulate matter in kanoya frequently exceeded the national environmental quality standards and  during summer and winter  was 2 3 times higher than that found in tashiro  women who were 30 59 y of age and who had resided in kanoya or tashiro for more than 3 y completed a modified ats dld questionnaire  the prevalence of nonspecific respiratory disease was low  i e   6 5  in kanoya and 6 2  in tashiro  similar prevalences were found in women who had never smoked  when we restricted the analysis to individuals without a history of occupational exposure to dusts and who had no exposure to passive smoking  there was a slightly higher prevalence of nonspecific respiratory disease in kanoya than tashiro  but the difference was not significant  eye symptoms were equally prevalent in the two areas  
class8	expression of blood group antigens by normal bronchopulmonary tissues and common forms of pulmonary carcinomas  the expression of abh and lewis antigens has been studied in a series of pulmonary carcinomas  in areas of squamous metaplasia  and in normal adjacent bronchopulmonary tissues by means of a panel of lectins and monoclonal antibodies  all respiratory epithelial cells can express antigens  with the exception of glandular serous cells  the expression of ab antigens is rather homogeneous  while lewis antigens are expressed in a more irregular pattern  alternating positively stained cells with negatively stained cells in the same microscopic field  the expression of blood group antigens allows the identification of residual pneumocytes inside the tumor and the proper classification of some neoplasms  metaplastic areas show a variation in the staining profile when compared with normal tissues and pulmonary carcinomas  the most significant findings are the deletion of a antigen and the strong expression of le antigen  pulmonary carcinomas are composed by a heterogeneous population and tend to express antigens in the more differentiated cases or areas  the most important findings are the deletion of ab antigens and the strong expression of le y  antigen  
class8	regurgitation of fat and marrow emboli into coronary veins during resuscitation  three groups of patients were examined at autopsy for the presence of fat and marrow emboli in the lungs  heart  and other organs  group 1 was composed of patients with massive pulmonary thromboembolism and attempted cardiopulmonary resuscitation  group 2  patients with pulmonary thromboembolism and without attempted cardiopulmonary resuscitation  and group 3  patients without pulmonary thromboembolism and with attempted cardiopulmonary resuscitation  the results confirm that pulmonary fat and marrow emboli are frequent in those patients who are resuscitated  a novel observation is the finding of multiple coexistent cardiac venous emboli in those resuscitated patients who have pulmonary artery obstruction with pulmonary thromboemboli  these findings suggest that these emboli regurgitate from the right side of the heart to the coronary sinus and cardiac veins in cases of pulmonary artery hypertension  
class8	fatal embolization of intestinal contents through a duodenocaval fistula  embolization of intestinal contents to the lung is an exceedingly rare event  which to our knowledge  has never been reported as a cause of death  equally rare is duodenocaval fistula resulting from a penetrating duodenal peptic ulcer  we present the case of a 51 year old man whose duodenal ulcer led to a fistulous tract with the inferior vena cava and subsequently to progressive pulmonary embolization of intestinal contents  ultimately resulting in death from respiratory failure  
class8	acute pulmonary oedema on the ruwenzori mountain range  a 40 year old man had an episode of severe pulmonary oedema at 4000 5000 m during the ascent of the margherita peak  5109 m  of mount stanley on the ruwenzori  he had taken acetazolamide and high dose dexamethasone to treat symptoms of acute mountain sickness  six years before he had been studied by right heart catheterisation as a healthy volunteer during hypoxic breathing at sea level  his pulmonary vascular reactivity had been within the normal range for 32 healthy subjects  this man had high altitude pulmonary oedema despite currently recommended treatments for acute mountain sickness and normal pulmonary vascular reactivity to hypoxia at sea level  
class8	interaction of chemical and high vascular pressure injury in isolated canine lung  published erratum appears in j appl physiol 1991 mar 70 3  964  because both chemical and mechanical insults to the lung may occur concomitantly with trauma  we hypothesized that the pressure threshold for vascular pressure induced  mechanical  injury would be decreased after a chemical insult to the lung  normal isolated canine lung lobes  n  n   14  and those injured with either airway acid instillation  aai  n   18  or intravascular oleic acid  oa  n   25  were exposed to short  5 min  periods of elevated venous pressure  hipv  ranging from 19 to 130 cmh2o  before the hipv stress  the capillary filtration coefficient  kf c  was 0 12     0 01  0 27     0 03  and 0 31     0 02 ml min 1 cmh2o 1 x 100 g 1 and the isogravimetric capillary pressure  pc i  was 9 2     0 3  6 8     0 5  and 6 5     0 3 cmh2o in n  aai  and oa lungs  respectively  however  the pattern of response to hipv was similar in all groups  kf c was no different from the pre hipv value when the peak venous pressure  pv  remained less than 55 cmh2o  but it increased reversibly when peak pv exceeded 55 cmh2o  p less than 0 05   the reflection coefficient  sigma  for total proteins measured after pressure exposure averaged 0 60     0 03  0 32     0 04  and 0 37     0 09 for n  aai  and oa lobes respectively  however  in contrast to the result expected if pore stretching had occurred at high pressure  in all groups the sigma measured during the hipv stress when pv exceeded 55 cmh2o was significantly larger than that measured during the recovery period  
class8	cough enhanced mucus clearance in the normal lung  we studied the effectiveness of cough for clearing mucus in 12 nonsmoking subjects with normal lung function  on 2 separate study days  each subject breathed 6 microns mass median aerodynamic diameter 99mtc labeled iron oxide particles under controlled breathing conditions while they were seated in front of a gamma camera  retention  r  of lung activity was measured over the initial 2 h and again at 24 h after particle inhalation  on the control day the subject sat quietly in front of the camera  while on the cough day each subject performed 60 controlled coughs during the 1st h of retention measurements  by paired analysis  retentions at both 1 and 2 h  r1 and r2  respectively  for the cough measurements were significantly less than control  mean control r1   85  vs  mean cough r1   72   p less than 0 002  mean control r2   75  vs  mean cough r2   65   p less than 0 02   retention at 24 h  r24  was not significantly different between cough and control measurements  mean cough r24   35  and mean control r24   32    thus coughing increased the rate at which the radiolabeled particles were cleared from the bronchial airways in these individuals  follow up experiments with subjects performing rapid inhalations rather than cough showed similar enhanced particle clearance to that seen with cough  these results suggest that the observed enhancement of mucus clearance by cough  and rapid inhalation  in the normal lung may be due to a stimulation of the mucociliary apparatus rather than via a two phase gas liquid flow mechanism  
class8	atelectasis affects the rate of arterial desaturation during obstructive apnea  chronic hemodynamic disturbances are more profound in patients with obstructive sleep apnea when underlying lung disease with abnormal gas exchange  low arterial po2  is present  previous studies suggest that pulmonary gas exchange could influence the rate of fall of arterial oxygen saturation  dsao2 dt  in obstructive sleep apnea  we postulated that abnormal gas exchange in the form of atelectasis would steepen dsao2 dt and thereby lower nadir arterial oxyhemoglobin saturation  sao2  for the same duration of apnea  apneas were created by clamping an indwelling cuffed endotracheal tube at end expiration in eight spontaneously breathing adult baboons  apneas of the same duration were then repeated during temporary endobronchial occlusion of one lobe of the lung  sao2 and mixed venous o2 saturation were continuously monitored  and cardiac output was calculated  worsening of pulmonary gas exchange during atelectasis was documented by an increase in calculated venous admixture from 10 5     0 8 to 25 0     0 7   p less than 0 001   the dsao2 dt was independent of apnea duration at 30  45  and 60 s  during endobronchial occlusion  apnea dsao2 dt increased 20   and nadir sao2 was significantly lower  possible mechanisms for steepening of dsao2 dt during atelectasis are discussed  
class8	failure of therapy with 2 3 dihydroxybenzoic acid to modify the course of sepsis induced lung injury  oxidant induced injury of the pulmonary microvasculature reportedly contributes to an increase in microvascular permeability and pulmonary hypertension  both of which are principal features of acute lung injury  ali   we tested the hypothesis that antioxidant therapy with 2 3 dihydroxybenzoic acid  dhb   initiated in awake sheep after the development of sepsis induced ali  would ameliorate the progression of these lesions  dhb has many actions that suggested to us the potential for demonstrating benefit in ali complicating sepsis  it is a nontoxic hydroxyl radical scavenger that also inhibits the cyclooxygenase pathway and acts as a weak iron chelator  in preliminary experiments  we demonstrated that pretreatment with dhb prevented an increase in mean pulmonary arterial pressure  plasma thromboxane a2  measured as its metabolite thromboxane b2  and lymph total protein clearance that otherwise followed an infusion of zymosan activated plasma  zap  in sheep  in subsequent experiments  12 additional sheep were rendered septic by cecal ligation and perforation  twenty four to 36 h after cecal ligation and perforation  an increase in lung microvascular permeability was confirmed  because pulmonary lymph flow had increased by 82  while the mean lymph to plasma total protein ratio was unchanged from baseline  at this point  six sheep were then treated with parenteral dhb and six with dhb vehicle for the subsequent 24 h  in contrast to the demonstrated benefit of dhb pretreatment in preventing ali secondary to an infusion of zap  the progressive increase in lymph total protein clearance that complicated septic lung injury in the dhb vehicle group throughout this 24 h study period was not ameliorated in the dhb treatment group  however  dhb did prevent a modest increase in mean pulmonary arterial pressures that was demonstrated in the dhb vehicle group throughout this 24 h treatment period  although pretreatment prevented ali after a zap infusion  we conclude that dhb only incompletely modified disease progression when administered after the onset of sepsis induced ali because it ameliorated the pulmonary hypertensive response without concurrently modifying an increase in lung microvascular fluid flux  
class8	modulation of bordetella pertussis infection with monoclonal antibodies to pertussis toxin  three monoclonal antibodies to pertussis toxin were characterized and used to investigate its role in immunity  antibody affinity correlated with toxin neutralization in in vivo and in vitro assays but was not the only determinant of protection against bordetella pertussis infection  b9  a high affinity anti s3 antibody  was the most effective in neutralizing toxin induced cho cell clustering and hemagglutination in vitro and lymphocytosis and histamine sensitization in vivo  a4  a similar affinity anti s1 antibody  was less active in the toxin neutralization assays but more protective in the mouse infection model  a12  a low affinity anti s1 antibody  was least active in the assays of toxin neutralization but as effective as b9 in the infection model  these data suggest that epitopes on the a protomer and b oligomer may induce protective immunity  measurement of pertussis toxin neutralization by monoclonal antibodies in in vitro and in vivo assays may not accurately predict protection against infection with b  pertussis  
class8	influence of chemotherapy administration on monocyte activation by liposomal muramyl tripeptide phosphatidylethanolamine in children with osteosarcoma  the purpose of these studies was to determine whether chemotherapy interfered with the ability of peripheral blood monocytes from patients with osteosarcoma to respond to the liposome encapsulated activating agent muramyl tripeptide phosphatidylethanolamine  l mtp pe   this was done in preparation of designing an adjuvant therapy protocol that includes l mtp pe combined with chemotherapy postoperatively for the treatment of primary osteosarcoma  the majority of patients who fail current adjuvant chemotherapy do so while on chemotherapy  therefore  we believe it is important to combine l mtp pe with chemotherapy early in the treatment course rather than waiting until all chemotherapy cycles are completed  the tumoricidal properties of monocytes from patients with osteosarcoma could be activated by l mtp pe to levels equal to or greater than those expressed by normal control monocytes  no intrinsic monocyte defect could be demonstrated  single agent chemotherapy consisting of cisplatin  cpd   high dose methotrexate  mtx   cytoxan  ctx  cyclophosphamide  bristol myers co  evansville  in   or adriamycin  adr  doxorubicin  adria laboratories  columbus  oh  did not interfere with this activation process  there was even a suggestion of enhanced activation potential following the administration of adr  however  when both adr and ctx were administered together on the same day  profound suppression in monocyte activation was observed  this suppressed function returned to normal by 3 weeks postcombination therapy  we therefore conclude that l mtp pe can be combined with adr  cpd  mtx  or ctx as single agents but recommend that adr plus l mtp pe is the most effective combination  by contrast  we discourage the use of l mtp pe when adr and ctx are given together  
class8	intensive weekly chemotherapy for good prognosis patients with small cell lung cancer  a weekly  intensive chemotherapy regimen has been used to treat 70 patients with small cell lung cancer  sclc   forty five patients had limited disease  ld  and 25 extensive disease  ed  with good prognostic features  the regimen consisted of cisplatin 50 mg m2 intravenously  iv  day 1 and etoposide 75 mg m2 iv days 1 and 2  alternating weekly with ifosfamide 2 g m2 iv day 8 and doxorubicin 25 mg m2 iv day 8  for a total of 12 weeks  dose modifications were made according to defined hematologic criteria  responding patients with limited disease subsequently received mediastinal radiotherapy  overall response to chemotherapy was 91  with a complete response  cr  rate of 50   forty five patients with limited disease  ld  achieved an overall response rate of 91  with a cr rate of 51   and 25 patients with extensive disease  ed  achieved an overall response rate of 92  with a cr rate of 48   median survival for the whole group was 54 weeks  ld  58 weeks  ed  42 weeks   hematologic toxicity was predictable  without the wide fluctuations in wbc count seen in conventional 3 weekly regimens  in all  one quarter of treatment courses were delayed  most frequently because of leukopenia  dose reductions were required in 63  of cases  the average delivered dose intensity was calculated and shown to be 73  of projected  nonhematologic toxicity was mild with nausea and vomiting being the most common  this weekly schedule of chemotherapy has proved to be active and well tolerated and is currently being compared with conventional 3 weekly chemotherapy in a randomized study  
class8	eosinophilic myositis an expression of l tryptophan toxicity  eosinophilia myalgia syndrome possibly due to l tryptophan is a new clinical entity that has been recently reported  we describe the clinical presentation of eosinophilia  eosinophilic pustular folliculitis  myalgia  and eosinophilic myositis  that led to respiratory failure in a young man taking an l tryptophan containing compound  
class8	effect of interleukin 1 beta on metastasis formation in different tumor systems  experiments were done to determine the effect of interleukin 1 beta  il 1 beta  on metastasis formation in different tumor systems  intravenous administration of 1 microgram of human recombinant il 1 beta given 1 hour before tumor cell injection augmented lung colony formation  experimental metastases  by the human a375 melanoma variants  the human ht 29m colon carcinoma  the sn12 k1 renal carcinoma in nude mice  the murine b16 melanoma variants  and the murine uv 2237m fibrosarcoma in syngeneic recipients  the same treatment did not induce lung colony formation by a human rectal carcinoma  hcc p2988  or by a murine reticulum cell sarcoma  m5076   both of which are not metastatic to the lung  spontaneous metastases were studied in c57bl 6 mice bearing the b16 bl6 melanoma  metastatic to the lung  in their footpad and the m5076 reticulum cell sarcoma  metastatic to the liver  subcutaneously  daily intraperitoneal treatment with 1 microgram of il 1 beta increased lung and liver metastases  these findings indicate that treatment of mice with il 1 beta can increase the number of artificial or spontaneous metastases and that this effect is not limited to a single tumor type or to a specific organ  
class8	phase i and imaging trial of indium 111 labeled anti epidermal growth factor receptor monoclonal antibody 225 in patients with squamous cell lung carcinoma murine monoclonal antibody  mab  225  igg1  against the epidermal growth factor  egf  receptor competitively blocks egf binding and inhibits egf induced activation of receptor tyrosine kinase and cell proliferation  the effect of mab 225 was studied in a phase i trial in patients with inoperable squamous cell carcinoma of the lung  which invariably expresses high levels of egf receptors  groups of three patients received total doses of mab 225 ranging from 1 mg to 300 mg  except at the lowest dose  each infusion included 4 mg of indium 111  111in  labeled mab 225  no toxicity was observed  tumors were imaged in all patients who received doses of 20 mg or greater  presumed metastases greater than or equal to 1 cm in diameter were imaged with doses of 40 mg or greater  single photon emission computed tomography could be carried out at the 120 mg and 300 mg doses and significantly improved tumor visualization  all patients produced anti murine antibodies  we conclude that treatment with an mab that inhibits egf receptor function is safe at the doses and schedule studied  111in labeled mab images squamous cell lung carcinoma  tumor uptake of the labeled mab is dose dependent  further studies are warranted to explore the potential therapeutic efficacy of anti egf receptor mabs and other agents that act in a comparable manner  
class8	brief intensive chemotherapy for metastatic non small cell lung cancer  a phase ii study of the weekly code regimen  fifty three patients  17 with stage iiib and 36 with stage iv non small cell lung cancer  were given code  cisplatin  vincristine  doxorubicin  and etoposide  plus antibiotic prophylaxis and an antiemetic regimen in an intensive chemotherapy program emphasizing weekly treatment and a planned brief duration  9 12 weeks   for 45 of these patients  the code program also included antifungal prophylaxis and supportive corticosteroids  of the total study population  33 patients  62   responded to treatment  including five  9   with complete response  the median survival for the entire group was 42 weeks  55 weeks for those with stage iiib and 39 weeks for those with stage iv   more than 40  were alive at 1 year  comparison of granulocyte counts of patients receiving prednisone with those of the subgroup to whom no corticosteroids were given showed less granulocytopenia for those receiving prednisone  use of prednisone thus allowed improved delivery of myelosuppressive drugs  code was halted in nine patients because of disease progression  although more constitutional side effects are associated with weekly chemotherapy than with standard chemotherapy  only 12 of the remaining 44 patients  27   failed to receive at least 9 weeks of treatment  serious toxicity was uncommon  there were no treatment related deaths and only three episodes of neutropenia with fever  code is a novel treatment for non small cell lung cancer that this pilot study provided entirely in an outpatient setting over a 9 12 week period with an acceptable incidence of toxicity and a promising level of efficacy  additional testing and comparison with other regimens or supportive care alone are warranted  
class8	management of primary nonrenal parenchymal malignancies with vena caval thrombus  we report our experience with the management of 7 primary nonrenal parenchymal malignancies with vena caval tumor thrombus  included are 3 cases of adrenal cortical carcinoma and 1 each of transitional cell carcinoma  embryonal cell testicular carcinoma  pheochromocytoma and primary small cell carcinoma of the lung with metastases to the kidney  surgical treatment and followup are presented  as well as a review of the literature  an aggressive surgical approach is warranted because prolonged survivals free of disease are possible  
class8	roentgenologic features of pulmonary blastomycosis  in 35 cases of pulmonary blastomycosis  the roentgenologic features were as follows  consolidation 26   mass 31   intermediate sized nodules 6   miliary pattern 11   solitary cavity 9   fibrotic and cavitary changes 6   interstitial pattern 6   diffuse alveolar involvement 3   and mixed alveolar and interstitial infiltrate 3   all symptomatic cases of consolidation were acute  symptoms for less than 1 month   and most were in young patients  mean age  34 years   consolidation constituted 58  of the acute cases in this series  two of the nine cases of consolidation were asymptomatic epidemic cases detected by screening  a pulmonary mass was the most common initial manifestation in this series  it tended to occur in patients with chronic symptoms  more than 1 month   the mass was considered suggestive enough of bronchogenic carcinoma to necessitate resection in 55  of cases  the military form of pulmonary blastomycosis occurred in older patients with disseminated disease  fibrotic and cavitary disease was chronic in nature  the presence of intermediate sized nodules elsewhere in the lung proved to be a helpful diagnostic finding in several patients with consolidation  mass  or cavitary disease  hilar adenopathy  postinfectious calcification  chest wall invasion  and pleural effusion occurred infrequently or not at all in this series  
class8	fungal tracheobronchitis  report of 9 cases and review of the literature  clinical  roentgenographic and pathologic findings are described in 9 patients with fungal tracheobronchitis and comparison is made with 25 additional cases in the literature  two morphologic patterns were identified  the first appears as a pseudomembrane of necrotic tissue  exudate  and fungal hyphae involving more or less the entire circumference of the bronchial wall or as mucus fungus plugs completely occluding the airway lumen  the second consists of single or multiple discrete plaques on the airway wall  sometimes associated with invasion of the adjacent lung parenchyma or pulmonary artery  as with more invasive forms of fungal infection  a compromise in host defenses is probably the most important factor leading to fungal colonization and subsequent local invasion  malignancies of the hematologic and lymphoreticular systems  solid neoplasms  granulocytopenia  and a history of a protracted course of broad spectrum antibiotics  corticosteroids  and chemotherapy were present in most of our patients and in those reported in the literature  despite this  there is some evidence that tracheobronchitis may occur in individuals with a relatively lesser degree of host defense impairment  local damage to the airway wall such as occurs with prolonged mechanical ventilatory support  neoplastic infiltration  or nonfungal infection may also be a factor predisposing to fungal colonization and invasion  in 4 of our patients  the fungal infection of the tracheobronchial tree probably contributed significantly to the development of terminal respiratory failure  although recognition of the infection may not have altered the course of the underlying disease in some of our patients  in others identification and early treatment might have been life saving  thus  culture and histologic examination of bronchoscopically identified tracheobronchial mucus plugs and necrotic material should be performed in all immunocompromised individuals  
class8	at the water s edge  where obstetrics and anesthesia meet conflict exists between satisfying the parturient s desire for oral intake and traditional restrictive standards of obstetric and anesthesia departments  surveys of institutions providing obstetric services reveal greatly varying oral intake policy  there is neither evidence of benefit in withholding fluids nor evidence of risk in allowing them  prolonged fasting has potential liabilities  maternal mortality is rare  and anesthesia related causes are not among the common etiologies  aspiration is not a significant factor in the modern era  higher risk for anesthesia morbidity is associated with general anesthesia  particularly difficult intubation  instead of implicating oral intake as a risk factor for pulmonary aspiration  the literature consistently emphasizes the critical role of properly trained and dedicated obstetric anesthesia personnel  unless parturients are not candidates for regional anesthesia  a nonparticulate diet should be allowed  liberal use of regional anesthesia as well as antacid prophylaxis is recommended  
class8	lung scanning for pulmonary embolism  clinical and pulmonary angiographic correlations  a group of 78 patients with suspected pulmonary embolism was studied by both ventilation perfusion lung scanning and pulmonary angiography  symptoms and clinical signs were analysed using bayesian techniques to produce pre test odds for pulmonary embolism in individual patients  while  as a group  those with embolism could be discriminated from those without on this basis  major overlap existed between the groups  invalidating the use of this approach for individual patients  strict diagnostic criteria for interpretation of lung scans were accurate using pulmonary angiography as the  gold standard   but at the expense of a significant number of patients  38 per cent  in the indeterminate  non diagnostic  group  in the 48 patients in whom the test yielded a diagnostic result  there was a sensitivity of 100 per cent  15 15  and a specificity of 97 per cent  32 33   in the series as a whole  the likelihood of lung scanning correctly diagnosing pulmonary embolism was 55 per cent  15 27  and of correctly excluding embolism  63 per cent  32 51   by the use of strict criteria for interpretation of lung scanning  reliable information can be obtained on the presence or absence of pulmonary embolism in a large proportion of patients suspected of having the condition  such information is more discriminating than clinical signs and symptoms  
class8	risk for postoperative congestive heart failure  to identify predictors of postoperative congestive heart failure  chf   a high risk population  mainly hypertensive and diabetic patients undergoing elective general operations  was studied  of the 254 patients  6 per cent had postoperative chf  among patients with preoperative cardiac disease  that is  previous myocardial infarction  valvular disease or chf   17 per cent had postoperative chf  in contrast with less than 1 per cent of those without cardiac disease  p less than 0 001   patients with diabetes were also at high risk  12 versus 2 per cent  p less than 0 005   particularly those with cardiac disease  patients who had equal to or greater than 40 millimeters of mercury increases or decreases intraoperatively in mean arterial pressure in relation to preoperative baseline had increased postoperative failure rates  p less than 0 02   of note  postoperative failure rates were highest among patients with less than 500 milliliters per hour of net intake  input and output   p less than 0 03   risk for postoperative chf was restricted to patients with preoperative symptomatic cardiac disease and was especially high if patients also had diabetes  intraoperative fluctuations in mean arterial pressure increased the probability of postoperative failure  while the intraoperative administration of higher net volumes of fluid was associated with decreased risk  
class8	the  natural history  of the transplanted lung  rates of pulmonary functional change in long term survivors of heart lung transplantation  long term pulmonary function in hlt is well preserved with no evidence of functional decline as a result of transplant  aging   providing the allografts remain free of complications  long term survivors with ob appear to be able to maintain adequate oxygenation despite the marked alterations of pulmonary function  the ability to preserve gas exchange at reasonable levels of oxygenation may be the factors permitting extended survival with ob for mean periods of 36 0 months or greater  preliminary studies suggest that a declining fef50 fvc  at a time when pulmonary function is normal  may be an index of impending airway disease  physiologically  from a long term point of view  hlt remains a viable option for selected patients with end stage cardiopulmonary disease  
class8	single lung transplantation for pulmonary vascular disease  six patients with end stage pulmonary vascular disease received right slts  though patients generally had difficult early postoperative courses  four of the six have survived from 3 to 23 months and have achieved good recovery of right ventricular function and good functional results  slt is a viable option in selected patients with severe pulmonary hypertension even when right ventricular function is severely impaired  
class8	gastroesophageal reflux and respiratory symptoms  is there an association  proposed mechanisms and treatment  gastroesophageal reflux  ger  is a dysfunction of the distal esophagus causing movement of stomach contents into the esophagus  patients may develop heartburn  regurgitation  dysphagia  odynophagia  and hemorrhage  respiratory symptoms occur in 10 60 percent of patients with ger or hiatal hernia  although there is evidence associating pulmonary symptoms and ger  causality has not been proven  the appropriate use of antireflux therapy or surgery to treat ger may consequently alleviate respiratory symptoms  
class8	hypertension with concomitant conditions  the changing role of beta adrenoceptor blockade  hypertension often is associated with concomitant conditions such as chronic obstructive lung disease  diabetes mellitus  ischemic heart disease  and peripheral vascular disease  moreover  other cardiovascular risk factors  including dyslipidemias and abnormalities of glucose and insulin metabolism  are common in patients with hypertension  conventional beta blockers used for antihypertensive therapy can have adverse effects in patients with airway disease  diabetes  and peripheral vascular disease  and can exaggerate the other risk factors  newer beta blockers such as celiprolol  which have selective partial agonist activity expressed at beta 2 receptors  appear to avoid these problems  celiprolol exhibits antianginal and antihypertensive efficacy without adversely effecting left ventricular systolic function or exercise performance  it also may cause regression of left ventricular hypertrophy  the stimulatory action of celiprolol on vascular beta 2 receptors enhances regional flow and may increase walking distance in patients with claudication  the reduction in renal vascular resistance demonstrated by this drug is associated with preservation of renal blood flow and function  spirometric measurements of airway function are unchanged during celiprolol treatment  similarly  there are no adverse effects on lipid or glucose concentrations  these new developments in beta blocker pharmacology indicate that this class of agents could be used in patients with hypertension with concomitant diseases or risk factors other than high blood pressure  
class8	body composition by bioelectrical impedance analysis compared with deuterium dilution and skinfold anthropometry in patients with chronic obstructive pulmonary disease  body composition is an important measure of nutritional status in patients with chronic obstructive pulmonary disease  copd   we generated a regression model for bioelectrical impedance  bi  by using deuterium dilution  2h2o  as a reference method in 32 copd patients  aged 63     9 y  mean     sd   in stable pulmonary and cardiac condition  height squared divided by resistance  ht2 res  correlated well with total body water  tbw  as measured by 2h2o  r   0 93  p less than 0 001  see   1 9 l   the best fitting regression equation to predict tbw comprised ht2 res and body weight  r2   0 89  see   1 8 l  p less than 0 001   bi predicted tbw was used to estimate bi fat free mass  ffm  that was compared with skinfold thickness based ffm predictions  anthr ffm   relative to bi ffm a significant overestimation of 4 4     0 8 kg was found by anthr ffm  our results suggest that bi is a useful measure of body composition in patients with severe copd  
class8	chest wall involvement by lung cancer  computed tomographic detection and results of operation  the aim of this prospective study was to evaluate   1  the role of computed tomographic scanning in predicting chest wall invasion by peripheral lung cancer and  2  the results of operation according to the depth of chest wall involvement and other potential indicators of long term survival  one hundred twelve patients with non small cell lung cancer adjacent to the pleural surface who underwent computed tomographic scanning and subsequent thoracotomy were entered into this study  tumor invasion was confined to the visceral pleura in 53 patients  to the parietal pleura in 18 patients  and to intercostal muscles in 25 patients  invasion extended beyond this layer in 16 patients  the computed tomographic criteria for chest wall invasion were  1  obliteration of the extrapleural fat plane   2  the length of the tumor pleura contact   3  the ratio between the tumor pleura contact and the tumor diameter   4  the angle of the tumor with the pleura   5  a mass involving the chest wall  and  6  rib destruction  the computed tomographic criteria 1 and 3 were significantly related to pathologic findings  sensitivity was 85  for criterion 1 and 83  for criterion 3  specificity being 87  and 80   respectively  long term survival of patients with t3 disease critically depended on the lymph node state and completeness of resection  the adenocarcinoma cell type and the t4 category were unfavorable prognostic factors  the depth of chest wall invasion did not affect survival  except for extensive rib and soft tissue infiltration  en bloc resection yielded better results than discontinuous resection  
class8	risk factors for nosocomial pneumonia after coronary artery bypass graft operations we attempted to determine risk factors for nosocomial pneumonia in patients undergoing a coronary artery bypass graft operation  we reviewed the microbiology and medical records for any patient with a sputum culture who had undergone a coronary artery bypass graft operation in 1988 to identify patients with pneumonia according to a standard clinical definition  we found 19 cases of pneumonia through our initial review  complete medical records were found on 15 cases  gram negative bacilli predominated as the most common etiologic agent causing pneumonia in this cohort  there were no clusters noted  mortality was 26 6   pneumonia occurred approximately 4 days after the operation  thirty six controls were randomly selected from patients undergoing coronary artery bypass graft operations in 1988  logistic regression analysis revealed that a history of chronic obstructive lung disease  duration of more than 2 days of mechanical ventilation after operation but before diagnosis of pneumonia  and receipt of gastric acid inhibitors  antacids or h2 blockers  were independent risk factors for nosocomial pneumonia  only the last risk factor was amenable to intervention at the time of operation  
class8	response to chemotherapy does not predict survival after resection of sarcomatous pulmonary metastases  between 1979 and 1988  26 patients with pulmonary metastases from adult soft tissue sarcomas were treated with adriamycin  doxorubicin hydrochloride   cytoxan  cyclophosphamide   and dtic before metastasectomy  thirty eight thoracotomies were performed with postoperative complications in 5 patients  5 38  13 2   and one postoperative death  1 38  2 6    two patients had benign lesions at thoracotomy and were excluded from further survival analysis  the median survival of the remaining 24 patients after thoracotomy was 18 5     5 9 months  and the actuarial 5 year survival was 22   five patients  5 24  21   achieved a clinically complete response with preoperative chemotherapy  but all had recurrence in the lung and underwent resection of pulmonary metastases  seven patients  7 24  29   achieved a partial response and had residual disease resected at thoracotomy  twelve patients  12 24  50   showed either no change or disease progression while receiving chemotherapy and were referred for resection  postthoracotomy disease free survival and postthoracotomy overall survival did not differ significantly between the three groups  one patient in the group showing no change or progression of disease while receiving chemotherapy is alive without recurrence 57 months after initial pulmonary metastasectomy  chemotherapy can be used for the initial treatment of pulmonary metastases from adult soft tissue sarcomas  however  survival after resection of pulmonary metastases cannot be accurately predicted based on the clinical response to preoperative chemotherapy  
class8	pulmonary embolectomy  a 20 year experience at one center between 1968 and 1988  96 consecutive patients with acute massive pulmonary embolism underwent pulmonary embolectomy under cardiopulmonary bypass  the operative mortality rate was 37 5   we analyzed 12 clinical and hemodynamic variables by univariate and multivariate analyses to assess the predictive factors of postoperative outcome  multivariate analysis disclosed that cardiac arrest and associated cardiopulmonary disease were independent predictors of operative death  long term follow up  range  2 to 144 months  mean  56 months  information was available for 55 of the 60 discharged patients  6 had died  and 5 complained of persistent mild or severe exertional dyspnea  new york heart association class ii   these results help assess the preoperative risk in patients undergoing pulmonary embolectomy  they also show that  in the few patients who do not benefit from optimal medical therapy  pulmonary embolectomy remains an acceptable procedure in view of the long term results  
class8	intrathoracic fibrin glue for postoperative pleuropulmonary fistula  twenty cases of persistent pleuropulmonary fistula after a thoracic surgical procedure were successfully treated with fibrin glue injection into the thoracic cavity through a drainage tube  a new technique  the overlying method  which is a modification of the conventional technique of fibrin glue injection  was devised  each patient received one to four injections  mean number  1 6   this method resulted in closure of the pleuropulmonary fistula in all but 1 patient  minor complications included pain in 1 patient and fever in 3 patients  a control study involving 24 patients with pleuropulmonary fistula was performed  autoblood  ok 432  and tetracycline were used instead of fibrin glue  the fistula resolved in 12 patients  complications after injection included pain in 15 patients  fever in 10  and occlusion of the chest tube in 4  with our new method  patients rarely exhibited pain and fever  and occlusion of the chest tube did not occur  
class8	aggressive surgical intervention in n2 non small cell cancer of the lung  an aggressive attitude toward surgical treatment was taken in patients with n2 non small cell lung cancer in the past 10 years  computed tomographic scanning was employed in the diagnosis of n2 disease  and had a true positive rate of 57   among patients with n2 disease detected by computed tomographic scanning  surgical intervention was attempted except for those with unresectable disease  of 190 patients with clinical n2 disease  115 underwent surgical exploration  9 patients had only an exploratory thoracotomy  53 patients underwent a curative operation  and 53 had a noncurative operation  the overall 5 year survival rate of these patients was 16  and that of curatively resected patients was 20   there were 47 patients whose n2 disease was not recognized before operation  the 5 year survival rate of this group was 20  overall and 33  in curatively resected cases  the overall 5 year survival rate of patients with n2 disease who underwent resection  106 with clinical n2 disease and 47 with clinically unrecognized n2 disease  was 17   and that of the 84 patients undergoing curative operations was 24   an aggressive attitude toward surgical intervention can be advocated for patients with n2 disease on the basis of our present results  
class8	diagnosis of poststernotomy infection  comparison of three means of assessment  of 737 adults undergoing cardiac operations through a median sternotomy over a 2 year period  january 1988 to january 1990   sternal substernal space infection requiring mediastinal exploration developed in 8  six of these patients as well as 18 additional patients were evaluated for possible poststernotomy wound infection by computed tomography  4 true positive  4 false positive  10 true negative  2 false negative   indium 111 leukocyte scanning  5 true positive  0 false positive  18 true negative  1 false negative   and epicardial pacer wire cultures  6 true positive  1 false positive  12 true negative  0 false negative   on the basis of this experience it is suggested that in addition to computed tomography  indium 111 leukocyte scanning and epicardial pacer wire cultures may be useful in the diagnosis of poststernotomy deep wound infection  
class8	misplaced caval filter and subsequent pericardial tamponade  use of the greenfield filter for partial caval interruption is generally accepted as the most reliable mechanical method of pulmonary embolus prophylaxis  however  there have been reports of a variety of  usually nonfatal  complications  we report here the near fatal complication of acute pericardial tamponade after misplacement of a greenfield filter  because of the filter s unusual location  retrieval required cardiopulmonary bypass  profound hyperthermia  and circulatory arrest  
class8	total unilateral lung gangrene in hodgkin s disease  treatment by thoracostomy  total gangrene of the left lung developed in a 30 year old male patient with a pulmonary recurrence of hodgkin s disease after mediastinal irradiation and chemotherapy  clinically  tension pyopneumothorax and severe septic shock were present  surgical repair was done by thoracostomy  resecting three ribs  a 2 x 0 5 cm hole in the necrotic wall of the left main bronchus was covered with an intercostal muscle bundle  the necrotic pleural surfaces were treated openly by daily change of dressings  the patient recovered satisfactorily and underwent four further courses of chemotherapy without any complications  
class8	intraoperative management of severe endobronchial hemorrhage endobronchial hemorrhage due to pulmonary artery perforation by a swan ganz catheter developed during coronary artery bypass grafting while weaning from cardiopulmonary bypass  after reinstitution of cardio pulmonary bypass with pulmonary artery venting  bleeding was localized to the right lower lobe bronchus using fiberoptic bronchoscopy  a fogarty embolectomy catheter was inflated in the bronchus to tamponade successfully only the right lower lobe  this case illustrates a method of distal bronchial blockade for maximal retention of pulmonary function and avoidance of pulmonary resection  
class8	nephrotic syndrome complicating adenocarcinoma of the lung with resolution after resection  nephrotic syndrome is an uncommon complication of lung cancer  we present a case in which adenocarcinoma was complicated by the nephrotic syndrome  which resolved after resection of the cancer  
class8	extracorporeal gas exchange in adult respiratory distress syndrome  associated morbidity and its surgical treatment  extracorporeal carbon dioxide removal  ecco2 r  over a membrane lung is a new therapy for patients with adult respiratory distress syndrome  ards  who frequently suffer from lung complications caused by long term artificial ventilation and who may require major thoracic surgery  this is a report of 76 patients with severe ards who were treated by ecco2 r  twenty six of these 76 patients required thoracotomy  19 for pneumothorax and pneumatocele  and seven for haemothorax  infected lung necrosis or oesophagotracheal fistula  most pneumothoraces were bilateral  ten of these 26 patients required reoperation  usually for extensive persisting alveolar air leaks  sixteen  62 per cent  of the 26 patients who had a thoracotomy and 22  44 per cent  of the 50 patients without surgery survived  these results demonstrate that performing a thoracotomy  if necessary  does not diminish the survival chance of high risk patients with severe ards  
class8	interpleural analgesia improves pulmonary function after cholecystectomy  the purpose of this study was to examine the effects of interpleural bupivacaine on analgesia and ventilatory capacity after cholecystectomy  forty two patients undergoing elective cholecystectomy were randomly assigned to two groups  one to receive interpleural administration of bupivacaine adrenaline mixture  group 1   22 patients  and the other standard administration of intramuscular meperidine  group 2   20 patients  for postoperative pain relief  the intensity of pain was evaluated by a visual analogue scale  vas  preoperatively as well as at 2  8  24 and 48 hr postoperatively  at the same time  fvc and fev1 0 measurements were obtained for all patients  the group given interpleural bupivacaine had better pain relief with mean vas of 0 6     0 9  mean     sd  1 1     1 4  0 6     0 9 and 0 8     1 2 compared with 5 2     2 2  5 8     2 7  5 5     2 2 and 4 5     1 8 for patients receiving meperidine  p less than 0 001   the patients in group 1 also had larger fvc and fev than those in group 2  fvc 22     14 5 per cent vs 32     15 2 per cent  p less than 0 005   fev1 0 25     15 5 vs 38     14 8 per cent  p less than 0 001   mean     sd   we conclude that the interpleural analgesia can achieve better pain relief with greater ventilatory capacity than a standard analgesic regimen in the first two days after cholecystectomy  
class8	improved outcomes from tertiary center pediatric intensive care  a statewide comparison of tertiary and nontertiary care facilities objective  to compare outcomes from pediatric intensive care in hospitals with different levels of resources  design  prospective  blinded comparison of outcome and care  setting  tertiary  n   3  and nontertiary  n   71  hospitals in oregon and southwestern washington  patients  all critically ill children admitted with respiratory failure and head trauma for 6 months  measurements and main results  severity of illness adjusted mortality rates were determined using admission day  physiologic profiles  pediatric risk of mortality score  and care modalities were assessed daily  the crude mortality rate of the tertiary patients was four times higher than for the nontertiary patients  23 4  vs  6 0   p less than  0001   in the tertiary patients  the numbers of outcomes were accurately predicted by physiologic profiles  observed  30 deaths and 98 survivors  predicted  29 3 deaths and 98 7 survivors  z     25  p greater than  4   however  for the nontertiary patients  the number of the deaths were significantly different than predicted  observed  20 deaths and 315 survivors  predicted  14 4 deaths and 320 6 survivors  z    2 08  p less than  05   the odds ratios of dying in a nontertiary vs  a tertiary facility were about 1 1  2 3  and 8  p less than  05  for mortality risk groups of less than 5   5  to 30   and greater than 30   patients in tertiary facilities received more  p less than  05  invasive  e g   arterial catheters  and complex  e g   mechanical ventilation  care  whereas patients in nontertiary facilities received more  p less than  05  labor intensive care  e g   hourly vital signs   conclusions  care of the most seriously ill children in tertiary pediatric icus could improve their chances of survival  
class8	reliability of the bronchoscopic protected catheter brush in the diagnosis of pneumonia in mechanically ventilated patients  objective  to assess the usefulness of the telescoping plugged catheter in the diagnosis of nosocomial pneumonia  design  prospective study  patients  a total of 103 ventilated patients with suspected pneumonia were prospectively studied over 20 months  results  the quantitative cultures of the protected brush specimen detected pulmonary bacterial infection  greater than 10 3  cfu ml  in 49  47 5   patients  subsequent follow up confirmed pneumonia in 41 patients  in only one patient was a positive protected brush specimen culture established as a false positive result  there were 54 patients with less than 10 3  cfu ml and the diagnosis was excluded in 36 of them  we identified eight patients with false negative protected brush specimen cultures  the results obtained by this technique allowed us to modify treatment in 49  47 5   patients  conclusions  the telescoping plugged catheter demonstrated significant bacterial infection in a relatively small proportion of patients in whom bacterial lung infection was suspected  this technique can be safely performed and is a sensitive and specific method to establish the cause of pneumonia  thus allowing specific treatment and the avoidance of inappropriate antibiotic therapy  
class8	high incidence of cardiopulmonary complications associated with implantation of adrenal medullary tissue into the caudate nucleus in patients with advanced neurologic disease  objective  the purpose of our study was to examine the cardiopulmonary complications of a group of patients who had undergone implantation of adrenal medullary tissue into the caudate nucleus for treatment of neurologic disease  design  prospective study with partially matched historical controls  setting  tertiary care community medical center  patients and methods  seven patients with advanced parkinson s disease and three patients with progressive supranuclear palsy underwent implantation of adrenal medullary tissue into the caudate nucleus  these patients were compared with respect to their cardiopulmonary complications with a control group who had undergone craniotomy and then compared with a control group who had undergone only abdominal surgery  results  in the study group  six patients developed major postoperative complications including development of large pleural effusions  lobar atelectasis  pneumonia  upper airway obstruction  and cardiac arrest  three patients had minor complications including development of small pleural effusions  subsegmental atelectasis  purulent bronchitis  mild congestive heart failure  and atrial flutter fibrillation  one patient had an unremarkable postoperative course  the first control group  whose only surgery was a craniotomy  had only one major complication  the second control group  the abdominal surgery control group  had one major and five minor complications  conclusion  the particular neurologic disease  its severity  and the type of surgery performed appear to be causative factors in the high incidence of complications in the study group  
class8	effect of prostaglandin e1 infusion on leukocyte traffic and fibrosis in acute lung injury induced by bleomycin in hamsters  objective  to determine whether the iv infusion of prostaglandin e1  pge1  could modify the early influx of neutrophils into bleomycin injured lungs and if that would affect subsequent development of inflammation and fibrosis  background and methods  in vivo controlled animal study performed in a university hospital pulmonary research laboratory  male syrian golden hamsters  100  to 110 g body weight  were divided into four treatment groups  a  no treatment  b  intratracheal bleomycin plus pge1 infusion  c  bleomycin plus saline infusion  d  pge1 infusion only  pge1  180 ng hr 100 g  or saline were infused iv 3 to 25 hr after intratracheal instillation of bleomycin sulfate  0 5 u 0 5 ml 100 g   total and differential counts of cells recovered by lavage  lavage fluid protein  and lung total protein and hydroxyproline levels were measured from 6 hr to 30 days later  results  pge1 infusion reduced the influx of neutrophils 6 hr after bleomycin injury by 53  compared with saline infusion  p less than  0001   but increased inflammatory cell traffic after 24 hr for 15 days  at 4 days  protein recovered in lung lavage fluid was also decreased in pge1 treated  bleomycin injured animals  reflecting reduced injury to lung permeability barriers  accumulation of lung collagen in the pge1 treated  bleomycin instilled hamsters tended to be lower than in the bleomycin injured  saline infused group at 15 and 30 days  although these differences did not achieve statistical significance  despite this fact  greater than 33  of the animals in the pge1 treated group died  possibly indicating an increased risk of sepsis in these animals  conclusions  pge1 infusion can decrease early neutrophil traffic and reduce injury to the lung permeability barriers  however  this treatment augments late inflammatory events and does not significantly alter the development of fibrosis  
class8	inhibition by methylprednisolone of leukocyte induced pulmonary damage  background and methods  the purpose of this study was twofold  the development of a chronic model of leukocyte mediated pulmonary injury and the evaluation of the protective effects of methylprednisolone  rabbits were inoculated ip with zymosan  blood gases and circulating leukocytes were evaluated  survivors were killed on day 10 for microscopic studies and for the evaluation of lung lipid peroxidation through the by product malondialdehyde  results  intraperitoneal zymosan resulted in a marked decrease of pao2 and circulating leukocytes  and increased cellularity of alveolar septa  interstitial edema  and increased lung malondialdehyde  pulmonary damage was partially prevented when methylprednisolone was administered before zymosan inoculation  but not when methylprednisolone was given 24 hr later  conclusions  the authors conclude that a local nonseptic inflammatory stimulus may provoke remote changes to the lungs and that methylprednisolone may counteract the process only if it is administered before or very early after the onset of inflammation  
class8	use of a biotinylated dna probe specific for the human y chromosome in the evaluation of the allograft lung  a cloned 3 4 kilobase dna probe derived from the heterochromatin of the y chromosome was used to investigate the regeneration and reepithelialization of allograft lungs of nine recipients who received sex mismatched donor organs  patients were monitored for varying periods of time  up to four years  by transbronchial biopsy  in situ hybridization on paraffin embedded biopsies utilizing the y probe revealed that bronchial and alveolar epithelium and arterial and venous endothelium of the peripheral lung retained a donor phenotype  irrespective of episodes of acute or chronic rejection  obliterative bronchiolitis  which are known to injure these cellular subsets  in contrast  migratory cells  lymphocytes and macrophages  gradually  at varying rates  infiltrated the allografted lungs  replacing preexisting donor elements  cases of active ob were manifested by infiltration of bronchioles by sex mismatched lymphocytes  however  in some instances  quiescent recipient lymphocytes colonized the allograft and were unassociated with histologic rejection  macrophages of similar sex seemed to cluster together within air spaces  use of a dna probe for the y chromosome and in situ hybridization techniques allow monitoring of cellular alterations over time in recipients with sex mismatched allografts  
class8	upper extremity deep venous thrombosis and pulmonary embolism  a prospective study  we prospectively evaluated the prevalence of pulmonary embolism  pe  in 30 consecutive patients with proved deep venous thrombosis  dvt  of the upper extremity  ten patients  seven male and three female  mean age  43 years  had primary dvt  and 20 patients  14 male and six female  mean age  52 years  had catheter related dvt  ventilation perfusion lung scans were routinely performed at the time of hospital admission to all but one patient  one patient was critically ill  and he died four days after dvt diagnosis because of massive pe   lung scan findings were normal in nine of ten patients with primary dvt  and they were indetermine in the remaining patient  by contrast  perfusion defects were considered highly suggestive of pe in four patients with catheter related dvt  two patients had indeterminate lung scans  and 13 patients had normal scans  we conclude that pe is not a rare complication in upper extremity dvt  and that patients with catheter related dvt seem to be at a higher risk  
class8	deep venous thrombosis  implications after open heart surgery  we reviewed the cases of 10 638 cardiac surgical patients to determine the incidence of deep vein thrombosis  dvt  after open heart surgery  ohs   seventy seven patients  0 7 percent  had dvt  group 1 included 36 patients who had dvt without pulmonary embolism  pe   occurrence was equal in either leg  anticoagulation with heparin and warfarin sodium  coumadin  was employed as treatment  extension of hospital stay was 10 8 days  group 2 consisted of 41 patients who experienced pe 9 9 days after ohs  sixteen patients had known dvt and were receiving heparin  in 25 patients  pe was the first event  risk factors for pe included perioperative myocardial infarction  16 percent   atrial fibrillation  41 percent   blood type a  70 percent   p less than 0 05   and coronary artery bypass graft  cabg   98 percent   twenty four patients were treated with anti coagulation alone  six died of recurrent pe  mortality was 25 percent  seventeen patients received anticoagulation plus inferior vena cava  ivc  interruption using a hunter balloon  there were no recurrent pes and there was one death from myocardial infarction  6 percent   deep vein thrombosis and pe are rare complications of ohs  routine prophylaxis with either heparin or warfarin is unnecessary  patients with dvt  atrial fibrillation  af   and perioperative myocardial infarction are at high risk of pe  aggressive diagnosis to identify major venous thrombi along with anticoagulation and early consideration of ivc interruption are recommended for these patients  patients who have undergone ohs and who have pe are at an unusually high risk for recurrent pe with death and are more safely treated with ivc interruption and anticoagulation than anticoagulation alone  
class8	serum leukotriene b4 levels in patients with obstructive pulmonary disease  leukotriene b4 has been found to be increased in the serum of cigarette smokers and some patients with bronchial asthma  as well as in the sputum of patients with cystic fibrosis and copd  corticosteroids supposedly may block the formation of ltb4  to determine if the effect of cs on airway disease is by reduction in ltb4  we studied serum ltb4 levels in clinically stable patients with asthma or copd who were treated with or without cs  the ltb4 was extracted from serum and assayed by radioimmunoassay  serum ltb4 concentrations  expressed as the mean     sd  were 0 36     0 15 ng ml in ten normal controls  0 56     0 18 ng ml in nine asthmatic subjects  0 67     0 2 ng ml in eight asthmatic subjects receiving cs  0 81     0 19 ng ml in seven patients with copd  and 0 97     0 29 ng ml in eight patients with copd receiving cs  serum ltb4 levels in normal controls differed significantly from all groups with copd or asthma  p less than 0 01   levels of ltb4 in asthmatic subjects differed from levels in patients with copd  p less than 0 03   and levels in asthmatic subjects receiving cs differed from subjects with copd receiving cs  p less than 0 03   concentrations of ltb4 within either the copd or the asthmatic groups were not lower in the patients treated with cs  we conclude that serum ltb4 concentrations are higher in copd than in asthma or normal controls and that administration of cs is not associated with low ltb4 levels  the beneficial effects of cs in obstructive airway disease appear to be mediated by mechanisms other than reduction of ltb4  
class8	lymphokine activated killer cell activity in lung cancer  this study evaluates local pulmonary immune effector cell lytic activity  purified lymphocyte populations were isolated from balf obtained from 18 patients with bronchogenic carcinoma  six patients with lung disorders other than cancer  and ten normal control volunteers matched for age and smoking history  these cells were evaluated for nk and lak cell lytic activity against nk resistant lak sensitive tumor targets  a549 pulmonary tumor and daudi tumor cells  and an nk sensitive tumor  k562   lak activity was detected in balf from 6 of the 18 patients with cancer  the remaining patients with cancer  the subjects with pulmonary disease other than cancer  and the normal volunteers had no detectable lytic activity  peripheral blood lymphocytes from all subjects had only nk lytic activity and did not kill the pulmonary tumor target  ams were not tumoricidal  interleukin 2  which is required for lak cell activation  was detected only in balf recovered from the six patients with pulmonary lak lytic activity  these results demonstrate that activated lak cells  capable of killing pulmonary tumor cells  are present in balf of some patients with bronchogenic carcinoma  this lytic lak cell population represents a local pulmonary response against the lung cancer in the absence of systemic tumoricidal activity  the functional status of pulmonary immune effector cells  as well as the type and quantities of cytokines in the lung determine local responsiveness to bronchogenic carcinoma and may well control the course of this disease  
class8	magnetic resonance imaging in the diagnosis of pulmonary infarction  we report for the first time  to our knowledge  mri features which could differentiate noninvasively pulmonary infarction from pneumonia  three subjects with angiographically proven pulmonary infarction showed high t1 weighted mri signals located in the embolic territory  three patients with pneumonia and one patient with emboli  but without infarction  did not have these t1 weighted images  
class8	long term therapy with deflazacort in chronic sarcoidosis  purpose  to evaluate the long term action of deflazacort  df   a new calcium sparing and bone saving corticosteroid  in chronic sarcoidosis patients needing prolonged therapy  patients and methods  40 patients with chronic histologically proved sarcoidosis requiring long term corticosteroid therapy were treated with df and followed for a mean period of 958     515 days  range 382 2  068   the indication for giving corticosteroid therapy was pulmonary impairment in most  36   but also other events including hypercalcemia  2   kidney stones  5  2 with recurrent colic   uveitis  2   lupus pernio  3   suspected heart impairment  5   hypersplenism  1   and other causes  follow up examination included serial ace  chest x ray  67ga lung scan  pulmonary function data  serum and urinary calcium levels  eleven patients  ut group  were not receiving glucocorticoids when first seen at our clinic  29 patients  pt group  were on therapy with glucocorticoids  27 wity prednisone  2 with df  for 870     1 128 days  range 27 4 310  results  in the pt group  df maintained the good results previously obtained with prednisone  in this group  chest x ray film showed improvement in 16 patients  67ga lung scan was better in 13  while worsening chest x ray film findings in 1 and 67ga lung scan in 2 was seen coincident with df tapering  respiratory function data showed a mild nonsignificant improvement  sace decreased significantly from 114 6     38 7 to 91 5     37 9 nm ml min  p less than  05   in the ut group the results were better  as expected in a population where the action of corticosteroids did not influence the first observation  fvc increased significantly from 76 3     13 0 to 89 9     19 5 percent predicted  p less than  01   the 67ga lung scan and chest x ray film findings improved in all but 1 patient  and ace dropped significantly  p less than  01  from 131 8     46 3 to 83 7     25 0  in both groups the side effects were mild  and only 2 patients discontinued the treatment  1 for gastric ulcer  and the other for amenorrhea plus a 14 kg weight gain  current status  one patient died of cancer  9 discontinued treatment  5 because therapy was no longer necessary  2 for the above described side effects  2 for non drug related reasons   4 dropped out and were last seen when taking df 22 5  18  12 and 6 mg daily respectively  twenty six are continuing the drug on a long term basis at the current mean daily dose of 12 1     7 3 mg  range 3 30   in a number of these  an attempt to discontinue df resulted in a sarcoid relapse  and df was restarted  conclusion  df is a good and safe approach to the long term corticosteroid therapy of sarcoidosis  
class8	soluble interleukin 2 receptor in sera of patients with pulmonary tuberculosis interleukin 2 receptor  the complex of il 2r alpha and or il 2r beta  is expressed mainly on t lymphocytes  and the soluble form of il 2r alpha  sil 2r alpha  has been reported to be detected in the serum of patients with lymphoproliferative disorders or disease characterized by the cellular immune reaction  we measured serum sil 2r alpha levels among patients with pulmonary diseases and found that sil 2r alpha levels were significantly elevated in patients with active pulmonary tuberculosis  1 327     209 u ml  and sarcoidosis  1 037     115 u ml  when compared with healthy volunteers  468     49 u ml  p less than 0 01   among patients with pulmonary tuberculosis  the sil 2r alpha levels were high in sera from patients with extensive parenchymal lesions on the roentgenogram  2 745     705 u ml  and patients with tuberculous pleurisy  2 111     679 u ml   in contrast  the sil 2r alpha levels in tuberculous patients with minimal lesion  455     92 u ml  or moderate lesion  1 082     189 u ml  were not significantly elevated when compared with healthy volunteers  after the treatment with antituberculosis agents  serum sil 2r alpha levels decreased in accordance with improvement of roentgenographic findings and laboratory data  these results suggest that serum sil 2r alpha level may be useful as a monitor for the disease activity in patients with pulmonary tuberculosis  
class8	pulmonary involvement in the eosinophilia myalgia syndrome  we describe the cases of three women with pulmonary involvement in the eosinophilia myalgia syndrome  the illness was characterized by elevated peripheral blood eosinophil counts  myalgias  fatigue  and dyspnea  two of three patients had bilateral infiltrates on chest roentgenograms  all three had markedly decreased carbon monoxide diffusing capacities and pulmonary hypertension  high dose prednisone therapy provided only partial resolution of the pulmonary symptoms  open lung biopsy specimens showed chronic interstitial and perivascular infiltrates in two of the patients and moderate fibrointimal hyperplasia of pulmonary vasculature in the third  high dose prednisone therapy prior to the biopsies may have modified the original histologic features  
class8	comparative study of legionella pneumophila and other nosocomial acquired pneumonias  we studied  in a prospective way  the characteristics of definitively diagnosed nosocomially acquired pneumonias in our hospital over 36 months  out of 55 cases  27 were due to legionella pneumophila and 28 to other  non legionella bacteria  the cases of legionellosis concentrated in july  august  and december  the only risk factors that showed significant differences  p less than 0 05  were general anesthesia and surgery and immunosuppressive disease  which were more frequent in the non legionella group  as were chronic liver disease and lowering of consciousness level  the absence of severe underlying disease  chronic or not  was uncommon in both groups  but more frequent in the legionella group  we observed no differences in the clinical features of the two groups  mean values of gamma glutamyltranspeptidase and total bilirubin were higher  p less than 0 05  in the non legionella group  the only x ray data that showed significant difference were pleural effusion  more frequent in the non legionella group  p less than 0 02   the mortality rate of legionellosis was 14 6 percent compared to 35 7 percent for the non legionella group  p less than 0 05   we conclude that a sure differential diagnosis based on clinical  roentgenographic and analytical features of both groups is not possible  the relatively low mortality rate of the legionella group  when compared to other series of nosocomial legionellosis  could be due to the standard use of erythromycin in the therapeutic approach to nosocomial acquired pneumonia in our hospital  
class8	adenosine deaminase in the diagnosis of tuberculous pleural effusions  a report of 218 patients and review of the literature  the activity of adenosine deaminase in the pleural fluid of 218 consecutive patients was studied  according to the etiology of exudative pleural effusions  the patients were divided into the following five groups   1  tuberculosis   2  lung cancer   3  pneumonias   4  miscellaneous  and  5  idiopathic  patients with pleural tuberculosis presented significantly higher ada activity than patients with nontuberculous pleural effusions  p less than 0 0001   the results indicated that in a population with a relatively high prevalence of tuberculosis  the analysis of ada levels in pleural effusions constitutes a useful marker for the diagnosis which  in addition  can be made quickly and cheaply  additionally  a comprehensive review of the literature on the role of ada in the diagnosis of tuberculous pleural effusions is presented  
class8	amiodarone induced pulmonary toxicity  immunoallergologic tests and bronchoalveolar lavage phospholipid content  amiodarone  a  is a widely used antiarrhythmic drug  pulmonary toxicity is the most serious adverse effect with an estimated mortality of 1 to 33 percent  in order to determine an element helpful for diagnosis  we examined four patients with amiodarone induced pulmonary toxicity  three patients treated with a  without evidence of pulmonary toxicity but with a main underlying pulmonary disease  and four healthy volunteers  daily and cumulative doses or duration of treatment were similar in the first two groups  pulmonary function tests  spirometry  co diffusing capacity  arterial blood gases   roentgenographic examinations  pulmonary biopsies or immunoallergologic tests  skin reaction  lymphoblastic transformation test and human basophile degranulation test  did not provide any discriminatory element  in apt   we observed an increased cellularity of the bronchoalveolar lavage  neither the differential cell count nor the presence of foamy macrophages were distinguishable between apt  and apt   the phospholipid composition of bal fluid showed a decreased total phospholipid and phospholipid protein ratio in all patients compared to normal subjects  these changes reflect more the severity of pulmonary disease than the specificity of the causative agent  however  we observed that the unique pl which decreases in apt  and remains normal in apt  is phosphatidyl serine   phosphatidylinositol  ps   pi   this has to be confirmed and should be evaluated at different stages of the disease to determine an eventual specific element  we conclude that there are no data currently available to establish the diagnosis of apt except perhaps for the analysis of bal pl content  
class8	utility of bronchoscopic sampling techniques for cryptococcal disease in aids  although cryptococcal pneumonia is a well recognized complication of the acquired immunodeficiency syndrome  optimal diagnostic approaches remain to be defined  during a 32 month period  october 1984 to june 1987   11 patients were diagnosed with cp at our institution  the diagnosis was established in all 11 patients from specimens obtained via fiberoptic bronchoscopy  ten  and or double lumen catheter lavage  one   direct stains of sedimented bronchoalveolar lavage were positive for organisms characteristic of cryptococcus neoformans in nine of 11 patients  transbronchial biopsies were positive  special histologic stains  in six of eight patients  bronchial washings were positive  direct smear  in seven of ten patients  the bronchial brushings were positive on stain in six of nine patients  and in one patient  a wang transbronchial needle aspirate was positive on stain  fungal cultures were positive on the bal in seven of 11 patients  and on the bronchial washings in four of ten patients  the tbbx culture samples were all negative  zero of three   the serum cryptococcal antigen titer was elevated  median   1 1024  in all eight patients in which it was assayed  our data suggest that bal and bronchial washings have a combined sensitivity on smear equal to that of tbbx and superior to that of tbbx fungal culture  the tbbx does not appear to be necessary in this setting  in addition  an elevated serum cryptococcal antigen titer appears to be an important adjunct in the evaluation of pulmonary infiltrates in aids  
class8	acute pulmonary embolism triggered by the act of defecation  pulmonary embolism associated with the act of defecation has not been previously well described  recently  we reported our experience with four patients who presented to us over a 12 month period with syncope  near syncope  or sudden death following the act of defecation  in all four cases  acute pulmonary embolism was shown to be the etiology of the defecation associated events  a retrospective chart review of all patients with the diagnosis of pulmonary embolism at our institution over a three year period yielded five additional patients with the diagnosis of defecation associated pulmonary embolism  these nine patients accounted for 6 8 percent of all patients with a discharge diagnosis of pulmonary embolism seen at our institution during the three year study period  six of the nine patients died from their defecation associated pulmonary embolism  these six deaths accounted for 25 percent of all deaths from pulmonary embolism seen at our institution during the study period  based on our experience  we suggest that the act of defecation may trigger the development of acute pulmonary embolism in some patients with deep vein thrombosis  
class8	macrophage colony stimulating factor activity in malignant pleural effusions  its augmentation by intrapleural interleukin 2 infusions  the activity of endogenous colony stimulating factor  csf  in malignant pleural effusions of lung cancer patients before and during daily intrapleural infusions of recombinant interleukin 2  il 2  was measured quantitatively by colony forming bioassay and radioimmunoassay  ria   before therapy  malignant pleural effusions had various levels of csf activities  and this csf activity was neutralized almost completely by anti m csf antibody  ria also showed that the effusions contained various amounts of m csf  daily intrapleural infusion of recombinant il 2 caused significant increase in the csf activities and m csf levels in pleural effusions  these results indicate that in vivo treatment with il 2 induces production of endogenous m csf  
class8	atopy and primary lung cancer  histology and sex distribution  atopy  defined as the ability to develop ige antibodies to commonly encountered allergens under conditions of normal exposure  has an inherited component with pleiotropic effects  an inverse relationship between the occurrence of atopy  allergy related diseases  and cancers at specific sites has been reported  the familial association of primary lung cancer is most evident among women  nonsmokers  and those with adenocarcinomas  in order to determine whether the relationship between a lower prevalence of atopy among patients with lung cancer compared to control subjects was consistent between histologic cell types  we used seven common allergens to allergy prick skin test 209 community control subjects  46 women   109 cases with primary squamous cell carcinoma of the lung  25 women   and 67 patients with primary adenocarcinomas of the lung  23 women   we have confirmed earlier reports of an inverse relationship between atopy and lung cancer risk  in analyses focusing on sex and histologic cell type  we found that women with adenocarcinomas were an exception and were as likely to be atopic as control subjects  the evidence does not support a protective role for atopy among these women  
class8	effect of fast vs slow intralipid infusion on gas exchange  pulmonary hemodynamics  and prostaglandin metabolism  intralipid  20 percent  500 ml  was infused fast  5 h  or slow  10 h  randomly in patients with lung injury to relate changes in plasma prostaglandin  pg  concentrations to gas exchange and pulmonary hemodynamics  data were collected at baseline  midpoint of infusion  and 2 h following infusion  vasodilator and vasoconstrictor pg metabolites  6 keto pgf1 alpha  and thromboxane b2  respectively  were measured in radial arterial blood samples  slow intralipid infusion increased shunt fraction  qs qt  without changing mean pulmonary artery pressure  mpap   whereas fast intralipid infusion increased mpap without changing qs qt  prostaglandin levels did not change significantly during either infusion  however  in both groups when the pg substrate was removed  hemodynamic and metabolite values decreased in parallel  in conclusion  we were unable to demonstrate a cause and effect relationship between plasma levels of 6 keto pgf1 alpha and thromboxane b2 and the observed pulmonary hemodynamic response to slow or fast intralipid infusion  
class8	auto peep during cpr  an  occult  cause of electromechanical dissociation  a 64 year old man with severe copd developed refractory nonperfusing sinus rhythm after intubation and positive pressure ventilation  fifteen minutes after resuscitative efforts were halted  the patient was noted to have spontaneous respirations and blood pressure  suggesting that dynamic hyperinflation was responsible for the observed electromechanical dissociation  emd   we recommend a brief trial of apnea for patients with copd and emd when conventional measures are unsuccessful  
class8	endobronchial actinomycosis simulating bronchogenic carcinoma  diagnosis by bronchial biopsy  five cases of actinomycosis of the main bronchi or trachea which were suggestive clinically of bronchogenic carcinoma are described  in four patients the correct diagnosis was made by a bronchial biopsy or wash  or both  three of them recovered following antibiotic treatment  and one died a few days after bronchoscopy  in one case the actinomyces were found in the bronchial wash retrospectively following diagnosis of pulmonary actinomycosis in the lobectomy specimen  a concomitant endobronchial lipoma was found in one of the patients  the diagnosis of pulmonary actinomycosis by bronchial biopsy may save the patient major surgical intervention  
class8	the acute and insidious onset of pulmonary metastatic transitional cell carcinoma  transitional cell carcinoma is a common urologic neoplasm  although pulmonary metastases from this tumor are often not appreciated clinically  they are frequently documented in autopsy studies  therefore  the clinical recognition of this condition can be problematic  to illustrate this point  we present three patients with progressive unexplained dyspnea and histories of transitional cell carcinoma  since ineffective and possibly detrimental therapeutic approaches may be initiated  a high index of suspicion for pulmonary metastatic embolization must be maintained  early histologic identification of these metastatic emboli and initiation of effective chemotherapy may prove beneficial for improved quality of life  
class8	pulmonary embolism presenting as exercise induced hypotension  a 68 year old man with remote history of previous myocardial infarction presented with a four week history of intermittent dyspnea  after developing hypotension during an exercise tolerance test  he underwent cardiac catheterization  revealing significant pulmonary hypertension and two vessel coronary artery disease  pulmonary angiography confirmed the presence of pulmonary emboli which partially resolved after thrombolytic therapy  subsequent treadmill testing confirmed the absence of exercise induced hypotension two months following treatment  this case underscores the importance of considering pulmonary embolism as a potential cause of exercise induced hypotension  since it can be successfully treated with thrombolytic agents weeks after the initial onset of symptoms  
class8	spontaneous pneumothorax in aids patients with recurrent pneumocystis carinii pneumonia despite aerosolized pentamidine prophylaxis  aerosolized pentamidine prophylaxis for pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome  aids  may predispose these patients to recurrent apical pneumocystis infection  bullous changes and pulmonary cysts develop in the lung apices due to repeated episodes of inflammation and cytotoxic effects of hiv on pulmonary macrophages  these changes progress despite prophylaxis against recurrent pneumocystis infection with aerosolized pentamidine  increasing the risk of spontaneous pneumothorax  two cases are presented of bilateral pneumothoraces in patients with aids and recurrent p carinii pneumonia despite aerosolized pentamidine prophylaxis  patients receiving aerosolized pentamidine prophylaxis for pneumocystis pneumonia appear to have an increased risk of pneumothorax due to recurrent apical infections with p carinii  
class8	pathologic bronchial vasculature in a case of massive hemoptysis due to chronic bronchitis  the cause of bleeding in a patient with recurrent massive hemoptysis was not apparent after bronchoscopy and gross examination of the lobectomy specimen  histologic submission of all major bronchi uncovered dilated  tortuous bronchial arteries just below the bronchial mucosa with sites of both current and healing arterial rupture  this bronchial arterial abnormality is common to several chronic pulmonary diseases  but is rarely diagnosed as a cause of massive hemoptysis  careful pathologic examination of major bronchi in the setting of hemoptysis of unknown causation is recommended  
class8	bilateral reexpansion pulmonary edema following unilateral pleurocentesis  acute ipsilateral pulmonary edema following reexpansion of the lung after pleurocentesis or pneumothorax is a well described entity  we report the unusual occurrence of bilateral pulmonary edema following unilateral pleurocentesis in a young male without heart disease  various hypotheses regarding the mechanism of reexpansion pulmonary edema include increased capillary permeability due to hypoxic injury  decreased surfactant production  altered pulmonary perfusion and mechanical stretching of membranes  this case suggests that forces leading to ipsilateral reexpansion pulmonary edema also affect the contralateral lung  
class8	treatment of atelectasis with selective bronchial suctioning  use of a curved tipped catheter with a guide mark  we applied our technique of selective bronchial suctioning  sbs  for the treatment of atelectasis  at  of middle and lower lobes  nine patients with refractory ats were successfully treated  we considered that sbs using a curve tipped catheter with a guide mark  ctcgm  is the technique of choice for the treatment of refractory at when conventional respiratory therapy is not effective and a bronchoscopist is not available  
class8	asthma and chronic obstructive lung disease  a pharmacologic approach  changing concepts are emerging that should improve our ability to adequately treat asthma  this volume of disease a month reviews the triggers and the role of inflammation in asthma  and outlines the treatment of acute asthma as well as the chronic management of reversible obstructive airways disease  there is general agreement that sympathomimetics are the treatment of choice for acute severe asthma  the role of theophylline for acute symptoms has been downplayed  and the role of corticosteroids continues to be debated  however  most authorities agree that patients with severe asthma will benefit from the addition of corticosteroids to the program  for the chronic management of asthma  appreciation that inflammation is a perpetuating feature suggests that treatment should generally be directed toward the inflammation  corticosteroid aerosols have taken on greater prominence and have been advocated as the first line of approach  new concepts regarding the role of allergy in the perpetuation of asthma and the role of immunotherapy in its amelioration also have emerged  medications not previously thought to be beneficial are being actively investigated  they include gold  methotrexate  and even intravenous gamma globulin  
class8	severe preeclampsia presenting as dysphonia secondary to uvular edema  a case report  in addition to hypertension and proteinuria  generalized edema is seen commonly in women with severe preeclampsia  a patient presented to us at term with the complaint of dysphonia  upon examination she appeared to be clearly preeclamptic and had a grossly edemetous uvula  which we think occurred secondary to generalized edema  this case might be the first reported one of preeclampsia presenting as dysphonia and of uvular edema in association with preeclampsia  
class8	accelerated silicosis in scottish stonemasons  a small group of stonemasons working with sandstone was exposed to levels of respirable quartz up to 130 times the workplace standard over a period of up to 6 years  two died of accelerated silicosis  a disease that caused serious diagnostic difficulties and was initially not recognised by the doctors of the then department of health and social security medical boarding centre  respiratory diseases   previous descriptions of this disease in the uk date back to the years of the industrial revolution  late 18th century   one other mason on the site proved to have an earlier stage of accelerated silicosis and two had radiographic changes of early classic silicosis  regulations intended to prevent silicosis have been in place in the uk for many decades and were strengthened by the health and safety at work act in 1974  although the workers had been aware of a health risk from quartz  they had not been able to persuade management to take effective preventive action until serious illness had occurred  current pressures on management to cut overheads and to achieve maximum productivity could  as in this instance  lead to neglect of health and safety standards  
class8	epidemiology of acute respiratory infections in young children from thailand  a prospective evaluation of the epidemiology and presentations of acute respiratory infections in children younger than 5 years of age admitted to children s hospital bangkok  1988 to 1989  was supported by the world health organization  there were 226 patients with the inclusion criteria  1 to 5 years of age  duration of illness less than 2 weeks  no prior antibiotic therapy  and low socioeconomic status  the disease categories included  croup  19 cases  bronchiolitis  60 cases  and pneumonia  147 cases  pathogens isolated were  respiratory syncytial virus  40   parainfluenza iii  1   influenza b  1   and adenovirus  1   bacterial infections were proved in 23 cases  no significant differences in clinical features between bacterial and viral pneumonia were found  interstitial radiographic patterns were more common in viral pneumonia whereas alveolar patterns were more common in bacterial pneumonia  however  91  of mixed radiographic patterns  interstitial and alveolar  in chest films were from viral pneumonia  
class8	viral pneumonia in the first month of life  we performed a 5 year review of 40 patients less than or equal to 30 days of age with viral pneumonia  isolates included respiratory syncytial virus  55    enteroviruses  15    rhinoviruses  15    adenoviruses  10    parainfluenza virus  7 5   and herpes simplex virus  5    most infants were previously healthy but had ill family members  nine were born at less than 37 weeks of gestation  symptoms and signs included tachypnea  decreased feeding  cough  cyanosis  lethargy  retractions  apnea  bradycardia  seizures and depressed consciousness  seasonality and clinical features  but not radiographic patterns  suggested specific pathogens  patients were moderately to severely ill  the median duration of hospitalization was 7 days  therapies administered included oxygen  90    mechanical ventilation  45    blood transfusions  25   and supplemental oxygen after discharge  27    the case fatality rate was 7 5   prematurity  ill appearance at presentation  lobar consolidation and adenovirus infection were risk factors for severe disease  
class8	klebsiella pneumonia in the modern era  clinicoradiographic correlations  a classic clinical and radiographic picture of klebsiella pneumonia has emerged in the literature  patients are typically male  older than 48 years  and have a history of chronic alcoholism  the majority of these pneumonias are community acquired  bulging interlobar fissures and cavitation are radiographic findings said to be distinctive for klebsiella pneumonia  we prospectively studied 15 cases of bacteremically proven klebsiella pneumonia and found clinical and radiographic features strikingly different from those described in the literature  immunosuppression  from corticosteroids  cytotoxic chemotherapy  neutropenia  hematologic malignancy  and transplantation  now rivals alcoholism as the primary risk factor  cases tended to be nosocomial rather than community acquired  neither bulging interlobar fissure nor cavitation was seen in any case  the right upper lobe was involved in 11 of our 15 cases  pneumonia due to klebsiella oxytoca was more likely to be isolated from patients with bilateral infiltrates  while klebsiella pneumoniae was more likely in patients with unilateral infiltrates  
class8	adenotonsillectomy in children with sickle cell disease  the pediatric patient with sickle cell disease risks having a vasoocclusive episode during adenotonsillectomy under general anesthesia  with proper patient selection and appropriate perioperative management  adenotonsillectomy can be accomplished safely in children with sickle cell disease  we review the management of 10 children with sickle hemoglobinopathies who had adenotonsillectomy  indications for surgery were recurrent streptococcal infections in four and obstructive sleep apnea in six of these children  no complications resulted from any of these procedures  and the mean length of postoperative hospitalization was 2 4 days  the principal feature of preoperative management was the transfusion of red blood cells to suppress the patient s endogenous erythropoiesis and to reduce the concentration of sickle cell hemoglobin to less than 30   though a prospective  multi institutional clinical trial will ultimately be required to settle the issue of the safest preoperative management of children with sickle cell disease  balancing the risks of transfusion related complications against anesthesia related complications  our experience supports the operative safety of hypertransfusion therapy in children with sickle cell disease  
class8	giant cell interstitial pneumonia  giant cell interstitial pneumonia is a distinctive and uncommon form of interstitial pneumonia  it is distinguished by the prominence of large  actively phagocytic alveolar giant cells of histiocytic origin in the presence of chronic interstitial pneumonia  multinucleated type 2 granular pneumocytes are also identified  the multinucleated cells lack viral intranuclear inclusions of the type seen in measles pneumonia  giant cell interstitial pneumonia may be idiopathic or it may occur with occupational exposure to hard metals or cobalt  we report this case to give recognition to an uncommon interstitial pneumonia  
class8	necrotizing tracheobronchitis  complication of mechanical ventilation in an adult  a 51 year old woman had localized interstitial pneumonia that rapidly progressed to involve all lung fields  after 9 days of conventional mechanical ventilation  pneumothorax developed in the presence of an obstruction of the right main bronchus  bronchoscopy and endobronchial biopsies revealed ntb involving the tracheobronchial tree distal to the tip of the endotracheal tube  with complete obstruction of the right main bronchus by hard  eschar like material  tracheal mucosa proximal to the tip of the endotracheal tube was normal  subsequent bronchoscopy  20 days later  showed marked resolution of ntb  though a frequent complication of mechanical ventilation in the neonate  ntb as a complication of conventional mechanical ventilation has not previously been recognized in an adult  necrotizing tracheobronchitis should be suspected in adults who have had mechanical ventilation and who are experiencing ventilatory difficulties  after routine problems have been treated or excluded  
class8	cavitary pneumocystis carinii pneumonia in patients receiving aerosol pentamidine prophylaxis  we have described two patients with aids who had cavitary pneumocystis carinii pneumonia while receiving aerosolized pentamidine prophylaxis  this is the first report of this complication  neither patient showed a clinical response to subsequent use of pentamidine either intravenously or by aerosol followed by intravenous use  clinicians should be aware of the possibility that cavitary pneumonia in patients receiving aerosolized pentamidine may be due to p carinii  
class8	embolism of cerebral tissue  a cause of coagulopathy and cerebral infarction  report of a case  we report a case of potentially survivable closed head injury  which was complicated by disseminated intravascular coagulation and bilateral cerebral infarction  autopsy disclosed pulmonary emboli composed of cerebral tissue  we suggest that the entry of brain tissue into the systemic blood circulation caused severe disseminated intravascular coagulation  with consequent thrombosis of cerebral veins and spreading infarction  
class8	return of tuberculosis  screening and preventive therapy approximately 25 percent of individuals exposed to mycobacterium tuberculosis become infected  of those  about 10 percent will develop clinically active tuberculosis at some time in their lives  the tuberculin skin test should be used to screen all patients  especially those at greatest risk of contracting the disease  such as the young and the old  and those with weakened immune systems from poor nutrition  alcohol and drug abuse  chronic illness and human immunodeficiency virus infection  depending on the characteristics of the local population and individual medical risk factors  a reaction  induration  between 5 and 15 mm  or more  generally represents infection  isoniazid therapy in persons with positive skin tests will decrease the risk of disease by 60 to 80 percent  family physicians will play a critical role in efforts to eliminate tuberculosis from the united states by the year 2010  
class8	an evaluation of the use of the statewide planning and research cooperative system of new york state as a resource planning tool for hiv infection  hospital discharge records of patients with pneumocystis carinii pneumonia  pcp  in new york state were studied to determine whether cases of human immunodeficiency virus  hiv  infection were identified  we estimate that as many as 13 percent of hospitalizations of patients with pcp in 1987 and 10 percent of those in 1988 were not appropriately identified as hiv related  identification of pcp as hiv related was a function of a hospital s volume of pcp admissions  
class8	survival trends of people with aids in washington state  survival rates of 609 cases of acquired immunodeficiency syndrome  aids  in washington state diagnosed between 1982 and 1987 according to pre 1987 aids surveillance definition were analyzed  people with a primary diagnosis of kaposi s sarcoma survived longer than those with pneumocystis carinii pneumonia  both groups survived longer than those with other diagnoses  median survival increased from 11 3  to 12 5  to 20 8 months for cases diagnosed in or before 1985  during 1986  and during 1987  respectively  
class8	adult respiratory distress syndrome  basic scientists and clinicians have written numerous articles on the diverse causes of adult respiratory distress syndrome  ards   there is no specific diagnostic test for ards  the condition is characterized by interstitial lung edema  reduction in lung compliance  alveolar and small airway closure  decrease in functional residual capacity  and persistent hypoxia with increasing amounts of pulmonary blood flow coursing through nonventilated or poorly ventilated alveoli  recent studies have emphasized the roles of macrophages and polymorphonuclear neutrophils in lung defense and injury  advances in understanding the pathophysiology of ards have produced little significant change in the clinical management of the syndrome  there is no specific treatment for ards  the cornerstone of therapy is the early recognition and elimination of initiating factors such as sepsis  ards is not a single disease process  but appears to represent a final common pathway for the manifestation of a variety of lung injuries  the goal of therapy is to eliminate the predisposing condition and support the patient  new modes of ventilatory and pharmacologic therapy are presented  
class8	gastro oesophageal reflux during elective laparoscopy  an oesophageal ph electrode was used to record gastro oesophageal reflux in 73 women who had elective laparoscopy for various gynaecological procedures  no refluxes were recorded during the 63 procedures from which results could be analysed  the upper 95  confidence limit from this observation is 3 in 63  4 8    two of the excluded women refluxed during episodes of hiccough that occurred shortly after induction of anaesthesia  tracheal intubation may be required during laparoscopy  although the need to protect against the possibility of aspiration of gastric contents may not be a valid reason unless  with the same logic  it is suggested that all patients who hiccough should be intubated  
class8	aspiration pneumonia and the laryngeal mask airway a case of aspiration pneumonia is reported after the use of a laryngeal mask airway in a young woman undergoing an elective cholecystectomy  the case illustrates the hazards of regurgitation with the laryngeal mask airway and the need for further evaluation when used with controlled mechanical ventilation  
class8	atlanto axial subluxation in down s syndrome  a case of atlanto axial subluxation in a patient with down s syndrome is described  the gradual deterioration in the patient s locomotor ability caused a delay in diagnosis  patterns of presentation of this condition are discussed  
class8	quantitation of abnormal 67ga uptake in pulmonary interstitial vascular disease  a new test to detect diffuse lung disease  gallium 67 has been used as a modality to diagnose and follow the clinical course of diseases such as tumors  infections  inflammatory disorders  and interstitial lung disease  it has been appreciated  however  that mild to moderate changes in scan activity  when these disorders are followed over time  are less than optimal  spect  single photon emission computed tomography  scanning is a new technique designed to obviate this problem  spect scanning utilizes computer acquisition to provide three dimensional scanning and the additional benefit of colorization to aid in discerning differences of uptake  spect scanning was performed on 22 patients with interstitial lung disease of various etiologies  additionally  7 patients had follow up spect scanning to determine their response to treatment  two patients are presented as examples  
class8	heparin induced thrombocytopenia  a case report  the authors report a case of heparin induced thrombocytopenia  in whom massive pulmonary embolism occurred in spite of heparin anticoagulation  successful pulmonary thrombectomy was carried out under cardiopulmonary bypass  with limitation of platelet clumping during bypass by aggregation inhibitors  this report is a comprehensive contribution to a better understanding of this rare immunoallergic complication of heparin administration  with a high incidence of serious thromboembolic events  the optimal management for cases of unavoidable reexposure to heparin is discussed  
class8	mechanisms of gas exchange impairment in idiopathic pulmonary fibrosis  to investigate the mechanisms of pulmonary gas exchange impairment in idiopathic pulmonary fibrosis  ipf  and to evaluate their potential relationship to the co diffusing capacity  dlco   we studied 15 patients with ipf  mean dlco  52  of predicted  at rest  breathing room air and pure o2  and during exercise  we measured pulmonary hemodynamics and respiratory gas exchange variables  and we separated the ventilation perfusion  vaq  mismatching and o2 diffusion limitation components of arterial hypoxemia using the multiple inert gas elimination technique  at rest va q mismatching was moderate  2 to 4  of cardiac output perfusing poorly or unventilated lung units   and 19  of aapo2 was due to o2 diffusion limitation  during exercise va q mismatch did not worsen but the diffusion component of arterial hypoxemia increased markedly  40  aapo2  p less than 0 005   we observed that those patients with higher pulmonary vascular tone  more release of hypoxic pulmonary vasoconstriction  showed less pulmonary hypertension during exercise  p less than 0 05   less va q mismatching  at rest  p less than 0 005  and during exercise  p less than 0 0025    and higher arterial po2 during exercise  p   0 01   we also found that dlco corrected for alveolar volume  kco  correlated with the mechanisms of hypoxemia during exercise  va q mismatching  p less than 0 025  and o2 diffusion limitation  p less than 0 05   and with the increase in pulmonary vascular resistance elicited by exercise  p less than 0 005   in conclusion  we showed that the abnormalities of the pulmonary vasculature are key to modulate gas exchange in ipf  especially during exercise  
class8	pneumocystis carinii pneumonia and respiratory failure in aids  improved outcomes and increased use of intensive care units  to determine whether the outcome of intensive care for patients with aids  pneumocystis carinii pneumonia  pcp   and respiratory failure has changed  we studied patients admitted to the intensive care units an san francisco general hospital from 1981 to 1988  we compared the course of patients with pcp and respiratory failure admitted to the intensive care unit from 1986 to 1988 with a similar cohort hospitalized from 1981 to 1985  the hospital survival rate for the 35 patients in the 1986 to 1988 cohort was 40   compared with 14  for the 42 patients in the 1981 to 1985 cohort  p less than 0 01   age  episode of pcp  time since aids diagnosis  anti pcp therapy  and important clinical variables were similar in both cohorts  corticosteroids were used commonly in the recent era  patients who received steroids had an in hospital survival rate of 46   compared with 22  for those who did not receive steroids  p   ns   in a stepwise logistic regression model  icu care in the recent era and higher serum albumin at the time of icu admission were the only variables significantly associated with survival  the hospital survival of patients with pcp and respiratory failure has improved  the improvement could not be explained by patient selection or by better anti pcp therapy  the apparent beneficial effect of corticosteroids deserves further study  the improvement in icu outcome was reflected in increased icu utilization by patients with aids  pcp  and respiratory failure  
class8	increased levels of oxidized methionine residues in bronchoalveolar lavage fluid proteins from patients with idiopathic pulmonary fibrosis  phagocytic cells are believed to play a crucial role in the development of inflammatory lung diseases  we assumed that the oxidation of methionine  met  to methionine sulfoxide  met o   by oxygen derived free radicals released from phagocytes is one parameter to identify the oxidative mechanisms of lung injury  to test this hypothesis we determined the molar ratio of met o  met in the soluble protein fraction of bronchoalveolar lavage  bal  fluids from healthy nonsmokers and from nonsmoking patients with idiopathic pulmonary fibrosis  ipf  or sarcoidosis  the met o  met ratio of the healthy nonsmoker group  n   11  was 0 046     0 008  mean     sem   in contrast  the met o  met ratio of the nonsmoking ipf group  n   11  was significantly increased to 0 223     0 053  p less than 0 0002   the bal fluids of this group showed strongly increased numbers of neutrophils but normal numbers of alveolar macrophages  am   in the sarcoidosis group  n   10  the met o  met ratio  0 048     0 010  was not significantly different from control values  a close relationship was found between the met o  met ratios and the relative as well as the absolute neutrophil counts  r   0 86  p less than 0 0002  n   22   in contrast  no significant correlation was found between the met o  met ratios and the absolute am counts  r   0 22  p   0 32  n   22   we conclude that mechanisms of oxidative lung injury in ipf can be characterized by oxidation of met and that this oxidation may be mediated by neutrophils  
class8	immunoglobulin g antineutrophil cytoplasmic antibodies are produced in the respiratory tract of patients with wegener s granulomatosis  wegener s granulomatosis  wg  is a small vessel vasculitis of unknown etiology that usually involves the upper and lower respiratory tract and the kidneys  recently  an association has been made between the presence of serum antineutrophil cytoplasmic antibodies  anca  and wg  because wg frequently involves the lung  we sought to evaluate bronchoalveolar lavage  bal  fluids obtained from 14 patients with wg for the presence of anca  immunoglobulin  ig  g anca was found in the bal with the same staining patterns as observed in the serum  patients with active disease had the highest serum and bal igg anca titers  iga or igm anca was not detected in the serum or bal of these patients  protein analysis of bal fluid revealed that patients with active  untreated wg had approximately a fourfold elevation in total protein  41 3 versus 10 5 mg dl   with a disproportionately greater increase in the ratio of igg to albumin  bal igg index   1 49  normal   0 74  p   0 027   the increase of the igg index in patients with active wg suggests that local production of igg anca occurs in the lungs  
class8	size distribution of human lung elastin derived peptide antigens generated in vitro and in vivo  the protease antiprotease hypothesis of emphysema development suggests that degradation of elastin in the lung interstitium may give rise to abnormal quantities of circulating elastin derived peptides  edp  during periods of inflammation  recent studies have shown a relationship between emphysema and high levels of edp in human plasma  this report characterizes elastin digests on the basis of antigenicity  size  and method of preparation  as well as the size distribution of edp found in the plasmas of nonsmokers  smokers  and emphysema patients  gel filtration of elastin digests prepared by hydrolysis of human lung elastin using a low  1 500  ratio of neutrophil elastase to elastin generated a broad protein peak of approximately 70 000 daltons  in contrast  a high  1 25  ratio of neutrophil elastase to human lung elastin gave a broad protein peak  with a size distribution in the 10 000 to 30 000 dalton range  this digest showed distinct immunochemical properties  a polyclonal antibody directed against the low ratio digest showed a minimum detection of 2 ng ml for the homologous antigen but required 1 000 ng ml of the high ratio digest for detectable inhibition in an indirect elisa assay  gel filtration of plasmas from normal nonsmokers and the majority of normal smokers revealed a single immunoreactive edp fraction of approximately 70 000 daltons  plasmas from selected normal smokers and emphysema patients with high levels of circulating edp  greater than 90 ng ml  fractionated into a complex pattern of peptides in which the 70 000 dalton component represented 50  of the immunoreactive material and several lower molecular weight peptides represented the remaining circulating elastin antigens  
class8	early post treatment with pentoxifylline or dibutyryl camp attenuates escherichia coli induced acute lung injury in guinea pigs  we examined effects of early post treatment with the methylxanthine pentoxifylline  ptxf   or the cell permeable adenosine 3   5  cyclic monophosphate  camp  analog dibutyryl camp  db camp  on escherichia coli induced acute lung injury in guinea pigs  acute lung injury was assessed by measurements of lung water  lung wet dry weight ratio  w d ratio   the concentration ratio of 125i albumin in bronchoalveolar lavage  bal  fluid and lung tissue compared with plasma  albumin index  bal ai or tissue ai   and total differential leukocyte count in bal fluid  mean arterial pressure  pa  and peripheral wbc counts were monitored continuously over the 8 h experiment  septicemia was induced by a bolus injection of 2 x 10 9  kg live e  coli  thirty minutes later the animals received a bolus injection followed by continuous infusion of ptxf  20 mg kg   20 mg kg h  n   8  or db camp  2 mg kg   2 mg kg h  n   8  or saline  septic control  n   8   nonseptic control groups were also studied  the lung w d ratio  bal ai  lung tissue ai  and bal leukocyte count increased significantly in the septic control group  the ptxf septic and db camp septic groups showed no significant increase in lung w d ratio  bal ai  and lung tissue ai  however  there was no difference in bal total and differential leukocyte count as compared with the septic control group  ptxf and db camp had no effect on e  coli induced changes in peripheral wbc count and pa  comparison in vitro experiments demonstrated that ptxf and db camp inhibited the endotoxin induced  e  coli  chemiluminescent response of isolated guinea pig polymorphonuclear leukocytes  pmn   
class8	a ten year follow up study of cotton textile workers  a follow up study of respiratory function in cotton textile workers was performed 10 yr after the original cross sectional study  1975 to 1985   there were 35 nonsmoking female and 31 smoking male textile workers restudied from the original group of 116  the majority of those lost to follow up had left the industry  the prevalence of byssinosis among the female workers at the time of follow up was 15 35  42 9   compared with 8 35  22 9   at the time of the initial study  p   0 063   for men the byssinosis prevalence at follow up was 16 31  51 6   compared with 8 31  22 9   at the time of the initial study  p   0 03   similarly  the prevalence of almost all other respiratory symptoms was significantly higher at the follow up than at the time of the initial study  significant across shift decrements in fev1 and fvc were documented at both surveys  the mean annual decline in ventilatory capacity was greater than expected for both female  fvc   0 036     0 005 l yr  fev1   0 059     0 009 l yr  and male workers  fvc   0 059     0 008 l yr  fev1   0 068     0 006 l yr   mean     se   the mean total airborne dust concentration measured at the time of the follow up study was 3 95 mg m3 with an average respirable dust concentration of 0 97 mg m3  we conclude that continued exposure to high dust concentrations in the cotton textile industry is associated with an increasing prevalence of respiratory symptoms and progressive impairment of lung function  the increase in respiratory impairment was seen both in smokers and nonsmokers  
class8	relationship of respiratory symptoms and pulmonary function to tar  nicotine  and carbon monoxide yield of cigarettes  the data from consecutive surveys of the tucson epidemiologic study  1981 1988  were used to evaluate the relationship in cigarette smokers of respiratory symptoms and pulmonary function to tar  nicotine  and carbon monoxide  co  yields of the cigarette  there were 690 subjects who reported smoking regularly in at least one survey  over age 15  after adjustment for intensity and duration of smoking and for depth of inhalation  the risk of chronic phlegm  cough  and dyspnea were not related to the tar and nicotine yields  in 414 subjects with pulmonary function tested in at least one of the three surveys the spirometric indices used were significantly related to the daily dose of tar  nicotine  and co  product of the cigarette yield and daily number of cigarettes smoked   the effects were more pronounced for past than for current doses  however  the differentiation of pulmonary function due to various yields of cigarettes was small in comparison to the difference in pulmonary function between smokers and nonsmokers  
class8	initial airway function is a risk factor for recurrent wheezing respiratory illnesses during the first three years of life  group health medical associates  we recently reported a significant relationship between lung function measured prior to any lower respiratory tract illness and subsequent wheezing illnesses during the first year of life  n engl j med 1988  319 1112 7   follow up has continued for this group of infants during the second and third years of life  when compared with never wheezers  infants who wheezed during the first year of life and had at least one additional lower respiratory illness had 22  lower initial levels of an indirect index of airway conductance derived from the shape of tidal breathing curves  p less than or equal to 0 01   22  lower respiratory conductance  p less than or equal to 0 05   25  lower maximal flows at the end expiratory point  p less than or equal to 0 01   and 10  lower functional residual capacity  p less than or equal to 0 05   infants who wheezed only once during the first 3 yr of life or who started wheezing during the second year of life had normal tidal breathing curves but significantly lower maximal expiratory flows  p less than or equal to 0 05   their functional residual capacity was also lower than that of never wheezers  p less than or equal to 0 05   we conclude that diminished initial airway function may be a predisposing factor for recurrent wheezing respiratory illnesses starting in the first year of life  infants who will have only one wheezing respiratory illness or who will start wheezing after the first year of life seem to have lower levels for some but not for all lung function tests performed in this study  
class8	the normal range of diurnal changes in peak expiratory flow rates  relationship to symptoms and respiratory disease  measuring peak expiratory flow rates  pefr  several times a day can provide an objective assessment of functional changes relative to environmental or occupational exposures  this report describes the pattern of diurnal changes in pefr in a reference population  and defines ranges of  normal  between  and within day variability  an index of diurnal changes was defined as the ratio between maximal and minimal values  where the maximal value was restricted to pefr measured at noon or in the evening  n  e  and the minimal value was restricted to the morning or at bedtime  m  b   a ratio greater than normal represented an exaggeration of the normal diurnal pattern in pefr  normal limits  based on the ninety fifth percentile in the reference population  were larger for children  130   than for adults 15 to 35 yr of age  117   and those older than 35 yr of age  118    the meaningfulness of excessive diurnal changes in pefr was examined by relating this ratio  max min   and a similar measure  the amplitude percent mean  to chronic respiratory symptoms and diseases in 938 adults and children who recorded pefr values 2 to 4 times per day for as long as 14 days  there was a strong relationship of diurnal changes in pefr that exceed normal limits with physician confirmed asthma  relative risk of 2 99 with max min   with exertional dyspnea  grade 2    and with more frequent reporting of acute symptoms of wheeze  attacks of wheezing dyspnea  cough  and chest colds  in addition  those exceeding the normal limits had about 2 9 times greater risk of having a fev1 below 80  of predicted  and nearly 7 times greater risk of being below 70   
class8	protective effect of theophylline on bronchial hyperresponsiveness in patients with allergic rhinitis  disorders of the upper respiratory tract  particularly allergic rhinitis are commonly associated with bronchial hyperresponsiveness  the latter may be responsible for chronic cough  a common symptom in patients with allergic rhinitis  which  as previously shown  can be the sole presenting manifestation of bronchial hyperresponsiveness  theophylline is widely used in patients with asthma for its bronchodilator effect  whereas its action on bronchial reactivity is controversial  the aim of this study was to determine the effect of theophylline administration on bronchial hyperresponsiveness in patients with allergic rhinitis complaining of chronic cough  fourteen patients were studied  all of them were judged atopic on the basis of positive skin tests to common allergens  during control  spirometry  flow volume curves and specific airway conductance  sgaw  were measured  bronchial challenges were then performed with increasing concentrations of carbachol  and dose response curves were constructed  the concentration of carbachol  which decreased sgaw by 35  from baseline  pd35  was determined by interpolating from the dose response curve  after control measurements patients received in a randomized  double blind crossover fashion either theophylline 10 mg kg day orally or placebo for 30 days  measurements were then redone  after a washout period of 8 days the measurements were repeated  and patients received theophylline or placebo for a second period of 30 days  measurements were again performed at the end of this last study period  during control all patients had normal baseline lung function data and showed marked bronchial hyperresponsiveness  pd35 amounting to 26     7 micrograms of carbachol  normal value greater than 160 micrograms   no significant changes in pd35 were noted after placebo and washout when compared with control values  
class8	airways inflammation in nocturnal asthma  nocturnal asthma is a frequent problem  but the mechanism is unclear  we investigated the possibility that airways inflammation occurred during the night  bronchoalveolar lavage fluid was analyzed in asthmatic patients with  n   7  and without nocturnal asthma  n   7  at 1600 and 0400 h  the nocturnal asthma group had an increase in the total leukocyte count  24 0     7 0 to 41 1     9 9 x 10 4  cells ml  p less than 0 05   neutrophils  1 1     0 6 to 3 7     1 5 x 10 4  cells ml  p less than 0 05   and eosinophils  0 5     0 1 to 1 7     0 7 x 10 4  cells ml  p less than 0 05  from 1600 to 0400 h  cellular components for the non nocturnal asthma group did not change  between groups  the 1600 h cells were similar  at 0400 h the nocturnal asthma group had significantly higher total leukocyte  neutrophil  eosinophil  lymphocyte  and epithelial cell counts  for all subjects  the overnight fall in peak expiratory flow rates was correlated to the change in neutrophils  r   0 54  p less than 0 05  and eosinophils  r   0 77  p less than 0 05   we conclude that the nocturnal worsening of asthma has an associated cellular inflammatory response that is not seen in patients without overnight decrements in lung function  this inflammatory response together with epithelial damage may be important factors in the etiology of nocturnal asthma  
class8	lymphokine induced airway hyperresponsiveness in the rat  we evaluated the potential role of the lymphocyte in chronic airway inflammation and responsiveness by repeated administration to rats of interleukin 2  il 2   the principal lymphokine responsible for lymphocyte proliferation  lewis rats  mean weight  184     2 g  received either 120 000 units of il 2  n   10  or vehicle  n   7  subcutaneously twice a day for 4 5 days  animals were anesthetized with urethane and intubated for measurements of pulmonary resistance  rl  and airway responsiveness to aerosol methacholine  mch   lung lavage was performed  the animals were exsanguinated  and the lungs were fixed in 10  formalin  histologic edema and the extent of infiltration of the bronchi  pulmonary veins  and arteries by cells was scored blindly  il 2 increased airway responsiveness to mch  the concentrations of mch causing a doubling of rl were 0 14 versus 1 39 mg ml  geometric mean  for the il 2 and vehicle group  respectively  p   0 001   il 2 significantly increased total cellular return and the percentage of lymphocytes  neutrophils  and eosinophils in lavage  il 2 caused edema and a mixed cellular infiltration of the bronchovascular tree  lymphocytes predominated around the airways and veins  a correlation  r   0 50  was present between airway responsiveness and airway inflammation but not with edema or vascular infiltration  release of il 2 by lymphocytes in the airways may be an important mediator of airway hyperresponsiveness  
class8	acute effects of interleukin 2 on lung mechanics and airway responsiveness in rats  we studied the acute effects of interleukin 2  il 2   the principal lymphokine responsible for lymphocyte proliferation  on lung mechanics and airway responsiveness to methacholine  mch  in rats  lewis  n   12  and fisher 344  n   13  rats were anesthetized and intubated  and intravenous and intra arterial lines were inserted  il 2  750 000 u kg  was infused intravenously over 2 to 4 min into seven lewis and seven fisher rats  and vehicle alone was administered to five lewis and six fisher rats  blood pressure  heart rate  respiratory frequency  f   tidal volume  vt   minute ventilation  ve   and lung resistance  rl  were measured before and every 5 min for 45 min after the infusion of il 2  lung compliance was measured before and 30 min after il 2  bronchial provocation testing with mch was performed 45 min after the infusion of il 2  subsequently  the animals were exsanguinated  and the lungs were removed for histologic examination  infused il 2 did not alter heart rate or blood pressure  vt  f  ve  and rl increased significantly by 15 min  p less than 0 05   but they returned to baseline by 45 min  lung compliance decreased significantly in both rat strains  il 2 increased airway responsiveness only in lewis rats  the concentration of mch that caused a doubling of rl  ec200rl  was 0 6 mg ml and 4 3 mg ml  p   0 003  in il 2 treated and control rats  respectively  the airway responsiveness did not change significantly in fisher rats  ec200rl was 0 13 and 0 35 mg ml for il 2 treated and control rats  respectively  p   0 09   
class8	complement activation is a secondary rather than a causative factor in rabbit pulmonary artery ischemia reperfusion injury  we have previously demonstrated that reperfusion of a rabbit lung in vivo after 24 h of unilateral pulmonary artery occlusion results in edema  transient leukopenia  and intravascular leukocyte aggregation  we hypothesized that complement was activated by reperfusion and that this in turn contributed to lung injury  in the preliminary phase of the study  we found that ischemia followed by reperfusion resulted in a drop in c3 to 15     10   mean     sem  of the prereperfusion value as compared with no change in a group of control animals that had undergone an identical thoracotomy but without pulmonary artery occlusion and reperfusion  p less than 0 05   we then studied three groups of animals to determine if complement depletion with cobra venom factor  cvf  prior to ischemia and reperfusion would prevent the injury  rabbits treated with cvf but without occlusion and reperfusion did not develop significant lung edema  with left and right lung wet dry ratios of 5 32     0 11 and 5 26     0 12  respectively  for rabbits that were not treated with cvf but underwent ischemia and reperfusion  the comparable numbers were 6 15     0 36 and 5 19     0 32  p less than 0 05 for right versus left   for cvf treated rabbits that underwent ischemia and reperfusion  the right left difference persisted  6 77     0 48 versus 5 35     0 14  p less than 0 01   immunocytochemistry documented c3 deposition in non cvf rabbits that underwent ischemia and reperfusion but not in cvf treated rabbits  we conclude that ischemia reperfusion of the lung results in complement activation  but it is not a complement dependent injury  
class8	morphometric analysis of the lung in bronchopulmonary dysplasia  we studied lung development in children with or without bronchopulmonary dysplasia  bpd  using light microscopic morphometry and thick lung sections stained for elastic fibers  one lung was obtained at autopsy from each of eight patients with bpd  ages  2 to 28 months  and six children  ages  5 days to 51 months  who died without lung disease  patients with bpd demonstrated severe somatic growth retardation and had reduced lung volumes with abnormal lobar volume proportions  in the central bronchi mean volume proportion of glands and smooth muscle was increased in bpd  bronchiolar density was also increased  but it tended to normalize with advancing age  mean bronchiolar diameter was slightly smaller in bpd  and bronchiolar smooth muscle hypertrophy was a constant histologic feature  the most striking change  however  was noted in alveolar structure and development  total alveolar number was severely decreased in patients with bpd compared with that in control subjects  and there was little evidence of compensatory alveolar development with increasing age  lung internal surface area was correspondingly reduced  and mean linear intercept was increased  sections stained for elastic tissue demonstrated in the patients with bpd a simplified acinar structure with thickened  tortuous  and irregularly distributed alveolar elastic fibers  we conclude that in severe  fatal bpd there is marked impairment of lung development with alveolar hypoplasia and reduced internal surface area  in addition  bronchial and bronchiolar smooth muscle hypertrophy and bronchial gland hyperplasia may be important contributing factors to airflow limitation  
class8	bronchoalveolar lavage analysis in wegener s granulomatosis  a method to study disease pathogenesis  a prospective analysis of bronchoalveolar lavage  bal  in 13 patients with wegener s granulomatosis  wg   20 disease control subjects with idiopathic pulmonary fibrosis  ipf   and 24 normal control subjects was conducted to  1  evaluate the quality of the alveolar inflammatory response associated with active wg   2  determine whether antineutrophil cytoplasmic antibody  anca  is present in alveolar fluid and produced in the lungs of patients with wg  and  3  determine whether inhaled particles or infectious agents may play an etiologic role in wg  bal in untreated active wg had a marked increase in neutrophils  mean   42  of total wbc count   and usually in eosinophils  mean   4   compared with that in normal control subjects  1 6  neutrophils  0  eosinophils   and untreated wg in remission  5 9  neutrophils  0  eosinophils   disease control subjects with ipf  a process known to be associated with neutrophilic alveolitis  had an increased population of neutrophils  15 4   and eosinophils  2 7   in bal  leukocyte remnants  as well as intact leukocytes  could be identified within bal macrophages in the patients with wg and ipf  and rarely in the normal control subjects  normal subjects and control patients with ipf were all negative for anca in serum  whereas anca was found in serum and bal in all patients with active wg who had generalized disease  protein analysis of bal revealed a disproportionate increase in the igg to albumin ration compared with serum values  igg index  in patients with active untreated disease  the increase in the igg index suggests that igg with anca reactivity is produced by pulmonary lymphoid tissue  an infectious agent in bal was not identified by any of the techniques applied in this study  
class8	cellular and molecular basis of the asbestos related diseases  asbestosis is an inflammatory and fibrotic process of the alveolar structures mediated  at least in part  by cytokines released by  activated  alveolar macrophages  the process of phagocytosis and  activation  of alveolar macrophages is poorly understood  are all macrophages activated or only subpopulations  which cytokines are up regulated  how does the local milieu modulate profibrotic and antifibrotic mediators  is protein release accompanied by up regulation of gene transcription  is there an ordered sequence of cytokine activity  what roles do neutrophils and lymphocytes play  how can disease progression best be quantified absent further exposure  answers to these questions are important to direct rational strategies at interdicting the fibrotic process  the question of cancer and asbestos is more vexing  the processes of inflammation  fibrosis  and carcinogenesis appear to be closely intertwined  for example  proto oncogenes such as c sis  pdgf b chain  are up regulated in activated alveolar macrophages from fibrotic lungs  these and possibly others may play an important role in asbestos carcinogenesis  second  asbestos can transfect dna into cells  furthermore  dna can adhere to asbestos fibers  and these fibers are capable of direct transmigration into cells  the questions of the mechanisms of cigarette smoke cocarcinogenicity and latency remain  lastly  if the bronchial epithelium is highly metaplastic throughout from cigarette smoking  what triggers a single  or several  nidus of cells to transform into carcinoma  malignant mesothelioma poses the most challenging questions because of association with brief asbestos exposure by history  mesothelial cells are susceptible to minute environmental manipulations  and changes occur after exposure to all fiber types  yet epidemiologic studies point toward long amphiboles as having greater mesothelioma risk  to test this hypothesis  experimental data must be generated differentiating tumorigenesis risk from short  chrysotile fibers that can migrate to the parietal pleura from the associations of long amphiboles persisting in lung tissue  despite the future decreasing numbers of clinical cases of asbestos related disease  solving the important mechanistic questions remaining will contribute significantly to our understanding of fibrosis and cancer  
class8	eosinophilic airway inflammation during exacerbation of asthma and its treatment with inhaled corticosteroid  we have compared the inflammatory changes in the bronchial mucosa and the increase in the airway hyperresponsiveness in an asthmatic patient during the deterioration of symptoms  a striking increase in the number of bronchial epithelial eosinophils was associated with an increase in both airway hyperresponsiveness and asthma symptoms  during 16 wk of treatment with the inhaled corticosteroid  budesonide  the patient s clinical status and airway hyperresponsiveness improved  this was accompanied by an improvement in the ultrastructure of bronchial mucosa and a decrease in the number of epithelial eosinophils  
class8	aggressive cavitary pulmonary sarcoidosis  pulmonary sarcoidosis in a young patient is usually a relatively benign disease that either resolves spontaneously or remains quiescent for many years  very rarely it pursues a more aggressive course leading to progressive lung destruction  we report a young patient who presented with stage iii sarcoidosis and over a period of 4 yr progressed to severe cavitary disease with frequent superinfections leading to bronchiectasis and chronic suppuration of the lung  eventually requiring a pneumonectomy  
class8	hypersensitivity pneumonitis versus invasive pulmonary aspergillosis  two cases with unusual pathologic findings and review of the literature  two brothers simultaneously exposed to moldy hay  who developed differing forms of aspergillus related lung disease  are presented  patient 1 developed a true case of hypersensitivity lung disease  whereas his brother developed invasive aspergillosis with bronchoalveolar lavage eosinophilia and unusual pathologic features including tissue eosinophilia  the possible overlap between hypersensitivity pneumonitis and invasive aspergillosis in the immunocompetent host is discussed  
class8	reversed helper suppressor t lymphocyte ratio in bronchoalveolar lavage fluid from patients with breast cancer and pneumocystis carinii pneumonia  pneumocystis pneumonia  pcp  usually occurs in patients with hematologic malignancies and acquired immunodeficiency syndrome  aids   patients with solid tumors represent a very small fraction of the reported cases of pcp  over an 18 month period  pcp was diagnosed in three patients who had received radiation and chemotherapy for breast cancer  in all three patients  there was no serologic or clinical evidence of aids  direct staining of bronchoalveolar lavage fluid  bal  revealed pneumocystis carinii  and cellular analysis of bal revealed an increased percentage of lymphocytes with reversed helper inducer suppressor cytotoxic t cell  cd4 cd8  ratio  because decreased cd4 cd8 ratio in bal is commonly accepted as findings consistent with hypersensitivity pneumonitis and aids  we conclude that similar findings in patients without aids are not specific for hypersensitivity pneumonitis  and p  carinii should be ruled out in the appropriate clinical setting  
class8	external fixation using microplates after laryngotracheal expansion surgery  an animal study  management of severe laryngotracheal stenosis requires treatment with open laryngeal surgical approaches  performing the necessary anterior  and possibly posterior  incisions to expand the cricoid and tracheal rings causes instability of the segments  placing an intraluminal stent has several disadvantages  ranging from injury of healthy tissue to airway obstruction  the availability of an external stent would avoid many of these complications  we performed expansion laryngeal surgery in dogs and explored the use of microplates for external fixation and determined the surgical outcome if no fixation is used  the results show that microplates are very effective in maintaining external fixation and that a need for placing an intraluminal stent when a posterior cricoid split is performed exists  
class8	single stage laryngotracheal reconstruction  the mainstay for repairing subglottic and tracheal stenosis has been the rib graft with prolonged stenting  a refinement of this treatment was the use of the anterior cricoid decompression  split   we present single stage reconstruction of the airway as an additional refinement of the laryngotracheoplasty  this article describes the experience of two institutions with single stage reconstruction and offers some observations on the principles of the technique  
class8	the characteristics of children with epiglottitis who develop the complication of pulmonary edema  a review was performed of 234 consecutive cases of epiglottis that occurred during a 20 year period to delineate the rate of  and clinical characteristics associated with  the complication of pulmonary edema  as a result of the prior utilization of a  dual  management protocol  there were 170 children who received endotracheal intubation  and 64 children managed without placement of an artificial airway  in all  five children  2 1   of varying ages developed this complication  all experienced severe airway obstruction progressing to respiratory arrest  with evidence of pulmonary edema developing shortly after endotracheal intubation  two of these five children died due to complications resulting from upper airway obstruction induced cardiorespiratory arrest  by contrast  no child with milder degrees of airway obstruction managed without an artificial airway exhibited clinical evidence of pulmonary edema  several possible mechanisms for the development of this complication are described  pulmonary edema associated with epiglottitis is an uncommon complication that can occur following endotracheal intubation in those patients with marked respiratory insufficiency  an artificial airway should be instituted in all cases of pediatric epiglottitis  the potential complication of pulmonary edema should be anticipated before placement of an artificial airway  especially in those patients with a severe degree of upper airway obstruction  
class8	salivary gland involvement in wegener s granulomatosis  salivary gland involvement is a rare clinical feature of wegener s granulomatosis  we report a series of five cases in which submandibular or parotid gland swelling was part of the initial manifestation of the disease  all patients had limited forms of wegener s granulomatosis  the value of determination of serum anti neutrophil cytoplasmic autoantibodies is demonstrated in four of the cases  and its use as a new diagnostic adjunct and promising tool to monitor disease activity is discussed  the use of trimethoprim sulfamethoxazole as part of alternative treatment regimens for limited wegener s granulomatosis is advocated  
class8	pupil cycle time and early autonomic involvement in ocular leprosy  ocular complications of leprosy patients often develop insidiously and with few if any symptoms  this study involves measurement of the pupil cycle time  pct  to evaluate the autonomic nerve system of the iris to determine the presence of subclinical intraocular involvement  the study included 19 lepromatous  ll   19 borderline lepromatous  bl   and five borderline tuberculoid  bt  leprosy patients and involved 25 healthy volunteers  10 patients with pulmonary tuberculosis and eight with duhring disease  the pct was measured in these groups  in all leprosy groups included in the study the pct was higher than in the control groups  moreover  the pct of the leprosy patients without any intraocular involvement was higher than in the controls  these results show that in the ophthalmic examination of leprosy patients without any symptoms the fact that autonomic nerve system of the eye is affected by the leprosy can often be determined by measuring the pct  
class8	small cell carcinoma of the prostate  this report details clinical and pathologic aspects of a patient with small cell undifferentiated carcinoma of the prostate and systemic hyperglucagonemia  a panel of potential serologic markers was evaluated in order to document additional evidence of ectopic hormonal production  immunocytochemical markers were sought in tissue samples from the primary neoplasm and a lung metastasis  stains were positive for corticotropin  acth  and gastrin in both the prostate and in the lung  but no evidence of excess secretion was documented  these findings are consistent with the notion that neuroendocrine activity is common in undifferentiated small cell carcinomas  regardless of their site of origin  
class8	hypersensitivity reactions to epipodophyllotoxins in children with acute lymphoblastic leukemia  the incidence  clinical characteristics  and outcome of hypersensitivity reactions to teniposide  vm 26   etoposide  vp 16   or both were determined in 108 children with acute lymphoblastic leukemia  all  treated with a contemporary regimen of intensive multiagent chemotherapy  fifty  46   of the 108 patients had one or more hypersensitivity reactions  the risk of any child having an initial reaction over the cumulative dose range studied was 52   95  confidence limits  41  and 63   for vm 26  compared with 34   95  confidence limits  24  and 44   for vp 16  the risk of having an initial reaction to vm 26 or vp 16 was clearly related to the cumulative dose  this risk peaked at 1500 to 2000 mg m2 for vm 26 and at 2000 3000 mg m2 for vp 16  all reactions were type 1 reactions according to the gell and coombs classification  characterized by urticaria  angioedema  flushing  rashes  or hypotension  and 86  of reactions were of grade 1 or 2 severity according to standard criteria  there was no evidence of increasing clinical severity on repeated rechallenge with premedication  and no deaths occurred  the findings suggested that hypersensitivity reactions to epipodophyllotoxins in children with all are more common than previously reported  but only rarely constitute dose limiting toxicity  
class8	cisplatin  continuous infusion 5 fluorouracil  and intermediate dose methotrexate in the treatment of unresectable non small cell carcinoma of the lung  forty one patients with unresectable non small cell carcinoma of the lung  nsccl  were treated with cisplatin 20 mg m2 d for 5 days as a daily bolus injection  5 fluorouracil 800 mg m2 d by continuous infusion for 5 days  and intermediate dose methotrexate 200 mg m2 on days 15 and 22 of a 28 day cycle  pfm   one complete and 23 partial responses were observed  yielding an overall response rate of 60   there was no significant difference in response rates based on histologic subtype or extent of disease  locally unresectable versus metastatic   median duration of response was 6 months  and the median survival of all patients was 10 months  two patients with unresectable disease at presentation became resectable after chemotherapy and remain disease free at 46  and 53  months  toxicity was modest  with oral mucositis the major adverse effect  clinically important neutropenia was uncommon  pfm is an active regimen in nsccl and deserves further study in the  neoadjuvant  setting  
class8	ultrasound guided hepatic cryosurgery in the treatment of metastatic colon carcinoma  preliminary results  cryosurgery  the in situ freezing of cancer  has been proposed in the past as a possible treatment for unresectable hepatic tumors  its advantage lies in the fact that it is a very focal treatment sacrificing less normal tissue than surgical resection  allowing treatment of multiple lobes  because cryosurgery does not affect large vessels  tumors in difficult locations  such as adjacent to the inferior vena cava  ivc   can be treated  with the use of intraoperative ultrasound to place the cryoprobes and monitor the freezing process  18 patients with unresectable metastatic colon carcinoma confined to the liver were treated  of the 18 patients treated  4  22   are in complete remission as determined by computed tomography  ct  scans and carcinoembryonic antigen  cea  levels  with a mean follow up of 28 8 months  four patients  22   were not adequately treated at the time of cryosurgery  the number of lesions frozen in each patient ranged from 1 to 12  with a mean of 6 lesions  fourteen patients had bilobar disease  three patients had previous right lobectomies with recurrences in their remaining left lobes prior to cryosurgery  and one patient had unilobar disease  mean survival of the 14 cases with recurrence was 21 4 months  with 2 of the 14 still alive  ultrasound guided hepatic cryosurgery appears to be an effective treatment for metastatic colon carcinoma to the liver that is unresectable  including patients with bilobar and multiple lesions   these preliminary results indicate that the procedure warrants further study  
class8	immunohistologic evaluation of parathyroid hormone related protein in human lung cancer and normal tissue with newly developed monoclonal antibody  with a newly developed monoclonal anti pthrp antibody  4b3  the immunohistochemical localization of the parathyroid hormone related protein  pthrp  was studied on the formalin fixed and paraffin embedded sections of normal human tissues and various subtypes of lung cancer  among normal epithelial tissues  keratinocytes in squamous epithelia  transitional and bronchial epithelia with squamous metaplasia  meningoepithelial cells  and mammary ductal cells with lactating changes showed positive immunoreactivity  also  among endocrine tissues  cells in the parathyroid gland  pancreatic islets  adrenal cortex  pituitary gland  and testis were sporadically positive for pthrp  these distribution patterns suggested that in a physiologic condition  pthrp was closely related to keratinization and local secretion and or the metabolism of calcium in specifically differentiated tissues  in lung cancer  however  pthrp was detected in all cases of well differentiated and moderately differentiated squamous cell carcinoma and in most cases of small cell carcinoma  irrespective of the patients  serum calcium level  however  pthrp was not detected in two of five cases of poorly differentiated squamous cell carcinoma and in all cases of adenocarcinoma  consequently  it was found that pthrp was commonly produced by squamous cell carcinomas of the differentiated type  and that humoral hypercalcemia of malignancy could be induced when the pthrp transgressed the homeostatic mechanisms  
class8	screening for lung cancer  a critique of the mayo lung project  the national cancer institute of the united states recently sponsored three large scale  randomized controlled trials of screening for early lung cancer  the trials were conducted at the johns hopkins medical institutions  the memorial sloan kettering cancer center  and the mayo clinic  participants were middle aged and older men who were chronic heavy cigarette smokers and thus at high risk of developing lung cancer  screening procedures were chest radiography and sputum cytology  the only screening tests of established value for detecting early stage  asymptomatic lung cancer  in the hopkins and memorial trials the study population was offered yearly chest radiography plus sputum cytology every 4 months  the control population was offered yearly chest radiography only  in these trials the addition of sputum cytology appeared to confer no lung cancer mortality rate advantage  the mayo clinic trial compared offering chest radiography and sputum cytology every 4 months to offering advice that the two tests be obtained once a year  this trial demonstrated significantly increased lung cancer detection  resectability  and survivorship in the group offered screening every 4 months compared with the control group  however  there was no significant difference in lung cancer mortality rate between the two groups  the statistical power of these trials was somewhat limited  nevertheless  results do not justify recommending large scale radiologic or cytologic screening for early lung cancer at this time  
class8	the applications of imaging in lung cancer  the applications of imaging to the lung cancer patient have become more focused recently  screening of high risk patients is not recommended even though intuition and clinical judgment prevail in practice to justify the use of chest radiographs in this patient category  cross sectional imaging procedures should be tailored to the staging process in the individual with a large central primary or to confirm an abnormality noted on the chest radiographs  the patient at high risk for thoracotomy is generally also subjected to radiologic staging  the radiologic staging process is reviewed and critiqued  emphasizing our role in identifying the disease sites that would suggest nonrespectability  
class8	prognostic implications of dna histogram  dna content  and histologic changes of regional lymph nodes in patients with lung cancer  forty six cases of resected lung cancer  including 20 cases at stages i and ii and 26 cases at stage iii  n2   were subdivided into two groups  a good prognosis group with a longer survival period and a poor prognosis group in which the patients died earlier of the cancer  from paraffin embedded lymph node tissues of these patients  the authors examined dna histogram pattern and dna content  using flow cytometry  and histologic hyperplasia of germinal center and paracortical area  they also evaluated their correlation with the prognosis  in the good prognosis group at stages i and ii  paracortical hyperplasia  ph  of the lymph nodes was observed significantly more frequently  in the good prognosis group at stage iii  the incidence of ph  g2m phase in the dna histograms  and dna content were all significantly higher  dna content was positively correlated with the grade of ph  
class8	primary and metastatic pulmonary meningioma  patient 1 was a 53 year old man who had a very rare primary pulmonary meningioma that developed in the left lingular segment  when this report was written  7 years had passed since he underwent operation  and no recurrence of the meningioma had been detected  in patient 2  a 61 year old woman  multiple pulmonary metastases were confirmed 19 years after she had undergone operation for multiple cerebellar meningiomas  and the metastases were resected  after 2 years  multiple intraperitoneal metastases were found  and thus aggressive surgery was performed  currently  22 years after the operation for the primary cerebellar meningioma  the patient is alive without any subjective symptoms  although intraperitoneal metastases have recurred  to date  only four cases  all in women  of primary pulmonary meningioma have been reported  case 1 reported in this article is thus the first case in a male patient to be reported  and  in addition  this patient also has the first reported case to have been evaluated for more than 5 years  in case 2  however  each of the excised extracranial tumor lesions was histologically homogeneous and showed a hemangiopericytomatous pattern  the histologic picture of those tumor lesions was exactly the same as the picture of a small portion of the cerebellar meningiomas excised 19 years earlier  thus  all those extracranial tumor lesions were diagnosed to be metastatic meningiomas  however  it is difficult to explain why there had been no symptoms for as long as 19 years until the pulmonary metastases were discovered  
class8	lung cancer in patients younger than 40 years of age  the records of 52 patients younger than 40 years of age who had bronchogenic carcinoma diagnosed between 1965 and 1985 were reviewed  the preponderance of adenocarcinoma  54    the lower male female ratio in this age group compared with patients age 40 or older  2 1   the importance of cigarette smoking as a causative factor  80  of patients   the long mean duration of symptoms  5 months   and the high incidence of advanced stage at diagnosis  77  stages iii and iv  in these patients are findings similar to those reported in other published series  there was no significant difference in resectability  23  versus 19    median survival length  5 3 months versus 6 9 months   median survival length of patients who had surgical resection  10 5 months versus 10 8 months   and 5 year survival rate  11 5  versus 6 3   in these patients compared with a randomly selected group of 260 patients with lung cancer who were age 40 or older  
class8	the use of ketoconazole in ectopic adrenocorticotropic hormone syndrome  the authors report a patient with ectopic adrenocorticotropic hormone  acth  syndrome  eas  resulting from small cell lung cancer  treatment with ketoconazole  kcz  resulted in significant suppression of serum cortisol levels  the authors confirmed kcz to be a useful adjunct in the treatment of cushing s syndrome  
class8	human leukoagglutinating antibody evokes cooperative leukotriene synthesis in pulmonary microvasculature  model of transfusion related acute lung injury  leukoagglutinating antibodies have been implicated in the development of transfusion related acute lung injury  in the present study  human neutrophil leukotriene generation was provoked by an anti 5b immunoglobulin g  isolated from a multiparous donor plasma that caused noncardiogenic lung edema during transfusion therapy  in 5b positive polymorphonuclear neutrophils  pmns   the antibody stimulated marked arachidonic acid metabolism  dependent on the presence of plasma as the complement source  quantity and profile of lipid mediators  leukotriene b4 and its omega oxidation products  5 hydroxyeicosatetraenoic acid  and nonenzymatic hydrolysis products of leukotriene a4  corresponded to those repeatedly described after pmn in vitro stimulation with the artificial calcium ionophore a23187  anti 5b challenge of pmns sequestered in the microvasculature of perfused rabbit lungs did  however  induce a markedly modified metabolite profile  nonenzymatic hydrolysis products of leukotriene a4 were not detected  and 5 hydroxyeicosatetraenoic acid was markedly reduced  in contrast  cysteinyl leukotrienes were measured as predominant compounds  with rapid appearance of leukotriene c4 and more protracted generation of leukotriene e4  leukotriene b4 and its omega oxidation products were released with similar kinetics  but in lower amounts  as compared with the isolated pmn stimulation  anti 5b challenge of pmns coincubated with pulmonary artery endothelial cells in vitro  but not stimulation of either cell type alone  provoked marked generation of cysteinyl leukotrienes  these findings suggest modulation of pmn 5 lipoxygenase metabolism in favor of leukotriene a4 transfer to adjacent acceptor cells with subsequent enzymatic conversion to cysteinyl leukotrienes under conditions of lung vascular sequestration  endothelial cells appear to serve as predominant cooperative cells under circumstances of blood free lung perfusion  pmn related transcellular eicosanoid synthesis may be involved in the pathogenesis of transfusion evoked acute lung injury  
class8	differentiation between the intensity of breathlessness and the distress it evokes in normal subjects during exercise  1  this study was designed to examine whether normal subjects could differentiate between the  intensity  of their breathlessness and the amount of  distress  it evoked  by specific wording of the instructions  2  a preliminary study showed no significant difference between  distress  score during exercise measured on two separate occasions  p   0 3   3  ten subjects each performed two identical incremental cycle ergometer exercise tests on separate occasions during which they were asked to quantify either  intensity  or  distress  by using modified borg scales  4  in all subjects there was a significant correlation  p less than 0 001  between  intensity  and minute ventilation  in eight subjects there was a significant correlation  p less than 0 05  between  distress  and minute ventilation  one subject displayed no significant correlation and one registered no distress  5  mean  intensity  was greater than the mean  distress   p   0 0001   the slope of  intensity  minute ventilation was greater than the slope of  distress  minute ventilation  p   0 0001   6  within individuals there was a significant correlation between  intensity  and  distress   p less than 0 05   there was a wide scatter in the slope of this relationship between subjects and maximum  intensity  and  distress  did not correlate  7  different elements of the breathlessness sensation could be identified and selectively measured depending on the wording of the instructions given to the subject  8  there was a wide intersubject variation in the magnitude of both breathlessness  intensity  and  distress  estimates  but the differences between subjects in these two components of the sensation did not appear to follow a common pattern  
class8	treatment of obstructive pneumatosis coli with endoscopic sclerotherapy  report of a case  the case of an 86 year old man with cardiac and pulmonary failure  in whom pneumatosis cystoides intestinalis caused segmental obstruction of the sigmoid colon is described  the patient was treated with endoscopic puncture and sclerotherapy of the cyst walls in four sessions  giving endoscopic and radiologic regress of the lesions and symptomatic relief  
class8	interstitial lung disease  the interstitial lung diseases are comprised of a group of pulmonary disorders characterized clinically by diffuse infiltrates on the chest radiograph and histologically by distortion of the gas exchanging portion of the lung  the physiologic correlates are restriction of lung volumes and impaired oxygenation  the term  interstitial  when applied to these diseases is actually a misnomer because it implies that the inflammatory process is limited specifically to the area between the alveolar epithelial and capillary endothelial basement membranes  the diseases currently grouped as  interstitial  also frequently involve the alveolar epithelium  alveolar space  pulmonary microvasculature  and less commonly  the respiratory bronchioles  larger airways  and even the pleura  the enormous differential diagnosis of interstitial lung disease can be made manageable by understanding that pneumoconiosis  drug induced disease  and hypersensitivity pneumonitis account for over 80  of the responsible entities and can usually be identified from the patient s history  the nine remaining diseases disease categories include  sarcoidosis  idiopathic pulmonary fibrosis  bronchiolitis obliterans organizing pneumonia  histiocytosis x  chronic eosinophilic pneumonia  collagen vascular disease associated interstitial lung disease  granulomatous vasculitis  wegener s granulomatosis  churg strauss syndrome  lymphomatoid granulomatosis   goodpasture s syndrome  and pulmonary alveolar proteinosis  the diagnosis of a specific interstitial lung disease can be made via various means including the patient s history  specific serologies  bronchoalveolar lavage  transbronchial biopsy  and biopsy of extrathoracic tissues or open lung biopsy  a directed diagnostic approach can be formulated based on an understanding of these techniques and a thorough knowledge of the clinical presentations and specific diagnostic criteria for each of the major diseases  this monograph will serve as a guide for the clinician to use in evaluating and treating patients with interstitial lung disease  we begin by reviewing the clinical presentation  diagnostic criteria  and management of specific interstitial lung diseases excluding pulmonary infection  neoplasm  and sarcoidosis  pneumoconiosis and drug induced syndromes are not discussed in detail  but the agents responsible and pertinent exposures are presented in tabular form in the discussion of the general diagnostic approach  
class8	pneumonia  update on diagnosis and treatment  pneumonia is the most common infectious disease necessitating hospitalization of elderly patients  a number of misconceptions exist regarding the clinical and radiological features of pneumonia in elderly patients  early recognition and appropriate therapy can reduce morbidity and enhance survival  this article explores the manifestations of pneumonia in the elderly  as well as the diagnostic approach and contemporary therapy  
class8	sedation for upper gastrointestinal endoscopy  results of a nationwide survey  a postal questionnaire inquiring about routine sedation and premedication practice for upper gastrointestinal endoscopy was sent to 1048 doctors  of 665 appropriate returns  81  were from consultant physicians and surgeons  most endoscopists  90   reported using an intravenous benzodiazepine for at least three quarters of endoscopies and 54  of physicians and 69  of surgeons always did so  midazolam was the intravenous sedative used by a third of all respondents and 13  also used an additional intravenous agent  usually pethidine  over the previous two years a total of 119 respiratory arrests  37 cardiac arrests  and 52 deaths were identified  adverse outcomes were reported more frequently by consultant physicians  by those who  titrated  the intravenous sedative  and by those who used an additional intravenous agent  but were reported equally frequently by endoscopists using midazolam and endoscopists using diazepam  there is an urgent need for a prospective study to identify the circumstances and risk factors associated with adverse outcomes related to endoscopy  
class8	delivery dependence of early proximal bicarbonate reabsorption in the rat in respiratory acidosis and alkalosis  in the intact rat kidney  bicarbonate reabsorption in the early proximal tubule  ep  is strongly dependent on delivery  independent of delivery  metabolic acidosis stimulates ep bicarbonate reabsorption  in this study  we investigated whether systemic ph changes induced by acute or chronic respiratory acid base disorders also affect ep hco3  reabsorption  independent of delivery  flhco3  filtered load of bicarbonate   hypercapnia was induced in rats acutely  1 3 h  and chronically  4 5 d  by increasing inspired pco2  hypocapnia was induced acutely  1 3 h  by mechanical hyperventilation  and chronically  4 5 d  using hypoxemia to stimulate ventilation  when compared with normocapneic rats with similar flhco3  no stimulation of ep or overall proximal hco3 reabsorption was found with either acute hypercapnia  paco2   74 mmhg  ph   7 23  or chronic hypercapnia  paco2   84 mmhg  ph   7 31   acute hypocapnia  paco2   29 mmhg  ph   7 56  did not suppress ep or overall hco3 reabsorption  chronic hypocapnia  paco2   26 mmhg  ph   7 54  reduced proximal hco3 reabsorption  but this effect was reversed when flhco3 was increased to levels comparable to euvolemic normocapneic rats  thus  when delivery is accounted for  we could find no additional stimulation of proximal bicarbonate reabsorption in respiratory acidosis and  except at low delivery rates  no reduction in bicarbonate reabsorption in respiratory alkalosis  
class8	expression of rat renal na h antiporter mrna levels in response to respiratory and metabolic acidosis  the mammalian proximal tubule is an important mediator of the renal adaptive response to systemic acidosis  in chronic metabolic and respiratory acidosis the bicarbonate reabsorptive  or proton secretory  capacity is increased  this increase is mediated  at least in part  by an increase in vmax of the luminal na h antiporter  to determine whether this adaptation involves increased mrna expression  na h antiporter mrna levels were measured by northern analysis in renal cortex of rats with metabolic  6 mmol kg body wt nh4cl for 2 or 5 d  and respiratory  10  co2 air balanced for 2 or 5 d  acidosis and of normal  pair fed rats  na h antiporter mrna levels were unchanged after 2 d of both metabolic and respiratory acidosis  after 5 d  however  na h antiporter mrna expression was increased 1 76     0 12 fold in response to metabolic acidosis  p less than 0 005  n   8   but was not different from normal in response to respiratory acidosis  1 1     0 2  ns  n   8   thus  the renal adaptive response to metabolic acidosis involves increased cortical na h antiporter mrna levels  in contrast  the enhanced proximal tubule na h antiporter activity and bicarbonate reabsorption in respiratory acidosis seem to involve mechanisms other than increased na h antiporter gene expression  
class8	septic shock and death due to occult sinusitis  we report a case of septicaemia and death due to occult sinusitis in an otherwise healthy adult  septicaemia was diagnosed on clinical grounds and blood culture grew streptococcus pneumoniae  maxillary sinusitis was discovered incidentally on a ct scan four days after the onset of symptoms  a sinus wash out revealed pus which on culture was positive for streptococcus pneumoniae  the patient deteriorated gradually and died despite appropriate therapy  we conclude that sinusitis should be suspected in any case of septicaemia where the primary focus is not known and the patient does not respond quickly to treatment  
class8	fatal pulmonary embolism caused by streptokinase treatment of deep venous thrombosis of the leg  during the last 10 years  four of 150  2 7   patients with deep venous thrombosis  dvt  treated with streptokinase  sk  at our department have died of pulmonary embolism  pe   a retrospective study of 1393 dvt patients treated with heparin during the period 1973 1986 showed that five  0 36   of these patients died of pe while still on heparin  in this paper we describe the four patients treated with sk who developed fatal pe  in our opinion this increase in mortality does not warrant the use of sk in routine treatment of dvt of the leg before a proper trial has been conducted to compare the frequencies of pulmonary embolism after both treatments  
class8	variables influencing tumor uptake of anti melanoma monoclonal antibodies radioiodinated using para iodobenzoyl  pib  conjugate tumor uptake was examined with respect to antigen expression  time dependent biodistribution  dose of mab injected  tumor size  and tumor site  i e   subcutaneous versus lung or liver metastases   nr ml 05  96 5  and p94 showed significantly greater uptake in subcutaneous tumors than cl207 and 5 1  p less than 0 05   nr ml 05 had a significantly higher tumor uptake at 24 hr  11 9     0 51  than at 72 hr  4 0     0 37  or 144 hr  2 7     0 84  after injection  p less than 0 001   the other four mabs had similar tumor distribution at all three time points  the tumor uptake of four mabs  96 5  p94  cl207  5 1  differed with respect to in vitro versus in vivo binding to tumor  tumor type  dose of mab  and tumor site  subcutaneous versus metastases   in contrast  nr ml 05 demonstrated consistent uptake in tumors independent of the above parameters  these data suggest that certain host parameters can influence in vivo tumor targeting depending on characteristics of each mab studied  
class8	dapsone as a single agent is suboptimal therapy for pneumocystis carinii pneumonia  in a prospective  noncomparative study  seven patients with mild pneumocystis carinii pneumonia  characterized by room air arterial po2 greater than 60 mm hg at the time of presentation  were treated with dapsone alone at a dose of 200 mg daily  two of the seven patients required mechanical ventilation for respiratory failure on day 5 of dapsone therapy  both died  four patients experienced major side effects during dapsone therapy  none of the seven patients successfully completed a full course of therapy with dapsone  we conclude that high dose  single agent dapsone is not suitable for further study as therapy for pneumocystis carinii pneumonia  
class8	pneumocystis carinii pneumonia in patients with aids  evaluation of lavage and staining techniques in diagnosis  the diagnostic yield of unilateral vs  bilateral bronchoalveolar lavage  bal  was prospectively evaluated in 65 consecutive patients suspected of having pneumocystis carinii pneumonia  pcp  complicating acquired immune deficiency syndrome  aids   gram weigert  gw   papanicolaou  pap   and gomori s methenamine silver  gms  stains were used for identification of p  carinii in all cases  forty eight patients had pcp that was identified by gw staining of bal in 47 48 patients followed by pap gms staining of bal in 44 48 patients and pap gms staining of bronchial washings in 40 48 patients  in patients with bilateral interstitial infiltrates  unilateral lavage was sufficient for diagnosis of pcp when gw stain was utilized  in patients with pcp complicating aids  the diagnostic yield of bal may be increased by use of both gw and gms stains  
class8	treatable abdominal pathologic conditions and unsuspected malignant neoplasms at autopsy in veterans who received mechanical ventilation  study objective  to determine  in medical patients who received mechanical ventilation  the frequency and types of major unexpected diagnoses at autopsy that  if known before death  would probably have led to improved survival  class i errors  or substantively changed management but not survival  class iib errors   design  retrospective cohort study  setting  six medical intensive care units in a department of veterans affairs cooperative study  patients  one hundred seventy two autopsied patients of the 401 veterans who received mechanical ventilation and died in the hospital  results  the class i error rate was 12   abdominal pathologic conditions  abscesses  bowel perforations  or infarction  were as frequent as pulmonary emboli as a cause of class i errors  while patients with abdominal pathologic conditions generally complained of abdominal pain  results of examination of the abdomen were considered unremarkable in most patients  and the symptom was not pursued  six percent of patients had extensive malignant neoplasms  class iib errors   conclusions  atypical presentation of potentially treatable abdominal pathologic conditions is a common cause of class i errors in veterans who receive mechanical ventilation  conversely  several patients with unrecognized terminal conditions underwent intensive intervention  if the information gained at autopsy had been known before death  management would have probably changed substantively in 18  of patients  
class8	protective efficacy of haemophilus influenzae type b polysaccharide and conjugate vaccines in children 18 months of age and older  to evaluate the protective efficacy of polyribosylribitol phosphate  prp  and polyribosylribitol phosphate diphtheria toxoid  prp d  vaccines in children 18 to 59 months of age  we conducted a case control study in los angeles  calif  county between july 1  1988  and july 31  1989  seventy nine children with invasive haemophilus influenzae type b disease 18 to 59 months of age were identified  and 212 controls were selected by random digit telephone dialing methods  cases and controls were stratified by age and month of disease onset of the case  seventeen prp vaccine failures and two prp d vaccine failures occurred more than 2 weeks after vaccination  the prp vaccine was shown not to be effective  point estimate  47   95  confidence interval   307  to 47    but the prp d vaccine was 88  protective  95  confidence interval  42  to 97    adjustment of the efficacy estimates for potential confounding variables did not change the results significantly  the prp d vaccine provided significantly better protection than the prp vaccine against invasive h influenzae type b disease in this population  
class8	mucoepidermoid carcinoma of the salivary glands  a reappraisal of the influence of tumor differentiation on prognosis  thirty nine cases of mucoepidermoid carcinoma of the salivary glands were reviewed for a reappraisal of the influence of the grade of differentiation on the outcome of the disease  the age of the patients ranged between 7 and 84 years  fifteen patients were females and 24 males  the tumors were located at the parotid gland  n   30   the submaxillary gland  n   1   the soft palate  n   5  and the oral mucosa nos  n   3   at presentation 4 tumors were intraglandular and 35 extraglandular  three patients had lymph node metastases and one patient lung metastases  the grade of differentiation was assessed using the criteria of healey et al  twelve tumors were classified as grade i  17 as grade ii  and 10 as grade iii  follow up information was obtained with a duration of 5 144 months  mean 44 7 months   six cases recurred locally and 5 developed metastases  five years cumulative survival was 100  for grade i  70 1  for grade ii  and 47 2  for grade iii  the results point to the usefulness of the assessment of the grade of differentiation as a guide to anticipate the outcome of the disease  
class8	is there ever a role for salvage operations in limited small cell lung cancer  combined modality treatment with chemotherapy and radiation produces tumor regression in most patients with small cell lung cancer  but the impact on survival has been small  and less than 20  of patients with limited disease survive 2 years  survival time is extremely short after failure to respond or relapse after treatment  local control remains a problem  with one third of patients having recurrence only at the primary site  in an attempt to prolong survival and perhaps achieve cure  we undertook surgical resection in 28 patients with limited small cell lung cancer who did not have complete remission with standard treatment or who had only local recurrence after treatment  there were 28 patients  22 male and six female  median age 61 years  range 41 to 76   all patients had been treated with chemotherapy and 13 had received preoperative radiotherapy to the primary site and mediastinum  eight patients underwent an operation for relapse after complete remission  five patients had had no response to treatment  three had had a slight response followed by progression during chemotherapy  and 12 had achieved partial response but had greater than 3 cm residual masses  twelve patients required pneumonectomy  15 lobectomy  one patient had unresectable disease  and two had bulky residual masses after the operation  three others had microscopic residual disease  pathologic examination showed only small cell lung cancer in 18 patients  mixed small cell and non small cell in four  and only non small cell lung cancer in six  there were only four patients with stage i disease  10 with stage ii  and 14 with stage iii  the median survival from the date of diagnosis for the entire group is 105 weeks and from the date of operation  74 weeks  the projected 5 year survival rate is 23   the two patients with residual masses died with local progression  and distant metastatic disease developed in 17 others  one patient died at 6 years without recurrent disease  eight patients are alive 2 to 5 years after diagnosis  seven of these patients required only a lobectomy  four had stage i disease  two had stage ii  and two had stage iii disease  five had pure small cell lung cancer and three had mixed small cell and non small cell tumors  all of the patients with pathologic stage i disease remain alive compared with one of 10 with stage ii disease and two of 14 with stage iii  in summary  relapse or failure to respond to chemotherapy may be due to non small cell lung cancer or a mixed tumor  abstract truncated at 400 words   
class8	radon and health radon and its daughter decay products are thought to be the cause of 5  of lung cancer in the uk  this assessment has been made by the national radiological protection board  nrpb  after a national survey of radon levels in homes  when more houses than anticipated were found to have high levels  and after a reappraisal upwards of the effectiveness of radon and its daughter products in causing lung cancer  a review of the scientific evidence reveals no direct evidence to incriminate radon or its decay products at the levels found in our homes in lung cell carcinogenesis  the issue involves different scientific disciplines and is highly complex  debate between scientists is required and more epidemiological studies of lung cancer and low radon exposure are necessary  meanwhile the indirect evidence linking low levels of radon exposure to lung cancer is insufficient to warrant the remedial action proposed by the nrpb and accepted by the uk government  
class8	perception of breathlessness during bronchoconstriction induced by antigen  exercise  and histamine challenges  perception of breathlessness was studied in eight patients with mild  stable asthma after a histamine and exercise challenge performed before and 24 and 48 hours respectively after an antigen challenge  fev1 and perception of breathlessness  evaluated by borg s 10 point category scale  were measured after each administration of doubling antigen or histamine concentrations to achieve a greater than 20  fall in fev1  and after six minutes of steady state exercise at 80  of maximal oxygen consumption  vo2max   the geometric mean provocative concentration of histamine causing a 20  fall in fev1  pc20  fell from 1 67 mg ml before antigen challenge to 0 52 mg ml 24 hours after the challenge  the median maximal   fall in fev1 with exercise was 24 9   range 10 5 40 5   before and 30 6   range 13 8 52 3   48 hours after antigen challenge  the median maximum   fall in fev1 after antigen inhalation was 20 1   range 13 3 35 2   within the first hour  only two subjects had a late fall in fev1  23  and 58    the median  range  of borg scores obtained when fev1 was reduced by 20  did not differ significantly for the three types of acute challenges  1 25  0 5 2 5  and 1 0  0 5 3 0  after histamine tests  1 0  0 5 4 1  and 1 55  0 5 2 0  after exercise  and 1 5  0 3 0  after antigen challenge  in the two subjects who had a late response to antigen the borg score was reduced for the same   fall in fev1 as with the early response  it is concluded that the perception of breathlessness does not differ appreciably during the early response to histamine  antigen exposure  or exercise  but that it is reduced during the late asthmatic response  it was not influenced by previous antigen exposure  despite an increase in airway responsiveness  
class8	modified muscle sparing posterolateral thoracotomy  a modified posterolateral thoracotomy is described that combines the advantages of complete muscle sparing through a thoracolumbar fascial slide with excellent exposure  the technique is easy to perform  the procedure was associated with relatively little postoperative pain  coughing was effective  and early ambulation was achieved  experience with this approach in the first 49 patients suggests that it offers an attractive alternative to the standard muscle cutting posterolateral thoracotomy approach for elective procedures  
class8	inhaled micronised gentamicin powder  a new delivery system  forty patients undergoing routine bronchoscopy were randomised to receive inhaled micronised gentamicin powder  180 mg  or nebulised gentamicin solution  160 mg  one hour before the procedure  similar levels of gentamicin were detected in bronchoalveolar lavage fluid in the two groups  micronised powder  n   20  9 3  sd 9 3  mg l  nebulised solution  n   20  8 0  7 8  mg l   the micronised gentamicin powder preparation caused cough in half the patients but this did not stop their receiving a full dose  dry powder gentamicin may be a convenient formulation for long term inhaled treatment if the problem of cough can be overcome  
class8	lung function 8 18 years after intermittent positive pressure ventilation for hyaline membrane disease  lung function and respiratory symptoms were studied in 40 children aged 8 18 years who had been ventilated for hyaline membrane disease after birth  11 had had bronchopulmonary dysplasia  also studied were 38 age matched children who had had hyaline membrane disease but had not required ventilation  25 unmatched children who were born prematurely but did not develop hyaline membrane disease  and 39 randomly selected pupils of similar age  there was no difference in thoracic gas volume  total lung capacity  inspiratory vital capacity  residual volume  or transfer factor for carbon monoxide between the groups  respiratory symptoms during the three years before the study and the frequency of clinically diagnosed asthma in patients and their family were similar in all the children with hyaline membrane disease irrespective of whether they had been ventilated or had had bronchopulmonary dysplasia  the children with bronchopulmonary dysplasia  however  had a lower forced expiratory volume in one second  fev1  before bronchodilator  73  predicted  than the other groups  88 95  predicted   children who had required ventilation had lower values for specific airways conductance  sgaw  and a greater increase in fev1  delta fev1  after salbutamol  13   than non ventilated children  6    delta fev1 was associated with the peak pressure of intermittent positive pressure ventilation  a family history of asthma and a history of wheezing  recurrent respiratory illnesses  and a doctor s diagnosis of asthma during the three years before the study  these findings indicate that after eight years of age patients with bronchopulmonary dysplasia have more reversible airways obstruction  compatible with increased bronchial smooth muscle tone  
class8	effects of hypothyroidism on bronchial reactivity in non asthmatic subjects  the effect of hypothyroidism on non specific bronchial reactivity was studied in 11 patients without pulmonary disease  mean age 40  sd 13  years  who had had a total thyroidectomy and radioiodine treatment for thyroid cancer 41  36  months before the study  all patients when mildly hyperthyroid while having long term thyroxine replacement treatment and once when hypothyroid two weeks after stopping triiodothyronine for the purpose of screening for metastases  bronchial reactivity was assessed by measuring specific airways conductance  sgaw  after increasing doses of inhaled carbachol  45 1260 micrograms   the dose producing a 35  decrease in sgaw  pd35  was determined from the cumulative log dose response curve by linear regression analysis  mean baseline sgaw values were similar when the patients were hypothyroid and when they were hyperthyroid  1 35  0 36  and 1 41  0 56  s 1 kpa 1   the interstudy coefficients of variation of baseline sgaw were higher in the thyroid patients than in a euthyroid control group  14  versus 8    geometric mean pd35 was lower when the patients were hypothyroid  97 micrograms  than when they were mildly hyperthyroid  192 micrograms   it is concluded that acute hypothyroidism increases non specific bronchial reactivity in nonasthmatic subjects  
class8	performance and prognosis in patients with lung cancer  the edinburgh lung cancer group  the edinburgh lung cancer group prospectively registered 651 new patients presenting with lung cancer during 1981  only 47 survived five years  7    the survival rate was highest in patients selected for surgery  35 116  30   and in this group was related to cell type  stage of disease  and possibly to karnofsky performance score  not statistically significant   by comparison with non surgical patients these 116 patients undergoing surgery were highly selected in terms of age  favourable histological type  stage of disease  and performance score  forty two of the 535 non surgical patients were given radical radiotherapy alone and seven  17   survived five years  the remaining 493 received palliative radiotherapy  chemotherapy  alone or combined with radiotherapy   or symptomatic treatment alone  only five  1   survived five years  median survival was related to cell type  adenocarcinoma 2 6 months  squamous cell carcinoma 6 2 months   stage  stage i 8 5 months  stage iii 4 months   and karnofsky performance index  greater than or equal to 90 9 3 months  less than or equal to 50 1 2 months   age and sex had no independent prognostic value in any group  performance score was highly correlated with stage  and age  and in this study represented the  best prognostic factor  in clinical practice  
class8	life threatening haemoptysis in cystic fibrosis  an alternative therapeutic approach  published erratum appears in thorax 1991 apr 46 4  274  desmopressin and vasopressin were used to control massive haemoptysis in a patient with cystic fibrosis  after bolus doses a continuous infusion of vasopressin was maintained for 36 hours and haemoptysis stopped  
class8	intercostal arteriovenous fistula due to pleural biopsy a 32 year old woman had a pleural biopsy for a left pleural effusion  which showed caseating granuloma typical of tuberculosis  when the fourth biopsy specimen was removed considerable bleeding occurred from the puncture site  four days later a bruit was audible over the punctured area  radiating to the back  eight days after the procedure the patient had a massive bleed into the left pleural space  selective aortic angiography showed an arteriovenous fistula between the 9th intercostal artery and vein and a pseudoaneurysm in the intercostal punctured area  thoracotomy showed bleeding from the site of the pleural biopsy  the intercostal vessels were ligated and pleural decortication was performed  and the patient recovered uneventfully  
class8	chylothorax secondary to obstruction of the superior vena cava  a complication of the leveen shunt  a case of thrombosis of the superior vena cava was complicated by bilateral chylothoraces and a widened mediastinum  removal of a clotted leveen shunt led to prompt resolution of the obstruction and chylothoraces  
class8	pulmonary embolization of iodine 125 seeds following prostate implantation  the optimal treatment of prostatic carcinoma limited to the gland remains controversial  treatment has included implantation of iodine 125 seeds via both a suprapubic approach and  more recently  a transperineal technique utilizing ultrasound guidance  we recently have noted a heretofore unreported complication with this latter technique  namely  embolization of seeds to the lungs  review of the chest x ray films of 31 patients who underwent suprapubic implants showed no evidence of this phenomenon  one of 5 patients undergoing transperineal implant was found to have seeds lodged in the lung  complications surrounding the various treatments of localized prostate carcinoma are reviewed  
class8	prognostic factors and value of adjunctive nephrectomy in patients with stage iv renal cell carcinoma  we reviewed 57 cases of stage iv renal cell carcinoma to clarify the factors influencing prognosis and to evaluate the value of nephrectomy  cumulative survival from the initial diagnosis was analyzed with respect to the patients  age  sex  side of primary tumor  initial performance status  ps   site of metastasis  and nephrectomy  overall survival for the patients was 51 percent at one year  22 percent at three years  and 11 percent at five years  age  sex  and side of primary tumor had no influence on survival  improved survival was correlated with good ps  metastases limited to single organ  and removal of the primary tumor  with regard to histopathologic features in nephrectomized patients  low grade and stage were correlated with longer survival  these factors should be considered in the analysis of results of future clinical trials of metastatic renal cell carcinoma  
class8	papillary carcinoma of the thyroid with mucoepidermoid features  the significance and differential diagnoses of signet ring cells found in the fine needle aspirate of metastatic mucoepidermoid carcinoma from the thyroid are reported and discussed  the primary tumor occurred in a 35 year old man  who had a history of neck irradiation during his childhood  despite postoperative treatment with 60 gy external radiation and 1 200 mci 131i  the patient has at present  12 years after the initial operation  progressive disease with local recurrence in the neck as well as lung metastases  
class8	continuous electrocardiographic monitoring in hypertensive crises in pregnancy  twenty four patients first seen with hypertensive crises during pregnancy were studied by continuous electrocardiographic monitoring for a period of 24 hours to detect the presence of serious ventricular arrhythmias  three patients were excluded from analysis because of low serum potassium levels  thirteen of the remaining 21 patients had ventricular tachycardia on subsequent analysis of the electrocardiogram  these arrhythmias subsided after induction of anesthesia when blood pressure control was optimal  this finding may be implicated in the pathogenesis of pulmonary edema and sudden death in these patients  
class8	neonatal complications at term as related to the degree of umbilical artery acidemia  the degree of umbilical arterial acidemia associated with immediate newborn morbidity has not been determined  therefore we compared 358 term infants with umbilical artery acidemia  ph less than 7 20  with 358 term  nonacidotic matched control infants  to evaluate immediate neonatal complications in both groups  nonacidotic was defined as an umbilical artery ph greater than or equal to 7 20  complications included seizures  persistent hypotonia  and or signs of end organ damage such as renal or cardiac dysfunction  none of the 693 newborns with an umbilical artery ph greater than or equal to 7 00 had such complications  two of 23 infants with an umbilical artery ph less than 7 00 had sequelae related to intrapartum asphyxia  in these two infants the umbilical artery ph was less than 7 00  the 1 minute and 5 minute apgar scores were less than or equal to 3 and the acidemia was metabolic in nature  
class8	ultrastructure of respiratory cilia of wic hyd male rats  an animal model for human immotile cilia syndrome  the wic hyd rat is a mutant from the csk  wistar imamichi rat  with spontaneous hydrocephalus  in male rats  the hydrocephalus is severe and about one half of hydrocephalic male littermates possess situs inversus totalis  ependymal cilia in these animals are immotile  and this defect is regarded as a mechanical cause of hydrocephalus  this paper presents the ultrastructural features of respiratory cilia in these rats in comparison with those in human immotile cilia syndrome  the respiratory cilia in these rats also are immotile and the dynein arms are missing  as in human cases  previously only eight dogs with immotile cilia syndrome and a mutant hydrocephalic polydactyl mouse were reported with respect to these phenomena  however the wic hyd rat is the first useful animal model for human immotile cilia syndrome  and further studies may serve to clarify the genetic background of this condition  
class8	selective differences in macrophage populations and monokine production in resolving pulmonary granuloma and fibrosis  alveolar macrophages  am  and their production of interleukin 1 like activity  il 1  and macrophage derived growth factor for fibroblasts  mdgf  were examined during chronic inflammatory reactions leading to either granuloma formation or fibrosis  groups of five rats each received  respectively  a single transtracheal injection of xonotlite  attapulgite  short chrysotile 4t30  uicc chrysotile b asbestos  or saline  one month later  such treatments induced either no change  xonotlite   granuloma formation  attapulgite and short chrysotile 4t30   or fibrosis  uicc chrysotile b   by 8 months  however  the granulomatous reactions had resolved or greatly diminished  whereas the fibrosis persisted irreversibly  parallel examination of cell populations obtained by bronchoalveolar lavage revealed that multinucleated giant macrophages  mgc  were present in lavage fluids of animals with resolving granulomatous reactions but absent in those obtained from animals with lung fibrosis  evaluation of monokine production by inflammatory macrophages also revealed significant differences  enhanced production of il 1 like activity was seen in both types of lung injury  although especially during the early stage  1 month  and decreased thereafter  8 months   by contrast  augmentation of mdgf production was observed in animals with lung fibrosis only and persisted up to 9 months  taken together  these data indicate that production of selected cytokines  as well as am differentiation along a given pathway  may modulate the outcome of a chronic inflammatory response  
class8	thromboxane synthetase inhibition decreases polymorphonuclear leukocyte activation following hindlimb ischemia  ischemia of the lower extremity has been shown to cause pulmonary leukostasis and increased pulmonary artery pressure  thromboxane  tx  has been implicated as a mediator in this process  the effect of oky 046  a tx synthetase inhibitor  on polymorphonuclear leukocyte  pmn  production of superoxide anion  o2   as determined by ferricytochrome reduction was examined  fourteen dogs were subjected to 6 hours of bilateral gracilis muscle ischemia followed by 1 hour of reperfusion  o2  production from resting pmns and pmns stimulated with opsonized zymosan  oz  0 1 mg ml  was measured prior to ischemia or drug treatment  baseline   and following reperfusion in both treated  n   7  and control groups  n   7   serum tx levels were measured using a radioimmunoassay  following reperfusion  tx levels in the treated group were decreased as compared with the control group  18     2 pg ml vs  72     26 pg ml  p less than 0 05   superoxide production by both resting and stimulated pmns was also decreased in the treated group  from 0 98     0 16 nmol to 0 43     0 12 nmol o2  in the resting state  p less than 0 05  and from 13 3     1 5 nmol to 9 0     1 1 nmol o2  after stimulation  p less than 0 005   o2  production was increased in the control group following reperfusion as compared with baseline samples  and this increase was attenuated by treatment with oky 046  tx synthetase inhibition decreases activation of pmns following hindlimb ischemia  
class8	treatment of intractable aspiration using a laryngeal stent or obturator  twenty five patients were treated with a laryngeal stent for potentially reversible chronic aspiration of life threatening magnitude  the causes of the intractable aspiration were diverse and included chronic neurologic disease  extensive head and neck surgery  and severe gastroesophageal reflux  the advantages of this technique are noted in comparison to those of more invasive procedures  disadvantages of the laryngeal stent and complications encountered are also covered  the long term results show that all but one patient had a significant improvement in their chronic aspiration with the stent in place  however  only eight patients achieved adequate oral deglutition without aspiration following stent removal  
class8	transtracheal delivery of oxygen  efficacy and safety for long term continuous therapy  transtracheal  tt  oxygen delivery involves administration of oxygen percutaneously through a catheter inserted in the suprasternal trachea  transtracheal oxygen delivery has been proposed as a means of overcoming the high visibility  inconvenience  and discomfort associated with nasal cannula use  this report describes our experience using tt delivery in 40 patients with chronic obstructive pulmonary disease  n   32  and other types of lung disease  n   8   overall acceptance of tt catheter use was high and only 5 subjects elected to discontinue use  we believe the tt route is a relatively safe approach for oxygen administration and a promising method of improving patient compliance  it also offers the potential of more adequately oxygenating patients with refractory hypoxemia  
class8	surgical applications of ultrathin flexible bronchoscopes in infants  ultrathin flexible bronchoscopes with controlled distal angulation allow the conventional diagnostic examination of the lower airways of even the smallest infants  these instruments may be passed through small endotracheal or tracheostomy tubes while ventilation is maintained  it is thus possible  under direct visualization  to control the manipulation of surgical instruments where they could not otherwise be seen  or to study airway dynamics and anatomy intraoperatively without extubating the patient  
class8	skull base malignancy following long term sinus mucocele and osteomyelitis  a case of skull base malignancy following long term sinus mucocele is presented  while the similarity in clinical signs between sinus mucocele and malignancy has recently been emphasized in the literature  no previous case of skull base malignancy following frontoethmoid mucocele has been reported  the literature is reviewed and the association between inflammatory conditions and sinus malignancy is outlined  
class8	laryngeal dystonia  a series with botulinum toxin therapy  laryngeal dystonia is a syndrome characterized by action induced  involuntary spasms of the laryngeal muscles  most patients have involvement of the adductor laryngeal muscles producing uncontrolled spasms during phonation  and a  strain strangle  speech pattern commonly termed  spastic dysphonia   other patients have involvement of the abductor muscles producing  whispering dysphonia   rare patients have paradoxical vocal cord motion during respiration with adductor spasms on inspiration  over the past 5 years we have used botulinum toxin  botox  to treat more than 200 patients with laryngeal dystonia  this group includes patients with adductor involvement  phonatory dystonia  recurrent laryngeal nerve section failure  respiratory dystonia  and those with abductor involvement  whispering dystonia   patients received benefit within 24 to 72 hours  with sustained improvement for 2 to 9 months with an average of 4 months  patients improved to an average of 90  of normal function  clinically significant adverse effects included extended breathy dysphonia and mild choking on fluids  botox has become our treatment of choice for dystonic conditions of the larynx  
class8	management of subglottic stenosis in the adult  twenty one adult patients were surgically treated for severe subglottic stenosis refractory to endoscopic treatment  patients were treated by anterior or anterior and posterior cricoid division with costal cartilage grafting  seventy six percent of the patients were successfully decannulated  success of treatment was not dependent on cause of the stenosis or age or sex of the patient  there was a significantly better outcome  p less than  05  in patients with isolated subglottic stenosis versus those with combined glottic and subglottic stenosis  
class8	radiological abnormalities among sheet metal workers in the construction industry in the united states and canada  relationship to asbestos exposure  we investigated the possible adverse health effects to sheet metal workers who had past exposure to asbestos  a cross sectional medical examination of 1 330 workers was conducted during 1986 and 1987 in seven cities in the united states and canada  a total of 1 016 workers had been employed for at least 35 y in the industry  and the mean duration from onset of asbestos exposure was 39 5 y  sd   7 41 y   chest x ray abnormalities were found in more than half of the group  pleural fibrosis  the most frequently found abnormality  was present in 47 0  of the cases and was the only abnormality found in 27 8  of cases  parenchymal interstitial fibrosis  found in 33 1  of cases  was the only abnormality found in 16 2  of cases  radiologic abnormalities increased as duration of exposure increased  a positive smoking history was associated with a higher prevalence of radiologically detectable parenchymal abnormalities  a finding confirmed by us and others  dyspnea on exertion was graded by a medical research council questionnaire  the examinee s self assessment  and a more detailed 12 point scale questionnaire  few persons had marked shortness of breath  and approximately one third had slight dyspnea  individuals who had radiologic abnormalities experienced more shortness of breath than did those who had no radiologic abnormalities  cigarette smoking also resulted in a higher prevalence of dyspnea  the results indicate that during the past  construction sheet metal workers have been significantly exposed to asbestos on the job  every effort should be made to minimize the anticipated serious health consequences  and further asbestos exposure for those who continue in this trade should be avoided  
class8	proportion of lung and bladder cancers in males resulting from occupation  a systematic approach studies conducted in several countries that investigated the relationship of occupation and cancer in men were reviewed and compared  estimates of the proportion of cancers due to occupational exposure that occurred in the general population were analyzed  and sources of variation were explored  a systematic and standardized evaluation of studies on lung and bladder cancer were undertaken  and only investigations that allowed for confounding from tobacco smoking were included  the proportion of lung cancers attributable to occupation ranged between 1 and 5   when considering only exposure to asbestos  and 40   in a study with a high proportion of subjects exposed to ionizing radiation   for bladder cancer  estimates were between 0 and 3  in a few studies and between 16 and 24  in several investigations  no similar attempt of systematic comparison was possible for other cancers  
class8	pulmonary tumor embolism to alveolar septal capillaries  a prospective study of 12 cases  pulmonary tumor embolism leading to subacute cor pulmonale has been extensively studied  however  to our knowledge  the involvement of pulmonary alveolar capillaries has not previously been studied in detail  a prospective study was conducted on 112 autopsied patients with cancer to determine the presence of microembolism in the alveolar septal capillaries  fifteen sections of predetermined lung areas were obtained and examined  tumor embolism to alveolar septal capillaries was detected in 12 cases  10 7    with simultaneous involvement of other vascular territories in 11  seven patients had dyspnea  four  right ventricular failure  four  hypertrophy of the right ventricle  and three  arterial vascular sclerosis  the present data have led us to conclude that pulmonary tumor embolism to alveolar septal capillaries occurs in association with the involvement of arterial or lymphatic vessels and should be analyzed within the context of the study of subacute cor pulmonale  
class8	pneumonia complicating abdominal sepsis  an independent risk factor for mortality  nosocomial pneumonia  np  is associated with a significant mortality  66  in a previous retrospective study of np complicating intra abdominal sepsis  ias   we prospectively compared the outcome of np complicating ias with that of recurrent ias  r ias  in the absence of np  data were collected prospectively on 300 patients with ias  34 patients who presented with pneumonia were excluded from the analysis  44  mortality   one hundred seventy one patients with no np and no r ias  group 1  had a hospital mortality of 20   34 patients   36 without np in whom r ias developed  group 2  had a 17  mortality  six patients   and 47 with np but no r ias  group 3  had a 53  mortality  25 patients   finally  12 patients who had both np and r ias suffered a 75  mortality  nine patients   we examined the relationships among the following putative risk factors and mortality  apache  acute physiology and chronic health evaluation  ii score  at initial presentation with ias   the need for mechanical ventilatory assistance following initial treatment for peritonitis  steroid requirement  generalized peritonitis vs abscess  and the need for surgical as opposed to percutaneous treatment  using mortality as the dependent variable  group 2 vs 3 as the explanatory variable  and the risk factors as confounders  logistic regression analysis indicated that the group difference was significant after controlling for confounders  we conclude that np complicating ias is an independent risk factor associated with a significant mortality compared with r ias  these data challenge the notion that death in ias is usually due to recurrent or persistent intra abdominal infection  
class8	detection of hiv 1 in human lung macrophages using the polymerase chain reaction  we have used the polymerase chain reaction to investigate hiv 1 infection of lung macrophages from 44 aids patients with pneumonia  proviral hiv 1 dna was detected in the lung macrophages of 47   21 of 44  of patients tested  32   seven of 21  of the patients had pneumocystis carinii pneumonia  pcp   and 56   11 of 21  had pneumonia caused by other aetiological agents  matched peripheral blood specimens were obtained from 22 patients in this study  and hiv 1 specific dna was detected in 100   22 out of 22  of non adherent white cell preparations tested  hiv was detected in blood monocytes of 11 out of 22 patients  50    and a virus signal was also found in the lung macrophages of eight of these patients  our results indicate that pcp does not predispose lung macrophages to hiv 1  nor does hiv 1 infection of lung macrophages increase the probability of contracting pcp  
class8	low dose dapsone prophylaxis of pneumocystis carinii pneumonia in aids and aids related complex  the efficacy  toxicity and cost of orally administered dapsone  50 100 mg day  for prophylaxis of pneumocystis carinii pneumonia  pcp  were evaluated in 30 patients with aids or aids related complex  arc   six patients received primary and 24 secondary prophylaxis  ten patients received a maximum dose of 100 mg day and 20 a maximum of 50 mg day for a median duration of 19 weeks  22 of the 30 patients continue to receive prophylaxis as of may 1989  four patients have died  none of pneumocystis infection  one patient with aids suffered a mild relapse while receiving 50 mg day  hematologic toxicity was mild and could not be definitively attributed to dapsone therapy  rash due to dapsone was documented in two patients  a review of 33 patients at our institution with a history of pcp who received no prophylaxis demonstrated seven relapses  three of which were fatal  cost analysis revealed a significant advantage for oral dapsone over aerosolized pentamidine  
class8	impact of hiv on tuberculosis in zambia  a cross sectional study objective  to examine the contribution of hiv infection to the apparently increasing incidence of tuberculosis in central africa  design  cross sectional study  setting  outpatient clinic in teaching hospital  lusaka  zambia  patients  346 adult patients with tuberculosis  results  overall  206 patients  60   95  confidence interval 54  to 65   were positive for hiv  in one or both assays used  the peaks for both tuberculosis and hiv infection were among men aged 25 34 years and women aged 14 24 years  of patients with confirmed pulmonary tuberculosis  73 149  49   41  to 57   were positive for hiv  67 83  81   70  to 89   patients with pleural disease and 16 19  84   60  to 97   patients with pericardial disease were positive  hiv positive patients with positive sputum culture were less likely to have had a positive sputum smear  and their chest x ray films less often showed classic upper zone disease or cavitation  of 72 patients who fulfilled clinical criteria for aids  17 were negative for hiv  conclusions  the high prevalence of hiv in patients with tuberculosis suggests that an epidemic of reactivating tuberculosis is arising in those who are infected with hiv  the redirection of public health priorities towards tuberculosis would focus on a major treatable and preventable complication of the aids epidemic  
class8	prevalence of acute mountain sickness in the swiss alps  objective  to assess the prevalence of symptoms and signs of acute mountain sickness of the swiss alps  design  a study using an interview and clinical examination in a representative population of mountaineers  positive symptoms and signs were assigned scores to quantify the severity of acute mountain sickness  setting  four huts in the swiss alps at 2850 m  3050 m  3650 m  and 4559 m  subjects  466 climbers  mostly recreational  47 at 2850 m  128 at 3050 m  82 at 3650  and 209 at 4559 m  results  in all  117 of the subjects were entirely free of symptoms and clinical signs of acute mountain sickness  191 had one or two symptoms and signs  and 158 had more than two  those with more than two symptoms and signs were defined as suffering from acute mountain sickness  at 4559 m 11 climbers presented with high altitude pulmonary oedema or cerebral oedema  or both  men and women were equally affected  the prevalence of acute mountain sickness correlated with altitude  it was 9  at 2850 m  13  at 3050 m  34  at 3650 m  and 53  at 4559 m  the most frequent symptoms and signs were insomnia  headache  peripheral oedema  and scanty pulmonary rales  severe headache  vomiting  dizziness  tachypnoea  and pronounced pulmonary rales were associated with other symptoms and signs and therefore characteristic of acute mountain sickness  conclusion  acute mountain sickness is not an uncommon disease at moderately high altitude  that is  above 2800 m  severe headache  vomiting  dizziness  tachypnoea  and pronounced pulmonary rales indicate severe acute mountain sickness  and subjects who suffer these should immediately descend to lower altitudes  
class8	physical and psychosocial consequences of total laryngectomy  the incidence and severity of respiratory symptoms after total laryngectomy and their influence on daily living were studied in 59 laryngectomized patients  daily sputum production was the principal complaint of these patients  98    followed by coughing  64   and the need for frequent forced expectoration  more than 5 times a day  in order to clear the airway  57    frequent stoma cleaning  more than 5 times a day  was required by 37  of the patients  significant correlation was found between respiratory symptoms  voice rehabilitation and several aspects of daily living  including fatigue  sleep problems  social contacts and psychological distress  these findings indicate that respiratory symptoms after total laryngectomy are both frequent and troublesome  the development of effective methods for minimizing and or preventing such respiratory problems would contribute significantly to improving the quality of life of laryngectomized patients  
class8	chronic otitis media  the significance of nasal obstruction  the nasal airway resistance of 15 patients with unilateral chronic otitis media and 15 controls was measured by anterior active rhinomanometry  airway resistance was measured on each side before and after decongestion to differentiate resistance due to structural abnormality from that due to mucosal swelling  the nasal resistance was significantly greater  p less than 0 01  on the side of the affected ear in patients with unilateral chronic otitis media before decongestion  but following decongestion the difference was not significant  nasal obstruction is a significant determinant in unilateral chronic otitis media and although septal displacement may be the underlying cause  the major component of the obstruction appears to be due to an associated mucosal oedema  
class8	lymphocytes and nonlymphoid cells in human nasal polyps  immunohistochemical stainings were performed on polyp specimens of 48 patients and on mucosal biopsy specimens of the middle and inferior turbinates of 23 and 28 patients  respectively  significantly more cd8   suppressor cytotoxic  than cd4   helper inducer  cells were found in the polyps  the number of cd2   cd4   and cd8  lymphocytes in nasal polyps were very similar to the number in the macroscopically unaffected mucosa of the middle turbinates  whereas scores in the inferior turbinates were lower  in healthy subjects  the differences were smaller  cd22  b cells were detected in varying numbers in the polyps in more or less organized clusters  significantly more hla dr  cells were found in polyps and middle turbinates than in the inferior turbinates  eosinophils were found in moderate to large numbers in polyps of 77  of the patients  mast cells and plasma cells were detected in moderate numbers  whereas neutrophils were found in 35  of the patients  in the middle and inferior turbinates varying but small numbers of eosinophils  mast cells  plasma cells  and neutrophils were found  in considering these findings  the role of chronic inflammation with t cell dependent disturbances is discussed with regard to the pathogenesis of nasal polyps  
class8	diagnostic value of anti neuronal antibodies for paraneoplastic disorders of the nervous system  the diagnostic value of the presence of anti neuronal antibodies in serum was examined in 21 patients suspected of paraneoplastic disorders of the nervous system  ns   group 1  and was compared to three control groups  group 2  25 patients with a neurological disease  without cancer and no sign of paraneoplastic disorder  group 3  27 patients with neurological disease and cancer and no signs of a paraneoplastic disorder  group 4  94 patients with cancer and without neurological disease  in group 1  anti neuronal nuclear antibodies were detected in eight patients  38    in titres from 1 1000 to 1 32 000  a small cell lung cancer was present in six patients  ovarian cancer in one patient and in one patient no tumour could be detected  the neurological symptoms preceded a diagnosis of cancer in five out of eight patients  anti neuronal antibodies were found in the serum of two out of 94 patients  2   from control group 3 but not in serum from any of the other control groups  these data indicate a moderate sensitivity of 38   but a high specificity of 98 6   95  confidence interval 95 5 99 8   for the presence of anti neuronal nuclear antibodies if a paraneoplastic ns disorder is suspected  
class8	bronchopulmonary dysplasia  improvement in lung function between 7 and 10 years of age  to evaluate the natural history of bronchopulmonary dysplasia  we studied the same 32 patients at a mean age of 7 and 10 years  the group as a whole had normal height and weight percentiles  and each child grew along his or her established somatic growth curve  although some children had abnormal values  the group maintained a normal mean total lung capacity and functional residual capacity  the mean residual volume and the residual volume total lung capacity ratios were elevated at both ages  at age 7 years the 19 patients  59   who had a forced expiratory volume in 1 second  fev1  of less than 80  had  catch up  improvement by 10 years of age  65     11  to 72     16  of predicted value  p less than 0 05   all the children who had a normal fev1 at 7 years of age continued to have a normal fev1 at age 10 years  resting single breath carbon monoxide uptake by the lung was normal when measured at age 10 years  the majority of patients had a positive methacholine challenge test result at both ages  although there was a low incidence of clinically diagnosed asthma  this study demonstrates that patients with bronchopulmonary dysplasia who have normal lung function at age 7 have had normal lung growth and that those with evidence of mild to moderate lung disease have continued lung growth or repair  or both  during their school years  
class8	relationship of parental smoking to wheezing and nonwheezing lower respiratory tract illnesses in infancy  group health medical associates  the relationship between parental smoking and lower respiratory tract illness  lri  was studied in a large cohort of infants followed prospectively from birth  illnesses were diagnosed by physicians using agreed on criteria  and parental smoking histories were obtained by questionnaire  the lris were differentiated into wheezing and nonwheezing episodes  and the age at first illness of either type was evaluated in relation to smoking by parents  the odds of having an lri were significantly higher in children whose mothers smoked  odds ratio 1 52  confidence interval 1 07 to 2 15   the odds were higher if the mother smoked a pack of cigarettes or more per day and if the child stayed home rather than attending day care  odds ratio 2 8  confidence interval 1 43 to 5 5   logistic regression indicated that the lri rate was significantly elevated both in children exposed to heavy maternal smoke in the absence of day care  and in those who use day care but were not exposed to maternal smoking of a pack or more per day  these findings could not be attributed to other confounding variables  neither paternal smoking nor smoking by other household members was consistently related to the lri rate  the relationship of maternal smoking to lri rate was evident for both wheezing and nonwheezing illnesses  maternal smoking of a pack or more per day was also related to an early age at first lri  for both wheezing  p less than 0 05  and nonwheezing  p less than 0 002  illnesses  in sum  maternal smoking is associated with a higher rate of lris in the first year  particularly when mothers smoked a pack or more per day and when the child did not use day care  
class8	community acquired influenza c virus infection in children  to clarify the epidemiologic and clinical features of community acquired influenza c infection in children  we took specimens throughout the year from a larger number of patients with acute respiratory illnesses in a pediatric clinic in yamagata  japan  during a 2 year survey  20 strains of influenza c virus were isolated from 13 426 specimens  these isolates were recovered throughout the year  the ages of patients with influenza c virus isolates ranged from 2 months to 11 years and peaked at the age of 1 year  the clinical diagnosis of patients with influenza c virus infection included bronchitis in one child and pneumonia in four  community acquired influenza c infection in children can cause a variety of respiratory illnesses that cannot be clinically differentiated from those caused by other viruses  
class8	decreased mortality rate among small premature infants treated at birth with a single dose of synthetic surfactant  a multicenter controlled trial  american exosurf pediatric study group 1  to determine whether a single prophylactic dose of synthetic surfactant would reduce mortality and morbidity rates  we performed a randomized  controlled trial of exosurf neonatal at 19 hospitals in the united states  the exosurf preparation  5 ml kg  was instilled into the endotracheal tube of premature infants weighing 700 to 1100 gm during mechanical ventilation  as soon as practical after birth  control infants were treated with air  5 ml kg   dose administration was performed in secrecy by clinicians who did not reveal for 2 years what they had instilled  a total of 222 infants received air and 224 received the synthetic surfactant  36 infants with congenital pneumonia or malformations were excluded from the primary efficacy analysis  by the age of 28 days  there were 44 deaths in the air group and 27 deaths in the surfactant group  p   0 022   by the age of 1 year after term there were 61 deaths in the air group and 35 deaths in the surfactant group  p   0 002   although there was no reduction in the incidence of respiratory distress syndrome  a significant reduction in the number of deaths attributed to respiratory distress syndrome  a significant reduction in the incidence of pulmonary air leaks  and significantly lower requirements for oxygen and mean airway pressure indicated that lung disease was less severe in the exosurf treated infants  there were no significant differences in the incidence of complications such as bronchopulmonary dysplasia  intraventricular hemorrhage  patent ductus arteriosus  necrotizing enterocolitis  and infection  the results indicate that a single prophylactic dose of exosurf  in high risk premature infants treated soon after birth  reduces the number of deaths from respiratory distress syndrome and the overall mortality rate  
class8	preoperative chemotherapy  cisplatin and fluorouracil  and radiation therapy in stage iii non small cell lung cancer  a phase ii study of the lung cancer study group  the lung cancer study group conducted a phase ii pilot study of concurrent chemotherapy and radiation therapy  chemoradiotherapy  before surgery in 85 eligible patients with non small cell cancer limited to the chest but in whom attempted resection would have been likely to leave residual disease  advanced stage iiia and minimal stage iiib disease   cisplatin  75 mg m2  was given on days 1 and 29  fluorouracil  1 g m2 per 24 hours  was administered as a continuous infusion on days 1 through 4 and on days 29 through 32  and thoracic radiation  30 gy in 15 fractions  was administered on days 1 through 19  two patients achieved a complete response and 46 patients had a partial response for an overall response rate of 56   toxicity from chemoradiotherapy was moderate but acceptable  eight weeks after therapy was initiated  54 patients underwent thoracotomy and tumor resection was attempted  29  34   had complete resection and 15  18   had incomplete resection  although surgical dissection was generally more difficult than in patients not pretreated with chemoradiotherapy  there was no apparent increase in postoperative complications  in 8 patients  9    no viable tumor was detected pathologically in the resection specimen  of the 18 patients whose tumors were completely resected and had disease recurrence  none had recurrence only in the chest  12  67   had recurrence only in distant sites  and 3 developed second primary tumors  median survival of all patients was 13 months  the overall results do not indicate a major benefit from this preoperative chemoradiotherapy regimen in patients with advanced but potentially resectable non small cell lung cancer  these results suggest a need to define better the relative roles of preoperative radiotherapy and chemotherapy  
class8	ibuprofen prevents deterioration in static transpulmonary compliance and transalveolar protein flux in septic porcine acute lung injury  the effects of intravenous ibuprofen on measurements of pulmonary function and alveolar capillary membrane permeability to protein in sepsis induced porcine acute lung injury  ali  were studied  young swine  15 25 kg  were anesthetized  cannulated  and ventilated  5 cm h2o peep  0 5 fio2  and 15 cc kg tidal volume   three groups were studied  septic animals  ps  n   10  received pseudomonas aeruginosa for 1 hr iv  controls  c  n   9  received 0 9  nacl  and ibuprofen treated septic animals  ps   ibu  n   7  received ibuprofen 12 5 mg kg at 0 and 120 min post ps  systemic  sap  and pulmonary  pap  arterial pressures  pao2  cardiac index  ci   static lung compliance  cl   evlw  thermal cardiogreen   and peripheral white blood cell counts  wbc  were measured  bronchoalveolar lavage  bal  was performed for protein and   neutrophil   pmn  content  results  ps produced significant  p less than 0 05  decreases in cl  pao2  sap  ci  and peripheral wbc and increases in pap  evlw  bal protein  and  pmn s vs  controls  ibu prevented the early increase in pap and attenuated the late increase in pap and evlw  ibu also maintained pao2  cl  bal protein  and  pmn s in bal at control levels  but exhibited no significant effect on peripheral leukopenia  these data strongly suggest that ibuprofen administered before and at 120 min after onset of pseudomonas infusion improves lung compliance and affects neutrophil function sufficiently to significantly ameliorate many of the physiologic derangements in acute sepsis  
class8	the rat lung organotypic culture  an in vitro model for studying surfactant metabolism abnormalities  the amount of surfactant present in the intra alveolar space is mainly regulated by the synthesis and recycling of surfactant by type ii pneumocytes  biochemical analyses have shown that the surfactant level is frequently diminished and that protein rich exudate can further interfere with surfactant function in the lungs of adult respiratory distress syndrome  ards  patients  the microenvironmental changes that occur in the alveoli of burned patients  who are prone to developing ards  are unclear  therefore  using an in vitro rat lung organotypic culture  we showed that the sera of rats with a 3 day old  third degree thermal injury  25 30  total body surface area  inhibited surfactant synthesis in organotypically cultured rat lung cells  surfactant precursor  3h choline  incorporation into the surfactant was 58  of control  using liposomes made of dipalmitoyl phosphatidylcholine and phosphatidylglycerol  8 1  v v  or surfactant we showed that surfactant endocytosis by purified type ii alveolar cells is an active  temperature dependent process  and correlates with the quantity of surfactant present in the milieu  we also found that plasma protein rich fluid interfered with surfactant endocytosis by the purified type ii pneumocytes  these two processes of inhibition of surfactant synthesis and its reutilization by these cells may contribute to the pathogenesis of ards  
class8	isolated hyoid bone fracture  a case report and review of the literature  isolated hyoid bone fractures secondary to trauma other than strangulation are rare and have few  if any  complications  we report a case of an isolated hyoid bone fracture that resulted in sudden and severe upper airway compromise  diagnosis of these fractures is difficult and usually can be made only with a strong degree of suspicion  patients who suffer neck injuries in whom a hyoid fracture is diagnosed or strongly suspected should be observed for 48 to 72 hours  considered for endoscopy  and treated as warranted  
class8	microscopic pulmonary tumor embolism causing subacute cor pulmonale  a difficult antemortem diagnosis  published erratum appears in mayo clin proc 1991 apr 66 4  439  microscopic pulmonary tumor embolism is difficult to diagnose  the most common initial clinical symptom is subacute progressive dyspnea  and the initial laboratory evaluation typically shows hypoxemia in a patient with clear lung fields on a chest roentgenogram  another distinguishing feature may be hepatic abnormalities  in general  pulmonary angiography discloses no evidence of emboli  but multiple subsegmental peripheral perfusion defects are noted on ventilation perfusion lung scans  the diagnosis of microscopic pulmonary tumor embolism can be confirmed by open lung or transbronchial lung biopsy or by microvascular pulmonary cytology  a less invasive procedure that could be performed at the time of pulmonary angiography  herein we describe two patients with unsuspected microscopic pulmonary tumor embolism that eventuated in subacute cor pulmonale and death  these cases illustrate the characteristic findings of this entity and emphasize the need for early diagnosis  
class8	oxygen exacerbated bleomycin pulmonary toxicity bleomycin is an antineoplastic agent with potential for producing pulmonary toxicity  attributed in part to its free radical promoting ability  clinical and research experiences have suggested that the risk of bleomycin induced pulmonary injury is increased with the administration of oxygen  we report a case in which the intraoperative administration of oxygen in the setting of previous bleomycin therapy contributed to postoperative ventilatory failure  our patient recovered with corticosteroid therapy  physician awareness of a potential interaction between oxygen and bleomycin may help reduce the morbidity and mortality related to bleomycin therapy  
class8	pulmonary aspergillosis in the acquired immunodeficiency syndrome background and methods  symptomatic pulmonary aspergillosis has rarely been reported in patients with the acquired immunodeficiency syndrome  aids   we describe the predisposing factors  the clinical and radiologic features  and the therapeutic outcomes in 13 patients with pulmonary aspergillosis  all of whom had human immunodeficiency virus  hiv  infection and 12 of whom had aids  results  pulmonary aspergillosis was detected a median of 25 months after the diagnosis of aids  usually following corticosteroid use  neutropenia  pneumonia due to other pathogens  marijuana smoking  or the use of broad spectrum antibiotics  two major patterns of disease were observed  invasive aspergillosis  in 10 patients  and obstructing bronchial aspergillosis  in 3   cough and fever  the most common symptoms  tended to be insidious in onset in patients with invasive disease  median duration  1 3 months before diagnosis   breathlessness  cough  and chest pain predominated in the three patients with obstructing bronchial aspergillosis  who coughed up fungal casts  radiologic patterns included upper lobe cavitary disease  sometimes mistaken for tuberculosis   nodules  pleural based lesions  and diffuse infiltrates  usually of the lower lobe  transbronchial biopsies were usually negative  but positive cultures were obtained from bronchoalveolar lavage fluid or percutaneous aspirates  dissemination to other organs occurred in at least two patients  and direct invasion of extrapulmonary sites was seen in two others  the results of treatment with amphotericin b  itraconazole  or both were variable  ten of the patients died a median of 3 months after the diagnosis  range  0 to 12 months   conclusions  pulmonary aspergillosis is a possible late complication of aids  if diagnosed early  it may be treated successfully  
class8	orofacial metastasis of pulmonary giant cell carcinoma  a patient was admitted to the hospital with multiple skin nodules of recent origin and signs and symptoms suggestive of acute pulmonary infection  because one of the skin masses was located overlying the left mandibular body region  the patient was referred to the hospital dentistry clinic for evaluation  historical  clinical  and radiographic assessments were consistent with reactive lymphadenopathy  and an intraoral excisional biopsy was performed  the biopsy results were indicative of giant cell carcinoma  which was confirmed by biopsy results from a similar skin lesion on the shoulder and by malignant cells recovered in the sputum and pleural fluids  although this carcinoma has been shown to rarely metastasize to the skin and lymphatics of the neck  this is the first case report of metastasis to facial lymphatics  
class8	ct and mr imaging in staging non small cell bronchogenic carcinoma  report of the radiologic diagnostic oncology group  the accuracies of magnetic resonance  mr  imaging and computed tomography  ct  in determining tumor classification and assessing mediastinal node metastases were compared in a prospective cooperative study of 170 patients with non small cell bronchogenic carcinoma  the sensitivity of ct in distinguishing t3 t4 tumors from t0 t2 tumors was 63   specificity was 84   these values for mr imaging were not significantly different  56  and 80    with receiver operating characteristic  roc  analysis  no difference existed between the accuracies of ct and mr imaging in diagnosis of bronchial involvement or chest wall invasion  but mr imaging was significantly more accurate than ct  p    047  in diagnosis of mediastinal invasion  lymph node sampling was performed in 155 patients  642 node stations   cancerous nodes were found in 14  of stations in 21  of patients  there was no significant difference between the accuracies of ct and mr imaging in detecting mediastinal node metastases  n2 or n3   the sensitivities were 52  and 48   respectively  and specificities were 69  and 64   roc analysis also showed no difference between ct and mr imaging  
class8	pulmonary atelectasis  signal patterns with mr imaging  to assess the signal characteristics of different types of pulmonary atelectasis on magnetic resonance  mr  images  the authors studied obstructive atelectasis  oa  in 17 patients and nonobstructive atelectasis  noa  in 25 patients  all patients underwent electrocardiographically gated mr imaging studies of the thorax with standard spin echo sequences  no signal differences were observed between either type of atelectasis on t1 weighted images  conversely  oa and noa appeared significantly different on spin density weighted images  p less than  001  and on t2 weighted studies  p less than  0001   on t2 weighted images  all 17 cases of oa appeared hyperintense  whereas 22 of 25 cases of noa demonstrated a very low signal intensity  differences in the pathophysiology of oa and noa presumably account for this observation  in oa  alveolar air is totally resorbed and secretions accumulate in the obstructed lung  the resulting increase in free fluid prolongs the t2 relaxation times and leads to high signal intensity on t2 weighted images  in noa  the short t2 relaxation time of lung tissue in the absence of secretions and potential magnetic susceptibility effects due to residual air are likely to be responsible for the low t2 signal pattern  
class8	fungal pulmonary infections after bone marrow transplantation  evaluation with radiography and ct  the authors reviewed 55 pairs of chest radiographs and computed tomographic  ct  studies obtained in 33 febrile bone marrow transplant  bmt  recipients  the images were read separately  without knowledge of the clinical diagnosis  twenty one episodes of fungal infection were documented  one chest radiograph showed a pneumonia like opacity  and 17 showed nodular opacities  five with cavitation  in 20 of 21 episodes  ct showed nodules with cavitation  n   7   halo  n   4   hazy margin  n   5   air bronchogram  n   2   cluster of fluffy nodules  n   1   or sharp margin  n   1   in none of the nine bacteremic episodes  however  were there opacities on chest radiographs or ct studies  ct studies demonstrating complicated nodules in febrile bmt patients strongly suggest a fungal infection  whereas negative ct studies suggest bacteremia or non filamentous fungal infection of nonpulmonary origin  ct appears to add useful information to radiographic analysis during the assessment of febrile episodes in bmt patients  especially when invasive diagnostic procedures pose a high risk  
class8	apical opacity associated with pulmonary tuberculosis  high resolution ct findings  to elucidate the nature of the apical opacity that is commonly seen in patients with tuberculosis  usually referred to as an  apical cap  or  apical pleural thickening   18 patients with upper lobe tuberculosis were studied with high resolution computed tomography  hrct   all had a homogeneous apical opacity at least 1 cm thick on chest radiographs  fifteen of the 18 had a history of pulmonary tuberculosis of more than 5 years duration  and nine showed evidence of ipsilateral pleurisy  hrct scans at the apex of the thorax in all nine patients scanned at this level showed that extrapleural fat with interspersed vessels accounted for most of the plain radiographic opacity  scans obtained at a level slightly above visible aerated lung showed extrapleural fat 3 25 mm thick peripherally and atelectatic lung centrally  at more caudal levels  at which both aerated lung and  thickened pleura  were visible on plain radiographs  hrct showed extrapleural fat  3 20 mm thick   thickened pleura  1 3 mm thick   and atelectatic lung peripherally and areas of emphysematous bullae  bronchiectasis  and atelectatic lung centrally  
class8	interstitial lung disease  impact of postprocessing in digital storage phosphor imaging  the ability to resolve the fine linear structures of interstitial lung disease is one measure of the limiting performance characteristics of an imaging system  conventional screen film radiography was compared with six algorithms of isodose storage phosphor digital radiography  0 2 mm x 10 bit pixel matrix  in the detection of interstitial lung abnormality documented by means of computed tomography in 40 patients with abnormalities and 25 healthy control subjects  performance was evaluated with an analysis of variance  the fisher paired comparison test  p less than  05  of the average receiver operating characteristic area of 2 730 observations by six readers  the moderately and the more markedly high frequency edge enhanced algorithms of storage phosphor digital radiographs were equivalent in performance to screen film radiography  the default mode  low  and medium frequency edge enhanced algorithms  and gray scale reversed mode of storage phosphor digital radiography were inferior to screen film radiography  the authors conclude that high frequency edge enhanced algorithms can perform as well as screen film radiography in the detection of interstitial disease  
class8	lesions that manifest as medial cheek and nasolabial fold masses  seventeen cases were collected in which the patient presented with a medial cheek or nasolabial fold mass  most of these lesions were uncommon  and some were rare  the most reliable differentiating finding was the type of associated bone involvement  the malignancies had bone erosion and as a group could be distinguished from the other masses  computed tomographic attenuation and magnetic resonance imaging signal intensities were nonspecific and did not allow a definitive diagnosis to be made  the types of pathologic conditions and their sectional imaging findings are reviewed  
class8	outpatient assessment of infants with bronchiolitis  two hundred thirteen infants younger than 13 months with bronchiolitis were prospectively followed up to identify the historical  physical  and laboratory clues at initial emergency department evaluation that would help to predict disease severity  based on their total course of illness  the patients were classified as having mild  139 patients  or severe  74 patients  disease  and the initial emergency department evaluation findings of these two groups were compared  six independent clinical and laboratory findings were identified that were strongly associated with more severe illness   1   ill  or  toxic  general appearance   2  oxygen saturation less than 95   as determined by pulse oximetry   3  gestational age  younger than 34 weeks   4  respiratory rate  70 min or greater   5  atelectasis on a chest roentgenogram  and  6  age  younger than 3 months  the infant s oxygen saturation as determined by pulse oximetry was the single best objective predictor of more severe disease  
class8	increased transient tachypnea of the newborn in infants of asthmatic mothers  objective  to compare the incidence of transient tachypnea of the newborn  ttn  in infants of asthmatic vs nonasthmatic mothers  research design  case control analysis  setting  group model health maintenance organization  patients  a volunteer sample of 294 pregnant asthmatic women and 294 pregnant nonasthmatic women with normal pulmonary function test results  matched on the basis of age and smoking status  all subjects entered the study before their third trimester of pregnancy  subjects with multiple gestations and abortions  less than 20 weeks  gestation  were excluded  intervention  asthma was treated in the allergy department  routine obstetric  neonatal  and pediatric care was provided to all patients by staff physicians  measurements results  transient tachypnea occurred in 11 infants  3 7   of asthmatic women and in one control infant  0 3    there were no significant differences between asthmatic and matched control subjects in previously defined ttn risk factors  such as the occurrence of longer labors  failure to progress  cesarean sections  premature births  male sex  apgar scores of less than 7 at 1 minute  or birth weight greater than 4 kg  although infants of asthmatic mothers were more likely to exhibit wheezing by age 15 months compared with control infants  12 0  vs 3 2    none of the infants with ttn manifested wheezing by age 15 months  no relationships could be identified in the asthmatic cohort between the occurrence of ttn and asthma severity or medication use  during the pregnancy in general or during labor and delivery in particular   conclusion  although the mechanism is uncertain  maternal asthma appears to increase the risk of infant ttn  
class8	should you cancel the operation when a child has an upper respiratory tract infection  cancelling an operation when a child has an upper respiratory tract infection  uri  is not always feasible or practical  yet we know very little about the additional risk posed by a uri occurring in a child undergoing anesthesia and surgery  using a large prospectively collected pediatric anesthesia database  we studied 1283 children with a preoperative uri and 20 876 children without a uri  we found that children with a uri were two to seven times more likely to experience respiratory related adverse events during the intraoperative  recovery room  and postoperative phases of their operative experience  although these children also experienced significant disruptions in temperature regulation  they were not at risk for any other deleterious events  the elevation in risk after uri as compared with children without a uri was not explained by differences in age  physical status scores  surgical site  and emergency or elective status  however  if a child had a uri and had endotracheal anesthesia  the risk of a respiratory complication increased 11 fold  95  confidence intervals 6 8  18 1   we conclude that the administration of general anesthesia to children with a uri is not benign and that these children require more observation management in all perioperative phases of their surgical procedure  
class8	pneumothorax in aids objective  to determine risk factors for the development of pneumothorax in patients with the acquired immunodeficiency syndrome  aids   design  prospective cohort study  setting  tertiary care center  patients  of 1030 patients with aids who were followed at memorial sloan kettering cancer center between 1 january 1980 and 30 september 1989  20  2   developed pneumothorax that was unrelated to trauma or a pulmonary procedure  results  of 20 patients with aids who presented with pneumothorax  19 had compelling evidence of concurrent pneumocystis carinii pneumonia  using bivariate analysis  patients receiving aerosol pentamidine prophylaxis  relative risk  17 6  and those with a history of p  carinii pneumonia  relative risk  14 5  were more likely to develop pneumothorax  by mantel haenszel stratified analysis  aerosol pentamidine use was a statistically significant risk factor independent of a history of p  carinii pneumonia  the pneumothorax related mortality rate was 10  and there was considerable morbidity  conclusions  patients with aids at the highest risk for developing pneumothorax are those with a history of p  carinii pneumonia who are receiving aerosol pentamidine prophylaxis but who nevertheless develop p  carinii pneumonia  the benefits of aerosol pentamidine prophylaxis in these patients far outweigh this risk  pneumocystis carinii pneumonia should be considered as the most likely diagnosis in any patient with aids who develops a pneumothorax  
class8	therapy of pulmonary nocardiosis in immunocompromised mice  we compared the bactericidal efficacies of various antimicrobial agents and combinations thereof in experimentally induced nocardia asteroides pneumonia in immunocompromised mice  cortisone acetate treatment  which produced impaired cell mediated immune function  was followed by nasal inoculation of 5 x 10 4  cfu of n  asteroides into each mouse  therapy was begun 24 h after inoculation and continued for the next 96 h  dosages of antimicrobial agents resulted in concentrations approximating levels in human serum  animals from each of nine treatment groups were sacrificed every 24 h  the pulmonary tissue obtained was homogenized and quantitatively cultured  results were calculated to indicate the number of cfu per gram of lung tissue  amikacin and imipenem were the two most effective single agents studied  sulfadiazine and ciprofloxacin were ineffective  and ceftriaxone reduced bacterial counts modestly  combination therapy did not enhance the bactericidal activities of the agents tested  we conclude that amikacin and imipenem  as well as select broad spectrum cephalosporins  represent therapy superior to the sulfonamides in this experimental model and may represent alternative treatment for patients who cannot tolerate sulfa agents  e g   human immunodeficiency virus infected patients  or who fail primary treatment  
class8	deferoxamine and eflornithine  dl alpha difluoromethylornithine  in a rat model of pneumocystis carinii pneumonia  the iron chelator deferoxamine and the polyamine biosynthesis inhibitor eflornithine  dl alpha difluoromethylornithine  were examined for anti pneumocystis carinii activity in the rat model of p  carinii pneumonia  the activity of deferoxamine at 250  500  and 1 000 mg kg given intraperitoneally provides evidence that iron chelation is a promising novel approach to p  carinii chemotherapy  results with eflornithine at 2  3  and 4  in drinking water confirm and extend previously reported activity in the rat model  
class8	recurrent wheezy bronchitis and viral respiratory infections fifty four patients aged from 1 to 6 years who had had recurrent attacks of wheezy bronchitis were prospectively followed up for three months to find out if there was an association between different viral respiratory infections and episodes of wheezing  of the 115 episodes of upper or lower respiratory tract symptoms  virus or mycoplasma pneumoniae infection were diagnosed in 52  45    thirty four of rhinoviruses  the patients had an average of 2 1 episodes of respiratory tract symptoms the total mean  sd  duration of which was 30  2  days of the 92 days that followed  wheezing occurred during 76  66   of the 115 episodes and during a third of these the patient was admitted to hospital because of severe dyspnoea  wheezing started a mean  sd  of 43  7  hours after the first symptoms of respiratory infection and persisted for 3 8  4 2  days in patients in whom virus infection was diagnosed  the incidence of wheezing was not associated with ige mediated atopy  with positive virological tests  or with fever during virus infection  but was associated with parental smoking and more than one sibling  
class8	wegener s granulomatosis presenting as temporal arteritis  a granulomatous giant cell vasculitis of the temporal artery was observed in a biopsy specimen from a patient with corresponding clinical symptoms  within weeks  the new onset of pulmonary infiltrates and renal failure prompted biopsy of the patient s kidney  a necrotizing glomerulonephritis  compatible with a diagnosis of wegener s granulomatosis  was present  vasculitis of the temporal artery may be a feature of wegener s granulomatosis  
class8	fatal pulmonary venoocclusive disease secondary to a generalized venulopathy  a new syndrome presenting with facial swelling and pericardial tamponade  we describe a patient who developed fatal pulmonary artery hypertension secondary to diffuse venulitis  this otherwise healthy young woman first presented with generalized venulopathy  with chemosis  facial swelling  pleural effusions  and pericardial tamponade  the symptoms partially responded to steroid therapy  but over a 2 year course  a rapidly progressive and fatal venoocclusive disease developed  no other primary condition was diagnosed  and at autopsy  the patient had striking venulitis throughout  including the pulmonary bed  we believe that this is a unique case of pulmonary hypertension resulting from a generalized venulopathy  
class8	tension pneumothorax associated with hyperbaric oxygen therapy  the authors present three patients who developed a tension pneumothorax while receiving emergent hyperbaric oxygen therapy for acute carbon monoxide poisoning  each patient was intubated and received closed chest compressions for cardiac arrest prior to hyperbaric oxygenation  despite the apparent absence of pneumothorax prior to hyperbaric therapy  tension pneumothorax was detected soon after decompression  these cases illustrate the need for vigilance in detecting and addressing pneumothorax prior to hyperbaric decompression in obtunded patients  serial physical examinations  arterial blood gas determinations  properly positioned chest radiographs  and a high index of suspicion for pneumothorax in the setting of emergent hyperbaric therapy are recommended  
class8	choroidal lesions in patients with aids  seven cases of bilateral  scattered  yellow white choroidal lesions have been seen in aids patients since january 1988  one resulted from presumed extension of cryptococcal meningitis into the optic nerve and choroid  all the remaining six patients had pneumocystis pneumonia at some time during the course of the disease and were receiving aerosolised pentamidine therapy  none died quickly of disseminated pneumocystis carinii infection  unlike previously reported patients  mycobacterial infection was also present in five of these six patients  the differential diagnosis of this entity in aids patients is discussed  
class8	treatment of end stage chronic obstructive pulmonary disease with double lung transplantation  six patients with end stage emphysema  age 44     2 years  underwent double lung transplantation  tx  from june 1988 through may 1990  all suffered from severe inanition and required oxygen therapy  the ischemic time was 193     28 minutes  post tx immune suppression was okt3  14 days   cyclosporine  trough levels of 150     25 ng ml   azathioprine to keep wbc at 3 000 to 5 000 cu mm  1 to 3 0 mg kg day  and following okt3  a tapering prednisone regimen  two rejection episodes that occurred in two patients on post tx day 5 and 10 were treated with bolus doses of methylprednisolone  the mean hospital stay was 32     7 days  range  20 to 69 days   four patients required treatment of cytomegalovirus  cmv  infection  gastritis   donor   recipient  in one and cmv pneumonia in two   donor   recipient   a fourth   donor   recipient  had right sided candida empyema six weeks post tx  developed cmv and staphylococcal sepsis  and died 64 days post tx  one patient required pyloroplasty eight weeks post tx and one patient underwent tracheal suture line repair at eight weeks  during a follow up of 81 patients months  range  8 to 24 months   one patient had developed epstein barr viral  ebv  induced lymphoproliferative disease in the lung and one patient had developed ebv lymphoma  three patients are at work  one is continuing rehabilitation  and one is at home  double lung tx offers a definitive benefit to patients with emphysema  however  a prolonged postoperative course can be expected  viral infections remain serious but treatable problems  
class8	acid phosphatase  ec 3 1 3 2  activity in alveolar macrophages from patients with active sarcoidosis  five main acid phosphatase  acp  zones have been recognized and studied by polyacrylamide gel electrophoresis  band 5 represents the only tartrate resistant form and is present in bone osteoclasts and in human alveolar macrophages  ams   this study was carried out to quantify the presence of total and tartrate resistant acp  tracp  in ams from bronchoalveolar lavage  bal  of 11 patients with first stage sarcoidosis and in 13 nonsmokers and 16 smokers serving as control healthy subjects  the ams from smokers showed an increase in total acp activity  115 9     77 8 mu 10 6    on the contrary  macrophages of patients with sarcoidosis revealed a consistent decrease in total acp  27 8     7 0 mu 10 6   and particularly the tracp subtype  14 8     3 7 mu 10 6   in comparison with control nonsmokers  acp   42 2     18 9 mu 10 6   p   ns   tracp   35 1     15 1 mu 10 6   p less than 0 005    the decrease in tracp activity was inversely correlated with the lymphocyte number  r    0 75  p less than 0 01   lymphocyte percentage  r    0 62  p less than 0 05   and cd4 cd8 ratio  r    0 61  p less than 0 05   after six months of follow up  the cytologic bal picture returned completely to normal in five patients with full spontaneous regression of sarcoidosis  and also at the same time  normal values of tracp activity were restored  since tracp activity can be easily detected  its possible use  along with the lymphocyte count and cd4 cd8 ratio  as a prognostic indicator of the clinical course of sarcoidosis deserves further investigation  
class8	safety of the transbronchial biopsy in outpatients  the objective of our study was to determine the safety of transbronchial biopsy  tbb  in nonhospitalized patients  the design was a prospective study of the consecutive cases from july 1987 until september 1988 in the setting of a university hospital of the third level with 1 800 beds  the patients were a consecutive sample of 169 patients who had 184 procedures of fiberoptic bronchoscopy  fob  with tbb performed  they suffered from different diseases  lung nodules or masses  diffuse interstitial disease  alveolar condensation  etc  an fob with tbb was performed in immunocompetent outpatients  who were kept under observation for four hours and then had a chest roentgenogram taken afterwards  we contacted them again after 72 hours to rule out delayed complications  in three cases  more than 100 ml of blood were obtained during the fob  without significant hemoptysis being recorded in those patients during the observation period  chest pain occurred in 15 patients during the tbb  pneumothorax occurred in two patients  1 percent   one of whom required admission to the hospital  without requiring chest tube drainage  other complications are reported  bronchospasm  parenchymal hemorrhage  and pneumonia   in conclusion  we consider the tbb to be a technique with a low incidence of complications for outpatients  so therefore we do not believe that admission to the hospital is mandatory for this type of patient  although we do recommend a longer observation period  
class8	lung mechanics and gas exchange during exercise in pulmonary sarcoidosis  to clarify how lung function at exercise is affected in sarcoidosis  and to analyze how exercise studies compare to testing measurements  63 patients with pulmonary sarcoidosis were examined with lung mechanics and arterial blood gases during exercise  these findings were compared with simultaneously obtained  but previously reported results of the static lung pressure volume curve and the lung resistance static lung pressure curve  while mechanical variables at maximal exercise were as sensitive as those determined by measuring the pstl v and rl pstl curves  mechanics during spontaneous breathing at rest was less sensitive  the derangement of mechanics was more evident than that of arterial blood gases  no measurement at rest was a good predictor of working capacity or of arterial pao2  a comprehensive exercise examination may be an alternative to resting investigations  which are either more elaborate or less sensitive  
class8	stair climbing as an exercise test to predict the postoperative complications of lung resection  two years  experience  the results of a clinically performed preoperative stair climb was compared to the presence of postthoracotomy complications in the retrospective hospital record review of 54 adult men  the stair climb was a maximum of five flights  125 steps  performed at the patient s rate and terminated at his request  pulmonary function measurements and facets of the stair climb physiology were also examined in reference to the presence  type  and severity of complications experienced  most minor complications such as transient arrhythmias  atelectasis  and pneumonia were clearly not predicted by the stair climb performance  the ability to climb three flights preoperatively most clearly separated those patients having the longer postoperative intubation and hospital stay  greater frequency of complications  and cumulative complication score  p less than 0 005   this retrospective study did not have sufficient numbers of fatal cardiopulmonary complications to exclude the possibility that these may be predicted by the results of this simple test  
class8	spirometric criteria for hospital admission of patients with acute exacerbation of copd  recent studies have demonstrated that there is a high relapse rate for patients discharged from the emergency department  ed  following treatment of acute exacerbation of chronic obstructive pulmonary disease  copd   objective criteria have not been established to determine when to hospitalize these patients  this study evaluated spirometric criteria for that use  eighty three patients with an acute exacerbation of copd were studied  45 percent were admitted to the hospital while 17 percent of the patients who were discharged suffered a relapse  an fev1 of less than 40 percent of predicted normal identified patients who required hospital admission or suffered a relapse with a sensitivity of 0 96  specificity of 0 58  and overall accuracy of 0 78  combining clinical assessment with spirometry led to an improvement in specificity to 0 73 with a minimal decrease in sensitivity  patients with an fev1 of 40 percent or greater of predicted normal or no clinical evidence of respiratory distress after treatment may be safely discharged from the hospital  patients not meeting these criteria are at high risk for relapse and should either be admitted or have further aggressive ed therapy  
class8	pulmonary tolerance of prophylactic aerosolized pentamidine in human immunodeficiency virus infected patients  the effects of primary and secondary long term prophylaxis of pneumocystis carinii pneumonia with aerosolized pentamidine on pulmonary function in hiv  patients were evaluated  eighty one patients  none of whom were drug addicts or had pulmonary kaposi s sarcoma  were studied  fifty patients were receiving ap as secondary prophylaxis  36 monthly and 14 twice monthly  eight patients with a history of pcp served as control subjects  twenty three patients were receiving ap as primary prophylaxis  12 monthly and 11 twice monthly  pulmonary function tests  including spirometry  lung transfer capacity for carbon monoxide  tlco  and alveolar arterial oxygen gradient  p a a o2  were evaluated at m1  ie  one month after the diagnosis of pcp  or at the beginning of the ap prophylaxis  and then at three month intervals  m4 to m13   no differences were observed in the results of spirometry or p a a o2  among the patients receiving secondary prophylaxis  a significant increase  paired student s t test  in tlco occurred at m7 compared to m1 in the group receiving monthly administrations  p less than 0 01  and in the untreated control group  p less than 0 05   there was no significant difference in tlco at m13 compared to m1 in the 12 patients who received monthly administrations for this period or at m7 in the 14 patients receiving ap twice monthly  no significant difference in tlco was observed at m7 in the primary prophylaxis groups  these results indicate that pulmonary tolerance of ap  as reflected by pulmonary function tests  is good  
class8	pneumocystis carinii pneumonia complicating multiple myeloma  pneumocystis carinii pneumonia complicated the course of two patients with multiple myeloma  the diagnosis was established in both cases by bronchoalveolar lavage  which demonstrated the typical pneumocysts  clinical and roentgenographic improvement in both patients was observed following a course of trimethoprim sulfamethoxazole  one patient had lymphocyte subsets performed with a cd4 cd8 ratio of 0 8  both patients were hiv antibody negative by elisa  both patients tolerated prophylactic tmp smx given concurrently with the subsequent chemotherapy for myeloma  we suggest that the immune defect seen in multiple myeloma may have placed these patients at risk for opportunistic infections such as p carinii pneumonia  however  as opposed to patients with aids  our patients tolerated therapy with tmp smz quite well  
class8	diagnosis of disease caused by mycobacterium avium complex  isolation of mycobacterium avium complex from sputum specimens in association with the appearance of a new cavitary  or infiltrative  lesion was studied in 299 patients from whom the organism was isolated one or more times  of the patients studied  114 showed only single isolation  of these 114  only two patients  2 percent  had association with appearance of a cavitary lesion  of 29 patients who showed two isolations  26  90 percent  had the association  of 40 patients who showed three isolations  39  98 percent  had the association  all 116 patients who showed four or more isolations had the association with appearance of a cavitary lesion  accordingly  of a total of 185 patients who showed two or more isolations  181  98 percent  had the association  of these 181  176  97 percent  showed two or more isolations in the sputum examinations made in the initial three days  therefore  the sputum examination in the first three days after onset of disease is most important for the diagnosis of disease caused by mycobacterium avium complex  since the probability that casual isolation of the organism occurs twice is extremely low  we can make the diagnosis of pulmonary infection caused by this organism by evidence of two or more isolations of the organism in the first few days after the onset of disease  which is associated with appearance of a new cavitary  or infiltrative  lesion  moreover  theoretical consideration made in this study has led us to conclude that patients who have had a single isolation of the organism together with a new cavitary lesion should be regarded as having an infection  
class8	erythromycin reduces the severity of bronchial hyperresponsiveness in asthma  it has been demonstrated that bronchial hyperresponsiveness is a characteristic feature of bronchial asthma  and airway inflammation plays an important role in bronchial hyperresponsiveness  erythromycin is an antibiotic extensively used worldwide which is also reported to have anti inflammatory action  this study was designed to clarify whether erythromycin could favorably alter bronchial responsiveness in patients with bronchial asthma  to estimate bronchial responsiveness  histamine challenge was performed in 23 patients with bronchial asthma  atopic type  11  nonatopic type  12   all patients were treated for ten weeks with erythromycin  200 mg three times daily  orally  after ten weeks  treatment  pc20  an index of bronchial sensitivity  was increased significantly  there was no difference between atopic and nonatopic patients in the improvement of pc20  it was concluded that erythromycin reduces the severity of bronchial responsiveness in patients with bronchial asthma  
class8	il 1 and il 1 inhibitory activity in the culture supernatants of alveolar macrophages from patients with interstitial lung diseases  under normal conditions  the release of interleukin 1  il 1  and il 1 inhibitors play a role in tissue homeostasis  we have already reported an increase in il 1 activity and a decrease in il 1 inhibitory activity  iha  in the supernatants of alveolar macrophages from healthy long term smokers as compared with healthy nonsmokers  in this study  we report an alteration in the release of il 1 and il 1 iha from alveolar macrophages in patients with interstitial lung diseases  sarcoidosis and idiopathic pulmonary fibrosis  ipf    il 1 activity released from alveolar macrophages stimulated by lipopolysaccharide was increased in patients with active sarcoidosis  mean     sd  2 52     1 33 u ml  n   6  vs 1 38     0 62 u ml  n   15  for healthy non current smokers  hns   p less than 0 05   il 1 iha released from alveolar macrophages was significantly different among the groups examined  a decrease of il 1 iha occurred in patients with active sarcoidosis  61 4     19 2  n   6  vs 85 9     13 9 percent hns  p less than 0 05  and ipf  64 7     18 5  n   9   p less than 0 05   prednisolone in the culture medium at physiologic concentrations suppressed the release of il 1 and enhanced the release of il 1 iha  il 1 iha inhibited not only mouse thymocyte proliferation but also human fibroblast proliferation in the presence of il 1  
class8	right ventricular dysfunction in chronic obstructive pulmonary disease  evaluation and management  cor pulmonale is an important consequence of copd  although the incidence is not precisely known  it is seen more frequently in patients with hypoxemia  co2 retention and severely reduced fev1  when present  it limits peripheral oxygen delivery  increases shortness of breath  and reduces exercise endurance  it is also associated with higher mortality rates independent of other prognostic variables  numerous factors may contribute to the development of cor pulmonale in patients with copd  but its primary cause is chronic alveolar hypoxia resulting in pulmonary vasoconstriction  vascular remodeling and pulmonary hypertension  the physical exam  chest radiograph and ecg may be helpful in detecting the presence of cor pulmonale  but because of anatomic changes that occur in the chest  these tests are often insensitive in patients with copd  noninvasive diagnostic techniques utilizing doppler echocardiography and radionuclide angiography allow for detection of rv dysfunction at an earlier stage and in most cases  preclude the need for right heart catheterization  lto2 is the only therapy shown to improve survival in patients with copd  however  statistical proof correlating improvements in pulmonary hemodynamics with increased survival is lacking  bronchodilators  such as the beta 2 agonists and especially theophylline  may have beneficial effects on pulmonary hemodynamics in addition to their effect on respiratory function and are useful in copd when rv dysfunction is present  diuretics and phlebotomy are also useful in improving symptoms in appropriate patients  vasodilators such as calcium channel blockers and ace inhibitors may improve pulmonary hemodynamics acutely  but may lower arterial po2 by worsening ventilation perfusion matching or blunt the improvement in pulmonary hemodynamics seen with supplemental oxygen  the long term benefits of these agents have not been proven and their routine use in patients with cor pulmonale due to copd cannot be recommended  
class8	indications for spirometry in outpatients with respiratory disease  it has been suggested that spirometry should be incorporated into the routine examination of every patient  analogous to obtaining vital signs  to determine the impact of spirometry on the management of outpatients with respiratory disease  spirometry was performed on 150 consecutive patients  123 men and 27 women  mean age 57     12 years  seen in our pulmonary disease outpatient clinics  patients with obstructive  n   75   restrictive  n   31   mixed  n   26  or other respiratory diseases  n   18  were initially assessed by history and physical examination and classified as improved  stable  or worse compared to previous visits  a clinical management plan  cmp  was formulated based on this initial evaluation  spirometric results were then made available to the examiner who could then make changes in the proposed cmp  the addition of spirometric results caused alteration of the cmp in only eight  5 percent  patients  in the remaining 142 patients  results did not affect the cmp  two clinical findings identified those patients whose cmp was most likely to be altered by spirometry  severity of lung dysfunction  determined from previous spirometry  and deterioration of clinical status  judged by history and physical examination   of the eight patients whose cmp was changed after review of spirometry  six  75 percent  had previous severe ventilatory dysfunction  fev1 or fvc less than or equal to 40 percent of predicted or fev1 fvc ratio less than or equal to 0 40   in 6 of 38 patients  16 percent  with severe ventilatory dysfunction  cmp was altered after spirometry while only 2 of 112 patients  1 8 percent  with mild or moderate dysfunction had changes in their cmp  patients who were clinically assessed as worse compared to their previous visit were more likely to have their cmp altered after review of spirometry when compared to those considered improved or stable by a ratio of 6 1  these results suggest that spirometry is most likely to supplement the physician s history and physical examination in the management of outpatients with pulmonary disease when the initial evaluation suggests that the patient has clinically deteriorated since the previous clinic visit  or when he or she has previous severe ventilatory dysfunction  
class8	paradoxic air embolism in the absence of an intracardiac defect  a 58 year old man experienced paradoxic air embolism with passage of air from the systemic venous to the systemic arterial circulation with subsequent stroke and death  no intracardiac shunt was present  pulmonary fibrosis concomitant with severe pulmonary arterial hypertension appears to have been responsible for the air traversing the pulmonary capillary bed  this unusual outcome of a complicated central venous catheterization must be borne in mind and guarded against in similar patients  
class8	hypercapnic respiratory failure due to l tryptophan induced eosinophilic polymyositis  a 24 year old man presenting with fever  rash  and myalgias subsequently developed hypercapnic respiratory failure and severe limb muscle weakness  muscle biopsy revealed eosinophilic myositis  due to the ingestion of large quantities of l tryptophan as a dietary supplement  complete recovery occurred with corticosteroid administration  significant involvement of the respiratory muscles can be a predominant feature of this newly described disease entity  
class8	subcutaneous and mediastinal emphysema associated with hypersensitivity pneumonitis  we report a rare case of a patient in whom severe subcutaneous and mediastinal emphysema occurred in association with summer type hypersensitivity pneumonitis and in whom overdistention or disruption of alveoli with obliteration of the respiratory bronchioles was revealed on open lung biopsy  this case suggests that obstructive bronchiolitis with hypersensitivity pneumonitis is an etiologic factor of mediastinal emphysema  
class8	use of indium 111 labeled white blood cell scan in the diagnosis of cytomegalovirus pneumonia in a renal transplant recipient with a normal chest roentgenogram  opportunistic infections are common in patients after renal transplantation  this report describes a case of cytomegalovirus pneumonia in a renal transplant recipient with a normal chest roentgenogram and normal arterial oxygenation  an abnormal 111in white blood cell scan led to the discovery of a pulmonary source of his recurrent fevers  
class8	central neurogenic hyperventilation in invasive laryngeal carcinoma  we describe a patient with central neurogenic hyperventilation secondary to extension of a laryngeal tumor into the base of the brain  resulting in extrinsic compression of the medulla  such an association has not been previously described  unique features which distinguish this patient from previously reported cases are emphasized  possible mechanisms involved in pathogenesis  as well as types of therapy  are outlined  
class8	hypertrophic osteoarthropathy in association with pulmonary tuberculosis  three white male patients with advanced cavitary pulmonary tuberculosis presented with hoa  no other pathology to explain the osteoarthropathy was detected  the osteoarthropathy responded symptomatically to nsai drugs and treatment of tuberculosis but resolved radiologically in only one patient  
class8	fatal adult respiratory distress syndrome following successful treatment of pulmonary strongyloidiasis  hyperinfection with strongyloides stercoralis occurs mostly in immunocompromised patients  including those treated with systemic steroids  a case of strongyloides induced adult respiratory distress syndrome was recently reported  and we now report a case in which fatal ards appeared to result from the successful therapy of massive parasitic infection  
class8	pleural pneumocystis carinii infection  extrapulmonary pneumocystis carinii infection is a rare occurrence in patients with aids  pleural involvement has been demonstrated in only one case  and this occurred after pneumothorax  this is a case report of pleural pneumocystosis in a patient with aids who did not have a pneumothorax  
class8	unusual presentation of recurrent wegener s granulomatosis  a 65 year old woman presented with recurrent wegener s granulomatosis following two years of immunosuppressive therapy and three years of complete remission  at her initial presentation  she had a characteristic x ray picture showing multiple nodules with total resolution of these findings at three months  five years later  at the time of clinical relapse  her chest x ray film showed bilateral diffuse infiltrative disease  this change in radiologic presentation upon relapse of wegener s has not previously been reported  other unusual features include diffuse infiltrates as the pulmonary presentation and the long interval between cessation of therapy and relapse  we review the radiologic manifestations of wegener s granulomatosis  
class8	the role of passive immunity in bovine respiratory syncytial virus infected calves  the role of passive immunity in bovine respiratory syncytial virus  brsv  infections in neonatal calves was evaluated  calves were divided into groups as follows  colostrum deprived  sham inoculated  colostrum deprived  brsv inoculated  and colostrum fed  brsv inoculated  calves were inoculated with a low passage field isolate of brsv for 4 consecutive days by a combined respiratory tract route and were euthanized 6 days after receiving the last inoculation  arterial oxygen tension  pao2  decreased significantly over time in colostrum deprived  brsv inoculated calves  p less than  01  and was significantly different among treatment groups  p less than  05   a significant decrease in arterial oxygen saturation was observed in this same group over time  p less than  01   mean percentage of pneumonic lung volume  determined by computer data digitalization  was significantly greater in infected  colostrum deprived calves compared with the other groups  p less than  01   and brsv antigen was detected in these calves by avidin biotin immunoperoxidase staining  thus  passive immunity derived from colostrum feeding decreased the severity of brsv infections in calves  
class8	vaccination of cotton rats with a chimeric fg glycoprotein of human respiratory syncytial virus induces minimal pulmonary pathology on challenge  the cotton rat model of human respiratory syncytial virus  rsv  infection was used to study the safety and efficacy of a chimeric fg glycoprotein that was expressed in insect cells using a baculovirus vector  histologic and virologic examination of vaccinated rat lungs was done after challenge with rsv  when rats were challenged 1 month after vaccination  severe pulmonary inflammation characterized by both a mononuclear and polymorphonuclear cell infiltrate and 30  40  involvement of lung tissue was observed with a formalin inactivated rsv vaccine  the fg glycoprotein induced minimal lung inflammation  involving 2  5  of the lung   while negative controls had 1  3  lung involvement  two doses with as little as 20 ng of fg glycoprotein formulated in an aluminum hydroxide adjuvant completely protected the cotton rats from rsv challenge  thus the chimeric fg glycoprotein is highly immunogenic and induces minimal pulmonary inflammation in the cotton rat model  
class8	immune responses to bordetella pertussis infection and vaccination  to assess antibody and cellular immune responses  156 healthy children were immunized at approximately 18 months of age with acellular diphtheria tetanus pertussis vaccine  changes in antibody responses to filamentous hemagglutinin  fha  and to pertussis toxin  pt  were similar in pattern  and antibody titers reached values equal to those from patients with convalescent stage pertussis  the fha induced dna synthesis in peripheral blood mononuclear cells was maximum at 4 weeks after the primary series  and these levels were equal to those of patients with pertussis  high amounts of pt induced dna synthesis were observed in both immunized and nonimmunized children  thus  pt seemed to act mainly as a nonspecific mitogen  almost the same responses to several mitogens that activate different subsets of lymphocytes were observed in young infants compared with older children  furthermore  young infants who had bordetella pertussis infection responded by fha stimulation almost as well as older children  
class8	hypogammaglobulinemia associated with cytomegalovirus pneumonia  transient but profound hypogammaglobulinemia occurred during cytomegalovirus  cmv  pneumonia in a patient who developed striking declines in number of t lymphocytes  a 66 year old  female  human immunodeficiency virus negative patient requiring long term hemodialysis had normal serum immunoglobulin concentrations before the onset of cmv pneumonia  igg  1070 1470 mg dl  iga  94 102 mg dl  igm  30 48 mg dl   during the pneumonia episode  serum immunoglobulin concentrations were profoundly reduced  igg  440 mg dl  iga  40 mg dl  igm  25 mg dl   total lymphocytes declined from 3048 mm3 to 212 mm3 with reductions in cd4 cd45  lymphocytes  inducers of b cells  to 9   nl  24  32   and cd4 cd45  lymphocytes  inducers of suppressor t cells  to 4   nl  14  22    cd8 lymphocytes were reduced to 5   nl  19  31    as the pneumonia resolved  serum immunoglobulin concentrations returned to normal  this is one of the few reported instances of cmv infection apparently causing hypogammaglobulinemia  
class8	serotypes of respiratory isolates of streptococcus pneumoniae compared with the capsular types included in the current pneumococcal vaccine  the serotypes of 474 clinically significant streptococcus pneumoniae respiratory isolates collected during a national surveillance study in 1987 1988 were compared to the capsular types included in the 23 valent pneumococcal polysaccharide vaccine licensed for use in the united states  overall  355 isolates  74 9   belonged to types included in the current vaccine  while another 65  13 7   were types serologically related to vaccine types and likely to be protective by virtue of cross reactivity  relatively few isolates  9 1   belonged to nonvaccine serotypes  and only 2 3  were nontypable  the mucoid serotype 3 was most frequent  13 1  of total   followed by 19f  9 3    23f  7 4    6b and 14  5 7  each   and 4 and 6a  5 5  each   the most frequent type not included in the vaccine was type 16  2 1  of all isolates   thus  nearly 89  of respiratory isolates included in this study were encompassed within the antigenic spectrum of the currently marketed pneumococcal vaccine  
class8	nosocomial legionnaires  disease and use of medication nebulizers  guidelines for the prevention of nosocomial pneumonia specify that only sterile fluids should be used for aerosol therapy  however  this recommendation may not be uniformly followed  thirteen patients with nosocomial pneumonia due to legionella pneumophila serogroup 3  lp3  were identified at a community hospital in the period from 1984 through 1988  12 patients  92   had chronic obstructive pulmonary disease  and 9 patients  69   died  an epidemiologic investigation suggested that the use of nebulizers to deliver medication was associated with acquiring legionnaires  disease  the hospital potable water system was contaminated with lp3  and a survey indicated that tap water was commonly used to wash medication nebulizers  lp3 in respirable size droplets was isolated from aerosols generated by a nebulizer containing lp3 at one tenth the concentration found in the hospital potable water  these findings support the recommendation that only sterile fluids be used for filling or cleaning respiratory care equipment and suggest that this guideline is not universally followed  
class8	no detection of characteristic fungal protein elongation factor ef 3 in pneumocystis carinii  the taxonomic status of pneumocystis carinii is uncertain  and p  carinii has been categorized both as a fungus and as a protozoan  recent comparisons of rna sequence homologies between p  carinii and several genera of fungi and protozoa suggest that p  carinii has closer affinities with the ascomycetes than with the protozoa  the translatory systems of the fungi  however  require three soluble protein factors for peptide chain elongation rather than the two necessary in other eukaryotic systems  to date the additional protein elongation factor  ef 3  appears to be unique to fungi  western blot analysis of cell free extracts of p  carinii  derived from rat  was done using a polyclonal antibody raised in rabbits to saccharomyces cerevisiae ef 3  anti ef 3 cross reacting material was detected only in lysates of candida albicans and s  cerevisiae included as fungal controls  no cross reaction was detected in lysates of p  carinii  p  carinii infected rat lung  or a protozoan control  trichomonas vaginalis   
class8	meta analysis in epidemiology  with special reference to studies of the association between exposure to environmental tobacco smoke and lung cancer  a critique meta analysis  a set of statistical tools for combining and integrating the results of independent studies of a given scientific issue  can be useful when the stringent conditions under which such integration is valid are met  in this report we point out the difficulties in obtaining sound meta analyses of either controlled clinical trials or epidemiological studies  we demonstrate that hastily or improperly designed meta analyses can lead to results that may not be scientifically valid  we note that much care is typically taken when meta analysis is applied to the results of clinical trials  the food and drug administration  for example  requires strict adherence to the principles we discuss in this paper before it allows a drug s sponsor to use a meta analysis of separate clinical studies in support of a new drug application  such care does not always carry over to epidemiological studies  as demonstrated by the 1986 report of the national research council concerning the purported association between exposure to environmental tobacco smoke and the risk of lung cancer  on the basis of a meta analysis of 13 studies  10 of which were retrospective and the remaining 3 prospective in nature  the council concluded that non smokers who are exposed to environmental tobacco smoke are at greater risk of acquiring lung cancer than non smokers not so exposed  in our opinion  this conclusion in unwarranted given the poor quality of the studies on which it is based  
class8	activated protooncogenes in human lung tumors from smokers  fourteen primary human lung tumor dnas from smokers were analyzed for transforming activity by two dna transfection assays  activated protooncogenes were detected in 3 of 11 tumor dnas by the nih 3t3 focus assay  whereas activated protooncogenes were detected in 11 of 13 tumor dnas by the nih 3t3 cotransfection nude mouse tumorigenicity assay  k  or nras genes activated by point mutation at codons 12 or 61 were detected in a large cell carcinoma  a squamous cell carcinoma  and 5 adenocarcinomas  an hras oncogene activated by a different mechanism was detected in an epidermoid carcinoma  one adenocarcinoma was found to contain an activated raf gene  two unidentified transforming genes were detected in a squamous cell carcinoma dna and two adenocarcinoma dnas  eight of 10 lung adenocarcinomas that had formed metastases at the time of surgery were found to contain ras oncogenes  no significant increase in metastasis was observed in the lung adenocarcinomas that contained one or more 6 kilobase ecori alleles of the lmyc gene  overall  12 of 14  86   of the lung tumor dnas from smokers were found to contain activated protooncogenes  ras oncogenes appear to play a role in the development of metastases in lung adenocarcinomas  
class8	lack of increased bleeding after paracentesis and thoracentesis in patients with mild coagulation abnormalities  to determine whether untreated mild coagulopathy in patients with no evidence of clinical bleeding is associated with an increased risk of hemorrhage after paracentesis or thoracentesis  retrospective examination was conducted of 608 consecutive procedures for which prothrombin time  pt   partial thromboplastin time  ptt   platelet  plt  counts  and preprocedure and postprocedure hemoglobin concentrations were available  there was no increased bleeding in patients with mild to moderate coagulopathy  defined as pt or ptt up to twice the midpoint normal range or pit count of 50 to 99 x 10 3  per microl  50 99 x 10 9  l    however  patients with markedly elevated serum creatinine levels  6 0 to 14 0 mg dl  530 1240 mumol l   had a significantly greater average hemoglobin loss   0 82     1 3 g dl   8     13 g l   n   11  than patients with normal serum creatinine levels   0 12     0 88 g dl   1     9 g l   n   450   p   0 011   overall  the frequency of bleeding complications requiring red cell transfusions was very low  0 2 percent of events  the most common diagnosis for patients who had paracentesis was alcoholic liver disease  72    for those having thoracentesis  it was infection  37    it can be concluded that  for these patients  prophylactic plasma or platelet transfusions are not necessary  patients with markedly elevated serum creatinine deserve close postprocedure observation  
class8	the use of monoclonal antibody 44 3a6 in cell blocks in the diagnosis of lung carcinoma  carcinomas metastatic to lung and pleura  and pleural malignant mesothelioma  monoclonal antibody  moab  44 3a6 recognizes a glandular differentiation associated antigen and has been used to identify exocrine differentiation in pulmonary carcinomas  the authors assessed its value in the diagnosis of lung carcinomas metastatic to lung pleura and pleural malignant mesothelioma  mm   using cell blocks derived from cytologic specimens  sixty three primary lung carcinomas  31 metastatic adenocarcinomas  acs   from breast  gastrointestinal tract  or genitourinary tract   and 36 mms were immunostained with 44 3a6  leu m1  and anti carcinoembryonic antigen  cea   the results confirm the value of 44 3a6 in identifying acs but do not allow distinction between those of pulmonary  breast  git  or ovarian mucinous derivation  endometrial  ovarian serous  and renal acs are essentially nonreactive  as are almost all mms  the occurrence of one positive mm predicates caution in interpreting 44 3a6 positivity in isolation  but  judiciously used with other discriminating antibodies such as leu m1 and anti cea  44 3a6 is of value in the differential diagnosis of acs and mms  further  its applicability to cytologic specimens may obviate the need for more invasive diagnostic procedures and lead to rapid  accurate diagnosis  
class8	results of bronchoscopically obtained lower airway cultures from adult sickle cell disease patients with the acute chest syndrome  purpose  the purpose of this study was to determine the frequency of bacterial pneumonia as a cause of the acute chest syndrome in adult patients with sickle cell disease based on bronchoscopically obtained lower airway cultures and to describe the clinical  laboratory  and roentgenographic features of the acute chest syndrome in a series composed entirely of adult patients with sickle cell disease  patients and methods  we reviewed the hospital records from 19 episodes  18 patients  of acute chest syndrome in adult patients with sickle cell disease  greater than or equal to 19 years of age  who had undergone flexible bronchoscopy to obtain lower airway cultures between january 1979 and july 1987  we also recorded patients  clinical  laboratory  and roentgenographic characteristics  results  pneumonia was diagnosed in four of 19 episodes  21   of acute chest syndrome based on quantitative cultures obtained at bronchoscopy  the pneumonia was caused by streptococcus pneumoniae in two patients and mixed aerobic and anaerobic organisms in the other two patients  forty four of 45 blood cultures were negative  and one grew staphylococcus epidermidis  which was considered a contaminant  chest roentgenograms revealed lower lobe involvement in 17 episodes  90   and bilateral infiltrates in six  32    pleural effusions occurred in seven episodes  37    and pleural fluid samples obtained from five of these revealed sterile exudates  conclusion  the results of this retrospective study suggest that bacterial pneumonia is an uncommon cause of acute chest syndrome in adult patients with sickle cell disease  these results are consistent with previous retrospective studies using noninvasive techniques to diagnose pneumonia  nevertheless  there appeared to be no reliable noninvasive variables that could accurately differentiate between patients with and without pneumonia and  consequently  we recommend empiric antibiotic therapy in addition to usual supportive care of these patients  
class8	emergency adenotonsillectomy for acute postoperative upper airway obstruction peri operative acute upper airway obstruction may be life threatening  a case is reported of a child with severe adenotonsillar hypertrophy who developed acute upper airway obstruction after a routine surgical procedure and required emergency adenotonsillectomy  the importance of pre operative assessment is stressed  
class8	treatment of decompensated chronic obstructive pulmonary disease in the emergency department  correlation between clinical features and prognosis  study objective  patients with decompensated chronic obstructive pulmonary disease  copd  are at high risk of relapse after treatment in an emergency department  the purpose of this study was to determine if the risk of relapse correlates with the clinical features of the disease  patients  three hundred fifty two patients with documented copd who were treated for dyspnea in the ed of the albuquerque veterans administration medical center over a three year period  methods  we reviewed the clinical features and pulmonary function tests of the patients  who were considered to have copd if the baseline prebronchodilator one second forced expiratory volume  fev1  was less than 80  predicted  and less than 80  of the forced vital capacity and inhaled bronchodilators failed to increase the fev1 to levels of more than 80  predicted  visits for pneumonia  pneumothorax  pleural effusion  or pulmonary emboli were excluded  a relapse was defined as an unscheduled revisit to the ed within 14 days of initial treatment  data were entered into a microcomputer data base and analyzed by a commercial statistical package  results  of 877 visits in which the patient was treated and released from the ed  281  32 0   resulted in relapse and were considered unsuccessful compared with successful visits  unsuccessful visits were characterized by a shorter duration of dyspnea  p    002   a lower entry fev1  p    027   a lower discharge fev1  p    040   a greater number of treatments with nebulized bronchodilators  p    009   more frequent use of parenteral adrenergic drugs  p    006   and less frequent use of oral prednisone on discharge  p    016   patients with one or more relapse visits during the study period  relapsers  differed from nonrelapsers in several respects  relapsers had a greater bronchodilator response on baseline fev1 than nonrelapsers  p    047   nevertheless  relapsers required more bronchodilator treatments in the ed  p less than  001   were treated more frequently with parenteral adrenergic drugs  p less than  001   iv glucocorticoids  p less than  001   and oral prednisone  p less than  001   and recovered less of their baseline fev1  p less than  014   conclusion  bronchodilator response on baseline pulmonary function testing appears to identify patients with copd who have a poor prognosis after emergency treatment  their poor response to intensive bronchodilator treatment suggests that loss of bronchodilator response may be involved in the pathogenesis of respiratory decompensation  
class8	the  fallen lung with absent hilum  signs of complete bronchial transection  published erratum appears in ann emerg med 1991 jun 20 6  671  a 19 year old pedestrian who was the victim of a motor vehicle accident had a left pneumothorax with a large air leak  despite a well placed chest tube  a chest radiograph showed that the left lung had fallen down and away from the mediastinum and that no hilar structures were visible  this  fallen lung with an absent hilum  is considered virtually diagnostic of complete mainstem bronchus transection  
class8	nutrition and bronchopulmonary dysplasia twenty two babies who developed bronchopulmonary dysplasia were compared with 22 babies matched for gestational age who did not  those with bronchopulmonary dysplasia weighed less at birth and had lower energy intakes from day 7 to day 56  undernutrition before and after birth is a major problem in babies who develop bronchopulmonary dysplasia  
class8	association of pneumothorax and hypotension with intraventricular haemorrhage  to test the hypothesis that acute hypotension resulting from pneumothorax would be associated with severe brain injury  grade 3 or 4 intraventricular haemorrhage   67 very low birthweight  vlbw  infants of 32 weeks  gestation or less with respiratory distress syndrome and pneumothorax were studied  thirty six had pneumothorax associated with systemic hypotension and 31 had pneumothorax with normal blood pressure  the groups were similar in gestational age and severity of their respiratory distress syndrome  thirty two of 36 of infants with pneumothorax associated with hypotension  89   had grade 3 or 4 intraventricular haemorrhage  this percentage was significantly greater than the percentage for infants with pneumothorax and normal blood pressure  three of 31  10    the risk ratio for grade 3 or 4 intraventricular haemorrhage for infants with pneumothorax associated with hypotension was 9 8 compared with neonates with pneumothorax and normal blood pressure  these observations are consistent with the hypothesis that systemic hypotension and cerebral hypoperfusion are important factors leading to intraventricular haemorrhage in vlbw infants  
class8	anaesthetic management of a 2 month old infant for laser resection of vocal cord granuloma  a 2 month old infant underwent excision of granulomata of vocal cords with a carbon dioxide laser  high frequency jet ventilation was given through a surgical metal suction tube during the operation  the anaesthetic technique for the infant and the problems of the use of carbon dioxide laser in laryngeal surgery are discussed  
class8	antithrombotic efficacy of continuous extradural analgesia after knee replacement  we have studied the effect of extradural analgesia on postoperative venous thrombosis in patients undergoing knee arthroplasty  forty eight patients were allocated randomly to receive either general anaesthesia or extradural analgesia with local anaesthetics for 3 days  all patients wore compressive elastic stockings and no anticoagulant drugs were administered  bilateral venography was performed 10 days after surgery  continuous extradural analgesia did not impede mobilization of the patients  one case of nonfatal pulmonary embolism occurred in a patient who received general anaesthesia  the use of continuous extradural analgesia resulted in a significant difference in the total incidence of deep vein thrombosis  18  compared with 59  after general anaesthesia  p   0 02   the incidence of calf vein thrombosis was 12  compared with 45  after general anaesthesia  p   0 05   
class8	traumatic subarachnoid pleural fistula in a child  a case report  a seven year old girl sustained a gunshot wound to the chest and spine  evaluation of a persistent pleural effusion demonstrated a subarachnoid pleural fistula  surgical closure of the dural defect resulted in resolution of the fistula  traumatic subarachnoid pleural fistulae are rare  the diagnosis is reached by an awareness of fistula formation from penetrating or blunt trauma to the chest  
class8	pneumocystis carinii infection of the thyroid in a hypothyroid patient with aids  diagnosis by fine needle aspiration biopsy  a 49 yr old homosexual man with acquired immunodeficiency syndrome presented with a left sided neck mass  he was found to have a firm goiter  he was clinically euthyroid  but had laboratory evidence of primary hypothyroidism  radioactive iodine scan of the thyroid showed homogeneous uptake over an enlarged right lobe and absence of uptake over the left lobe  two fine needle aspiration biopsies of the thyroid revealed the presence of pneumocystis carinii  p  carinii  organisms on the gomori s methenamine silver strain  after courses of iv and oral therapy with trimethoprim sulfamethoxazole  a third fine needle aspiration biopsy failed to reveal any organisms  a repeated radioactive iodine scan of the thyroid showed return of uptake over the left lobe  thyroid function tests normalized with levothyroxine  and the goiter decreased in size  to our knowledge  this is the first report of hypothyroidism associated with p  carinii infection of the thyroid  p  carinii infection should be considered in the differential diagnosis of human immunodeficiency virus infected individuals presenting with cold thyroid nodules  fine needle aspiration biopsy is a valuable tool in assessing these patients  
class8	monoclonal immunofluorescence compared with silver stain for investigating pneumocystis carinii pneumonia  two hundred and eighty two specimens from 220 patients positive for hiv with respiratory tract symptoms  or febrile illness  or both  were examined for the presence of pneumocystis carinii  specimens were either induced sputum samples or bronchoalveolar lavage fluids  to establish the optimal method for laboratory diagnosis a comparison was made of detection of the organism by use of monoclonal antibody and immunofluorescence with conventional silver staining methods  three commercially available reagents for immunofluorescence were also compared  immunofluorescence was significantly more sensitive than the silver stain and the best results for immunofluorescence were obtained using  northumbria biologicals ltd reagents  
class8	mechanical ventilation in medical and neurological diseases  11 years of experience  mechanical ventilation  mv  is imperative in many forms of acute respiratory failure  arf   the aim of this work was to review all episodes of mv in a medical intensive care unit  micu  during the 11 year period 1976 1986  four per cent  n   1008  of 24 899 admissions to the micu were treated with mv  the mean age of ventilator treated patients was 53     18 years  and obviously it increased during the period of study  the average duration of mv was 4 7 d  micu mortality  hospital mortality and 2 year mortality rates for patients subjected to mv were 33   38  and 46   respectively  the mortality rate did not change during the study period  cerebrovascular and malignant diseases carried the highest mortality rates  75 and 79   respectively  whereas mortality in patients ventilated because of drug overdose  n   313  was only 2   the results of this study confirm previously published findings concerning the outcome of mv  and we conclude that the effects of mv remain discouraging in medical and neurological patients  improved quality of ventilator therapy and monitoring  as well as continued research directed at the causes of arf  are equally important in reducing the mortality in arf  
class8	pneumothorax in a patient with wegener s granulomatosis during treatment with immunosuppressive agents  we present the case of a 16 year old woman with wegener s granulomatosis  who developed a pneumothorax while receiving treatment with cyclophosphamide and glucocorticoids  the lung was re expanded by tube drainage  and the patient recovered completely while the immunosuppressive treatment was continued in combination with sulphamethoxazole trimethoprim  a possible role for this antimicrobial drug in the treatment of wegener s granulomatosis is briefly discussed  
class8	chemotherapy of brain metastases from lung carcinoma  a controlled randomized study  a controlled randomized study was carried out to evaluate the effects of chemotherapy in patients with brain metastases from lung carcinoma  one hundred patients were randomly divided into three groups at the time of diagnosis or after surgery for metastases  group a received radiotherapy alone  group b received radiotherapy and chloroethylnitrosoureas  methyl ccnu  100 120 mg m2  or acnu 80 100 mg m2  every 6 8 weeks   and group c received radiotherapy and a combination of chloroethylnitrosoureas and tegafur  300 mg m2  daily   of the 100 patients  88 could be evaluated  the reduction rates of the tumors of the patients in whom tumor was not surgically removed or not totally removed were compared  complete resolution of the tumor was noted in 29  69  and 63  of the patients in groups a  b  and c  respectively  tumor regression of greater than or equal to 50  was seen in 36  69  and 74  of the patients in groups a  b  and c  respectively  the difference in the response rates of groups a and c was statistically significant  p less than 0 05   median survival after the start of treatment for brain metastasis was 27  30 5  and 29 weeks in groups a  b and c  respectively  there was 1 long term survivor  more than 5 years  in group a  3 in group b  and 1 in group c  the main cause of death was deterioration attributable to the primary lesion or systemic metastasis  and no statistical difference was noted in survival time among the groups  
class8	pott s puffy tumor  a complication of frontal sinusitis  in children sinusitis is a frequent complication of upper respiratory infections but an infrequently considered diagnosis  although most sinus infections are resolved without complications  when complications do occur they can be serious or life threatening  the most common ones occur in the orbit  but cns extension is not infrequent  osteomyelitis and resulting subperiosteal abscess of the frontal bone  the so called pott s puffy tumor  is a less common  and perhaps less frequently recognized  serious complication of frontal sinusitis  this paper describes two patients with subperiosteal abscess resulting from frontal sinusitis  one with cns and orbital extension  a brief literature review is presented  and presentation  diagnosis  and treatment are discussed  
class8	presentation and management of an acute caffeine overdose  a one year old white female ingested approximately two to three grams of caffeine  200 300 mg kg   the patient survived the ingestion with a maximum caffeine concentration of 385 micrograms ml four hours postingestion  the child developed ventricular arrhythmias  seizures  metabolic disturbances  and severe pulmonary edema  she survived without apparent long term sequelae despite having reached a serum caffeine concentration that is the second highest reported level in a survivor  
class8	respiratory distress in a child in the office  we have reviewed respiratory distress from a pathophysiologic approach  two specific disease entities  epiglottitis and asthma  which commonly present with respiratory distress  are reviewed  the office management of respiratory distress encompasses early recognition of disease to prevent symptoms from progressing  referral should be considered in any difficult cases  
class8	upper respiratory tract infections  upper respiratory tract infections are among the most common acute infections in humans  this review discusses the clinically important aspects of the epidemiology  etiology  clinical presentation  diagnosis  management  complications  and prevention of the common cold  pharyngitis  otitis media  and sinusitis  most episodes of the common cold and pharyngitis are of viral origin  and curative therapy is not available  streptococcal pharyngitis  acute otitis media  and sinusitis are secondary to bacterial infections  and antibiotic therapy is important  
class8	lower respiratory tract infections  although lower respiratory tract infections are frequently diagnosed in a primary care setting  they are still associated with a significant morbidity and mortality  which warrants a careful approach to treatment  knowledge of the most common cause based on the age of the patient  location where the infection was acquired  and clinical presentation helps to direct empiric treatment  a few basic laboratory studies  especially a sputum gram stain  can allow for more specific treatment  identification of patients at increased risk for virulent organisms should make the primary care physician consider inpatient treatment along with an aggressive diagnostic workup and broad spectrum antimicrobial treatment  prevention should always be considered  
class8	cerebral venous thrombosis  new causes for an old syndrome  the range of disorders affecting the cerebral veins and sinuses is increasing and now includes blood disorders  abnormalities in the patterns of blood flow  and infiltrative or inflammatory conditions  all of which may promote thrombosis  we describe 10 patients with cerebral venous thrombosis  two had protein s deficiency  one had protein c deficiency  one was in early pregnancy  and there was a single case of each of the following  dural arteriovenous malformation  intracerebral arteriovenous malformation  bilateral glomus tumours  systemic lupus erythematosus  wegener s granulomatosis  non hodgkin s lymphoma  the recognition of such diverse aetiology may be importance since clinical features are non specific  and may consist only of raised intracranial pressure  allowing confusion with  benign intracranial hypertension   the existence of effective treatment both for the thrombosis and for many of the underlying disorders makes early diagnosis essential  the prognosis of treated patients may be favourable  
class8	antibodies directed against neutrophils  c anca and p anca  are of distinct diagnostic value in systemic vasculitis  in a prospective study  sera from over 700 patients with suspected vasculitis  including over 200 patients undergoing renal biopsy  were examined for antibodies to neutrophil cytoplasmic antigen  anca   an indirect immunofluorescence assay on ethanol fixed human neutrophils identified two types of autoantibody  c anca  which produces diffuse cytoplasmic staining and p anca  which produces an artefactual nuclear perinuclear staining pattern  the diagnosis of patients in whom anca of either form was found was established following case note review according to defined diagnostic criteria  forty of 45 patients whose sera contained c anca at a titre of greater than or equal to 1 40 satisfied the diagnostic criteria for wegener s granulomatosis or microscopic polyarteritis  twelve of 30 patients with p anca at a titre of greater than or equal to 1 40 were also classified as having one of these disorders  seventeen of the remaining 18 patients had immune mediated disorders with deep organ damage  of 47 anca positive patients who underwent renal biopsy  21 had glomerulonephritis associated with wegener s glomerulonephritis and a further 22 had a necrotizing or crescentic glomerulonephritis  ethanol fixation is important for discrimination of c anca and p anca  c anca are highly specific for wegener s granulomatosis and microscopic polyarteritis  in patients undergoing renal biopsy  the presence of these antibodies is highly specific for a necrotizing or crescentic glomerulonephritis  
class8	radiographic manifestations of congenital anomalies affecting the airway  congenital anomalies of the airway are generally uncommon  but a vast array of possibilities exists  some present life threatening emergencies at birth  and others go undiagnosed for years  clinical symptoms are often nonspecific  and radiographic evaluation is frequently requested to localize and characterize the lesion before endoscopy  surgery  or medical management  the most common intrinsic congenital anomalies causing airway compromise in infants include choanal atresia  mandibular hypoplasia  laryngomalacia  vocal cord paralysis  and congenital subglottic stenosis  the radiologist must be on the alert for unsuspected additional anomalies involving the airway  lungs  and esophagus  which occur with relative frequency  numerous extrinsic congenital masses of the head  neck  and mediastinum may compromise the airway  hemangiomas  lymphangiomas  and teratomas are more likely to be noted at birth  whereas branchial cleft cysts  thyroglossal duct anomalies  and dermoid cysts frequently present later  mass location and radiographic characteristics usually allow accurate preoperative diagnosis  intracranial involvement by nasal or nasopharyngeal masses  intrathoracic involvement by lower neck mass  and intraspinal involvement by posterior neck mass must always be sought for radiographically  persistence of respiratory symptoms after removal of such masses is not uncommon because tracheal deformity and laxity may take months or years to resolve  recent advances in cine ct and mr imaging promise to improve imaging of the airway in general and in the pediatric population in particular  significant limitations in imaging of the pediatric larynx remain  as a result  endoscopy continues to be the primary diagnostic tool for airway anomalies of this region  
class8	bronchopulmonary and neurenteric forms of foregut anomalies  imaging for diagnosis and management  bronchopulmonary foregut malformations encompass a great variety of anomalies that may arise from abnormal differentiation of the respiratory and alimentary tracts  abnormal separation of the two systems  or abnormal development of blood supply  perhaps singly or in combination  during early embryogenesis  the pulmonary and neurenteric forms share the common features of a pulmonary parenchymal opacification and or intrathoracic mass  with the addition of vertebral anomalies in the instance of the neurenteric malformations  plain radiographs serve as the starting point for diagnostic evaluation and sometimes are all that is needed  more often  though  the plain film findings suggest which road to follow in further imaging  no single imaging approach can be advocated for all patients  the lesion may be found initially  for example  on prenatal sonography  ultrasonography also can establish the cystic nature of a mass and may help define vascular supply  although it cannot yet be said to have supplanted angiography s role in evaluating suspected sequestrations  for most intramediastinal or intrapulmonary masses without associated vertebral anomalies  ct will satisfactorily establish the cystic nature and should afford a reasonably confident preoperative diagnosis of bronchogenic cysts or type 1 or 2 cystic adenomatoid malformations  type 3 cystic adenomatoid malformation  because of its relatively  solid  imaging characteristics  may not be diagnosed confidently by preoperative imaging  the finding of vertebral anomalies associated with a mediastinal mass especially warrants mr imaging to define intraspinal involvement  however  the association of vertebral or rib anomalies with apparent unilateral pulmonary agenesis or hypoplasia arouses suspicion of a bronchopulmonary foregut malformation that communicates with the gastrointestinal tract  and this uncommon situation calls for a barium examination  radionuclide scintigraphy has an ancillary role in assessing foregut anomalies  but many findings from scintigraphy are relatively nonspecific and anatomic definition is poor  scintigraphy may yield supportive information in cases of sequestration that have inconclusive findings as determined by plain radiographs and ct  
class8	radiographic manifestations of anomalies of the lung  congenital nonvascular anomalies of the lung can be subdivided into those affecting the bronchial tree and those affecting parenchymal abnormalities  embryologic development of the lung is briefly reviewed to facilitate an understanding of developmental pulmonary anomalies  clinical  radiographic  and therapeutic aspects of these anomalies are discussed  
class8	pharmacokinetics of cefepime in patients with respiratory tract infections  the steady state pharmacokinetics of cefepime were evaluated in 10 middle aged and elderly patients with acute lower respiratory tract infections who were receiving 1 g intravenously every 12 h  one preinfusion and 15 postinfusion serum samples and total urine output were collected over one dosing interval between days 3 and 8 of therapy  cefepime concentrations in serum over time exhibited a multicompartmental profile  peak and trough concentrations in serum determined by a validated high performance liquid chromatography method were 71 2     17 2  mean     standard deviation  and 6 0     4 9 mg liter  respectively  the steady state volume of distribution was 0 22     0 05 liter kg  elimination half lives ranged from 1 93 to 6 04 h  3 92     1 28 h   and total body clearances ranged from 36 9 to 102 ml min per 1 73 m2  73 0     19 7 ml min per 1 73 m2   the disposition of cefepime at steady state in patients was comparable to previous observations in healthy elderly volunteers  the predictive performance of regression equations derived from single dose studies in volunteers relating creatinine clearance with total body and renal clearances of cefepime exhibited slight biases  mean predictive errors   9 7 and 2 1 ml min per 1 73 m2  respectively  and similar precisions  predicted and observed total body clearances  63 3     25 1 versus 73 0     19 7 ml min per 1 73 m2  respectively  and renal clearances  51 3     24 4 versus 49 3     19 6 ml min per 1 73 m2  respectively  were not significantly different  the pharmacokinetics of cefepime in infected patients appeared to be unaltered by illness  and the steady state disposition of cefepime was predictable from data derived from single dose studies in volunteers  
class8	nasal midline masses in infants and children  dermoids  encephaloceles  and gliomas  nasal dermoids  gliomas  and encephaloceles are uncommon congenital lesions that result from aberrant embryologic development  we have treated 46 children with these nasal lesions  in view of the potential intracranial connection  patients are at risk for intracranial infection  and early surgical correction is thus imperative  neuroimaging studies may help to predict intracranial involvement  
class8	somatostatin and analogues in the treatment of cancer  a review somatostatin is a naturally occurring cyclic tetradecapeptide that inhibits release of growth hormone and all gastrointestinal hormones  the beneficial effect of somatostatin in the treatment of certain hypersecretory disorders of hormone excess in well recognized  however its clinical usefulness has been limited in the past by its extremely short plasma half life  the development of long acting somatostatin analogues has provided clinically useful agents for treatment of hormone producing tumors  in addition to well known inhibiting effects on hormone release and actions  recent studies using experimental tumor models have demonstrated an antiproliferative effect of somatostatin and its analogues on growth of a variety of neoplasms  the exact role of somatostatin analogues in cancer therapy has yet to be established  however studies suggest that these agents could provide a useful and relatively nontoxic adjuvant therapy in the treatment of certain tumors  in this review  the oncologic application of somatostatin and possible mechanism of action are examined and current clinical and experimental studies are summarized  
class8	hemodynamic effects of lobar pulmonary artery occlusion in a porcine sepsis model  we induced severe pulmonary hypertension and acute lung injury in 6 pigs by pseudomonas aeruginosa infusion  we studied the effect of pulmonary artery catheter inflation of a pulmonary artery catheter balloon in the left lower lobar pulmonary artery was accompanied by a significant  p less than 0 05  paired t test  increase in pulmonary artery pressure  a decrease in left atrial pressure  a decrease in cardiac output  and a decrease in mean arterial pressure  no significant changes occurred when the catheter was advanced into the wedged position without balloon inflation  balloon inflation had no significant effect on these variables before bacterial infusion  we conclude that with sufficiently severe pulmonary hypertension in association with diffuse lung injury  lobar pulmonary artery occlusion may cause alterations in cardiac output and left atrial pressure  this may confuse interpretation of pulmonary artery catheter measurements  
class8	computed tomography guided minithoracotomy for the resection of small peripheral pulmonary nodules  small peripheral pulmonary nodules ranging in size from 1 mm to 20 mm were excised in 58 patients  computed tomography was used to mark the skin overlying the nodules to minimize the surgical exposure needed for operative identification  the nodules were 1 cm or less in maximum diameter in 76  of the patients  twenty six patients had single nodules and 32 patients had multiple nodules  the preoperative diagnosis was inaccurate in 67  of the patients  in 61  of the patients in whom malignancy was suspected  no tumor was demonstrated  conversely  of the 20 patients in whom a malignant nodule was excised  the preoperative diagnosis was correct in only 50   thirty one patients required no further treatment apart from their biopsy and 27 required additional intervention  small peripheral pulmonary nodules require biopsy for diagnosis  when percutaneous needle aspiration biopsy is unsuccessful  or technically difficult  a computed tomography guided thoracotomy is an effective and minimally invasive surgical alternative  
class8	left ventricular pseudoaneurysm with hemoptysis  a 53 year old man who had previously undergone resection of a left ventricular aneurysm was admitted because of hemoptysis  preoperative evaluation with computed tomographic scan and cardiac catheterization demonstrated a pseudoaneurysm of the inferior ventricular wall measuring 16 cm in diameter with protrusion into the left hemithorax  the neck of the pseudoaneurysm was a defect in the ventricular wall extending from the base of the mitral valve annulus to the insertion of the posterior papillary muscle  operative repair was performed using an albumin coated  low porosity dacron patch  
class8	procainamide induced respiratory insufficiency after cardiopulmonary bypass  a 46 year old man could not be weaned from ventilatory support while receiving procainamide  when the drug was discontinued  the patient was successfully weaned shortly thereafter  
class8	carcinosarcoma of the lung with hypertrophic pulmonary osteoarthropathy  carcinosarcoma of the lung is a rare malignancy  endobronchial and parenchymal variants are classically described  clinicopathological features are often related to anatomical location  as is the case for most lung neoplasms  this case report details the surgical management of a carcinosarcoma in a patient seen with pulmonary osteoarthropathy  
class8	false aneurysm formation of the great arteries after arterial switch operation  an infant with simple transposition of the great arteries underwent a two staged arterial switch operation  after which mediastinal infection occurred  continuous irrigation with povidone iodine solution was performed for 10 days  after that  the patient experienced life threatening hemorrhage three times  at the time of the second hemorrhage  greater omental transfer was performed  on postoperative day 109  false aneurysm was recognized  having developed from both great arteries  successful repair was performed on postoperative day 110  
class8	fistulas between the aorta and tracheobronchial tree  aortobronchial fistula is a rare condition that is invariably fatal if not diagnosed and surgically treated  with appropriate surgical intervention  survival rates greater than 70  can be achieved  a review of the literature and an illustrative case report are presented  a total of 63 fistulas in 62 patients have been described  the case we present is unusual in the use of serratus anterior muscle for repair of the fistula  eighty seven percent of the cases documented in the literature were associated with an aneurysm of the thoracic aorta  eighty six percent of the fistulas were between the descending aorta and left bronchopulmonary tree  more than 95  of patients experienced at least a single episode of hemoptysis  and massive hemoptysis occurred in more than half of the reported cases  a correct preoperative diagnosis was made in only 54  of cases  plain chest radiographs definitively demonstrated an aneurysm in only 16   the computed tomographic scan was the most rewarding test  identifying an aneurysm in 11 of 12 patients and the fistula in 50  of them  surgical repair resulted in a 76  survival rate  
class8	enhanced antitumor reactivity of tumor sensitized t cells by interferon alfa  tumor draining lymph node cells from mice bearing the methylcholanthrene induced mca 106 tumors can be sensitized in vitro to acquire antitumor reactivity  we examined the effect of interferon alfa on the function of cells that underwent in vitro sensitization in adoptive immunotherapy  interferon alfa increased the antitumor reactivity of in vitro sensitized cells in the treatment of mca 106 pulmonary metastases  this effect was evident in irradiated mice  indicating that a host response to the interferon alfa was not required  interferon alfa treatment increased class i major histocompatibility complex antigen expression on tumor cells and increased their susceptibility to lysis by in vitro sensitized cells  these results suggest that interferon alfa enhancement of adoptive immunotherapy was mediated by its effect on tumor cells  interferon alfa may be a useful adjunct to the adoptive immunotherapy of human cancer  
class8	bilateral iliac vein filtration  an effective alternative to caval filtration in patients with megacava  greenfield filters were placed bilaterally in the iliac veins in five of 250 patients undergoing percutaneous filter placements  four of the five patients had megacava  inferior vena cava diameter greater than 28 mm   in all patients  the filters were effective in preventing pulmonary embolism  follow up at 9 months in two patients revealed no changes of chronic venous insufficiency or venous stasis  iliac filtration should be considered in patients in whom a caval filter cannot be placed because of large caval size or because it is technically difficult due to iliac vein tortuosity  
class8	cytologic diagnosis of aspergillosis in cardiac transplantation  fine needle aspiration of the lung is now widely utilized to diagnose pulmonary neoplasms  but often serologic techniques or open lung biopsy is relied on for the diagnosis of infectious pulmonary processes  we report a series of four patients in whom the fine needle aspiration technique was used to make the rapid cytologic diagnosis of pulmonary aspergillosis  culture confirmation was also obtained on the aspirated material  a discussion of the available techniques for the laboratory diagnosis of pulmonary aspergillosis is presented and the advantages of fine needle aspiration cytology are stressed  our favorable results support expanded use of fine needle aspiration cytology in the evaluation of lung nodules appearing in immunosuppressed populations  
class8	endoscopic repair of supraglottic laryngeal clefts  we describe the technique of endoscopic diagnosis and endoscopic surgical repair used in the management of supraglottic interarytenoid laryngeal clefts in 11 children seen between 1981 and 1988 at the hospital for sick children  london  england  six of the children had primary type i clefts that required endoscopic repair  the symptoms included inspiratory stridor  choking during eating  and aspiration  five of the children had previous transcervical repair of type ii clefts that had partial breakdown in the interarytenoid area causing symptoms of aspiration  which required secondary repair endoscopically  all the patients had successful microlaryngoscopic closure  in two children  however  the breakdown of the repair necessitated repeated endoscopic correction  the only complication occurred in a case of postoperative supraglottitis  which was successfully managed with intubation and antibiotics  we conclude that endoscopic repair is a useful and reliable technique and an elegant alternative to the open transcervical approach for the closure of supraglottic laryngeal clefts  
class8	endoscopic and computed tomographic findings in ostiomeatal sinus disease  previously  there has been no organized format for the documentation of the findings of the nasal endoscopy and the coronal computed tomographic sinus scan  the findings from 100 nasal endoscopies and computed tomographic scans were reviewed and summarized  the summarized findings were incorporated into two forms   the nasal endoscopy exam form  and the  computed tomographic scan findings  form    utilizing computerized graphics techniques  the forms are presented along with their illustration of pathologic ostiomeatal findings  these forms represent a method of documentation of nasal endoscopic and coronal computed tomographic scan findings  they may be used in the demonstration of disease  treatment  planning  resident training  communication of information  and assisting in a future classification of degrees of severity of sinus disease  
class8	reconstruction of pediatric larynx and upper trachea with the sternohyoid rotary door flap  the sternohyoid myocutaneous flap  the rotary door flap  is optimally oriented to serve in laryngotracheal reconstruction  it provides immediate  highly vascularized lining and structural support to the augmented airway  therefore  it is one of the most versatile alternative methods available for surgical reconstruction of the stenosed larynx and trachea  thirteen of 14 patients who were managed by the rotary door flap technique have been successfully decannulated  the features of the flap and the surgical technique are described with reference to modifications in the pediatric age group  
class8	nasal reconstruction with articulated irradiated rib cartilage  nasal structural reconstruction is a formidable task in cases where there is loss of support to both the nasal dorsum and tip  a multitude of surgical approaches and materials have been used for the correction of the saddle nose deformity with varying degrees of success  articulated irradiated rib cartilage inserted through an external rhinoplasty approach was used to reconstruct nasal deformities in 18 patients over a 6 year period  simultaneous use of a midline forehead flap to reconstruct the overlying soft tissue was required in four cases  follow up ranged from 1 to 6 years  mean  2 8 years   results were rewarding in most cases with marked improvement in nasal support and airway  revision and or replacement secondary to trauma or warping of the graft was required in four cases  none of the patients exhibited infection  extrusion  or noticeable resorption  a description of the surgical technique  review of all the cases  and recommendation for continued use of this graft material are discussed  
class8	changing disease patterns in patients with aids in a referral centre in the united kingdom  the changing face of aids objective  to study the changes in morbidity  mortality  and survival patterns in a population of patients with aids in the united kingdom from 1982 to 1989  design  a retrospective analysis of inpatient and outpatient records of patients with aids  subjects  347 patients with aids  predominantly homosexual or bisexual men  setting  departments of immunology and genitourinary medicine  st mary s hospital  london  main outcome measures  presenting diagnosis of aids  occurrence of other opportunist diseases  cause of death  and survival since aids was diagnosed  in particular for those patients with pneumocystis carinii pneumonia or kaposi s sarcoma  results  the overall proportion of patients who developed p carinii pneumonia dropped from 56   20 36  in 1984 to 24   46 194  in 1989  although it has remained the index diagnosis in about half of new patients  kaposi s sarcoma has decreased as index diagnosis from 30   20 67  to 20   15 74  over the same period  though the prevalence has remained constant at around 35   p carinii pneumonia accounted for 46   16 35  of known causes of death in 1986 but only 3   1 31  in 1989  conversely  deaths due to kaposi s sarcoma rose from 14   1 7  to 32   10 31  between 1984 and 1989  lymphoma accounted for an increased proportion of deaths among these patients with 16   5 31  of deaths in 1989  their median survival increased from 10 months in 1984 6 to 20 months in 1987  conclusions  the changing patterns of disease in patients with aids have important implications both for health care provision and future medical research  medical and nursing provision must be made for the increased morbidity of these diseases and the increased survival of these patients  research should now be directed towards developing effective treatments for the opportunist infections which are currently more difficult to treat  the secondary malignancies of aids  as well as more effective immunorestorative treatments  future changes in disease patterns must be recognised at an early stage so that resources can be adequately planned and allocated  
class8	spontaneous pneumothorax  marker gas technique for predicting outcome of manual aspiration  published erratum appears in bmj 1991 mar 23 302 6778  697  objective  to determine whether in a patient with spontaneous pneumothorax the presence or absence of a pleural leak can be shown at the time of manual aspiration by use of a marker gas  also  to find out if the technique can predict whether manual aspiration will be successful  hence avoiding the need for intercostal tube drainage  design  prospective study of 25 episodes of pneumothorax during which patients breathed air from a douglas bag that contained chlorofluorocarbon gases from a metered dose inhaler while the pneumothorax was aspirated  setting  medical unit of a district general hospital  patients  22 patients who presented over nine months with acute pneumothorax  main outcome measures  presence or absence of chlorofluorocarbon marker gases in the aspirate  presence or absence of sustained re expansion of the affected lung in the chest radiograph  results  marker gas was detected in the aspirate from 16 out of 25 pneumothoraces  of these  13 required intercostal tube drainage because of failure of the lung to re expand  marker gas was not detected in nine cases  and in all of these cases manual aspiration resulted in sustained re expansion of the lung  conclusions  the presence or absence of a pleural leak during manual aspiration of spontaneous pneumothorax can be shown by using this technique  the absence of marker gas in the aspirate implies that manual aspiration will be successful  whereas its presence predicts  in most cases  either failure of manual aspiration to expand the lung or early re collapse of the lung  
class8	exercise testing in the assessment of pulmonary disease  in this chapter  the different types of exercise tests and the indications for requesting a particular type of test have been discussed  the normal physiological responses to exercise have been reviewed and examples of the abnormal responses seen in a variety of disease states that have been discussed  the relatively small number of these responses limits the specificity of exercise tests in actually establishing a diagnosis  but can be helpful in narrowing the differential diagnosis  perhaps exercise tests are most valuable in cases where the patient s symptoms are mainly limited to exercise and where investigations done at rest have failed to resolve a diagnostic question  when exercise testing is used under these circumstances  it serves a unique function in the diagnosis and management of pulmonary disease  
class8	bronchoalveolar lavage  the technique of bal performed through the fiberoptic bronchoscope has  in two decades  provided clinicians and researchers with the ability to safely sample the inflammatory immune cell milieu of the human lung  standardized bal and processing of the lavage constituents provides assistance in determining the optimal care of patients with a variety of lung diseases  and renders diagnosis in selected cases  it has become indispensable in the diagnosis of pulmonary infiltrates in immunocompromised patients  and plays an important role in improving clinical management  finally  it continues to yield an ever increasing amount of data for the researchers studying the mechanisms and pathogenesis of lung disease  it is likely that bal will become an even more valuable tool with increasing relevance to the practice of chest medicine in the 1990s  
class8	pulmonary aspiration during emergency endoscopy in patients with upper gastrointestinal hemorrhage  objective  to evaluate the frequency and significance of aspiration and its clinical importance in patients with upper gi bleeding undergoing esophagogastroduodenoscopy in the icu  design  thirty consecutive patients with active and severe upper gi bleeding were studied  setting  icu  patients  ranged in age from 20 to 78 yr with an equal number of males and females  interventions  all patients had continuous pulse oximetry monitoring and had chest radiographs obtained less than 12 hr before endoscopy and less than 4 hr after endoscopy  measurements  six  20   of 30 patients developed new lung infiltrates after esophagogastroduodenoscopy  in this group of patients  preendoscopy chest radiographs were obtained after less than 4 hr  in five of these patients  infiltrates were accompanied by fever and or leukocytosis and oxygen desaturation to less than 90  during the esophagogastroduodenoscopy  conclusion  clinically significant aspiration pneumonia frequently complicates esophagogastroduodenoscopy in upper gi bleeding patients and is an important mechanism of esophagogastroduodenoscopy induced hypoxia  
class8	helium oxygen mixture in the treatment of postextubation stridor in pediatric trauma patients  objective  to assess the effectiveness of a helium oxygen mixture in reducing post extubation stridor in children hospitalized for burns or trauma  design  randomized  controlled crossover trial  setting  harborview medical center s burn and trauma icus from march to september 1989  patients  children less than 15 yr old who were electively extubated and had symptoms of postextubation stridor  but required less than or equal to 35  oxygen  intervention  each treatment  helium oxygen and oxygen supplemented room air  was given in random order for 15 min after extubation  measurements  respiratory distress was assessed by a physician blinded to treatment order using a standard stridor score and clinical judgment  results  there were 13 children with 15 extubations  seven  47   of 15 patients required subsequent treatment with racemic epinephrine or reintubation  stridor scores were lower with helium oxygen than with oxygen supplemented room air  2 8 vs  3 7  p less than  005   and helium oxygen was preferred in eight of nine trials in which one treatment was clearly favored by the physician  conclusion  because helium oxygen therapy can reduce stridor scores and is clinically preferred by physicians caring for stridorous children  it may be a useful adjunctive therapy in pediatric trauma patients with postextubation stridor  
class8	pulmonary artery occlusion left atrial pressure gradient  an important factor in determining pulmonary venous vascular resistance in acute pulmonary failure  objective  to determine whether pulmonary artery occlusion pressure  paop  accurately reflects left atrial pressure  lap  in acute pulmonary failure  design  sham controlled laboratory investigation on goettingen minipigs  interventions  induction of acute respiratory failure by a 4 hr infusion of live escherichia coli bacteria in 11 animals  two animals served as the control group  anesthesia was obtained with methohexital piritramide and pancuronium bromide  measurements and main results  cardiac output and pressures were measured by means of femoral artery  pulmonary artery  and left atrial catheters  arterial alveolar po2 ratio was calculated to evaluate pulmonary function  measurements were obtained before and after 1 and 2 hr of the e  coli infusion  statistical significance was tested with analysis of variance  e  coli infusion caused the hypodynamic shock and respiratory failure  the paop lap gradient was  0 3     1 6 mm hg before bacteremia and increased significantly  p less than  001  to 2 9     1 8 and 3 4     2 0 mm hg after 1 and 2 hr of bacteremia  respectively  no significant changes occurred in the sham group  conclusions  a paop lap gradient may develop during acute respiratory failure  therefore  pulmonary venous vascular resistance may be underestimated if its determination is based on paop  an increase in bronchial to pulmonary blood flow and pulmonary venoconstriction are discussed as hypothetical causes of a paop lap gradient during acute respiratory failure  
class8	stable and reproducible porcine model of acute lung injury induced by oleic acid  background and methods  previous studies on acute lung injury induced with oleic acid did not attempt to limit the influence of secondary changes on pulmonary circulation  and cardiopulmonary variable data were only collected and processed intermittently  our study was designed to continuously monitor the following variables in five swine  systemic and pulmonary pressure  mixed venous oxygen saturation  svo2  and arterial oxygen saturation  sao2   minute oxygen consumption and co2 production before  during  and for 4 hr after the infusion of oleic acid  a personal computer was programmed to produce 20 sec updates of deadspace ratio  vd vt   venous admixture  qsp qt   pulmonary  pvr  and systemic vascular resistance  svr   and cardiac output  qt  from these data  results  during the oleic acid infusion  there were increases in pvr  svr  heart rate  hr   mean pulmonary arterial pressure  mpap   qsp qt  and vd vt  and a decrease in qt  sao2  and svo2  thirty minutes after the oleic acid infusion  there was a further increase in hr  qsp qt  and vd vt  while mpap  pvr  and svr gradually decreased to pre oleic acid infusion levels  no further decrease in sao2  svo2  and qt was observed during that time  after the 30 min period  there was no further change in the cardiopulmonary variables  conclusion  our method of continuous monitoring was able to demonstrate in swine both the dynamic changes during  and stability after  the oleic acid infusion  
class8	 two stage turbinectomy   sequestration of the inferior turbinate following submucosal diathermy  submucous diathermy of the inferior turbinates is a widely practised procedure  three cases are presented in which surgery was complicated by avascular necrosis of the turbinate bone  each patient required a debridement procedure before healing and recovery of normal mucociliary function could take place  
class8	paraneoplastic limbic encephalitis  clinico pathological correlations  three new cases of limbic encephalitis in association with malignancy are reported  the literature on this condition is reviewed and the clinical  laboratory and histopathological features of cases proven at necropsy are correlated  the possible pathogenic mechanism of this disorder is discussed  
class8	a target feedback device for ventilatory muscle training  in a previous study  we successfully used a target feedback device  together with an external resistor  to train the ventilatory muscles of patients with chronic obstructive pulmonary disease  in this article  we describe the details of the design and function of the target feedback device  when used in conjunction with an external resistance  the target feedback device provides timing and pressure targets  together with feedback information  on whether these targets are achieved  the target feedback device consists of readily available electronic components and is relatively simple to construct  adjustment of an external pressure knob permits setting of pressure targets  adjustment of internal components is possible and allows control of breathing frequency  inspiratory time  and breathing waveform  
class8	treatment of limited small cell lung cancer with concurrent etoposide cisplatin and radiotherapy followed by intensification with high dose cyclophosphamide  a southwest oncology group study  between march 1986 and may 1988  the southwest oncology group enrolled 58 previously untreated patients with limited small cell lung cancer on a treatment program that administered high dose cyclophosphamide  150 mg kg  as late intensification  treatment consisted of induction chemo radiotherapy   weeks 1 to 11   consolidation chemotherapy  weeks 11 to 18   and intensification  week 18   median age was 61 5 years  eighty nine percent of patients had a southwest oncology group  swog  performance status of 0 1  twenty one patients completed all prescribed treatments  there were seven treatment related deaths  four as a result of intensification  fifty six patients are available for response analysis  thirty two patients achieved a complete remission  cr   57   and fifteen achieved a partial remission  pr   26    median survival for all patients is 11 1 months  among the 21 patients who received intensification  nine remain alive in a cr with a median survival of 27 months  this sequence of treatments was not associated with a survival advantage for the group as a whole  possibly because of the toxicity of induction and consolidation treatment and the delayed administration of high dose cyclophosphamide  
class8	dose intensity meta analysis of chemotherapy regimens in small cell carcinoma of the lung  to determine if chemotherapy dose intensity  di  influences treatment outcome  60 published studies in limited  and extensive stage small cell carcinoma of the lung  sccl  were retrospectively analyzed for relationship between intended di and response  complete response  cr  or partial response  pr   or median survival  ms   agents used in the regimens included cyclophosphamide  c   doxorubicin  a   vincristine  v   etoposide  e   and cisplatin  p   relative di  rdi  of each study regimen was calculated against a reference regimen  and weighted regression analysis was used  additionally  analysis of individual drug rdi within combinations was performed  for cav  increasing rdi of the regimen showed no correlation with outcome  for the individual drugs  c rdi correlated positively  while a rdi correlated negatively with attainment of cr in limited disease  but both only after unduly influential observations were eliminated  in extensive stage disease  a rdi correlated positively with cr   pr but only in randomized trials  and this correlation lost statistical significance after unduly influential observations were eliminated  for cae and cave  the rdi of the regimens correlated positively with ms in extensive stage disease as did the c rdi  in limited disease  the c rdi correlated negatively with ms  for ep  no significant correlations were seen  we conclude that di outcome correlations are not consistent for these chemotherapy regimens in sccl  meta analysis of retrospective data can generate hypotheses for testing in prospective clinical trials  but study sample and method of analysis can appreciably affect conclusions  
class8	differences in access to zidovudine  azt  among symptomatic hiv infected persons  object  to evaluate socioeconomic factors that determine whether symptomatic hiv infected persons are offered zidovudine  azt   design  cross sectional survey conducted as part of the robert wood johnson foundation s aids health services program  setting  public hospital clinics and community based aids organizations in nine american cities  patients  880 hiv seropositive outpatients interviewed between october 1988 and may 1989  main results  males were more likely to have been offered azt than were females  adjusted odds ratio 2 99  95  confidence interval 1 67 to 5 36   those with insurance were more likely to have been offered azt than were those without  adjusted odds ratio 2 00  95  confidence interval 1 25 to 3 21   and whites more likely to have been offered azt than were non whites  adjusted odds ratio 1 73  95  confidence interval 1 11 to 2 69   intravenous drug users were less likely to have been offered azt than were non drug users  adjusted odds ratio 0 44  95  confidence interval 0 28 to 0 69   persons who had had an episode of pneumocystis carinii pneumonia were more likely to have been offered azt than were persons who had aids and had not had pneumocystis carinii pneumonia  adjusted odds ratio 2 95  95  confidence interval 1 71 to 5 11   conclusion  the authors conclude that traditionally disadvantaged groups have less access to azt  the only antiretroviral agent demonstrated to increase survival of patients who have symptomatic hiv infection  
class8	fundoplication and gastrostomy in familial dysautonomia  fundoplication with gastrostomy has become a frequent treatment for patients with familial dysautonomia  so we evaluated the use of both procedures in 65 patients  although patients differed widely in presenting signs and age  from 5 weeks to 40 years  gastroesophageal reflux was documented in 95  of patients by cineradiography or ph monitoring  panendoscopy was a useful adjunct  preoperative symptoms of gastroesophageal reflux included vomiting  respiratory infections  and exaggerated autonomic dysfunction  severe oropharyngeal incoordination frequently coexisted and resulted in misdirected swallows with aspiration  dependence on gavage feedings  or poor weight gain and dehydration  follow up after surgical correction ranged from 3 months to 11 years  55 patients  85   were available for a 1 year postoperative assessment  we had no instances of surgical death  the long term mortality rate was 14   primarily related to severe preexisting respiratory disease  beyond the first postoperative year  30 patients had pneumonia attributed to continued aspiration  exacerbation of preexisting lung disease  or recurrence of gastroesophageal reflux  of 11 patients who vomited postoperatively  six had recurrence of reflux  recurrence of gastroesophageal reflux was documented in eight patients  12    and we revised the fundoplication in three patients  the number of patients with cyclic crises was reduced from 18 to 7  retching replaced overt vomiting in all but two of these seven patients  neither of whom had recurrence of reflux  because oropharyngeal incoordination was prominent  concomitant use of gastrostomy and an antireflux procedure was especially effective in the treatment of younger patients with familial dysautonomia  before the development of severe respiratory disease  despite the development of severe morning nausea in 15 patients  the combination procedure resulted in significantly improved nutritional status  decreased vomiting  and decreased respiratory problems  appropriate use of gastrostomy feedings also contributed to success of the operation  the generally good outcome of fundoplication with gastrostomy confirms the benefit of this procedure in familial dysautonomia  
class8	radiotherapy alone versus combined chemotherapy and radiotherapy in nonresectable non small cell lung cancer  first analysis of a randomized trial in 353 patients  we report the results observed in a large  randomized study that compared the effects of radiotherapy alone  the standard therapy  with those of a combination of radiotherapy and chemotherapy in nonresectable squamous cell and large cell lung carcinoma  the radiation dose was 65 gy in each group  and chemotherapy included vindesine  cyclophosphamide  cisplatin  and lomustine  in this study  177 patients received radiotherapy alone  group a   and 176 patients received the combined treatment  group b   the 2 year survival rate was 14  in group a and 21  in group b  p    08   the distant metastasis rate was significantly lower in group b  p less than  001   local control was poor in both groups  17  and 15   respectively  and remained the major problem  
class8	mortality among workers at oak ridge national laboratory  evidence of radiation effects in follow up through 1984  published erratum appears in jama 1991 aug 7 266 5  657  white men hired at the oak ridge  tenn  national laboratory between 1943 and 1972 were followed up for vital status through 1984  n   8318  1524 deaths   relatively low mortality compared with that in us white men was observed for most causes of death  but leukemia mortality was elevated in the total cohort  63  higher  28 deaths  and in workers who had at some time been monitored for internal radionuclide contamination  123  higher  16 deaths   median cumulative dose of external penetrating radiation was 1 4 msv  638 workers had cumulative doses above 50 msv  5 rem   after accounting for age  birth cohort  a measure of socioeconomic status  and active worker status  external radiation with a 20 year exposure lag was related to all causes of death  2 68  increase per 10 msv  primarily due to an association with cancer mortality  4 94  per 10 msv   studies of this population through 1977 did not find radiation cancer mortality associations  and identical analyses using the shorter follow up showed that associations with radiation did not appear until after 1977  the radiation cancer dose response is 10 times higher than estimates from the follow up of survivors of the bombings of hiroshima and nagasaki  japan  but similar to one previous occupational study  dose response estimates are subject to uncertainties due to potential problems  including measurement of radiation doses and cancer outcomes  longer term follow up of this and other populations with good measurement of protracted low level exposures will be critical to evaluating the generalizability of the results reported herein  
class8	surgical treatment for limited small cell lung cancer  the university of toronto lung oncology group experience  since 1977  119 patients with limited small cell lung cancer have undergone combined modality therapy including surgery at our institution  seventy nine patients  58 male  21 female  median age 63 years  had surgery first  and 67 of these had adjuvant chemotherapy  forty  27 male  13 female  median age 59 years  had chemotherapy first  and 94  had a complete or partial response before the operation  pretreatment staging revealed 69 stage i  27 stage ii  and 23 stage iii tumors  twenty six patients required pneumonectomy  88 lobectomy  and five had no resection  four patients had gross and six had microscopic residual disease  postoperative pathologic examination showed small cell lung cancer only  n   95   non small cell lung cancer  n   3   mixed  n   17   and no residual tumor  n   4   postoperative staging revealed 35 stage i  36 stage ii  and 48 stage iiia tumors  the median survival of the entire group is 111 weeks and the projected 5 year survival rate is 39   no survival difference was seen between patients treated with chemotherapy before the operation and those undergoing an initial operation followed by chemotherapy  p   0 756   the median survival for patients with pathologic stage i disease has not been reached  and the projected 5 year survival rate is 51   this is significantly better than for the patients with stage ii  median 82 weeks  p   0 001  or stage iii  median 83 weeks  p   0 001  disease  who have projected 5 year survival rates of 28  and 19   respectively  seven of the 12 patients who had no adjuvant chemotherapy remain alive at 6 to 48  months  sixty seven patients have died  11 had no evidence of disease   only 10 patients had a relapse in the primary site alone  seven at the primary and distant sites  and 39 only in distant sites  in summary  resection improves control at the primary site  and a significant proportion of patients with stage i  n0  disease achieve long term survival and cure with combined modality therapy including surgery  stage ii and iiia patients have survival predictions similar to stage iiia non small cell lung carcinoma treated surgically  
class8	discriminate use of electrocautery on the median sternotomy incision  a 0 16  wound infection rate  between june 1978 and june 1989  superficial or deep mediastinitis  or both  developed in only five  0 16   of 3118 consecutive patients  all patients studied underwent cardiac procedures through a median sternotomy and survived more than 7 postoperative days  the surgical team disciplined itself to divide presternal soft tissues with a scalpel and used electrocautery for pinpoint hemostasis only  this 0 16  infection rate was statistically significantly lower than those in 28 previously published studies  pearson s chi 2 test  p less than 0 05   twenty four predisposing factors were evaluated by fisher s exact test  among these only an operating time longer than 3 hours is related to sternotomy infections  p   0 0208   and this effect was not a strong one  statistical evidence strongly suggests that discriminate use of electrocautery is a major reason for the lowest median sternotomy infection rate reported to date  
class8	co trimoxazole for childhood febrile illness in malaria endemic regions  the efficacy of co trimoxazole for the treatment of plasmodium falciparum parasitaemia in children younger than 5 years of age was evaluated in malawi  46 children with p falciparum parasitaemia  37  of whom also met clinical criteria for a diagnosis of acute lower respiratory tract infection  were treated with 20 mg kg co trimoxazole twice daily for five days  parasitaemia  mean clearance time 2 7 days  and symptoms were rapidly abolished and improvement was maintained during follow up for 14 days  co trimoxazole may be an effective single treatment for febrile illness in young children in areas where malaria is endemic  resources are few  and diagnosis must rely on clinical findings alone  
class8	cutaneous vasoconstrictor response to glucocorticoids in asthma  the aim of the study was to find out whether asthma patients whose airways obstruction is sensitive  cs  or resistant  cr  to corticosteroid treatment also differ in their cutaneous vasoconstrictor response to a potent topical glucocorticoid  corticosteroid resistance was defined by failure of forced expiratory volume in 1 s  fev1  and peak expiratory flow rate to improve by at least 15  after a 2 week trial of corticosteroids  prednisolone 20 mg daily for 1 week  then 40 mg daily for 1 week  despite more than 15  improvement with inhaled beta agonists  beclomethasone dipropionate in concentrations of 3 micrograms ml  10 micrograms ml  30 micrograms ml  and 100 micrograms ml was applied to forearm skin  the site was occluded under plastic and the degree of blanching assessed after 18 h  cs asthmatic subjects  n   31   asthma patients with mild airways obstruction  n   26   asthma patients taking long term prednisolone  n   13   and healthy volunteers showed similar vasoconstrictor responses  in cr asthmatic subjects  n   15   the response  expressed in terms of either blanching intensity or the proportion of patients showing a positive response  was significantly lower than that in the cs group at concentrations of 3 micrograms ml  p less than 0 01   10 micrograms ml  p less than 0 01   and 30 micrograms ml  p less than 0 05   but not at 100 micrograms ml  this resistance to glucocorticoids in the skin  together with reported evidence of glucocorticoid resistance in peripheral blood leucocytes  suggests a general defect in the ability of tissues to respond to glucocorticoids in cr asthma  
class8	surfactant apoprotein a concentration in sputum for diagnosis of pulmonary alveolar proteinosis  pulmonary alveolar proteinosis  pap   a disease characterised by accumulation of surfactant in alveoli  is diagnosed on the basis of invasive biopsy procedures  we have measured apoprotein a  sp a  concentrations in sputum to see if this is useful for the diagnosis of pap  sputum samples from three patients with pap and twenty patients with other pulmonary disease were assayed using monoclonal antibodies to sp a  sp a concentrations were 400 times higher in patients with pap than in the controls  suggestions that this measurement is useful for the diagnosis of pap especially where lung biopsy is contraindicated  
class8	increased airways reactivity after smoke inhalation  13 fire victims who required treatment after smoke inhalation underwent lung function assessment within 3 days of injury and 3 months later  initial airways hyperreactivity improved over this period  but fev1 and airways specific conductance did not change significantly  there was a strong correlation between exposure carboxyhaemoglobin concentration  an indicator of smoke exposure  and initial airways specific conductance  r   0 79  p   0 006   airways obstruction after smoke inhalation in house fires may be more common and more persistent than is generally recognised  early lung function tests would allow the incidence of pulmonary complications after smoke inhalation and the potential benefits of early use of inhaled antiinflammatory drugs to be assessed  
class8	cutaneous hypersensitivity reactions due to thiacetazone in hiv 1 seropositive patients treated for tuberculosis the effects of the human immunodeficiency virus  hiv  on tuberculosis management was investigated in 227 patients initially treated with a regimen containing streptomycin  isoniazid  and thiacetazone  sth   93 of these 227 were hiv seropositive  60 patients  of whom 18 were hiv seropositive  received a regimen consisting of streptomycin  isoniazid  rifampicin  and pyrazinamide  shrz  in the initial phase  and thiacetazone and isoniazid  th  in the continuation phase  cutaneous hypersensitivity reactions occurred in 22 of 111  20   hiv seropositive patients  and in 2 of 176  1   hiv seronegative patients  rr   18  95  ci 4 4 76  p less than 10  7   during the first 8 weeks of treatment 18 reactions occurred among the 93 hiv seropositive patients on sth  whereas no reaction occurred in 17 hiv seropositive patients during the initial phase of shrz th  p   0 04   none of the 18 hiv seropositive patients with cutaneous reactions who were subsequently challenged with isoniazid reacted  nor did any of the 10 tested with streptomycin  but 6 of the 7 challenged with thiacetazone reacted  3 patients  all hiv positive and with toxic epidermal necrolysis  died as a result of the cutaneous reaction  these results have major implications for tuberculosis control programmes in africa  
class8	origin of nasal polyps  the nasoethmoid complexes from 6 patients with nasal polyps were systematically examined  first  the location and place of the origin of the polyps were recorded and photographed  the polyps and their places of origin were removed  serial sectioned  and examined  in all 6 patients  the polyps originated from the nasal mucosa  most of the polyps extended laterally from the mucosa into the anterior part of the middle meatus  several polyps originated from the mucosa near the ethmoid cell ostium or directly from the mucosa lining the edge of the ostium  the ostia themselves were not blocked by the polyps  and there was no indication of polyp formation in the ethmoid cells  
class8	a comparison of surfactant as immediate prophylaxis and as rescue therapy in newborns of less than 30 weeks  gestation background  exogenous pulmonary surfactants are administered into the trachea either to prevent respiratory distress syndrome in premature infants or to treat it  in a randomized  multicenter trial  we compared the results of surfactant therapy initiated as prophylaxis with the results of rescue therapy with surfactant  methods  before birth  479 infants with an estimated gestational age of less than 30 weeks were randomly assigned to receive surfactant as prophylaxis  n   235  or rescue therapy  n   244   the infants in the prophylaxis group received a 90 mg intratracheal dose of an exogenous calf lung surfactant extract at the time of delivery  whereas the infants in the rescue therapy group received 90 mg of the surfactant several hours after delivery if the fractional inspiratory oxygen concentration was at least 0 40 or if the mean airway pressure was at least 0 686 kpa  7 cm of water   or both  infants in both groups received additional doses of surfactant at intervals of 12 to 24 hours if these criteria were met  results  the proportion of infants surviving until discharge to their homes was significantly higher in the prophylaxis group than in the rescue therapy group  88 vs  80 percent  p   0 028   this difference was due primarily to the longer survival of very premature infants  less than or equal to 26 weeks  gestation  in the prophylaxis group than in the rescue therapy group  75 vs  54 percent  p   0 006   according to proportional hazards regression analysis  the distribution of survival times was better for all infants in the prophylaxis group  p   0 007  and for the subgroup of infants in the prophylaxis group who were delivered at 26 weeks  gestation or earlier  p   0 0048   infants in the prophylaxis group who were delivered at 26 weeks  gestation or earlier had a lower incidence of pneumothorax than similar infants in the rescue therapy group  7 vs  18 percent  p   0 03   conclusions  we found a significant advantage to the administration of the initial dose of surfactant as prophylaxis rather than as rescue therapy in very premature infants  
class8	orthopedic complications  compartment syndrome  fat embolism syndrome  and venous thromboembolism  specialized education in the care of orthopedic patients includes an understanding of the common complications for which patients require monitoring  with a socioeconomic backdrop of decreasing hospital stays and prospective payment  patient care must be managed proactively  for all three complications presented  there are unique sets of risk factors that  when present  contribute to a high index of suspicion for morbidity  clusters of symptoms have also been discussed representing the expected normal patterns  with this knowledge as a foundation  clinical application is essential to incorporate other salient aspects of individual situations  nurses diagnose and treat human responses to health problems  the end result of human responses to injury or orthopedic conditions can be the development of complications  stringent adherence to patient monitoring protocols can promote timely nursing interventions to prevent  minimize  or detect complications or treatment side effects  although definitive treatment is often physician directed  nurses are in a key role to impact final patient outcomes  
class8	what to do when an x ray film suggests lung cancer  the chest film is one of the most common methods of detecting lung cancer  which often appears as solitary nodules or hilar masses  once the diagnosis is established  the most effective treatment can be determined and staging of the tumor can be done  surgical resection is the only cure for non small cell carcinoma  although radiotherapy and chemotherapy may shrink some tumors  because 90  of all cases are caused by smoking  a preventive approach to the disease is crucial  screening of high risk patients  ie  smokers with airflow obstruction  using chest films and sputum cytology may aid this approach  
class8	maxillary sinus hypoplasia masquerading as chronic sinusitis  maxillary sinus hypoplasia is a common condition that may be misdiagnosed as chronic sinusitis  although hypoplasia can usually be seen on conventional sinus films  computed tomography may be necessary  as in the cases described by the authors in this article  
class8	a mouse model for investigating the molecular pathogenesis of adenovirus pneumonia  intranasal inoculation of type 5 adenovirus  ad5  produced pneumonia in mice even though the virus did not replicate  to induce the pneumonia  however  a large viral infectious dose was required  i e   10 10  plaque forming units  four strains of inbred mouse were studied  c57bl 6n  c57bl 10scn  cba n  and c3h n   all showed similar inflammatory responses  although the greatest infiltration occurred in the c57bl 6n mice  the pathological response to ad5 infection resembled that previously described in cotton rats  it consisted of overlapping early and late phases  and the infiltration contained primarily lymphocytes and monocytes macrophages with a scattering of polymorphonuclear leukocytes  the prominent early phase and the presence of polymorphonuclear leukocytes suggested that induction of cytokines may play an important role in the pathogenesis of this pneumonia  assays showed the appearance of tumor necrosis factor alpha  tnf alpha   interleukin 1  il 1   and il 6 in the infected mouse lungs concomitant with the developing early phase infiltration  only il 6 was found in the peripheral blood  il 6 reached maximum titers 6 24 hr after infection  whereas maximum levels of tnf alpha and il 1 were attained 2 3 days after infection  specific rnas for each of these cytokines were demonstrated in the infected lungs  to test the hypothesis that a cytotoxic t cell response was responsible for the second phase  which primarily consisted of a perivascular and peribronchial infiltration of lymphocytes  ad5 was used to infect c57bl 10scn nu nu and parent mice  the nude mice showed a normal early phase response  but essentially no peribronchial and only minimal perivascular infiltrations occurred  
class8	effects of epidermal growth factor and analogues of luteinizing hormone releasing hormone and somatostatin on phosphorylation and dephosphorylation of tyrosine residues of specific protein substrates in various tumors  analogues of somatostatin  ss  and luteinizing hormone releasing hormone  lh rh  activate tyrosine phosphatases in mia paca 2 human pancreatic cancer cell line membranes and inhibit growth  we compared the substrates phosphorylated by epidermal growth factor  egf  to those dephosphorylated by the ss analogue rc 160  d phe cys tyr d trp lys val cys trp nh2  and  d trp6 lh rh in cancer cell lines such as mia paca 2  human pancreatic cancer   hcpc  hamster cheek pouch carcinoma   a 549  human lung cancer   ht 29  human colon cancer   and r3230ac  breast cancer   egf phosphorylated proteins of 170  65  and 60 kda and analogues of ss and lh rh promoted the dephosphorylation of these proteins in mia paca 2 and hcpc cell lines  the egf receptor is 170 kda  pp60src  60 kda  is known to be a substrate for egf receptor  the lh rh receptor is also 60 kda  the effects of rc 160 and  d trp6 lh rh were quantitatively different  examinations of ht 29  a 549  and r3230ac cancer cell lines revealed no phosphorylation by egf or dephosphorylation by rc 160 and  d trp6 lh rh  in addition to the 170   65   and 60 kda proteins  35 kda proteins were also phosphorylated in some cancer cell lines  this work demonstrates that analogues of ss and lh rh can reverse the effects of egf biochemically as well as functionally  
class8	computed tomography and the tnm classification of lung cancer  computed tomography  ct  of the thorax and upper abdomen was prospectively evaluated in 84 patients with potentially operable lung cancer  invasion into the thoracic wall and the mediastinal structures was not accurately demonstrated by ct  for metastatic mediastinal lymph nodes  the sensitivity and specificity of ct were  respectively  86  and 61  and the positive and negative predictive indices 49  and 91   for t1  t2 and t3 tumours the negative indices were 100   96  and 71   positive predictive index did not differ between squamous cell carcinoma and adenocarcinoma  adrenal metastases were ct suspected in 17 cases and liver metastases in eight  but were verified by ultrasonography in only one and four cases  ct should be used in preoperative investigation of lung cancer  irrespective of stage  demonstration of thoracic wall or mediastinal invasion need not exclude tumour resection  preoperative mediastinoscopy is indicated if ct shows nodal metastases or if there are signs of tumour invasion  but not in ct negative t1 or t2 tumour  abdominal metastases indicated by ct should be investigated with ct guided needle biopsy  
class8	perioperative effect of methylprednisolone given during lung surgery on plasma concentrations of c3a and c5a  methylprednisolone or saline  placebo  solution was infused intravenously in 28 patients undergoing elective lobectomy for lung cancer  the state of the complement system during and after surgery and the effects of methylprednisolone on biologically active products of complement were studied by measurements of plasma c3a and c5a anaphylatoxins and leukocyte counts in peripheral blood perioperatively  in the placebo group plasma concentrations of c3a were significantly increased on postoperative days 1 and 2  whereas c5a had risen significantly 6 hours after surgery and on days 1 and 2  methylprednisolone infusion during surgery eliminated the postoperative elevation of c3a and c5a  the postoperative leukocyte count in peripheral blood was higher in the methylprednisolone group than in the controls  the observations indicated that methylprednisolone may reduce the influx of leukocytes from peripheral blood into the airways by attenuating production of biologically active complements  
class8	community acquired pulmonary infections in a public municipal hospital in the 1980s  the relative and absolute incidences of community acquired bacterial and tuberculous pulmonary infections  in patients admitted to a public municipal hospital  and the clinical and radiographic characteristics of these infections were retrospectively determined for the first time in 20 years  the data were compared to those previously reported in the literature  such data were also specifically determined for alcoholics and compared to those found in nonalcoholics  the absolute numbers of infections due to pneumococci and anaerobes  and to tuberculosis  were not dissimilar to those reported in the literature  even though relatively few hemophilus infections were documented  the lack of klebsiella sp infections was remarkable but not unexpected  alcoholic patients had significantly higher rates of tuberculosis  cavitary disease  lung disease presumably due to anaerobes  and blood culture positive pneumonia  the relative concordance of our results for bacterial and tuberculous infections with those predicted from the published literature was striking  the high frequency of tuberculosis in our patients was particularly striking at a time when the incidence of tuberculosis nationwide  in patients without acquired immunodeficiency syndrome  has declined significantly  
class8	spontaneous rupture of the stomach in an adult  we have reported a case of spontaneous rupture of the stomach in an adult  immediate onset of severe upper abdominal pain after overindulgence in food and drink along with radiographic evidence of pneumoperitoneum and the clinical findings of massive abdominal distention  epigastric tenderness  shock  and occasionally subcutaneous emphysema should suggest the possibility of gastric rupture  the treatment is simple  but mortality is high when surgical intervention is not rapid  
class8	late arterial hemorrhage secondary to a greenfield filter requiring operative intervention  retroperitoneal hematomas associated with greenfield filters have been described and are generally characterized as clinically insignificant  we report a retroperitoneal hematoma that was associated with a greenfield filter and that required operative intervention because of hemodynamic instability  at operation a lumbar arterial laceration apparently caused by a protruding filter prong was identified and ligated  the implications of this occurrence for filter placement indications are discussed  the potential life threatening severity of filter associated hematomas is emphasized  
class8	gastroesophageal reflux in infants  clinically significant gastroesophageal reflux occurs in one in 500 infants  symptoms resolve in 60 to 80 percent of infants by 18 months of age  thickened formula and position changes are often recommended  medication and surgical intervention may be needed in refractory cases  
class8	cardiac arrest in seattle  conventional versus amiodarone drug evaluation  the cascade study   this randomized study evaluates survivors of out of hospital ventricular fibrillation  vf  not associated with a q wave acute myocardial infarction who are deemed to be at a high risk of recurrence of vf  it compares the outcome of treatment with empirically administered amiodarone with the outcome of treatment with other antiarrhythmic agents guided by electrophysiologic testing or holter recording  or both  the goal of therapy guided by electrophysiologic testing is to suppress inducible ventricular tachycardia  vt  or vf  holter recording is used as the primary means of adjusting therapy only if patients are noninducible at the baseline electrophysiologic study  patients are stratified according to cardiac diagnosis  ejection fraction  and whether they had previously received an antiarrhythmic agent that failed to suppress their arrhythmias  the primary end point of the study is total cardiac mortality  the first patient was enrolled in a pilot study on april 26  1984  by october 1988  142 patients had been enrolled in the full study and  as of may 1990  199 patients have been enrolled  compliance with therapy has been good  with no patients lost to follow up and 8  of patients  equal in both drug groups  crossing over to alternate therapy  baseline clinical characteristics remain similar in amiodarone and conventional drug groups  pulmonary toxicity with amiodarone is 7  at 1 year  with no patients dying of pulmonary toxicity  in the first 142 patients  the overall 1 year cardiac mortality was 19   with a 17  arrhythmic mortality  either vf or presumed arrhythmic death   
class8	the intratracheal administration of endotoxin and cytokines  iii  the interleukin 1  il 1  receptor antagonist inhibits endotoxin  and il 1 induced acute inflammation  endotoxin  a lipopolysaccharide  lps  component of gram negative bacteria  induces alveolar macrophages to express interleukin 1  il 1   lipopolysaccharide and il 1 both cause severe acute neutrophilic inflammation in the lung after intratracheal injection  suggesting that lps induced il 1 expression contributes to the pathogenesis of lps induced acute inflammation  in the present study  the role of il 1 in lps induced acute pneumonia was investigated by quantitating the acute inflammation occurring at 6 hours after the intratracheal injection of lps as compared to the same timepoint after the intratracheal coinjection of lps and il 1 receptor antagonist  il 1ra   the il 1ra was found to inhibit lps induced acute inflammation  p greater than 0 0001  as measured by the number of neutrophils recovered in bronchoalveolar lavage  the lps induced emigration of neutrophils was inhibited by as much as 45   recombinant il 1 beta induced neutrophil emigration into the lung was inhibited by 95  when il 1ra was coinjected intratracheally with il 1 beta  coinjection of recombinant il 1 beta and lps increased the neutrophilic exodus as compared to the intratracheal injection of either agent alone  intratracheal injection of lps induces a progressive increase in il 1ra mrna expression in whole lung rna preparations  suggesting that endogenous il 1ra may play an important role as a negative feedback mechanism to downregulate lps initiated il 1 mediated acute inflammation  in conclusion il 1ra inhibits both lps  and il 1 induced neutrophilic inflammation and may therefore prove clinically useful as an anti inflammatory agent for the therapy of either septic or aseptic il 1 mediated acute inflammation  
class8	contrasting roles for tumor necrosis factor in the pathogeneses of iga and igg immune complex lung injury  recent studies suggest that development of acute gamma g immunoglobulin  igg  immune complex lung injury is partially dependent on a tumor necrosis factor  tnf  dependent mechanisms of neutrophil  pmn  recruitment  the authors have sought to further define the role of intrapulmonary tnf in igg alveolitis and to examine its role in iga immune complex alveolitis  a neutrophil independent model of acute lung injury  igg immune complex lung injury resulted in a marked rise in intrapulmonary tnf activity accompanied by progressive pulmonary pmn accumulation  intratracheal instillation of neutralizing concentrations of anti tnf markedly reduced pmn influx measured at 4 hours but had no effect on pmn recruitment quantitated at 2 hours  iga immune complex deposition resulted in acute lung injury accompanied by increased numbers of intrapulmonary mononuclear phagocytes but few neutrophils  lung lavage fluids obtained from iga immune complex injured rats contained both neutrophil and monocyte chemotactic activities  albeit at twofold to fourfold lower concentrations than observed in igg mediated alveolitis  in contrast to igg complex mediated alveolitis  lung lavage fluids from iga injured rats contained no tnf activity  intratracheal administration of anti tnf antibodies had no effect on the development of iga lung injury as assessed by morphology and measurements of vascular permeability  in vitro exposure of isolated alveolar macrophages to performed igg immune complexes resulted in dose dependent tnf secretion  while exposure to iga complexes resulted in very low levels of tnf secretion  these data suggest that tnf mediated pulmonary neutrophil recruitment  in igg lung injury  is manifest chiefly in the late phase  approximately 4 hours  of developing alveolitis  the virtual absence of intrapulmonary tnf activity in evolving iga immune complex alveolitis may in part account for the limited pmn recruitment observed in this model  
class9	the role of bacterial adherence in otitis media with effusion  adherence of nontypable haemophilus influenzae and streptococcus pneumoniae to nasopharyngeal epithelial cells was investigated in vitro  both strains had higher affinity to the epithelial cells of children than to those of adults  in children  the adherence was significantly greater in patients with otitis media with effusion than in normal subjects  secretory iga in nasopharyngeal secretions was found to have antibody activity against the bacteria  adherence of both bacteria was significantly smaller in the group having secretory iga antibody activity than in the group having no activity  these results suggest that bacterial adherence to the nasopharynx may play an important role in the pathogenesis of otitis media with effusion in children  and that secretory iga in nasopharyngeal secretions may be related to the decrease of adherence  
class9	induction chemotherapy with a new regimen alternating cisplatin  fluorouracil with mitomycin  hydroxyurea and bleomycin in carcinomas of nasopharynx or other sites of the head and neck region  sixty six patients with locally advanced  stages iii and iv  carcinoma of the head and neck were treated with three cycles of induction chemotherapy  consisting of cisplatin  fluorouracil  fu  infusion  bleomycin  mitomycin  and hydroxyurea  followed by radiotherapy and or surgery  there were 48 men and 18 women with a median age of 55 years  range  18 to 75 years  and karnofsky performance status of 80  range  40 to 90   primary site was nasopharynx  28 patients   followed by larynx  12  and others  26   forty one  62   patients were presented with stage iv disease  the response rate to induction chemotherapy was 27  complete response  50  partial response  20  stable disease  and 3  progressive disease  there was no significant difference in response rate between patients with cancer of nasopharynx or other sites  p greater than 0 1   survival was 61  at 24 months  patients with cancer of nasopharynx had a better survival than those with other primaries  p   0 033   toxicities from chemotherapy included alopecia  73    nausea vomiting  66    leukopenia  54    stomatitis  36    anemia  32    thrombocytopenia  16    and diarrhea  9    grade iv toxicity was not observed  induction chemotherapy with this new regimen resulted in a high response rate but may not be superior to cisplatin and fu alone  it can be safely combined with radiotherapy as a potentially curative therapy in squamous cell carcinoma of the head and neck  chemotherapy followed by radiation therapy may yield survival similar to radical surgery in laryngeal and other head and neck cancers  
class9	relationship of 4f2 antigen with local growth and metastatic potential of squamous cell carcinoma of the larynx  the 4f2 antigen is a cell membrane glycoprotein which arises early in the g0 g1 phases of the cell cycle  this molecule is present in all established human cell lines and most malignant human cells  the authors used an indirect immunophosphatase method to study 50 squamous cell carcinomas of the larynx and ten lymph node metastases  corresponding to six primary tumors  for 4f2 expression  the tumors showed several patterns of 4f2 staining which were correlated with different behaviors and prognoses of the neoplasms  three different patterns  no staining  peripheral staining  and diffuse 4f2 expression  are described as are their relationships with metastatic behavior of the carcinomas  tumors with metastases were found only in the third group  p   0 0001   these results led to the following conclusions   1  the 4f2 antigen is present in squamous cell carcinomas   2  its distribution reflects the tumor spreading pattern  and  3  it correlates with differentiation and metastatic behavior  
class9	pyoderma gangrenosum complicating felty s syndrome  the case of a 54 year old woman with felty s syndrome whose course was complicated by mucocutaneous lesions clinically typical of pyoderma gangrenosum is described  necrotizing sinusitis and saddle nose deformity were distinctive clinical features  lymphocytic vasculitis and rheumatoid nodule formation observed within panniculus at the base of a cutaneous lesion and in a nasal mucosal lesion were unexpected histopathologic findings  
class9	conservation surgery for glomus jugulare tumors  the value of early diagnosis  the results of lateral cranial base surgery for glomus jugulare tumors are gratifying when normal anatomy and function can be preserved  the goal of conservation surgery is to preserve normal ear anatomy and cranial nerve function  in general  conservation surgery is tumor size dependent  thus  excellent states of functional recovery depend upon accurate early diagnosis  this paper reviews the technical aspects of transtemporal conservation skull base tumor surgery while also reviewing our experience with nearly 100 glomus jugulare patients  adjuvants to early diagnosis will be highlighted from a review of presenting symptoms  clinical signs  and related diagnosis  our objective is to provoke a high index of suspicion in physicians charged with the responsibility of diagnosing these tumors  diagnostic guidelines are proposed  
class9	surgery for sinusitis and aspirin triad  an 11 year retrospective study was conducted to evaluate the surgical treatment of sinusitis in aspirin triad patients  twenty five patients were selected for surgery when their sinus disease and asthma progressed despite intense medical treatment  sixteen patients had radiographic evidence of severe ethmoid disease  and their initial surgical procedures were limited  i e   bilateral intranasal ethmoidectomies   of these 16 patients  6 required subsequent surgery for recurrent sinusitis  nine of the 25 patients had radiographic evidence of severe antral  as well as ethmoid  disease  their initial surgical procedures were radical  i e   bilateral caldwell luc operations with intranasal and transantral sphenoethmoidectomies  none of these 9 patients required further surgical treatment for control  this review indicates that if antral and sphenoid disease are detected in association with ethmoid involvement  a radical surgical approach is the operation of choice  
class9	lidocaine in the middle ear  anesthesia of the ear canal is produced by injection of lidocaine hydrochloride into the skin of the lateral external ear canal  ear canal  tympanic membrane  and middle ear surgeries are performed with this injection  the fluid found in the middle ear during tympanotomy was collected and analyzed  the percentage of lidocaine in the fluid was calculated by an enzyme immunoassay technique  fifteen surgical cases were undertaken in which perilymphatic fluid in the middle ear would not be suspected  such as tympanotomy for otosclerosis  lidocaine was found in all middle ears in which there was sufficient fluid to collect  the authors question the validity of using the presence of clear fluid in the middle ear  even with reaccumulation  as the sole criterion for identifying perilymph and cerebrospinal fluid  
class9	imaging of pharyngeal and laryngeal carcinomas with indium 111 labeled monoclonal anti cea antibodies  localization of primary tumors  metastases  or recurrences in 13 consecutive patients with histological verification of squamous cell or adenocarcinoma was made with radioimmunodetection using monoclonal radiolabeled anti cea antibody  all surgical specimens stained immunohistochemically  except one  were positive for cea  of the known 19 tumor sites 17 were visualized in antibody scans  there were two positive findings that did not prove to be positive during 12 month follow up  the scintigram findings did not correlate with cea serum concentrations that  with one exception  were normal in all patients  
class9	stapedotomy technique and results  ten years  experience and comparative study with stapedectomy  fifty of the 810 patients who underwent stapedotomy for otosclerosis from 1969 through 1988 were randomly chosen for follow up of at least 5 years  most of the patients  65   had follow up of 10 years after stapedotomy  but another 50 patients who underwent stapedectomy had follow ups of longer than 10 years  in 50 patients  stapedectomy under local anesthesia was performed by removal of the footplate of the stapes  using an endaural incision  and covering the oval window with gelfoam  in the other 50 patients  stapedotomy was performed under general anesthesia  using an endopreauricular incision  making a small hole in the footplate  and covering the hole only with blood from the surgical area  although both groups showed improvement in hearing after the operation  the air bone gap in the stapedotomy group was significantly better than that in the stapedectomy group  the use of the endopreauricular incision under general anesthesia was preferable to endaural incision under local anesthesia because the operative field was wider  more convenient for the surgeon  and conducive to patient safety  there were no significant complications in either group  
class9	endoscopic laser surgery for early glottic carcinoma  a clinical and experimental study  the purpose of this study is to define the indications for using the co2 laser for the treatment of early glottic cancer  for this purpose  52 consecutive laser resections of tis to t2 vocal cord carcinomas were studied prospectively  in addition  laser resection was performed in eight human cadaver larynges  which were then examined histologically using whole organ sections  both tumor size and tumor location had important influences on tumor resectability by laser  all of the tis  78  of t1  and one of four t2 carcinomas were successfully treated by laser surgery alone  of the 10 carcinomas involving the anterior commissure  only four could completely be resected with the laser  of these four  two recurred in the anterior commissure  this finding is corroborated by the histologic study  which clearly shows that anterior commissure resection poses problems  the only laser resection complication of early glottic cancer was persistent hoarseness in one third of the patients  it is concluded that co2 laser resection is a safe and effective alternative treatment for patients with tis and t1 glottic carcinoma  provided the anterior commissure is free of tumor  
class9	gentamicin iontophoresis in the treatment of bacterial otitis externa in the guinea pig model  pseudomonas otitis externa is one of the most common infections treated by otolaryngologists  infections induced in 30 guinea pigs appeared similar to that seen in humans  the ears were then placed into four treatment groups  group a  which received a single cleaning  group b  which received a single cleaning followed by gentamicin drops 4 times daily  group c  which received a single cleaning followed by a single gentamicin iontophoresis treatment  and group d  the control group  which received no treatment  infections were analyzed by grading edema  purulence  and erythema  an average of 10 2 days was required for control group to return to normal appearance  groups a  b  and c had mean resolution times of 5 9  4 7  and 4 3 days  respectively  gentamicin iontophoresis appears to be promising  with results as good as drop therapy in otitis externa in the guinea pig model  
class9	an improved stent method for choanal atresia repair  short intranasal stents secured sublabially have a number of advantages  they provide secure fixation without an external ligature across the columella  the short length of the stents allows them to sit only in the operative area where the atretic plate had been removed  this lessens the chance of intranasal syechiae formation and eliminates the possibility of erosion in the anterior septal and nasal alar region from pressure exerted by a stent  since the stents do not protrude from the nose  they cannot be grasped by infants or young children and are not visible externally  school aged children who have undergone repair of a unilateral choanal atresia can attend school without having to suffer the embarrassment of being teased about a tube protruding from the nose  when compared with other stenting methods  the posterior stent is more secure and less likely to become dislodged  
class9	understanding dizziness  how to decipher this nonspecific symptom  dizziness is a common but often nonspecific symptom  through careful history taking and physical examination  primary care physicians can usually determine the type of sensation  vertigo or light headedness  and its source  although most causes of dizziness are benign  disorders of the central nervous system tend to be ominous and require immediate referral to a specialist  
class9	cervical lymph node metastasis  assessment of radiologic criteria  to estimate the accuracy of different radiologic criteria used to detect cervical lymph node metastasis in patients with head and neck carcinoma  seven different characteristics of 2 719 lymph nodes in 71 neck dissection specimens from 55 patients were assessed  three lymph node diameters  their location  their number  the presence of a tumor  and the amount of necrosis and fatty metaplasia were recorded  the minimal diameter in the axial plane was found to be the most accurate size criterion for predicting lymph node metastasis  a minimal axial diameter of 10 mm was determined to be the most effective size criterion  the size criterion for lymph nodes in the subdigastric region was 1 mm larger  11 mm   groups of three or more borderline nodes were proved to increase the sensitivity but did not significantly decrease the specificity  radiologically detectable necrosis  3 mm or larger  was found only in tumorous nodes and was present in 74  of the positive neck dissection specimens  shape was not a valuable criterion for the radiologic assessment of the cervical lymph node status  
class9	three dimensional reconstructed mr imaging of the inner ear  the three dimensional fourier transform fast imaging with steady precession  fisp  technique was used to obtain high resolution magnetic resonance  mr  images of the temporal bone region and to generate three dimensional reconstructed images of the inner ear  the three dimensional reconstructed images of the inner ear were directly synthesized from two dimensional images of the temporal bone region by means of an external processing computer  with use of three dimensional reconstructed images and stereoscopic observations  structures inside the temporal bone region and the positional relationship among them were easily recognized  these structures are difficult to demonstrate with two dimensional images  this three dimensional method was also shown to be useful for recognition of disease and anatomic malformations in the temporal bone region  
class9	sphenochoanal polyps  evaluation with ct and mr imaging  a sphenochoanal polyp is a solitary mass of low attenuation on computed tomographic  ct  scans that arises from the sphenoid sinus and extends through the sphenoid ostium  across the sphenoethmoid recess  and into the choana  the boundary between the nasal cavity and nasopharynx   more often  however  a choanal polyp is an antrochoanal polyp  which arises from the maxillary antrum  protrudes through the middle meatus  extends into the nasal cavity  and continues back to the choana  contiguous axial or coronal magnetic resonance and ct images help clearly differentiate the rare sphenochoanal polyp from the more common antrochoanal polyp  the sinus of origin is important to identify  as the surgical approach depends on the target sinus  
class9	relationship between asthma and seasonal allergic rhinitis in schoolchildren  the relationship between sensitization to common allergens and the development of asthma and seasonal allergic rhinitis  sar  was investigated in a total of 419 schoolchildren in a farming community where allergens of both dermatophagoides farinae  df  and orchard grass  og  pollen predominate  twelve subjects  2 9   were found to have asthma and 35 subjects  8 4   sar  there was no significant association between occurrences of asthma and sar  the incidence of asthma correlated with df specific ige levels but not with og specific ige levels  whereas that of sar correlated with og specific ige levels but not with df specific ige levels  no significant correlation was detected between ige antibody levels against df and og  these results suggest that asthma occurs independently of sar  
class9	fat myringoplasty in the guinea pig  fat myringoplasty is a simple office technique for repairing tympanic membrane perforations  it involves wedging a piece of fat from the ear lobule into the perforation  a search of the literature failed to reveal any controlled studies on the efficacy of this method  which may allow patients to avoid more invasive procedures  controlled perforations in guinea pig tympanic membranes were treated with fat myringoplasties  paper patches  or no intervention  four weeks following the procedures  ears were examined and photographed under the microscope and studied histologically  the fat myringoplasty healing rate exceeded the rates of both the control and paper patch groups  results were stratified with respect to location and size of perforations  the results and histological studies suggest that controlled studies in humans are warranted  
class9	otolaryngologic management of patients with subdural empyema  from 1979 to 1988  17 patients presented to duke university medical center for treatment of subdural empyema  empyemas were caused by sinusitis in 53  of the patients and by otitis media in 12   none of those with otologic causes required mastoid drainage  while all patients with sinus infections required sinus drainage  external frontoethmoidectomies were associated with a lower incidence of frontoethmoid re exploration  p   0 048   and antrostomies with a lower incidence of maxillary re exploration  p   0 111   than were more limited drainage procedures  sinus drainage performed simultaneously with neurosurgical drainage reduced the incidence of sinus re exploration  p   0 167   neurosurgical reexploration  p   0 048   and length of hospitalization  p   0 020   
class9	rapid sequence treatment of advanced squamous cell carcinoma of the upper aerodigestive tract  a pilot study  a review of the literature suggested that prolonged treatment time may lessen the probability of cure for patients with advanced squamous cell carcinoma of the upper aerodigestive tract  to shorten treatment time  rapid sequence treatment  rst  was devised in which chemotherapy  surgery  and irradation were administered in a total treatment time of 8 weeks  twelve patients were treated and followed 3 years or longer  medical complications were minor  osteonecrosis occurred in each of the first five patients and was the only major complication of the protocol  surgical techniques were modified  and no additional patient developed osteonecrosis  no patient developed local or regional recurrence  two patients developed distant metastases and three other patients developed second primaries  absolute survival was 50   rapid sequence treatment is an aggressive and potentially hazardous protocol that yielded encouraging results in this pilot study  
class9	monothermal differential caloric testing in patients with meniere s disease  the monothermal differential caloric test allows determination of vestibular recruitment and decruitment  variables which may help discriminate peripheral from central vestibular lesions  previous reports indicated a strong association between vestibular recruitment and meniere s disease  this study examined patients having unilateral meniere s disease  nystagmus beat frequency  nbf  and slow component velocity  scv  responses were recorded by electronystagmography  eng   electronystagmographic findings showing unilateral dysfunction were present in 54  of patients by slow component velocity and in 31  by nystagmus beat frequency  unilateral hypofunction was the most frequent lateralizing eng finding  absolute vestibular recruitment occurred in less than 10  of patients but relative recruitment was found in nearly 20  of patients  slow component velocity had higher sensitivity than nystagmus beat frequency  with excellent clinical concordance  monothermal caloric testing as described in this study best detects peripheral vestibular disease in meniere s patients using slow component velocity to determine unilateral hypofunction and relative vestibular recruitment  
class9	paranasal sinus bony anatomic variations and mucosal abnormalities  ct analysis for endoscopic sinus surgery  coronal plane computerized tomographic  ct  scanning has dramatically improved the imaging of paranasal sinus anatomy as compared to sinus radiographs  increasingly  subtle bony anatomic variations and mucosal abnormalities of this region are being detected  data regarding the  background  prevalence of these findings are needed to determine their clinical relevance  a detailed analysis of coronal plane ct scans of the paranasal sinuses obtained in 202 consecutively imaged patients was conducted  special attention was directed toward identifying bony anatomic variations and mucosal abnormalities  anatomic variations studied included pneumatization of the middle turbinate  paradoxical curvature of the middle turbinate  haller s cells  and pneumatization of the uncinate process  such bony anatomic variations were detected in 131  64 9   of 202 patients and were found with a similar frequency in patients scanned for sinus complaints and in those scanned for nonsinus reasons  mucosal abnormalities were detected in 168  83 2   of 202 patients  for those patients scanned during the evaluation of sinus like complaints  mucosal abnormalities were noted in 153  92 2   of 166 cases  and were predominantly detected in the anterior ethmoid region  for patients scanned during nonsinus evaluations  mucosal abnormalities were detected in 15  41 7   of 36 cases  without predilection for the anterior ethmoid region  discussion regarding the prevalence and clinical significance of paranasal sinus bony anatomic variations and mucosal abnormalities is included as a guide to assist the otolaryngologist and or radiologist in the evaluation of coronal sinus ct scans  
class9	whole blood filterability in sudden deafness  sixteen patients with sudden deafness  sd   diagnosed on the basis of a battery of audiometric tests  but with no other medical or surgical pathology requiring drug treatment  underwent monitoring of their hemorheological profiles to see whether disturbances in the microcirculation could be linked to sd  plasma viscosity  the filterabilities   using a low shear positive pressure system  through 5 microns diameter pore nuclepore filters  of whole blood and red and unfractionated white cells were monitored in 16 sd patients and 32 controls matched for age  sex and socioeconomic status  whole blood filterability and the filterability of the red blood cells were significantly impaired in the sd patients  which suggests that alterations in the microcirculation are linked  in some way  to sudden deafness  
class9	molecular pathologic study of human papillomavirus infection in inverted papilloma and squamous cell carcinoma of the nasal cavities and paranasal sinuses  nasal inverted papilloma is a rare benign tumor occasionally associated with squamous cell carcinoma  to determine the etiological role of human papillomavirus in inverted papilloma  and to clarify the relationship between human papillomavirus and malignant transformation of this benign tumor  we retrospectively analyzed inverted papillomas from 26 patients  7 of whom had squamous cell carcinoma  we used an immunohistochemical method and molecular pathologic techniques  or dot blot hybridization of dna extracted from paraffin embedded tissues  in situ hybridization  and polymerase chain reaction  human papillomavirus was detected in 5 of 26 patients  19    3 patients with human papillomavirus 11 and 2 patients with human papillomavirus 16  the latter 2 patients had inverted papillomas associated with squamous cell carcinoma  we speculate that human papillomavirus may be related to the malignant transformation of inverted papillomas  
class9	neurotologic findings in basilar migraine  treatment of a patient with otologic symptoms and associated migraine like headache presents the otolaryngologist with formidable problems  although clinical practice and scientific publications recognize their frequent association  relationships have yet to be well defined  this study seeks to add order to disarray by delineating symptoms and signs of a clearly identified group of migraine patients  fifty patients with well defined basilar migraine underwent a thorough neurotologic examination  as well as comprehensive auditory and vestibular testing  patients were selected from 5880 patients seen over a 2 year period and were prospectively entered into the study after detailed questionnaires and testing were completed for each patient  the most common symptoms found were dysequilibrium  phonophobia  and head pressure  the most common signs were positional nystagmus  low frequency hearing loss  abnormal loudness discomfort level  and an abnormality on caloric examination  advanced vestibular testing showed abnormal amplitude scaling  abnormal toes down pertubation  and an abnormal sway  condition 6  on dynamic posturography  there was frequently an asymmetry on computerized rotation  the author concludes that the majority of patients have subtle findings on testing  but a few have severe peripheral injury due to the basilar migraine  findings are consistent with the theory that basilar migraine is a central nervous system maladaptation syndrome which creates otoneurologic symptoms and  in a small percentage of cases  may injure the peripheral end organ  
class9	stridor  intracranial pathology causing postextubation vocal cord paralysis  during an 18 month period in a pediatric intensive care unit  nine patients with vocal cord paralysis were identified using flexible bronchoscopy  when tracheally extubated  each child was found to have stridor  the children ranged in age from 17 days to 5 1 2 years  two patients had unilateral paralysis  but neither required tracheostomy  seven patients displayed bilateral abductor vocal cord paralysis  of these  six patients required tracheostomy  surgical injury to the recurrent laryngeal nerve was the probable cause in two patients  the other seven patients had neurologic disorders with documented or suspected increases of intracranial pressure  four of the seven patients with bilateral abductor vocal cord paralysis regained cord mobility within 4 months  both children with unilateral cord paralysis have no stridor and vocalize well 1 year later  cord paralysis in the setting of intracranial hypertension probably results from compression or ischemia of the vagus nerve before it exits the skull  early visualization of the larynx should be done in patients who become stridulous when extubated  especially those with prior thoracic procedures or with neurologic disorders associated with intracranial hypertension  
class9	bacteremia with otitis media  to investigate the occurrence and outcome of bacteremia associated with otitis media  charts were reviewed from patients who were 3 to 36 months of age  had temperatures greater than or equal to 39 degrees c  and were diagnosed with isolated clinical otitis media  a total of 2982 patients were identified  blood cultures were obtained from 1666  56    of the 1666 patients  who had blood drawn for cultures  50  3 0   had bacteremia  these included 39 with streptococcus pneumoniae  4 with haemophilus influenzae  2 with neisseria meningitidis  3 with salmonella species  and 2 with staphylococcus aureus  the incidence of bacteremia increased at higher temperatures  being 1 9  at temperatures less than or equal to 40 degrees c and 5 0  at temperatures greater than 40 degrees c  younger children were more likely to have bacteremia  3 7  less than or equal to 12 months of age  2 4  13 to 24 months of age  and 1 9  25 to 36 months of age had blood culture results that were positive  not significant   reevaluation of the 50 bacteremic patients showed that 9 patients had continued fever  3 patients had persistent bacteremia  pneumonia developed in 1 patient  and meningitis developed in 1 patient  it was concluded that  1  3  of young febrile children with otitis media have bacteremia at the time of evaluation  a rate comparable to that previously reported in children with no focus of infection   2  the incidence of bacteremia increases at higher temperatures  and  3  most febrile children with otitis media do well  the clinician must therefore weigh the potential benefit of drawing a blood culture to identify children at risk for complications against the inherent cost  inconvenience  and discomfort  
class9	delayed detection of congenital hearing loss in high risk infants objective  to examine the methods used to investigate children at high risk of congenital hearing impairment  and to see whether the introduction of evoked response audiometry has reduced the mean age at which hearing loss is identified  design  clinicians who notified children to the national congenital rubella surveillance programme were asked retrospectively to complete a questionnaire examining the methods used to identify hearing impairment and the age at testing in two consecutive five year cohorts  the presence or absence of hearing loss was confirmed by obtaining the results of audiometric evaluations and  whenever possible  a recent pure tone audiogram  setting  the united kingdom  patients  children notified to the national congenital rubella surveillance programme and born in 1978 87 in whom igm specific for rubella was detected shortly after birth  main outcome measures  the age at which hearing loss was identified and the degree of loss in decibels at 250  500  1000  2000  and 4000 hz measured by pure tone audiometry  results  61  52   of 117 children born in 1978 82 had a hearing impairment of 40 db or greater in both ears  the mean loss was 93 db  in the following five years 75  47   of 159 children had impaired hearing  their mean loss being 96 db  the age at which the hearing loss was confirmed decreased from 11 6 to 9 8 months as a result of earlier auditory evoked response testing  nevertheless  only eight  13   of the children with hearing impairment born in 1978 82 and 16  21   of those born in 1983 7 had these tests performed in the first six months of life  conclusions  unacceptable delays in identifying hearing loss occurred in this high risk group because of failure to arrange auditory evoked response testing in early infancy  evoked response audiometry is sensitive and specific and should be undertaken within the first few months of life for all infants known to be at risk of sensorineural hearing loss  
class9	human papillomavirus in oesophageal squamous cell carcinoma  thirty seven cases of oesophageal squamous cell carcinoma were studied by applying dna slot blot analysis and in situ hybridisation using type specific probes for hpv 6  11  16 and 18  cases of condyloma accuminata  cervical carcinoma  and laryngeal papilloma were used as controls  blocks including areas of invasive carcinoma  intraepithelial neoplasia  and normal epithelium were studied in each case  no hpv genome was detectable in any of the oesophageal cases  it is concluded that these types of hpv do not have an association with oesophageal squamous cell carcinoma  
class9	detection of human papillomavirus type 16 dna in carcinomas of the palatine tonsil  twenty eight tonsillar carcinomas of various histological types were investigated for the presence of epstein barr virus  ebv   cytomegalovirus  cmv   and human papillomavirus  hpv  types 6  11  and 16 by in situ hybridisation using highly stringent procedures  in six cases an autoradiographic signal was obtained in the tumour cell nuclei with the hpv type 16 specific probe  no signal was obtained with any of the other probes  immunohistochemical investigations with mouse monoclonal antibodies directed against the l1 protein of hpv type and a rabbit antiserum that detects common protein determinants of hpv gave negative results  thus indicating latent infection  furthermore  a series of tonsils from controls with comparable age distribution was negative by both in situ hybridisation and immunohistology  these results indicate a possible role for hpv 16 in the aetiology of a proportion of tonsillar carcinomas  
class9	human papillomaviruses  pediatric perspectives on a family of multifaceted tumorigenic pathogens as summarized here human papillomaviruses are associated with a wide spectrum of epithelial lesions  ranging from benign warts to invasive carcinomas  they have been difficult to study in part because they have not yet been propagated in tissue culture  fortunately advances in molecular biology have allowed characterization of hpv genomes and identification of some hpv gene functions  in addition to their clinical importance hpvs represent an important tool for exploring virus cell interactions  gene expression  cellular differentiation and cancer  hpv infections are not only common but also difficult to treat and prevent  depending on the hpv type and location  the modes of hpv transmission may involve casual physical contact  sexual contact and perinatal vertical transmission  hpv dna genomes replicate at a low copy number in basal cells and  as most clinicians know  are difficult to eradicate  there is often a long latent period and subclinical infections  and hpv dna can be found in normal tissue adjacent to lesions  hpvs can cause widely disseminated lesions  especially in the immunocompromised host and in epidermodysplasia verruciformis  aside from the rare carcinomas  the most serious life threatening hpv induced illness in children is recurrent respiratory papillomatosis  somewhat surprisingly in malignant lesions hpv dna is also found as fragments incorporated into the cellular genome  unlike retroviruses such as human immunodeficiency virus which integrate into the cellular genome as part of their life cycle  hpv integration is a terminal event for viral replication  such integration may be critical  however  for viral induced abnormal cell growth  perhaps the most important implication of the finding that some anogenital cancers are in part sexually transmitted infectious diseases is that they may be preventable  the data overwhelmingly suggest that avoidance of exposure to hpv via abstinence or monogamy in both partners markedly reduces the risk of cervical cancer  a more realistic goal  however is prevention of hpv transmission by the use of barrier method contraceptives  which may be protective against development of cervical carcinoma  the america association of pediatrics committee on adolescents has outlined the obligation of pediatricians to be actively involved in adolescent education on sexually transmitted diseases  certainly a fundamental knowledge of hpv epidemiology  the risks of hpv related sequelae and prevention of hpv infection are important considerations for adolescent sexuality  although helpful  such awareness alone falls far short of making an impact on sexual behaviors  a significant reduction in hpv infection rates could be achieved only by inundating adolescents at an early age with a highly visible society wide campaign directed at these issues  
class9	influence of otitis media on the correlation between rectal and auditory canal temperatures  in a noninterventional  controlled  single blinded trial  251 children were examined in a university hospital emergency department setting to study the influence of acute otitis media on the relationship between rectal and auditory canal temperatures  bilateral auditory canal temperatures were measured using an infrared detection probe and microprocessor by nursing staff blinded to the presence of acute otitis media  correlation between rectal and auditory canal temperatures in children with  r    81  and without  r    75  acute otitis media were not significantly different  there was no significant difference between infected  38 1 degrees c     1 0 degree c  and uninfected ears  38 0 degrees c     1 0 degree c  with unilateral otitis  n   75   although significantly higher than in uninfected children  auditory canal temperatures of children with acute otitis media reflected elevated rectal temperatures and not differences in auditory canal temperatures between ears  
class9	arytenoid subluxation  diagnosis and treatment  both arytenoid subluxation and recurrent laryngeal nerve paralysis  rlnp  may result from injury to the larynx  and they may be difficult to distinguish clinically  a patient with arytenoid subluxation who was initially believed to have rlnp was treated with medialization laryngoplasty 1 year after the injury  preoperative magnetic resonance imaging and computed tomography effectively demonstrated the cricoarytenoid subluxation  which was confirmed by intraoperative electromyography  emg  showing normal electrical activity in the thyroarytenoid muscle  photographs from preoperative fiberoptic laryngoscopy are presented to identify the appearance of arytenoid subluxation  computed tomographic findings and photographs from laryngoscopy of two patients with rlnp documented by intraoperative emg evaluation are presented to help distinguish the clinical appearance of this disorder from arytenoid subluxation  an integrated approach to the diagnosis and treatment of arytenoid subluxation is presented  
class9	electrical pacing for dynamic treatment of unilateral vocal cord paralysis  experiment in long denervated muscle  in order to explore the possibility of clinical application of laryngeal pacing as a treatment for unilateral vocal cord paralysis  we examined the reactivity of atrophic muscle to electrical stimulation in dogs whose recurrent laryngeal nerves were damaged by crushing  dissection followed by resuturing  or a 3 cm neurectomy  the threshold level to induce enough vocal cord adduction reached the maximum at 2 weeks after nerve injury  decreased with time  and never surpassed 7 v in each case  on the basis of results of these preliminary probings  laryngeal pacing was conducted on a dog 15 months after resection of the laryngeal nerve  adduction of the paralyzed vocal cord for synchrony with the intact cord was achieved by 7 v of electrical stimulation of the thyroarytenoid muscle that was triggered by signals from the cricothyroid muscle  
class9	vertical partial laryngectomy  a critical analysis of local recurrence  the purpose of this study was to evaluate local recurrence following vertical partial laryngectomies in 416 patients with either t1n0m0 or t2n0m0 glottic carcinoma  local failure was reported according to the t stage  the precise tumor location within each stage  the true vocal cord mobility  and the surgical procedure performed  no local recurrences were observed among 42 patients who underwent thyrotomy and cordectomy when the tumor was confined to the middle third of the mobile true vocal cord  local failure occurred in 8 of 111  7 2   patients in whom hemilaryngectomy was performed for tumors confined to one mobile true vocal cord  there was a diverse group of lesions within each t stage that responded differently to the surgical approaches  the differences in the initial recurrence rates are discussed in terms of careful preoperative assessment and choice of surgical technique for early glottic carcinoma  
class9	relationship between histologic features  dna flow cytometry  and clinical behavior of squamous cell carcinomas of the larynx  flow cytometric analysis of dna content was done on 133 primary squamous cell carcinomas of the larynx  overall  76 tumors  57 1   were not diploid  aneuploid or tetraploid   the dna index  di  was calculated and grouped into three levels  fifty seven cases had a di in a range of 1 85 to 2 15  44 diploid and 13 tetraploid   the cases were grouped in relation to ploidy  proliferative index  and the tumor node metastasis  tnm  system  every group was analyzed with respect to survival rate  ploidy was related to histocytologic grade  in well differentiated tumors  g1  survival rates at 48 months were 41 7  in diploid cases and 27 7  in nondiploid ones  relative risk  rr   2 01  95  confidence interval  ci   0 89  4 52   in no cases that underwent surgery  survival rates at 48 months were  respectively  81 8  and 49 2   rr  5 07  95  ci  0 76  33 93   these results suggest that ploidy may be a new independent parameter of prognosis in squamous cell carcinoma of the larynx  this is useful in clinical practice because it allows the clinician to recognize those cases with poorer prognosis among the early tumors at a stage where other prognostic parameters are not yet available  
class9	elective radical neck dissection in epidermoid cancer of the head and neck  a retrospective analysis of 853 cases of mouth  pharynx  and larynx cancer  a retrospective analysis of 853 patients with cancer of the mouth  pharynx  and larynx operated on over a 30 year period was performed  four hundred fifty seven of them had a radical neck dissection  rnd  at some point  five hundred ninety patients had no clinically positive nodes  n o  necks at the time of primary treatment  99 of these had elective neck dissection  whereas 95 others had a delayed rnd when nodes became clinically involved  twenty three percent of all n o patients had microscopically involved nodes and less than half of these were among those patients selected for elective rnd  furthermore  58  of those patients who had elective rnd did not have positive nodes  comparative analysis of elective rnd  delayed therapeutic rnd after clinical appearance of nodes  and composite operations for patients with n1 n3 disease indicates little difference in disease free survival when the nodes in the elective rnd were positive microscopically for tumors  56   49  and 47  respectively   it thus seems that elective rnd offers no real advantage over a careful watchful waiting approach in most patients  
class9	a comparison of ho s  international union against cancer  and american joint committee stage classifications for nasopharyngeal carcinoma  five hundred sixty four nasopharyngeal carcinomas  npc   mostly of undifferentiated histologic type  were studied for survival  distant metastasis  and local recurrence  all had computerized tomography of the nasopharynx and skull base  ct np  and fiberoptic nasopharyngoscopy for evaluation of the primary tumor  regional disease was assessed by palpation  a computer data base was formed on presentation  containing all information required for staging according to ho s  the international union against cancer  uicc   and the american joint committee  ajc  classifications  the three were compared for their efficacy in predicting prognosis  ho s classification was superior to the other two because its overall stages differed from one another more significantly in the actuarial survival  asr   disease free survival  dfs   and freedom from distant metastasis  fdm  rates  and its n staging was more accurate in predicting fdm  stages t1 and t2 of uicc ajc were similar in the freedom from local recurrence rate  flr  and should be grouped together  equivalent to ho s t1  a more even patients number distribution among the stages also favored the use of ho s classification  
class9	comparative epidemiology of cancer between the united states and japan  a second look  vital statistics were examined for the years 1955 through 1985 for japanese natives and united states whites to elucidate changes in cancer mortality and related antecedent patterns of life style in these two populations  results show that lung cancer rates are rapidly accelerating among japanese males as a consequence of their prior history of heavy cigarette smoking  oropharyngeal cancer rates are also rising in japan paralleling increases in alcohol and tobacco utilization  as the japanese life style and diet continue to become more  westernized   the rates of malignancies of the breast  ovary  corpus uteri  prostate  pancreas  and colon also continue to rise  nevertheless  the mortality patterns of certain malignancies  viz   laryngeal  esophageal  and urinary bladder cancer  are discrepant with their established risk factor associations  suggesting the existence of other differences in risk factor exposure between the two countries  epidemiologists and health educators need to develop innovative international programs of investigation and health promotion with preventive impact on common malignancies associated with risk factors of life style  
class9	comparative in situ hybridisation study of juvenile laryngeal papillomatosis in papua new guinea and australia  a comparative study of cases of juvenile laryngeal papillomatosis from papua new guinea  n   3  and brisbane  australia  n   9  was carried out  in situ hybridisation reactions for human papillomavirus  hpv  types 6 and 11 occurred in 11 cases  all three cases from papua new guinea and eight from australia gave positive signals  a negative reaction was observed in one australian case  the intensity of the reaction was strong in seven cases  moderate in one  and weak in three  an equivocal reaction was also noted with probes for types 16 and 18  and types 31  33  and 35 in two cases from australia and one from papua new guinea  it is concluded that as similar staining patterns and intensities occurred in cases from both areas  the aetiology is the same  the equivocal reactions noted in three cases were probably due to cross hybridisation rather than multiple infection  
class9	conservative management of epistaxis  a retrospective study to assess the clinical usefulness of non surgical management of epistaxis was performed on 340 patients requiring hospitalisation at the ent department of la paz hospital  madrid   the previous history  type of management  hospitalisation time  and volume of transfusion were considered  nasal packing was employed in 94 1 per cent of the patients  most patients  82 9 per cent  were hospitalised less than seven days  and 84 1 per cent of the patients required no transfusion  there was one death  this study supports the clinical usefulness of conservative management in the treatment of patients with epistaxis  
class9	vertical partial laryngectomy on demand  the author proposes the term  vertical partial laryngectomy on demand  for all modifications of vertical laryngectomies  frontal  frontolateral  vertical and hemilaryngectomy   this term includes two conditions  the first is complete oncological removal of the tumour  proven by histological examination and with the use of magnification or the operating microscope during the operation   secondly  reconstruction of the laryngeal defect by various procedures  the author uses the sternohyoid fascia in vertical and frontolateral partial laryngectomies  from 120 operated cases  a five year survival rate of 81 per cent was achieved  the fascia showed resistance to post operative complications and irradiation  
class9	use of emla cream as an analgesic in the management of painful otitis externa  a new application of emla cream is described  relief of pain in otitis externa is difficult and systemic analgesics for this localized condition are often ineffective  meticulous cleaning of the external auditory meatus is an essential step in the treatment  emla cream is an effective analgesic which can be used to relieve pain and anaesthetize the external auditory meatus to allow cleaning in patients with intact tympanic membranes  
class9	mucocutaneous leishmaniasis due to leishmania  leishmania  infantum  biochemical characterization  a vegetative mass in the right nasal cavity of a 62 year old man from palma de mallorca  spain  was found to be due to leishmania  the organism was isolated in culture and characterized by in situ hybridization  southern blot hybridization  and isoenzyme analysis  it was thus demonstrated to be the most common enzyme variant 1  mon 1  of leishmania  leishmania  infantum  
class9	acquired von willebrand s syndrome  therapeutic and diagnostic implications  acquired von willebrand s syndrome is a newly recognized bleeding diathesis thought to be caused by autoantibodies to the von willebrand factor  acquired von willebrand s syndrome has been reported in association with lymphoproliferative disorders and benign monoclonal gammopathies  clinical features and laboratory abnormalities of this disease are similar to congenital von willebrand s disease  but the optimal treatment may differ  we describe a 75 year old man with chronic lymphocytic leukemia and recurrent epistaxis and also discuss the pathogenesis  diagnosis  and treatment of both the congenital and acquired disorders  
class9	assessment of middle ear status during experimental otitis media using magnetic resonance imaging  magnetic resonance imaging has proved to be a useful tool for in vivo imaging of a variety of tissues  in this study  magnetic resonance imaging was applied to the middle ear of experimental animals with otitis media  results showed that the presence and distribution of effusion within the middle ear space could be readily determined  moreover  following injection of gadolinium diethylenetriaminepentaacetic acid  a contrast agent  the inflamed middle ear mucosa could be resolved  a comparison between magnetic resonance imaging and tympanometry with respect to the diagnosis of effusion showed that negative pressure tympanograms were equivocal  50  effusion  and that flat or normal tympanograms were in error in approximately 20  of the observations  these data document a role for magnetic resonance imaging in in vivo studies of the pathogenesis of otitis media with effusion  
class9	upper respiratory tract infections in young children  duration of and frequency of complications  this study was performed to determine the usual duration of community acquired viral upper respiratory tract infections and the incidence of complications  otitis media sinusitis  of these respiratory tract infections in infancy and early childhood  children in various forms of child care arrangements  home care  group care  and day care  were enrolled at birth and observed for 3 years  families were telephoned every 2 weeks to record on a standardized form the type and severity of illnesses experienced during the previous interval  only children remaining in their original child care group for the entire study period were compared  the mean duration of an upper respiratory tract infection varied between 6 6 days  for 1  to 2 year old children in home care  and 8 9 days  for children younger than 1 year in day care   the percentage of apparently simple upper respiratory tract infections that lasted more than 15 days ranged from 6 5   for 1  to 3 year old children in home care  to 13 1   for 2  to 3 year old children in day care   children in day care were more likely than children in home care to have protracted respiratory symptoms  of 2741 respiratory tract infections recorded for the 3 year period  801  29 2   were complicated by otitis media  during the first 2 years of life  children in any type of day care were more likely than children in home care to have otitis media as a complication of upper respiratory tract infection  in year 3  the risk of otitis media was similar in all types of child care  
class9	use of gadolinium enhanced mr imaging for differentiating mucoceles from neoplasms in the paranasal sinuses  the purpose of this study was to determine whether additional clinically useful information could be obtained from gadolinium enhanced magnetic resonance  mr  imaging compared with the information obtained from nonenhanced mr imaging and computed tomography  ct   therefore  the authors selected 41 patients  whose results at ct examinations demonstrated a variety of pathologic conditions of the paranasal sinuses  to undergo mr imaging both with and without the use of gadopentetate dimeglumine for contrast enhancement  in 22 of 35 cases of neoplasms and mucoceles occurring separately  the lesions were correctly differentiated by established mr signal criteria alone  however  32 of these 35 cases were accurately differentiated when gadolinium enhanced mr images were obtained  six cases demonstrated co existing neoplasm and mucocele  gadolinium enhanced mr enabled correct differentiation of five of these lesions  while unenhanced mr enabled correct differentiation of three  on the basis of these results  the authors conclude that the use of gadopentetate dimeglumine for contrast enhancement at mr imaging is useful for differentiating mucoceles from neoplasms in the sinonasal tract  
class9	assessment of nasal patency by rhinoscopic measurement of cross sectional nasal airway area  correlation with subjective nasal symptoms  assessment of nasal patency by the recording of nasal symptom scores was compared with an objective method of determining nasal airway area using a fiberoptic rhinoscope  sixty patients with active allergic rhinitis and nasal congestion requiring treatment were studied  nasal symptoms were recorded and nasal airway area was measured before and at fixed time intervals after administration of either pseudoephedrine or oxymetazoline  both methods detected a decongestant response to both drugs  and the symptom of congestion correlated with the measured nasal airway area  rhinoscopic measurement of cross sectional nasal airway area is an objective method that may be used to complement other methods for evaluation of nasal patency  
class9	systemic sulfonamides as a cause of bilateral  anterior uveitis  between september 1976 and may 1989  12 cases of uveitis attributed to the systemic use of sulfonamide derivatives were reported to the national registry of drug induced ocular side effects and the us food and drug administration  we evaluated these reports in addition to one case previously reported in the literature and one patient seen at the uveitis clinic  oregon health sciences university  portland  the patients  median age was 34 years  twelve of 14 patients were treated with trimethoprim sulfamethoxazole  all patients for whom the location of the eye disease was specified presented with an iritis  six reports included a description of ocular symmetry  with all patients having bilateral inflammation  of the nine patients for whom data on the duration of drug use was available  seven experienced adverse effects within 8 days of beginning trimethoprim sulfamethoxazole therapy and four showed effects within 24 hours  three patients had histories of rechallenge with trimethoprim sulfamethoxazole  and in each case acute iritis recurred within 24 hours of reinstitution of therapy  five patients had additional evidence of an adverse reaction manifested as stevens johnson syndrome  erythema multiforme  diffuse macular or vesicular rashes  stomatitis  glossitis  conjunctival and scleral injection  and granulomatous hepatitis  the consistent presentation including bilateral  anterior inflammation and the recurrence with rechallenge strongly indicate a cause effect relationship  although uveitis secondary to sulfonamides is a rarely diagnosed clinical event  recognition of the distinct presentation of this entity is important in the differential diagnosis of uveitis  
class9	delayed hearing loss after neurovascular decompression  we report two unusual cases of delayed hearing loss after neurovascular decompression of structures within the cerebellopontine angle  in the first case  the patient noted a unilateral hearing loss 3 weeks after undergoing vascular decompression of the trigeminal nerve for tic douloureux  this gradually improved over an 18 month period  in the second case  the patient awoke on the 4th day after vascular decompression of the facial nerve for hemifacial spasm with a bilateral hearing loss that has remained unchanged after the onset  these are examples of delayed acoustic dysfunction occurring with a shift in surgically freed vessels and may have been induced by newly directed neurovascular compression or distortion  
class9	improved technique for inserting a t tube in patients with subglottic stenosis  an improved method for inserting a silicone t tube through a tracheostomy stoma in patients with subglottic stenosis is presented  a silicone t tube is pulled into the trachea with a catheter that is inserted into the tracheostomy stoma  advanced through the stenotic subglottic space  and pulled out the mouth  a cone shaped dilator is placed beforehand at the proximal end of the vertical limb of the t tube to facilitate the passage of that end through the stenotic subglottic space  this method was used in 4 patients with good results  we suggest this technique be tried when attempts to insert a t tube by the usual method fail  as it can be performed under local anesthesia without special instruments and is technically easy  
class9	acoustic reflectometry for assessment of hearing loss in children with middle ear effusion  we sought associations between acoustic reflectometry and hearing loss in ears with and without middle ear effusion in 137 new zealand children ages 3 to 16 years  reflectometry was significantly associated with conductive hearing loss  these associations were present in the entire sample  correlation coefficients varied between 0 31 at 2000 hz  p less than 0 001  and 0 55 for a three frequency pure tone average  p less than 0 001   the associations persisted for the sample of ears deemed to be filled entirely by effusion  correlation coefficients varied between 0 27 at 4000 hz  p   0 026  and 0 47 at 500 hz  p less than 0 001   using a reflectivity of 6 0 or greater to detect a three frequency pure tone average loss of 30 db or more  the sensitivity was 88  and the specificity was 44   the technique of acoustic reflectometry should be explored and extended to permit rational decisions about management of middle ear effusions  
class9	adenotonsillectomy in children with sickle cell disease  the pediatric patient with sickle cell disease risks having a vasoocclusive episode during adenotonsillectomy under general anesthesia  with proper patient selection and appropriate perioperative management  adenotonsillectomy can be accomplished safely in children with sickle cell disease  we review the management of 10 children with sickle hemoglobinopathies who had adenotonsillectomy  indications for surgery were recurrent streptococcal infections in four and obstructive sleep apnea in six of these children  no complications resulted from any of these procedures  and the mean length of postoperative hospitalization was 2 4 days  the principal feature of preoperative management was the transfusion of red blood cells to suppress the patient s endogenous erythropoiesis and to reduce the concentration of sickle cell hemoglobin to less than 30   though a prospective  multi institutional clinical trial will ultimately be required to settle the issue of the safest preoperative management of children with sickle cell disease  balancing the risks of transfusion related complications against anesthesia related complications  our experience supports the operative safety of hypertransfusion therapy in children with sickle cell disease  
class9	glossopharyngeal schwannoma  review of five cases and the literature  glossopharyngeal schwannomas are rare tumors in spite of the fact that acoustic schwannomas account for 8  10  of intracranial tumors  there have been 23 reported cases in the literature  this report of five cases is the largest series of these tumors  the presentation  radiological workup  operation  and long term postoperative results will be presented  along with a review of the literature  
class9	external fixation using microplates after laryngotracheal expansion surgery  an animal study  management of severe laryngotracheal stenosis requires treatment with open laryngeal surgical approaches  performing the necessary anterior  and possibly posterior  incisions to expand the cricoid and tracheal rings causes instability of the segments  placing an intraluminal stent has several disadvantages  ranging from injury of healthy tissue to airway obstruction  the availability of an external stent would avoid many of these complications  we performed expansion laryngeal surgery in dogs and explored the use of microplates for external fixation and determined the surgical outcome if no fixation is used  the results show that microplates are very effective in maintaining external fixation and that a need for placing an intraluminal stent when a posterior cricoid split is performed exists  
class9	single stage laryngotracheal reconstruction  the mainstay for repairing subglottic and tracheal stenosis has been the rib graft with prolonged stenting  a refinement of this treatment was the use of the anterior cricoid decompression  split   we present single stage reconstruction of the airway as an additional refinement of the laryngotracheoplasty  this article describes the experience of two institutions with single stage reconstruction and offers some observations on the principles of the technique  
class9	culture positive allergic fungal sinusitis  allergic aspergillus sinusitis is a well defined clinical and histologic entity  although surprisingly few reported cases have yielded any fungal growth on culture  taking advantage of recent changes in the identification and classification of certain groups of fungi  we were able to identify a specific fungal organism in 19 of 22 consecutive patients with a histologic diagnosis of allergic fungal sinusitis over the past 2 1 2 years  aspergillus was found in only one patient  while an organism in the family of dematiaceous fungi was found in 18 patients  of these patients  the genus bipolaris was the most commonly represented  while exserohilum  curvularia  and alternaria species were seen with less frequency  thus  it appears that aspergillus may not be the most common etiologic agent in allergic  aspergillus  sinusitis  allergic fungal sinusitis is not unusual and its incidence may be increasing  on initial clinical evaluation it may be easily mistaken for malignancy or invasive fungal disease with the potential for overly aggressive treatment  preoperative suspicion of allergic fungal sinusitis based on clinical and roentgenographic findings along with careful communication with the mycology laboratory about the possibility of dematiaceous fungal growth are necessary for proper diagnosis  
class9	bacteriology of the ethmoid bullae in children with chronic sinusitis  cultures from 105 children with chronic sinusitis who had failed aggressive medical management were retrospectively studied  patients with immunodeficiency and cystic fibrosis were excluded from the study  because the most common sites of disease were the infundibula and anterior ethmoid sinuses  samples of mucosa removed from the anterior ethmoid bullae during endoscopic ethmoidectomy were routinely cultured for aerobic and anaerobic organisms  fungal cultures were performed for 55 bullae  the principal organisms isolated were alpha hemolytic streptococcus  staphylococcus aureus  moraxella catarrhalis  streptococcus pneumoniae  and haemophilus influenzae non type b  only 12 anaerobic organisms and four fungi were isolated  of the 204 bullae cultured  multiple organisms were found in 61 bullae and 40 showed no growth  isolates of other less common organisms were also found  these data are analyzed on the basis of age and duration of symptoms  and antibiotic treatment is described  
class9	quantitation of dna ploidy in squamous intraepithelial neoplasia of the laryngeal glottis  the dna contents in 56 laryngeal glottic biopsy specimens with a spectrum of squamous intraepithelial neoplastic  sin  changes were evaluated by image analysis  a combination of dna histogram features were used to define abnormal dna containing cell populations that were interpreted as representing intraepithelial neoplastic transformation  eighteen biopsy specimens were classified as dysplasia keratosis and graded sin i  six  33   of which were aneuploid  eighteen  78   of 23 biopsy specimens graded sin ii were aneuploid  and all 15 biopsy specimens graded sin iii had abnormal quantities of nuclear dna  twelve biopsy specimens  six of sin ii grade and six of sin iii grade  were considered to represent keratinizing forms of dysplasia  and all 12  100   were found to contain increased  aneuploid  quantities of dna  we conclude that the proposed sin grading scheme for laryngeal epithelial abnormalities exhibits strong correlations with nuclear dna content  in addition  aneuploidy was observed in all sin ii  and sin iii graded biopsy specimens with prominent keratinization  
class9	plasma cell granuloma of the nasal cavity treated by radiation therapy  plasma cell granuloma is a rare  benign tumor most commonly found in the lungs in patients younger than 30 years  although presentation has been reported at a number of other anatomic sites  this report is the first of plasma cell granuloma of the nasal cavity  the tumor was initially resected  but progression was seen at 1 month follow up  because further surgery to completely eradicate the tumor would have been extensive and disfiguring  40 gy external beam radiation was given in 20 fractions using a three field wedge technique  most recent clinical follow up at 27 months showed local control  surgery remains the treatment of choice for plasma cell granuloma when the disease can be completely resected  however  irradiation can also be effective in patients with recurrent or inoperable local disease  
class9	receptors for epidermal growth factor and steroid hormones in primary laryngeal tumors  the authors investigated the presence of epidermal growth factor  egf r   estrogen  er   progesterone  pr   and androgen  ar  receptors in 42 laryngeal squamous cell carcinomas and 20 normal laryngeal mucosa specimens  egf r were expressed in all tumor specimens analyzed  with significantly higher levels in tumor samples compared with normal mucosa  p less than 0 05   the immunohistochemical study demonstrated the presence of egf r in basal and parabasal cells of normal mucosa and in most of the cancer cells  there was no correlation between egf r and tumor localization or t classification  on the other hand  the authors did find an interesting correlation between egf r levels and grading  egf r levels being significantly higher in g3 than in g1 g2 tumors  moreover  the three patients whose tumors expressed the highest egf r levels had disease recur within 8 months  among tumor specimens  9 5   35 7   and 9 5  expressed very low but detectable er  pr  and ar levels  respectively  no statistically significant difference was found between the levels of steroid receptors in the tumor and normal mucosa specimens  and neither was there any correlation of er  pr  and ar with the pathologic findings  the authors  results suggest that the egf r system may play a role in regulating the growth of laryngeal cancer  additional studies should demonstrate whether  as in other tumor types  egf r expression may have prognostic significance in human laryngeal cancer  
class9	noise induced hearing loss in orthopaedic staff  in the light of eec proposals on the avoidance of damage to hearing caused by noise  a study was undertaken to determine the risk posed by powered orthopaedic instruments  the noise levels from a number of air powered and electric tools were measured and analysed and found to exceed the recommended levels  the predicted daily personal noise exposure was calculated and the potential for hearing damage confirmed  twenty seven senior orthopaedic staff were then assessed by audiometry  evidence of noise induced hearing loss was found in half the subjects  the increasing use of powered instruments in elective orthopaedics and fracture fixation may present a significant cumulative risk to the hearing of orthopaedic surgeons and theatre personnel  the use of ear defenders should be promoted  and manufacturers should be encouraged to develop instruments with lower noise emission levels  
class9	modification of the fluorescent allergosorbent test as an inhibition assay for determination of cross reactivity among aeroallergens  the fluorescent allergosorbent test was adapted as an inhibition assay to determine cross reactivity between aeroallergens  with this method  similar antigenic determinants were found between short ragweed and giant ragweed  cocklebur  lamb s quarter  rough pigweed  marsh elder  and goldenrod  cocklebur and giant ragweed were highly potent in their ability to competitively bind to short ragweed ige  the other pollens demonstrated lower potency of cross reacting antigens  the fluorescent allergosorbent test inhibition assay appears to be a useful method to determine cross reactivity among aeroallergens  
class9	audiological findings following head trauma  traumatic head injury is the principal cause of death and serious physical disability in adolescents and young adult  hearing loss is a common sequela of head trauma  the results of pure tone and auditory brain stem response  abr  assessment of minor head injury revealed that 20 per cent of these cases showed impairment of hearing including both conductive and sensorineural hearing loss mostly in the high frequencies loss  abr findings showed a significant difference of absolute wave v latency and interwave  iii v  latencies at repetition rate 11 1 click sec   and a highly significant difference at a repetition rate of 51 1 click sec   compared with the control group  in severe head injury  conductive hearing loss was found in only one case  in which a longitudinal fracture of the temporal bone was identified radiologically  no abr could be recorded at a repetition rate of 11 1 click sec  in either ear of this case  this patient died a few days later  three cases were found with a mixed sensorineural hearing loss  one of them showed a longitudinal fracture radiologically  abr findings in two cases showed prolongation of wave v and i v interwave latencies  and the third case showed absence of abr recording  in comatose patients  an abr grading system is a more sensitive index of brainstem dysfunction than the simple division of normal versus abnormal abr waves and interwave latencies  presence or prolongation of wave v and interwave latency i v even in one ear is of good prognostic value in the comatosed patient  
class9	point and period prevalence of otitis media with effusion evaluated by daily tympanometry  previous studies on daily tympanometric screening using an automatic impedance tympanoscope indicated relatively high incidences of type b tympanograms of one day s duration  which is contrary to our conceptions of the pathogenesis and pathology of otitis media with effusion  we therefore repeated the study in 51 otherwise healthy children  100 ears  attending kindergarten  tympanometry was performed daily for one month using both the conventional impedance apparatus az7 and the automatic impedance tympanoscope zs 331  the impedance apparatus did not indicate any one day type b tympanograms and only a few short lasting episodes occurring either in the beginning or end of the study period  several ears had type b tympanograms on all days examined  the point prevalence was 15 per cent and the period prevalence 17 per cent  which accord well with findings of previous epidemiological studies of secretory otitis  the impedance tympanoscope indicated 16 cases of b curves lasting only one day and considerably higher point and period prevalences  which make the impedance tympanoscope unsuited for both scientific and clinical purposes  
class9	tympano cartilago stapediopexy  a method to improve hearing in open technique tympanoplasty  canal wall down technique tympanoplasty was indicated in about 41 per cent of our cases with chronic suppurative otitis media  in this series done during the last four years  of 576 tympanoplasties  240 cases needed type iii tympanoplasty  in 145 cases  myringostapediopexy was carried out using temporalis fascia grafting over the head of the stapes  tympano cartilago stapediopexy was performed in the other 95 cases by using tragal cartilage and perichondrium over the stapes  a comparison between the results of both methods of grafting is discussed  improvement in hearing was achieved after tympano cartilago stapediopexy  this method proved to be suitable for those cases which need open technique tympanoplasty  
class9	inner ear cholesteatoma and the preservation of cochlear function  labyrinthine destruction by direct cholesteatoma invasion has always been considered a serious threat to the inner ear function  a number of reports in the literature have cited both patients who had preservation of hearing despite widespread erosion of the labyrinth by cholesteatoma and patients who had retained auditory function despite surgical removal of the matrix from the labyrinth  in most cases the vestibular portion of the inner ear was invaded but cases of cochlear involvement have been described as well  twelve cases with pre operative auditory function preservation despite extensive labyrinthine destruction treated at our institution are reported  seven cases retained cochlear function post operatively  possible explanations of this occurrence and implications of related with hearing preservation in the presence of widespread inner ear destruction by chronic inflammatory disease are discussed  
class9	lateral sinus thrombosis  a problem still with us lateral sinus thrombosis is now a rare complication of ear disease in the developed world  since the advent of the widespread use of antibiotics  the classic picture is often modified by previous antibiotic treatment making diagnosis and management difficult  lack of familiarity with this condition amongst present day otologists may lead to late diagnosis and treatment  we review three cases that we have managed recently and compare their clinical courses with the classic description of the disease  
class9	cochlear otosclerosis  statistical analysis of relationship of spiral ligament hyalinization to hearing loss  this paper presents an analysis of the relationship of the amount of hyalinization of the spiral ligament  secondary to cochlear otosclerosis  spongiosis   to the amount of hearing loss  this relationship was previously studied by parahy and linthicum  it was found that the larger the amount of hyalinization  the greater the hearing loss  this hyalinization is a measure of the amount of toxic enzymes being excreted into the inner ear fluid  these enzymes are suspected to affect the metabolic function of the hair cells  
class9	a new syndrome  hearing loss and familial salivary gland insensitivity to aldosterone in two brothers  two male siblings presented in infancy with hyponatremia  the levels of plasma renin activity and aldosterone were elevated  sodium supplement was necessary to maintain normal sodium balance  the salivary sodium concentrations were markedly elevated  with sweat sodium levels being in the upper normal range  urinary sodium concentration and renal epithelial exchange between sodium and potassium were normal  this was felt to be due to an autosomal recessive disorder  both siblings were later diagnosed as having a bilateral moderate to severe sensorineural hearing loss with intermittent conductive overlay due to middle ear fluid  the sensorineural loss was also felt to be autosomal recessive in origin  but the possibility of a disturbance of sodium balance in the inner ear has been questioned  
class9	non hodgkins lymphoma of the head and neck  experience in the grampian area  the records of 44 cases of non hodgkins lymphoma  nhl  presenting to the ear  nose and throat department in the grampian area from 1980 1988 were examined in relation to site of occurrence  histology  age at presentation  clinical stage  treatment and survival  the median age was 67 years and there was a preponderance of high grade histology  especially in disease affecting the tonsil  most deaths occurred in the first year  patients with high grade disease and those in stages three and four had a significantly poorer survival during the first year  the site of disease had no influence on survival  
class9	isolated congenital round window absence  an adult with unilateral round window atresia is presented  with care  ct scanning may be used to demonstrate round window occlusion  cochlear fenestration resulted in only a modest hearing improvement  previously reported cases are reviewed  
class9	postauricular cerebellar encephalocoele secondary to chronic suppurative otitis media and mastoid surgery  cerebellar herniation into the mastoid through the posterior aspect of the temporal bone as a result of chronic suppurative otitis media and mastoid surgery is a rare event  a case is reported in which such a hernia presented subcutaneously behind the pinna  its repair is discussed  
class9	burkitt s lymphoma of the tonsil  a case of burkitt s lymphoma involving the tonsil in a 10 year old bedouin boy  is presented  the biological behaviour and the clinical presentation of this unusual neoplasm are discussed and the english language literature is reviewed  the diagnosis was made by histological examination  electron microscopy and confirmed by immunohistochemistry  the patient showed an excellent symptomatic response to surgery and chemotherapy  
class9	correlation between antibodies to type ii collagen and treatment outcome in bilateral progressive sensorineural hearing loss  our aim was to assess whether  idiopathic  bilateral progressive sensorineural hearing loss  bpshl  has an immunological cause in some patients  antibodies to native type ii collagen were sought by an elisa in eighteen patients with bpshl  before and after corticosteroid treatment  and in twelve patients with meniere s disease  fifteen with otosclerosis  eighteen with rheumatoid arthritis  nine with fibrositis  and nine healthy controls  a positive result was defined as a mean dilution titre of 2 or more  eight of eighteen bpshl patients had positive titres  significantly  p less than 0 005  more than in any other group  one meniere s disease  two otosclerosis  and no others   the mean antibody titre was higher in the bpshl group than in any other group  2 02  sem 0 62  vs 0 17  0 17   meniere s disease  0 44  0 32  otosclerosis  0 all others  p less than 0 005   the nine bpshl patients who showed a clinical response to corticosteroids  improvement in at least one tone by audiogram or 25 db in speech discrimination score  had the highest mean antibody titre  3 46  0 88  vs 0 59  0 59  for the nine non responsive patients  p less than 0 04   we suggest that in some patients with bpshl  immunity to type ii collagen  a major constituent of the inner ear  may be important in the pathogenesis of the disorder  
class9	management decisions in laryngeal carcinoma in situ  twenty one patients with laryngeal carcinoma in situ  n   12  or carcinoma in situ with microinvasion  n   9  were treated with laser mucosal dissection of the vocal cords and or superficial laser cordectomy  the normal architecture of the vocal cords was preserved because the depth of vaporization was usually superficial in these early cases  five patients had recurrence  new tumor  or persistence of abnormal tissue that required additional laser surgical treatments  with a follow up range of 6 months to 4 years  all patients currently are free of laryngeal abnormality  and no patient has needed open laryngeal surgery or radiation therapy  transoral endoscopic laser resection of laryngeal carcinoma in situ with or without microinvasion should be the treatment of choice for these early lesions  
class9	the hypotympanum and infralabyrinthine cells in chronic otitis media  despite the localization implied by the term  chronic otitis media   little attention has been paid to the role of the hypotympanum in chronic active otitis media  most authors have emphasized the role of recurrent cholesteatoma or unexenterated cells in the mastoid cell system as causes of recurrent disease  seven cases are reported in which clinical evidence indicated that recurrent chronic otitis media was limited to the hypotympanum and infralabyrinthine cell system  in the five cases in which revision surgery was done  exenteration of this area resulted in an asymptomatic ear  the anatomy  radiographic evaluation  and surgical approach to the hypotympanum are reviewed  careful inspection of the hypotympanum in primary surgery for chronic ear disease and exenteration of the hypotympanic and proximal infralabyrinthine cell tract are advocated when these regions contain cholesteatoma or extensive granulomatous disease  
class9	characterization of cytokines present in middle ear effusions  retention of inflammatory mediators and cells in the middle ear cleft during chronic otitis media with effusion  come   results in ongoing inflammation with the potential for pathologic changes and hearing loss  cytokines are glycoproteins produced by macrophages and other cells  activities of cytokines include fever production  osteoclast  fibroblast  phagocyte and cytotoxic cell activation  regulation of antibody formation  and inhibition of cartilage  bone and endothelial cell growth  using enzyme linked immunospecific assays we measured levels of six cytokines in middle ear effusions  mee  from children with come  significant levels of four cytokines  interleukin 1 beta  greater than 50 pg ml   interleukin 2  greater than 300 pg ml   tumor necrosis factor alpha  greater than 40 pg ml   and gamma interferon  greater than 6 25 pg ml  were found in 51   54   63   and 19  of mee  respectively  in contrast  levels of a fifth cytokine  granulocyte macrophage colony stimulating factor  and a sixth cytokine  interleukin 4  were undetectable  age was observed to have a significant effect on the levels of specific cytokines  interleukin 1  il 1  correlated inversely  p less than  02  with age such that the younger the child  the higher the level of il 1 in mee  tumor necrosis factor alpha  tnf  correlated directly  p less than  005  with age such that the older the child  the higher the level of tnf in mee  children undergoing tympanostomy on multiple occasions had average mee tnf levels  234 2     109 1 pg mg total protein  that were nearly 14 times higher  p less than  005  than those from children undergoing their first tympanostomy  16 9     3 0 pg mg total protein   thus il 1 correlated with the early stages of come  while tnf correlated with persistence of disease  the presence of these cytokines in mee may be responsible for the mucosal damage  bone erosion  fibrosis  and resulting hearing loss seen in some cases of come  
class9	the glasgow benefit plot  a new method for reporting benefits from middle ear surgery  conventionally  the results of middle ear surgery are reported in terms of postoperative closure of the air bone gap or the improvement in air conduction thresholds  while these are relevant in that they assess the technical success of the procedure and the lessening of monaural disability  they do not necessarily assess whether the patient has benefited  this is determined by many factors  not least of which is the hearing in the nonoperated ear  in this paper  we suggest that preoperative and postoperative plots of the air conduction thresholds in both ears be used as an additional method of presenting the results  first  the proportion of patients that fall into each of three main preoperative impairment groups are identified  this is important  as the potential benefits from surgery are not the same in each group  thereafter  the percentages of patients that achieve various postoperative hearing categories can be calculated  allowing surgeons to audit their results and make comparisons between series  
class9	the changing direction of nystagmus in acute meniere s disease  pathophysiological implications  the direction s  and pathophysiologic basis of nystagmus during an acute attack of meniere s disease have been subject to much debate in the world literature  clinical recordings from two patients whose nystagmus was captured near the very beginning of the acute vertiginous episode are presented  previous clinical observations in meniere s disease  experimental animal models concerned with initiation of peripheral nystagmus  and the phenomenon of recovery are discussed  
class9	ultrastructure of respiratory cilia of wic hyd male rats  an animal model for human immotile cilia syndrome  the wic hyd rat is a mutant from the csk  wistar imamichi rat  with spontaneous hydrocephalus  in male rats  the hydrocephalus is severe and about one half of hydrocephalic male littermates possess situs inversus totalis  ependymal cilia in these animals are immotile  and this defect is regarded as a mechanical cause of hydrocephalus  this paper presents the ultrastructural features of respiratory cilia in these rats in comparison with those in human immotile cilia syndrome  the respiratory cilia in these rats also are immotile and the dynein arms are missing  as in human cases  previously only eight dogs with immotile cilia syndrome and a mutant hydrocephalic polydactyl mouse were reported with respect to these phenomena  however the wic hyd rat is the first useful animal model for human immotile cilia syndrome  and further studies may serve to clarify the genetic background of this condition  
class9	stapes surgery in osteogenesis imperfecta  analysis of postoperative hearing loss  the disappointing results in 12 of 58 stapedectomies  including 4 revision operations  performed on osteogenesis imperfecta patients were analyzed and compared with reports in the literature  it is concluded that the results described as disappointing were not always the product of the stapes operation  a progressive sensorineural hearing loss arising independently of the operation as a result of progression in the disease process of osteogenesis imperfecta appears to have a severe influence on the final hearing threshold  
class9	ultrastructural evidence of a merocrine secretion in the human endolymphatic sac  the results of a light and transmission electron microscopic analysis of an endolymphatic sac  es  from a patient suffering from episodic vertigo  tinnitus  and hearing loss are presented  a biopsy of the intraosseous portion of the es was obtained during a translabyrinthine approach to section the vestibular nerve in the internal acoustic meatus  the material consisted mainly of tubular epithelial structures filled with heavily stained material  pathologically dilated and degranulated rough endoplasmic reticuli and disaggregation of polyribosomes with accumulation of solitary ribosomes in the cytosol and endoplasmic reticulum suggested a disturbed epithelial cell protein synthesis  ultrastructural evidence of an increased merocrine secretion of glycoprotein conjugates into the es was noted  this made it possible to analyze the presumed intracellular secretory pathways  an increased number of intraepithelial lymphocytes and monocytes was observed  since the inner ear had been subjected to surgical intervention before the vestibular nerve section  no conclusions can be drawn as to whether the patient s symptoms were related to the disturbed protein metabolism and hypersecretion of glycoprotein conjugates into the es  the findings support earlier experimental results that indicate that the es has not only a resorptive function but also a secretory one  
class9	tumor necrosis factor alpha in middle ear cholesteatoma and its effect on keratinocytes in vitro  tumor necrosis factor alpha  tnf alpha  was found in human middle ear cholesteatoma tissues by the immunoperoxidase method using rabbit anti human tnf alpha immunoglobulin g  it appeared to be localized in the epithelium and connective tissue of cholesteatomas studied  particularly on basal and spinous cells  and macrophages  the epithelium of normal external ear canal skin was lightly stained  but the staining was much weaker than that of the cholesteatomas observed  in vitro  recombinant mouse tnf alpha stimulated proliferation  protein synthesis  and terminal differentiation of basal keratinocytes  these stimulatory effects were blocked by the anti tnf alpha immunoglobulin g  which by itself had no effect on basal keratinocytes  these findings suggest that tnf alpha plays an important role in the development of cholesteatomas seen clinically  
class9	management of subglottic stenosis in the adult  twenty one adult patients were surgically treated for severe subglottic stenosis refractory to endoscopic treatment  patients were treated by anterior or anterior and posterior cricoid division with costal cartilage grafting  seventy six percent of the patients were successfully decannulated  success of treatment was not dependent on cause of the stenosis or age or sex of the patient  there was a significantly better outcome  p less than  05  in patients with isolated subglottic stenosis versus those with combined glottic and subglottic stenosis  
class9	surgical treatment of laryngeal web with mucosa graft  surgical treatment of laryngeal webbing varies with the extent and site of the web  an extensive one seems to be best treated by laryngofissure and skin or mucosa transplantation  recent experiences with four cases of thick glottal webbing indicated that a mucosa graft was better for the voice result than a skin graft  for success in the airway and voice results  the salient points in surgery include 1  precise midline thyrotomy  2  shaping of the vocal cord under fiberoptic control  and 3  mucosa grafting with the combined use of a pliable stent or fibrin glue for fixation  
class9	ototoxic reaction to erythromycin  we report a case of bilateral hearing loss in a patient treated with intravenous erythromycin lactobionate  the ototoxic reaction occurred despite the patient s having normal renal and hepatic function and the fact that serum erythromycin levels were within the predicted normal range  in addition to hearing loss  a marked labyrinthic hyporreflexia was also observed  hearing loss improved after the treatment was discontinued  but labyrinthic abnormalities persisted suggesting that erythromycin had caused a permanent vestibular damage  
class9	indications for the surgical treatment of osteomas of the frontal and ethmoid sinuses  sixty one patients with an osteoma of the frontal or ethmoid sinuses have been studied  the following indications for surgical removal of these osteomas are suggested  osteomas extending beyond the boundaries of the frontal sinus  if enlarging  if localized in the region adjacent to the nasofrontal duct  if signs of chronic sinusitis are present  osteomas of the ethmoid sinuses  irrespective of their size and if patients with osteomas complain of headache and other causes of headache have been excluded  the operation of choice is the osteoplastic flap operation  
class9	microdrill versus perforator for stapedotomy  the purpose of this study was to compare the hearing results of performing stapedotomy using either a microdrill or a perforator  two groups of patients  otherwise similar  were followed up for at least 2 years after the stapedotomy  it was possible to create 0 8 mm fenestra in 91 6  of our patients  there was no significant difference between the two groups in hearing results  the results showed a continuous improvement in the first 6 post operative months after which the hearing stabilized  in our hands  the microdrill has not proved to be more traumatic than the perforator to the inner ear  
class9	external ear resonance in children with otitis media with effusion  a middle ear effusion has been shown  in kemar  to increase the height of the resonant peak of the external auditory canal by 6 db spl  it has also been shown that the hearing impairment due to otitis media with effusion is related to the volume of middle ear fluid  therefore  it was hypothesized that measurement of the height of the resonant peak of the external auditory canal could be used as a method of assessing the magnitude of any hearing impairment due to otitis media with effusion  182 ears from 182 children aged 3 12  mean 6 3  years were studied  pure tone audiometry and impedance tympanometry were performed  and the acoustics of the external auditory canal were measured using the rastronics cc1 10 frequency response analyser  the mean height of the resonant peak  17 9 db spl  of children with a type a tympanogram was significantly different from the mean value  23 6 db spl  of those with a type b tympanogram  there was a significant correlation between the height of the resonant peak and the speech frequency average of the pure tone thresholds  the sensitivity and specificity of using the height of the resonant peak to detect hearing impairments in different age groups were calculated and compared with the sensitivity and specificity of tympanometry  the test did not provide the same degree of sensitivity as tympanometry but was more specific  the additional advantages of the test are that it is quick  taking less than 1 min per ear  and is well tolerated by children in whom there was a 99  compliance  
class9	chronic otitis media  the significance of nasal obstruction  the nasal airway resistance of 15 patients with unilateral chronic otitis media and 15 controls was measured by anterior active rhinomanometry  airway resistance was measured on each side before and after decongestion to differentiate resistance due to structural abnormality from that due to mucosal swelling  the nasal resistance was significantly greater  p less than 0 01  on the side of the affected ear in patients with unilateral chronic otitis media before decongestion  but following decongestion the difference was not significant  nasal obstruction is a significant determinant in unilateral chronic otitis media and although septal displacement may be the underlying cause  the major component of the obstruction appears to be due to an associated mucosal oedema  
class9	occupational exposure and head and neck carcinoma  an epidemiological case control study was conducted to investigate occupational risk factors in cancers of the upper respiratory and digestive tract  cases were men with squamous cell carcinoma of the oropharynx  667   hypopharynx  348   glottis  246   supraglottis  219   epilarynx  204   and 4 subsites of the oral cavity  787   controls were healthy patients or patients with cancer of another site or another histological type  147 men   past occupational exposures of cases and controls were compared  the analysis was performed independently for each site of cancer  controlling for age  amount and type of alcohol and tobacco consumption  and state of dentition  results showed that cancer of the supraglottis was associated with exposure to oil and grease  odds ratio   2 4  95  confidence interval 1 0 5 8   and with exposure to cement  odds ratio   4 2  95  confidence interval   1 1 16 4   cancer of the glottis was also associated with exposure to dye  odds ratio   6 4  95  confidence interval   0 7 56 6   exposure to flour occurred more frequently among controls than among patients with pharyngeal or oral cancer  this might reflect an association between this occupational exposure and some particular types of cancer included in the control group  
class9	nuclear medicine in otolaryngology  nuclear medicine has a distinct role to play in otolaryngological practice  accurate diagnosis of endocrine conditions is now possible using precise in vitro hormone measurement  specific clinical questions can be answered using in vivo investigations  99mtco 4 123i scintigraphy is used to evaluate thyrotoxicosis and solitary thyroid nodules  99mtc 201t1 subtraction scanning is of value in the preoperative localization of parathyroid adenomas and 99mtco 4 is particularly useful in assessing salivary and lachrymal gland function and drainage  99mtc mdp bone scanning is useful in the evaluation of osteomyelitis  temporomandibular joint dysfunction  bone graft viability and some facial fractures  the role of radioisotopes in the management of differentiated and medullary carcinoma of the thyroid is now well established  although there are many other agents available to image head and neck cancer  few can actually achieve the required diagnostic sensitivity and specificity  the introduction of monoclonal antibodies into routine imaging has been hampered by distinct practical problems and the search is now on for more sensitive non specific diagnostic agents  it is now possible to evaluate new 99mtc labelled tumour imaging agents using animal tumour model systems and the use of radioactivity in all aspects of otolaryngological research adds an extra quantitive dimension  together with spect  and the introduction of positron emission tomography  pet  to image the physiology of normal tissues and tumours  the use of radionuclide investigations can lead only to an increase in ent diagnostic sensitivity and specificity and  subsequently  to an overall improvement in the way we diagnose  stage and treat head and neck cancer  
class9	predictive factors for hand eczema  factors related to hand eczema were studied  their relative importance as predictors was ranked by multiple logistic regression analysis  questionnaires were sent to 20 000 individuals aged 20 65 years  randomly selected from the population register  those subjects  1385  considering themselves to have had hand eczema within the previous 12 months were invited to a dermatological examination  it was found that a history of childhood eczema was the most important predictive factor for hand eczema  second was female sex  followed by occupational exposure  a history of asthma and or hay fever  and a service occupation  a small decrease in risk with advancing age was also found  the difference in the probability of having had eczema in a 1 year period  between individuals having the most important risk factors studied and those having none of them  proved to be for females 48  compared to 8   and for males 34  compared to 4   a history of childhood eczema was found to be more common among young persons  indicating an increase in the prevalence of atopic dermatitis  of those individuals who reported childhood eczema  27  reported hand eczema on some occasion during the last 12 months  
class9	alterations of muscarinic acetylcholine receptors in the nasal mucosa of allergic patients in comparison with nonallergic individuals  cholinergic nasal hyperresponsiveness in nasal allergy may be due to changes of the characteristics in muscarinic cholinergic receptors  radioligand receptor binding and in vitro autoradiographic studies of nasal mucosa in nonallergic  na  and allergic patients were performed to investigate this hypothesis  the heterogeneous na group was subdivided into control individuals and patients with chronic sinusitis and vasomotor rhinitis  the 3h     quinuclidinylbenzilate binding to muscarinic receptors in human nasal mucosa membranes was saturable and of high affinity in all groups  no significant differences could be demonstrated between the subgroups of the na patients  in allergic patients the dissociation constants and receptor densities were significantly decreased in comparison with those of na and with those of control individuals  no differences in agonist binding or coupling of the muscarinic receptor to the effector system via the g protein could be observed in allergic patients  in vitro autoradiographic experiments demonstrated specific 3h     quinuclidinylbenzilate labeling of the glandular acini in na and allergic patients  no specific labeling could be observed in the epithelium  blood vessels  or connective tissue  in conclusion  the increased sensitivity and decreased muscarinic receptor number may reflect the cholinergic induced hypersecretion in nasal allergy but are probably too small to explain the complex allergic reaction  
class9	alterations of adrenoceptors in the nasal mucosa of allergic patients in comparison with nonallergic individuals  nasal hyperreactivity in nasal allergy may be due to changes of the characteristics in adrenergic receptors  radioligand receptor binding studies with the antagonists  3h prazosin  alpha 1 adrenoceptor   3h rauwolscine  alpha 2 adrenoceptor   and 125i     cyanopindolol  beta adrenoceptor  were performed in homogenates of nasal mucosa of allergic and nonallergic  na  patients to investigate this hypothesis  the heterogeneous na group was subdivided into control individuals and patients with chronic sinusitis and vasomotor rhinitis  no significant differences in affinities or densities of alpha 1  and alpha 2 adrenoceptors could be demonstrated in allergic patients in comparison with na and control individuals  the beta adrenoceptor density was significantly reduced in allergic patients in comparison with that of control individuals  neither changes in agonist binding or in the effect of gpp nh p on the agonist binding to beta adrenoceptors could be observed in allergic patients  the subtype selective antagonist  lk203 030  demonstrated the presence of a homogeneous population of beta 2 adrenoceptors in human nasal mucosa of both na and allergic patients  in vitro  autoradiography demonstrated specific 125i     cyanopindolol labeling of the epithelium in na and allergic patients  in conclusion  no changes in characteristics of alpha 1  or alpha 2 adrenoceptors in the nasal mucosa could be demonstrated in nasal allergy  however  a decreased number of beta adrenoceptors may reflect a beta adrenergic abnormality in nasal allergy  
class9	dexamethasone in the prevention of postextubation stridor in children  to assess whether there is any advantage in the use of corticosteroid to prevent postextubation stridor in children  we conducted a prospective  randomized  double blind trial of dexamethasone versus saline solution  the patients were evaluated and then randomly selected to receive either dexamethasone or saline solution according to a stratification based on risk factors for postextubation stridor  age  duration of intubation  upper airway trauma  circulatory compromise  and tracheitis  dexamethasone  0 5 mg kg  was given every 6 hours for a total of six doses beginning 6 to 12 hours before and continuing after endotracheal extubation in a pediatric intensive care setting  there was no statistical difference in incidence of postextubation stridor in the two groups  23 of 77 children in the placebo group and 16 of 76 in the dexamethasone group had stridor requiring therapy  p   0 21   we conclude that the routine use of corticosteroids for the prevention of postextubation stridor during uncomplicated pediatric intensive care airway management is unwarranted  
class9	emerging techniques in the diagnosis of sinusitis  in recent years  the high prevalence of chronic sinusitis has been noted in isolation and in association with bronchial asthma  aspirin sensitivity  and perennial rhinitis  many sinus associated symptoms arise from nasal rather than sinus pathology  thus  it is important to detect the presence  extent  and nature of any disease within the sinus cavities  conventional plain radiographs have limited sensitivity and have been supplanted by more widespread use of computerized tomography  the role of other modalities such as ultrasound and magnetic resonance imaging has not yet been completely determined  other tests such as cytology and endoscopy can detect the presence of infection without the need for invasive antral puncture  practitioners should consider the impact of a negative imaging test on their therapeutic plan and order tests on that basis  
class9	a pilot study of pemirolast in patients with seasonal allergic rhinitis  pemirolast is a potent  long acting  orally effective antiallergic agent evaluated for clinical activity in prevention of symptoms of seasonal allergic rhinitis  it was evaluated in a randomized  double blind  placebo controlled parallel group in season trials to test its safety  tolerance  and prophylactic activity  thirty one patients with a history of fall seasonal allergic rhinitis were treated for 6 weeks with pemirolast  50 mg bid  or placebo beginning approximately 2 weeks before the onset of the ragweed season in atlanta  daily evaluation of symptom scores disclosed statistically significantly less sneezing  rhinorrhea  and stuffy nose during treatment with pemirolast  there was  however  no difference for other evaluated symptoms or for the use of rescue medicines  there were no side effects during this short study  this preliminary study indicates that pemirolast may warrant further evaluation for the treatment of allergic rhinitis  
class9	central neurogenic hyperventilation in invasive laryngeal carcinoma  we describe a patient with central neurogenic hyperventilation secondary to extension of a laryngeal tumor into the base of the brain  resulting in extrinsic compression of the medulla  such an association has not been previously described  unique features which distinguish this patient from previously reported cases are emphasized  possible mechanisms involved in pathogenesis  as well as types of therapy  are outlined  
class9	nasopalatine duct cyst  an analysis of 334 cases  the nasopalatine duct cyst  npdc  is the most common cyst of nonodontogenic origin in the maxilla  however  the information reported about this lesion consists primarily of small surveys and isolated case reports  the purpose of this retrospective investigation was to gather demographic  clinical  and histologic data on a large series of npdcs  and to compare the findings with those of previous studies  in this study  the overall mean age at diagnosis was 42 5 years  and there was a slight male predilection  the mean radiographic diameter was 17 1 mm  but 75  of the lesions were 20 mm or less in diameter  symptoms were present in at least 70  of the cases  only 28  of the specimens contained respiratory epithelium  there was no correlation between radiographic size  patient s age  presenting symptoms  or type of epithelium  recurrence was noted in only 2  of the cases  
class9	reversible hearing loss from cerebellopontine angle tumors  we report two patients who presented with a dramatic recovery from severe sensorineural hearing loss after total surgical removal of cerebellopontine angle tumors  meningioma and jugular foramen neurinoma   the factors that differentiate these  non acoustic tumors  in relation to the prognosis for hearing are discussed  a surgical approach that maintains the labyrinthine structure and preserves the arachnoid membrane of the superior cerebellopontine angle cistern during tumor removal is stressed  
class9	adult peripheral neuroepithelioma in meckel s cave  a case of peripheral neuroepithelioma arising from the trigeminal nerve in meckel s cave is presented  the discussion emphasizes the pathological criteria for the diagnosis of a peripheral neuroepithelioma and the current controversy about the classification of this and related tumors  
class9	loracarbef concentrations in middle ear fluid  loracarbef concentrations in plasma and middle ear fluid  mef  were measured in specimens obtained approximately 2 h after doses of 7 5 or 15 mg kg  the mean     standard deviation concentrations in mef were 2 0     2 6 mg liter  48  of the concentration in plasma  after the smaller dose and 3 9     2 6 mg liter  42  of the concentration in plasma  after the larger dose  with the larger dose  the concentrations in mef were greater than the mic for 90  of strains of the usual pathogens of acute otitis media tested in 16 of 17 specimens  
class9	nasal midline masses in infants and children  dermoids  encephaloceles  and gliomas  nasal dermoids  gliomas  and encephaloceles are uncommon congenital lesions that result from aberrant embryologic development  we have treated 46 children with these nasal lesions  in view of the potential intracranial connection  patients are at risk for intracranial infection  and early surgical correction is thus imperative  neuroimaging studies may help to predict intracranial involvement  
class9	endoscopic and computed tomographic findings in ostiomeatal sinus disease  previously  there has been no organized format for the documentation of the findings of the nasal endoscopy and the coronal computed tomographic sinus scan  the findings from 100 nasal endoscopies and computed tomographic scans were reviewed and summarized  the summarized findings were incorporated into two forms   the nasal endoscopy exam form  and the  computed tomographic scan findings  form    utilizing computerized graphics techniques  the forms are presented along with their illustration of pathologic ostiomeatal findings  these forms represent a method of documentation of nasal endoscopic and coronal computed tomographic scan findings  they may be used in the demonstration of disease  treatment  planning  resident training  communication of information  and assisting in a future classification of degrees of severity of sinus disease  
class9	circulating c1q binding macromolecules and their relationship to radiographic characteristics of laryngeal cancer  circulating macromolecules capable of binding the first component of complement  c1qbm  may represent subcellular components of tissue tumor debris generated from rapidly proliferating invasive disease  thirty eight patients were randomly selected from 74 untreated patients with laryngeal cancer on the basis of disease stage and c1qbm levels  c1qbm levels were correlated with computed tomographic evidence of tumor necrosis and or thyroid cartilage destruction  results show that patients with stage iii iv disease with tissue necrosis and or cartilage invasion had demonstrably higher c1qbm levels than did individuals with similarly staged disease with no evidence of these radiographically defined characteristics  120     81 micrograms ml vs 18     15 micrograms ml   the strongest association was reflected by the area of necrosis within regional lymph metastases  elevated c1qbm level in patients with stage iii iv laryngeal cancer thus reflects highly aggressive disease  which is less responsive to therapeutic intervention  
class9	radiotherapy  the mainstay in the treatment of early glottic carcinoma  early squamous cell carcinoma of the glottis may be effectively treated with surgery or radiation therapy  controversy exists as to whether radiation therapy effects survival at the expense of vocal function by ultimately requiring more total laryngectomies for salvage of local tumor recurrence  this study reviewed the medical records of 185 patients with t1 or t2  no invasive squamous cell carcinoma of the glottis treated with primary radiation therapy between 1969 and 1984  all patients were followed up for a minimum of 5 years after completion of therapy  one hundred sixty one patients met the criteria for local control analysis  radiation therapy controlled disease in 93   105 of 113  of patients with t1 lesions and 73   38 of 48  of those with t2 tumors  ultimate control of disease for t1 and t2 lesions  including surgical salvage  was 111  98   of 113 and 44  92   of 48 patients  respectively  the rate of successful surgical salvage was 75   t1  and 70   t2   the t2 lesions with impaired vocal cord mobility or anterior commissure disease were identified as being at increased risk for recurrence after primary radiation therapy  overall voice preservation was 90   our data demonstrate that radiation therapy effects disease free survival rates that are comparable to those produced by surgery  without sacrificing voice  although a small percentage of patients with selected early glottic lesions may be more effectively treated with primary conservation surgery  these data do not support a change in philosophy concerning primary treatment of early glottic cancer with radiation therapy  
class9	reconstruction of pediatric larynx and upper trachea with the sternohyoid rotary door flap  the sternohyoid myocutaneous flap  the rotary door flap  is optimally oriented to serve in laryngotracheal reconstruction  it provides immediate  highly vascularized lining and structural support to the augmented airway  therefore  it is one of the most versatile alternative methods available for surgical reconstruction of the stenosed larynx and trachea  thirteen of 14 patients who were managed by the rotary door flap technique have been successfully decannulated  the features of the flap and the surgical technique are described with reference to modifications in the pediatric age group  
class9	noncongenital hereditary hearing loss in children  prospective documentation  younger siblings of children with sensorineural hearing loss of possible hereditary cause underwent interval audiologic examination  seven siblings  in unrelated families  were found to have progressive sensorineural hearing loss despite early audiograms documenting normal hearing levels for age  continued testing of these children allowed for early identification and intervention  we advocate regular otolaryngologic and audiologic follow up even after normal audiologic assessments are made for younger siblings of children with documented sensorineural hearing loss  unless a definite nongenetic origin of the hearing loss in the older child is known  recessive sensorineural hearing loss with onset in infancy or childhood may present with no antecedent family history and with normal behavioral audiograms early in life  
class9	usefulness of immunotherapy in patients with severe summer hay fever uncontrolled by antiallergic drugs objective  to evaluate the efficacy and safety of immunotherapy  hyposensitisation  in patients with severe summer hay fever  design  a randomised  double blind  placebo controlled study of a biologically standardised depot grass pollen extract  setting  allergy clinic  royal brompton and national heart hospital  london  patients  40 adults  mean age 35 years  with a history of severe grass pollen allergy uncontrolled by standard antiallergic drugs  patients with perennial asthma were specifically excluded  intervention  patients were randomised to receive either an active preparation  alutard sq  a grass pollen  phleum pratense  extract  or placebo at a rate of two subcutaneous injections a week in increasing doses until a maintenance dose was reached  this maintenance dose was given once a month  main outcome measures  clinical efficacy was evaluated by symptom and drug diary cards  visual analogue scores during the grass pollen season  and a postseasonal assessment by the patients and a doctor  conjunctival and skin sensitivity to local allergen provocation was measured before and after eight months of treatment  results  there was a highly significant decrease  median alutard sq v median placebo  95  confidence interval for difference between medians  in total symptom scores  p 0 001  in the alutard sq treated group  360 v 928  238 to 825   significant differences were also found in total drug use  p 0 002  129 v 627  178 to 574   visual analogue symptom scores were also reduced in the active group  p 0 02  2 2 v 5 5   4 8 to  0 5   the postseasonal assessment  by either the doctor or the patients  showed a large improvement  p less than 0 001  in favour of alutard sq  provocation tests showed a greater than 10 fold reduction for the active group in immediate conjunctival allergen sensitivity  p 0 001   a 40  decrease in early phase response  p 0 02   and a 57  decrease in the late phase  p 0 001  cutaneous response after intradermal allergen  a total of 523 active injections were given  there was one systemic reaction at 10 minutes after injection  which was rapidly reversed with intramuscular adrenaline  there was one mild delayed urticarial reaction at 2 1 2 hours  conclusion  immunotherapy is effective in patients with severe summer hay fever  but immediate anaphylactic reactions limit its use to specialised centres  patient selection is extremely important  and chronic perennial asthma should be specifically excluded  as serious reactions occur within minutes a two hour wait for all patients after each injection seems unnecessary  
class9	the neck eye reflex in patients with reduced vestibular and optokinetic function  it is accepted that the neck eye loop  cervico ocular reflex  cor  is enhanced following loss of vestibular function and that this helps to restore gaze stability during head movements  in this paper we address the question of which structures and or mechanisms may participate in such plastic enhancement by investigating the cor in 2 patients with absent vestibular function and reduced smooth pursuit optokinetic eye movements  sp okn   the patients had multisystem atrophy involving the vestibular system and the cerebellum  the cor  elicited by angular motion of the trunk relative to the fixed head and angular motion of the head relative to the fixed trunk  was not enhanced in these 2 patients when compared with normal subjects  in contrast to previous findings in a group of patients with absent vestibular function alone  measurements of slow phase eye movement velocity during sp okn stimuli and during combined cor okn stimulation  head oscillation relative to the stationary trunk in the light  showed identical values in these two conditions  which indicates that the neck eye loop did not contribute to gaze stability during head movements  the absence of plastic enhancement of the cor in these patients may be secondary to interruption of sp okn pathways at various possible sites and or to involvement of the vestibulocerebellum  which is known to mediate adaptive plasticity in the vestibulo ocular reflex  
class9	patrick watson williams and the concept of focal sepsis in the sinuses  an historical caveat for functional endoscopic sinus surgery  from 1900 to 1940 the theory of focal sepsis was invoked to justify a number of dubious surgical procedures  surgeons believed they were acting rationally  patrick watson williams advocated suction exploration of the paranasal sinuses for mental patients  claiming to cure criminal insanity by sphenoidotomy  favourable contemporary reviews showed international approval  the rational basis of treatment was emphasised  but there was little systematic evaluation of outcome  current enthusiasm for functional endoscopic sinus surgery is also based on a rational approach  logical deductions from pathophysiological  facts   outcome has still not been evaluated scientifically  we should learn from history  treatment should not be based too readily on what seems to be rational now  ideas of physiology and pathology change  what seems logical today may appear ridiculous tomorrow  careful analysis of outcome  preferably by controlled clinical trials  is needed as a rational treatment requires empirical validation just as much as any other  
class9	management of posterior epistaxis with the use of the fibreoptic nasolaryngoscope  posterior epistaxis is usually treated by repeated nasal packing and in failed situations by ligation of feeding arteries with considerable morbidity and mortality  the most logical approach should be location of the bleeding site and arrest of haemorrhage by local treatment  the exact location of the bleeding area can be identified in actively bleeding noses with the fibreoptic naso laryngoscope and the bleeding arrested by chemical  or thermal cautery and in failed situations by using small nasal packs confined to the bleeding site  this approach to the management of posterior epistaxis is effective and reduces the duration of hospital stay  it significantly reduces the discomfort to the patient  the current practice of indiscriminate blind nasal packing in the hope of arresting nasal haemorrhage by incidental pressure on the bleeding site should be re evaluated  
class9	attachment of bacteria to tonsillar epithelium during acute tonsillitis  epithelial cells were scraped from the tonsillar surfaces of 15 patients with current acute tonsillitis  at  and of 15 individually matched healthy persons  the cellular mixture was stained with acridine orange and bacteria seen to be attached to the epithelial cells under the fluorescent microscope were calculated  conventional bacterial culturing was also performed simultaneously  significantly more bacteria were attached to epithelial cells from the at group than from the controls  greater than 10 attached bacteria per cell p   0 0103  greater than 50 attached bacteria per cell p   0 0212   in vivo determination of bacteria attached to epithelial cells offers prospects of gaining a better understanding of the aetiopathogenesis of acute tonsillitis  
class9	radiation induced cranial nerve palsy  hypoglossal nerve and vocal cord palsies  cranial nerve palsies are an unexpected complication of radiotherapy for head and neck tumours  we present a case of this radiation induced cranial palsy  an 18 year old female with nasopharyngeal carcinoma developed a right hypoglossal nerve palsy 42 months after cancericidal doses of radiotherapy  in addition  she developed a bilateral vocal cord palsy 62 months after therapy  follow up over four years has demonstrated no evidence of tumour recurrence and no sign of neurological improvement  
class9	massive metastasis from squamous carcinoma of the tonsil  squamous carcinomas of the oro pharynx are associated with a high incidence of distant metastases at post mortem  a case of a massive distant metastasis from a squamous cell carcinoma of the tonsil is presented  this occurred despite excellent local control  the pathology and the possible management implications are discussed  
class9	ototoxicity of cis platinum and its relationship to eye colour  the following hypothesis is presented  that the susceptibility of an individual patient to hearing loss as a result of cis platinum administration can be predicted on the basis of eye colour  the rationale is that the melanin content of the inner ears is related to that of the eyes  dark eyes contain more melanin than light coloured eyes  and melanin causes the accumulation of the ototoxic drug within the inner ear  hence those with dark eyes will suffer greater damage to the hearing than those with pale eyes  an investigation that confirmed this hypothesis is reported  in addition to cochlear damage there is a significant likelihood of damage to the auditory nerve as a result of the treatment  
class9	muscle fibre type and habitual snoring  although anatomical abnormalities of the upper airway have been recorded in some patients with obstructive sleep apnoea  osa   a muscle tone dysregulation also seems to have an important role in this disorder  since habitual snoring is the initial stage of osa  the structural characteristics of upper airway muscles  medium pharyngeal constrictor muscle  mpcm   from 13 men  9 non snorers and 4 habitual snorers  were studied  mpcm fibre structure in non snorers was broadly similar to that in normal limb muscles  with the exception that fibre diameters were smaller for all fibre types  compared with limb muscles  mpcm had a smaller proportion of type iib fibres and a higher proportion of types i and iia fibres  mpcm in habitual snorers had an abnormal distribution of fibre types  low percentage of type i and type iib fibres and high percentage of type iia fibres  compared with non snorers  p less than 0 001  and the type iia fibres were hypertrophic  no myopathic or neurogenic changes were seen  two possible hypotheses explain the abnormal distribution of fibre types in snorers  first  a constitutionally determined reduction of slow alpha motor neurons induces an adaptive transformation of type iib to type iia fibres and a hypertrophy of type iia fibres  or  second  motor neurons change their patterns of discharge and  hence  of activation  and modify fibre type distribution of mpcm as an adaptation to the anatomical characteristic of upper airway and habitual snoring  
class9	meniere s disease  an immune complex mediated illness  the cause of meniere s disease is unknown  recent clinical research suggests that one etiology is immune mediated damage to the inner ear  the diagnosis of autoimmune meniere s syndrome is largely based on history  response to steroids  or results of nonspecific laboratory tests such as serological studies  polyethylene glycol  peg  assay was used to determine levels of circulating immune complexes  cic  in 30 patients with meniere s disease and 20 control subjects  patients with meniere s disease had a statistically significant elevation of serum circulating immune complexes when compared to the control group  this suggests that cics may be involved in the pathogenesis of meniere s disease  either as a direct cause of damage  or as a by product of an underlying autoimmune abnormality  therapeutic implications include use of plasmapheresis to remove the complexes or cic monitoring to serve as a marker for treatment efficacy  
class9	argon laser stapedotomy  lasers have been used in otology for 10 years  there have been reports of excellent hearing results using laser energy in surgery for otosclerosis  we used the argon laser in 75 consecutive primary stapedotomy procedures  the postoperative air bone gap was 10 db or less in 87  of patients and 20 db or less in 95   one ear  1 5   had no postoperative hearing secondary to a granulomatous reaction  complications were otherwise uncommon and mild  most patients were treated on an outpatient basis  our results compare favorably with other reports of laser surgery for otosclerosis  we conclude that excellent hearing results can be obtained using the argon laser for stapedotomy procedures  
class9	intracranial complications of paranasal sinusitis  a combined institutional review  intracranial complications of paranasal sinusitis constitute true surgical and medical emergencies  the charts of all patients  n   649  admitted for acute or chronic sinusitis to the university of minnesota hospital and to the university of michigan medical center during a 13 year period  1975 to 1988  were retrospectively reviewed to determine the incidence of complications  the clinical presentation  bacteriology  involved sinuses  influencing host factors  white blood cell count on presentation  length of hospitalization  and postinterventional complications are presented  twenty four patients with intracranial complications from paranasal sinusitis are studied for an incidence of 3 7   aggressive medical and semi emergent surgical intervention are required to prevent excessive morbidity and or mortality  intracranial complications included subdural empyema  frontal lobe abscesses  intrahemispheric abscesses  cavernous and superior sagittal sinus thrombosis  and osteomyelitis  
class9	prognostic factors in craniofacial surgery  from 1979 to 1989  21 patients underwent craniofacial resection for malignancies involving the anterior skull base  histologic types included 8 squamous cell carcinomas  3 chondrosarcomas  2 melanomas  2 basal cell carcinomas  2 adenocarcinomas  2 poorly differentiated carcinomas  1 malignant schwannoma  and 1 malignant hemangiopericytoma  survival was 57   with follow up of 41 months  a 50  complication rate included osteomyelitis  cerebrospinal fluid rhinorrhea  meningitis  brain abscess  epidural abscess  and syndrome of inappropriate antidiuretic hormone  recurrent disease occurred in 9 patients  41    the most reliable predictor being dural invasion indicated preoperatively by ct scan or at operation  patients demonstrating dural involvement  n   9  had a 22  survival rate  while patients without  n   12  had a survival rate of 83   the impact of dural invasion on long term survival is emphasized  though complications were frequent  long term results were favorable  
class9	the response to human ril 1  ril 2  and rtnf in the middle ear of guinea pigs  human recombinant interleukin 1  ril 1   interleukin 2  ril 2   or tumor necrosis factor  rtnf  were injected transtympanically into the middle ear of normal guinea pigs  effusion volume and cellular content were determined after sacrifice and rapid dissection of the ear  by 24 hours  ril 2  100 u  had produced a cellular effusion  77  to 92  polymorphonuclear neutrophil leukocytes   which cleared by 72 hours  rtnf  10 u  yielded a cellular effusion  12  to 67  lymphocytes  at 24 hours  which cleared by 48 hours  ril 1  100 u  did not produce significant effusion when compared to control  ril 2 and rtnf cause an inflammatory effusion in the middle ear  to the extent they are generated in the middle ear during otitis media  these cytokines have the potential to contribute to the pathogenesis of otitis media with effusion  
class9	detection of epstein barr virus dna in formalin fixed paraffin embedded tissue of nasopharyngeal carcinoma using polymerase chain reaction and in situ hybridization  the polymerase chain reaction method for amplification of dna in formalin fixed  paraffin embedded tissue sections was used to detect epstein barr virus dna in nasopharyngeal carcinomas from japanese patients  thirty one cases of nasopharyngeal carcinoma and 8 cases of lymph node metastasis of nasopharyngeal carcinoma were studied  detection rates of epstein barr virus in various types of nasopharyngeal carcinoma according to the world health organization classification were as follows  10 of 10 undifferentiated carcinomas  8 of 13 nonkeratinizing carcinomas  and 5 of 7 keratinizing carcinomas  eight lymph node metastases  for which the primary was positive for epstein barr virus  also contained epstein barr virus dna  by in situ hybridization using a biotinylated epstein barr virus probe  it was clearly demonstrated that epstein barr virus dna was localized in the nuclei of the neoplastic cells  the clinical features of nasopharyngeal carcinoma with or without epstein barr virus were not different  these results demonstrate that nasopharyngeal carcinoma in japanese patients is closely associated with epstein barr virus infection  similar to nasopharyngeal carcinoma of other endemic and nonendemic areas  
class9	the effect of indoor air pollutants on otitis media and asthma in children  this case control study investigated the possible association between home environmental air pollutants and their effect on otitis media and asthma in children  patients with physician diagnosed otitis  n   125  74  response   with asthma  n   137  80  response   and controls  n   237  72  response  from a private pediatric practice seen between october 1986 and may 1987 were studied  a questionnaire inquired about housing characteristics  i e   age  insulation  heating system  and sources of indoor air pollution such as cigarette smoking  use of woodburning stoves  household pets  etc  analysis of the responses confirmed previous findings of significant relationships between maternal smoking  p    021   and the presence of pets  p    034  and the occurrence of asthma  a newly reported relationship between exposure to woodburning stoves and the occurrence of otitis  p less than  05  was reported  this implicates yet another risk factor  wood burning  in the etiology of otitis media  
class9	immunologic defects in patients with refractory sinusitis  sixty one patients with chronic sinusitis who were referred for an allergy evaluation were evaluated for immunologic competence including assessment of quantitative serum immunoglobulin levels  igg subclass levels  and response to pneumococcal and haemophilus influenzae vaccines  in addition to chronic sinus disease  recurrent otitis media and asthma exacerbation were common problems in this group  five patients had an elevated age adjusted ige level and 22 patients had positive prick tests to one or more environmental inhalants  these findings suggest an allergic component in this subgroup  twelve additional patients had highly reactive intradermal tests to common environmental allergens  which also may be clinically significant for underlying atopy  eleven patients had low immunoglobulin levels  6 had low immunoglobulin levels and vaccine hyporesponsiveness  and 17 had poor vaccine response only  thus  34 of 61 patients with refractory sinusitis had abnormal results on immune studies  with depressed igg3 levels and poor response to pneumococcal antigen 7 being most common  in addition to allergy  immunologic incompetence may be an important etiologic factor in patients with chronic  refractory sinusitis  
class9	age related balance changes in hearing impaired children  this study compared balance skills of hearing impaired children with those of hearing children in order to determine whether a deficit in balance exists in hearing impaired children and to ascertain whether this deficit is age related  twenty eight hearing impaired subjects were chosen as a sample of convenience from the pennsylvania school for the deaf and placed into one of three age groups  ten subjects were in the 4 5 to 6 5 year old age group  8 in the 8  to 10 year old age group  and 10 in the 12 5 to 14 5 year old age group  selection criteria included bilateral sensorineural hearing loss of greater than or equal to 65 db and normal intelligence  iq greater than or equal to 80   balance was measured by the use of the balance subtest of the bruininks oseretsky test of motor proficiency  for each age group  a z test was used to compare the subjects  scores with the balance subtest standard scores  the results showed that for each age group  the mean score for the hearing impaired children was lower than the standard score  both older groups had significantly higher scores than the youngest group  but the mean scores of the older groups were not significantly different  no difference between the subjects  balance scores and the balance subtest standard scores was found among the age groups  suggesting that the balance deficit was not age related  gender differences were not found for balance scores  
class10	mistaken diagnoses in continuous muscle fiber activity of peripheral nerve origin  the syndrome of continuous muscle fiber activity of peripheral nerve origin has manifestations that resemble those of many other more common neurologic disorders during childhood and infancy  this similarity often leads to misdiagnosis when an adequate index of suspicion is not entertained and a comprehensive electromyographic examination is not performed  two affected patients from 1 family are reported to illustrate the type of diagnostic errors that were made before the establishment of the correct diagnosis  
class10	haemophilus influenzae meningitis with prolonged hospital course  a retrospective evaluation of haemophilus influenzae type b meningitis observed over a 2 year period documented 86 cases  eight of these patients demonstrated an unusual clinical course characterized by persistent fever  duration  greater than 10 days   cerebrospinal fluid pleocytosis  profound meningeal enhancement on computed tomography  significant morbidity  and a prolonged hospital course  the mean age of these 8 patients was 6 months  in contrast to a mean age of 14 months for the entire group  two patients had clinical evidence of relapse  four of the 8 patients tested for latex particle agglutination in the cerebrospinal fluid remained positive after 10 days  all patients received antimicrobial therapy until they were afebrile for a minimum of 5 days  subsequent neurologic examination revealed a persistent seizure disorder in 5 patients  62 5    moderate to profound hearing loss in 2  25    mild ataxia in 1  12 5    and developmental delay with hydrocephalus which required shunting in 1  12 5    one patient had no sequelae  
class10	eeg correlation of improvement in hemolytic uremic syndrome after plasma infusion  we report a previously undescribed electroencephalographic pattern of epochs of diffuse delta background  85 240 sec  alternating with epochs of classic  burst suppression   90 270 sec  in a 13 month old girl with hemolytic uremic syndrome  a dramatic electroencephalographic improvement was evident on continuous monitoring of cerebral function 3 hours after initiating fresh frozen plasma infusion  well before any clinical improvement was apparent  this patient  in addition to the unusual electroencephalographic findings  illustrates the role of continuous electrophysiologic monitoring of cerebral function and supports the use of fresh frozen plasma in hemolytic uremic syndrome  
class10	reversible myopathy due to labetalol  a severe  generalized myopathy developed in 2 children treated with labetalol  an 11 year old girl and a 14 year old boy demonstrated proximal weakness and markedly elevated creatine kinase levels during labetalol therapy  clinical improvement began immediately when labetalol administration was halted  muscle strength was normal within 2 months  muscle biopsies were consistent with rhabdomyolysis  
class10	threat of unemployment and cardiovascular risk factors  longitudinal study of quality of sleep and serum cholesterol concentrations in men threatened with redundancy  objective  to assess whether the threat of unemployment affects risk factors for cardiovascular disease  design  longitudinal study of a cohort of middle aged shipyard workers followed up for a mean of 6 2  sd 1 9  years and a group of controls observed for the same period  the first investigation took place during a period of relative economic stability for the shipyard and the second during the phase of its closure  setting  an age cohort health screening programme in malmo  sweden  participants  715 male shipyard workers and 261 age matched male controls  main outcome measures  changes in 19 variables related to the risk of cardiovascular disease  and psychological variables  alcohol consumption  smoking  and dietary habits as assessed by questionnaire  results  serum cholesterol concentrations increased more  mean 0 25  sd 0 68  mmol l v 0 08  0 66  mmol l  and serum calcium concentrations decreased less   0 06  0 10  mmol l v  0 08  0 09  mmol l  in the shipyard workers than in the controls  a correlation was found between scores for sleep disturbance and changes in serum cholesterol concentration  in the whole series there was a greater increase in serum cholesterol concentrations among men threatened with unemployment  437 976  44 8   than among those who were not  in stepwise regression analysis the change in serum cholesterol concentration was correlated with changes in haemoglobin concentration  body weight  and serum triglyceride and calcium concentrations  a positive correlation was found between change in cholesterol concentration and change in blood pressure  indicating that the overall risk profile had worsened among men with increased serum cholesterol concentrations  conclusions  risk of unemployment increases the serum cholesterol concentration in middle aged men  the increase being more pronounced in those with sleep disturbance  the increase in serum cholesterol is related to changes in other established risk factors for cardiovascular disease  these findings might partly explain the excessive mortality due to cardiovascular disease recorded among the unemployed and people with sleep disturbance  
class10	permanent external striated sphincter stents in patients with spinal injuries  nine patients with complete quadriplegia underwent external striated sphincter stenting with the wallstent in place of an external striated sphincterotomy  although suprapubic catheters were placed to provide an outlet should problems develop with the stent  they were successfully removed within 6 weeks in all but 1 patient  complete bladder emptying with reduced voiding pressures was achieved  together with a significant reduction in the duration of hyper reflexic contractions  epithelialisation of the stent was almost complete within 3 months and intermittent catheterisation or endoscopy  and resection  is possible through the stent  although this is a preliminary report of this new technique  it is hoped that sphincter stenting will provide a rapid  safe and effective method of treating high pressure hyper reflexia and detrusor sphincter dyssynergia in quadriplegic patients  
class10	hypercalcemia in infants presenting with apnea  to our knowledge apnea in infants has not been associated with hypercalcemia  we describe seven hypercalcemic infants aged 2 days to 3 months who had presented with apnea  six of the seven were otherwise healthy  the apneic attacks were brief  and normal breathing was restored spontaneously or after tactile stimulation  the attacks stopped and the apnea monitoring was discontinued when the children were 1 month to 2 years of age  the only abnormal finding common to all of the patients was hypercalcemia  idiopathic infantile hypercalcemia was diagnosed in six of the patients and familial benign hypercalcemia in one  our findings suggest that determination of the plasma calcium level be included in the investigation of apnea in infancy  
class10	headache  a marker of depression patients who presented with a chief complaint of headache in the outpatient family practice setting were found to have a high prevalence of depression  63   by the zung self rating depression scale  sds  index  a statistically significant relationship was found between the frequency of headaches  p    03  with level of depression  in fact  74  of patients with headaches recurring almost every day had a clinically significant depression diagnosed as defined by the zung sds score  the zung sds score also correlated with the length of time that the problem of headache existed  p less than  05   item analysis of the individual 20 item depression score revealed that four questions accounted for 93  of the variance  this analysis suggests that shorter  more abbreviated screening questions could be developed and refined in the future for use by the busy clinician  headache is an important marker for depression in the primary care setting  it can be inferred from this study that the clinician may need to focus more on treating the entity of depression than on treating just the symptom of headache  
class10	botulinum toxin treatment of cranial cervical dystonia  spasmodic dysphonia  other focal dystonias and hemifacial spasm  in the past five years  477 patients with various focal dystonias and hemifacial spasm received 3 806 injections of botulinum a toxin for relief of involuntary spasms  a definite improvement with a global rating greater than or equal to 2 on a 0 4 scale  was obtained in all 13 patients with spasmodic dysphonia  94  of 70 patients with blepharospasm  92  of 13 patients with hemifacial spasm  90  of 195 patients with cervical dystonia  77  of 22 patients with hand dystonia  73  of 45 patients with oromandibular dystonia  and in 90  of 21 patients with other focal dystonia who had adequate follow up  while the average duration of maximum improvement lasted about 11 weeks after an injection  range seven weeks in patients with hand dystonia to 15 weeks in patients with hemifacial spasm   some patients benefited for over a year  only 16  of the 941 treatment visits with follow up were not successful  except for transient focal weakness  there were very few complications or systemic effects attributed to the injections  this study supports the conclusion that botulinum toxin injections are a safe and effective therapy for patients with focal dystonia and hemifacial spasm  
class10	botulinum toxin treatment in spasmodic torticollis  botulinum toxin a was administered to 19 patients in a double blind placebo controlled trial  toxin was more effective than placebo for improving both head position and pain which was measured by an objective rating scale and videofilm assessments  following the controlled trial  treatment with botulinum toxin was continued in an open fashion  a total of 60 patients with torticollis received toxin in a total of 117 treatment periods  the mean follow up period was 8 4 months  in 39 patients with pain there was benefit in 77  of treatment periods  some improvement in neck posture occurred in 83  of the treatment periods with a mean duration of 12 weeks  side effects were frequent with dysphagia being the most common  28  of treatment periods   botulinum toxin is an effective treatment for toticollis but treatment should be initiated with doses at the lower end of the range used in this study  400 600 mouse units   
class10	central nervous system haemangioblastoma  a clinical and genetic study of 52 cases  fifty two cases of haemangioblastoma were reviewed for their clinical  genetic and prognostic features  of 34 patients with apparently isolated cerebellar lesions  postoperative outcome was good in 79   six isolated spinal lesions presented more insidiously and morbidity was related to incomplete resection  twelve  23   of the patients definitely had von hippel lindau disease  vhld   the true proportion may be higher as this diagnosis was not definitely excluded in many of the remainder  only ten patients with seemingly isolated cerebellar tumours were appropriately investigated and two had evidence of vhld  four out of 26 cases  15   with apparently completely resected  isolated  cerebellar lesions later developed recurrent tumours  brainstem and supratentorial haemangioblastomas were rare and were always associated with vhld  the cerebellar or spinal haemangioblastomas due to vhld had no distinctive clinical features compared with isolated tumours and there was considerable overlap in age of onset between the two groups of cases  all patients with an apparently isolated cns haemangioblastoma should be investigated for evidence of von hippel lindau disease  
class10	vesicular changes in the myopathies of aids  ultrastructural observations and their relationship to zidovudine treatment  six patients with aids and aids related complex  arc  who developed neuromuscular symptoms associated with vesicular changes in muscle fibres are reported  two patients in the advanced stages of aids  who did not receive zidovudine  developed proximal limb weakness and wasting  both had a necrotising myopathy with an unusual segmental vesicular change of myofibres  there were numerous vesicles 0 1 to 2 microns in diameter produced by dilatations of the sarcoplasmic reticulum in fibres depleted of myofibrils  four patients developed a myopathy while receiving zidovudine for aids  one of these had an inflammatory myopathy which showed the development of vesicular change due to enlargement and electron lucency of mitochondria  the three other patients with arc developed muscle pains or weakness and elevated serum ck while on zidovudine  these patients also showed vesicular changes due to enlargement and electron lucency of mitochondria associated with disruption of sarcomeres and the presence of cytoplasmic bodies  the muscular symptoms resolved when ziduvodine was stopped and repeat biopsy in one case revealed no abnormalities  
class10	the relationship of antibody levels to the clinical spectrum of human neurocysticercosis  one hundred proven cases of cerebral cysticercosis were studied with an enzyme linked immunoassay  elisa  employing cyst fluid as antigen  with a view to detecting specific antibodies in serum and cerebrospinal fluid  csf   antibody levels were correlated with the clinical presentation of the patients  the type and number of cysts detected on their brain scans  the anatomical position of these cysts and the presence of lymphocytes in the csf  patients could be divided into two distinct categories  one with low levels of antibody in the serum and absent antibody in the csf  and the other with high levels in both the serum and the csf  this differentiation matched the clinical presentation of a benign and a malignant group  antibody levels could not be related to the type of cysts as observed on the brain scan  but depended on the anatomical position of the cyst  being lower if the cysts were confined to the cerebral cortex  a correlation of antibody levels with the number of cysts was only found in the benign group  
class10	low plasma iron status and akathisia  thirty patients were examined to test the hypothesis that a depletion of iron levels is associated with symptoms of akathisia  fifteen akathisic patients were pair matched with 15 non akathisic patients  plasma ferritin levels were significantly decreased in the akathisic patients  and there was a significant inverse correlation between plasma iron levels and akathisia rating  in addition  akathisia ratings were found to be correlated with a scale measuring symptoms of tardive dyskinesia  
class10	extradural implantation of sacral anterior root stimulators  a technique for extradural deafferentation of the s2 to s5 segments and extradural implantation of stimulating electrodes is described  and its application to twelve patients with spinal cord lesions is reported  nine patients use their implants for micturition  and seven are fully continent  the advantages and disadvantages of this technique compared with the more usual intrathecal procedure are discussed  
class10	bimanual simultaneous motor performance and impaired ability to shift attention in parkinson s disease  the ability to share time and to shift attention between bimanual simultaneous motor tasks were studied in 18 patients with parkinson s disease  pd  and 19 age  and intelligence matched controls  the task consisted of drawing triangles with the dominant hand and squeezing a rubber bulb with the nondominant hand  motor performance was measured using the variables  amplitude of squeezing  frequency of squeezing and velocity of drawing triangles  after eliminating variance due to baseline differences in single handed performance  the bimanual simultaneous performance of pd and controls turned out to be similar to the frequency of squeezing and the velocity of drawing triangles  the amplitude of squeezing  however  differed between the two groups  it was significantly reduced in pd  arguably the disturbance in the bimanual performance of pd patients was not due to a disorder of time sharing  but to a decreased ability to shift attention from the visually cued task to the non visually cued task  the results agree with current evidence that pd patients are more impaired when they have to rely upon internal control for the regulation of shifting attention than when external cues are available  
class10	the treatment of gilles de la tourette syndrome by limbic leucotomy  a patient with gilles de la tourette syndrome and severe self injurious compulsions who had failed to respond to drug treatment and behavioural therapy obtained a complete and sustained resolution of his destructive behaviour and improvement in his tics following bilateral limbic leucotomy  
class10	stiffman syndrome  a rare paraneoplastic disorder  an unusual case of the stiffman syndrome  associated with an oat cell carcinoma of the bronchus  is reported  pathological examination showed that it was due to an encephalomyelitis similar to that seen in paraneoplastic disorders  this suggests that atypical cases of the stiffman syndrome may occasionally be paraneoplastic  
class10	ldh isoenzymes in cerebrospinal fluid in various brain tumours  this study examined the isoenzymatic pattern of ldh in the cerebrospinal fluid  csf  as well as the ratio between the five fractions of ldh among patients with various brain tumours  carcinomatous meningitis and control groups  ldh 1 ldh 2 less than 1 was found significant for carcinomatous meningitis  p less than 0 001  and brain metastases  p less than 0 001   ldh 1 ldh 2 ratio was found to be significantly lower in carcinomatous meningitis than in brain metastases  p less than 0 05   no ldh 1 ldh 2 ratios smaller than 1 were found in the other groups  the ldh 1 ldh 2 ratio smaller than 1 was found in the early stage of carcinomatous meningitis without other evidences of the involvement of the leptomeninges  examination of ldh 1 ldh 2 can be found as an adjunctive method to identify brain metastases and carcinomatous meningitis at the initial stage  
class10	misperceptions of comprehension difficulties of stroke patients by doctors  nurses and relatives  doctors  nurses and relatives involved with 30 recently aphasic stroke patients were asked to predict how the patient would perform on a comprehension test  results show that not only do doctors  nurses and relatives underestimate the receptive disability of these patients  but they also illustrate a lack of agreement between health professionals  implications for management are considered  
class10	practice effects on the preprogramming of discrete movements in parkinson s disease  the effects of practice on the simple and choice reaction times  rts  of parkinson s disease  pd  and control subjects in a discrete aiming task were analysed  for controls  practice led to a selective decrease in choice rts  as has been reported previously  an opposite effect was seen in the pd group  with little change in choice rts and substantial reduction in simple rts  the results suggest that pd subjects can use advance information to initiate discrete movements more rapidly  but that this ability to  preprogramme  movements requires practice  reconciliation of these results with studies reporting an inability to preprogramme in pd are made in a discussion of task characteristics which may allow or preclude preprogramming  
class10	blood pressure reactivity predicts myocardial infarction among treated hypertensive patients  high blood pressure  bp  defines a prognostically heterogeneous group  because bp varies according to time  setting and means of observation  it has been postulated that bp reactivity might better predict cardiovascular disease  cvd  than does unidimensional measurements  to assess bp reactivity  the difference between pretreatment nurse  rn  and physician  md  diastolic bp  dbp   systematically recorded in that order  or md rn dbp  was obtained in 1737 previously untreated patients with sustained  rn bp greater than or equal to 160 and or 95 mmhg  patients stratified by tertiles of md rn dbp   i  less than or equal to   3   ii   2 to 3 and  iii  greater than or equal to 4 mmhg  were similar by sex  race  age  body mass index  cholesterol  electrocardiography  prior cvd  smoking and pretreatment or attained in treatment bps  during 14 years of followup  myocardial infarction  mi  incidence per 1000 year were  tertile i  3 2   ii  3 7   iii  7 6   relative risk   2 4  iii vs i   ii  p less than 0 05   whereas stroke incidence and non cvd mortality were evenly distributed  by cox survival analysis  controlling for other entry characteristics only age  sex and dbp reactivity remained predictive  p less than or equal to 0 03  of mi or total cvd  thus  bp reactivity  probably a centrally mediated phenomenon  identifies a subgroup of hypertensives with an increased propensity for mi despite successful bp control  
class10	the relationship of headache symptoms with severity and duration of attacks  efforts to develop clinically useful headache classification schemes have generally focused on linking specific symptom groupings with specific headache subtypes  an alternative conceptual approach  the  severity model  of headache  considers a continuum of headache ranging from mild to severe forms with specific headache subtypes distinguished by level of severity rather than unique constellations of symptoms  a population based telephone interview was carried out among 10 169 subjects aged 12 29 to estimate the prevalence of serious headaches and better characterize symptoms that accompany headache attacks  in an analysis of frequency of occurrence  pain and duration of recent  within 4 weeks prior to interview  headache attacks  the data revealed that common symptoms  such as forehead pain and pain in the back of the head  neck and shoulders  were reported frequently  but headaches with these symptoms were generally characterized by low levels of pain and short duration  although not an original study objective  the data were analyzed to determine whether distinct symptom constellations could be identified or whether symptoms overlapped between headache types  symptoms of migraine were frequently experienced concomitant with tension type symptoms  the resultant headaches were usually characterized as moderate in intensity  in contrast  symptoms usually associated with migraine in the absence of concomitant tension type symptoms were infrequently experienced  but resulted in headaches causing the greatest disability  the data provide some support for the severity model of headache  
class10	surgical management of exophytic chiasmatic hypothalamic tumors of childhood  sixteen children underwent 18 operations for radical resection of chiasmatic hypothalamic tumors  the clinical presentation correlated with age  infants under 1 year of age presented with macrocephaly  failure to thrive  and severe visual failure  children aged 1 to 5 years predominantly had precocious puberty with mild visual deficits  and older children  greater than 5 years old  had slowly progressive loss of vision  all three infants had biologically aggressive tumors in spite of low grade histology  and died from progressive tumor growth  eleven of the 13 children aged 1 year or over are alive and well  without clinical or radiographic evidence of disease progression  4 months to 4 1 2 years following surgery  six of these patients  with a follow up period of 10 months to 4 1 2 years  mean 27 months   have had no adjuvant therapy following radical surgical resection  the authors conclude that  1  radical surgical resection of chiasmatic hypothalamic tumors can be performed with minimal morbidity  2  radical resection may delay the time to disease progression in older children and postpone the need for irradiation  3  resection of postirradiation recurrent tumors may provide neurological improvement and long lasting clinical remission  and 4  chiasmatic hypothalamic tumors of infancy are aggressive neoplasms that require multimodality therapy  
class10	long term follow up review of 31 children with severe closed head trauma  thirty one children aged 3 to 15 years were followed for 5 to 11 years after suffering severe closed head trauma which caused coma for 1 week or more  median duration of coma 3 weeks   one patient remained in a persistent vegetative state until his death 9 years later  the other 30 recovered consciousness and were discharged  all suffered diminution of their abilities  and 24 of them had major permanent disability  the most common motor disabilities were pure spastic hemiparesis  seven cases   basal ganglia syndromes  four cases   ataxia  three cases   and a combination of hemiparesis and ataxia  five cases   of the 30 patients  26 regained independent ambulation  seven were epileptic  and 14 were dysarthric in various degrees  only 10 had the cognitive ability to profit from the normal educational system  and none had attempted postsecondary education  social problems were common  the worst outcomes were associated with intracranial bleeding and or brain contusion seen on computerized tomography  ct  scans at the acute stage  the best were associated with normal ct scans  the degree of residual disability in these children seems no less than that of adults with trauma of similar severity  
class10	initial ct findings in 753 patients with severe head injury  a report from the nih traumatic coma data bank  in this prospective multicenter study  the authors have examined data derived from the initial computerized tomography  ct  scans of 753 patients with severe head injury  when the ct findings were related to abnormal intracranial pressure and to death  the most important characteristics of the scans were  midline shift  compression or obliteration of the mesencephalic cisterns  and the presence of subarachnoid blood  diffuse hemispheric swelling was also found to be associated with an early episode of either hypoxia or hypotension  
class10	neurobehavioral outcome 1 year after severe head injury  experience of the traumatic coma data bank  the outcome 1 year after they had sustained a severe head injury was investigated in patients who were admitted to the neurosurgery service at one of four centers participating in the traumatic coma data bank  tcdb   of 300 eligible survivors  the quality of recovery 1 year after injury was assessed by at least the glasgow outcome scale  gos  in 263 patients  87    whereas complete neuropsychological assessment was performed in 127  42   of the eligible survivors  the capacity of the patients to undergo neuropsychological testing 1 year after injury was a criterion of recovery as reflected by a significant relationship to neurological indices of acute injury and the gos score at the time of hospital discharge  the neurobehavioral data at 1 year after injury were generally comparable across the four samples of patients and characterized by impairment of memory and slowed information processing  in contrast  language and visuospatial ability recovered to within the normal range  the lowest postresuscitation glasgow coma scale  gcs  score and pupillary reactivity were predictive of the 1 year gos score and neuropsychological performance  the lowest gcs score was especially predictive of neuropsychological performance 1 year postinjury in patients who had at least one nonreactive pupil following resuscitation  notwithstanding limitations related to the scope of the tcdb and attrition in follow up material  the results indicate a characteristic pattern of neurobehavioral recovery from severe head injury and encourage the use of neurobehavioral outcome measurements in clinical trials to evaluate interventions for head injured patients  
class10	meningiomas mimicking cerebral schwannoma  a brain tumor with histological features reminiscent of schwannoma with underlying meningioangiomatosis was subjected to electron microscopic and immunohistochemical analysis  which confirmed the neoplasm as a meningioma  this prompted reexamination of a similar tumor  described in a previous publication as a cerebral schwannoma  with identical immunohistochemical techniques  the results obtained favored alteration of this diagnosis to that of meningioma  this experience has led the authors to recommend the use of immunohistochemistry techniques when evaluating unusual intracranial neoplasms  
class10	use of ct and mr imaging to distinguish intracranial lesions and to define the need for biopsy in aids patients to explore the potential usefulness of imaging studies in the diagnosis of focal central nervous system  cns  lesions associated with acquired immunodeficiency syndrome  aids   the authors retrospectively examined the radiographic studies of 149 aids patients who presented with signs and symptoms of the three most common focal cns lesions  of these patients  74  50   had toxoplasma abscesses  45  30   had primary cns lymphoma  and 30 patients  20   had progressive multifocal leukoencephalopathy  pml   magnetic resonance  mr  imaging was more sensitive than computerized tomography  ct  in detecting lesions  especially in cases of pml  whereas ct was unable to distinguish mass lesions caused by toxoplasmosis from those caused by lymphoma  71  of the solitary lesions seen on mr images were lymphomas  these results indicate that empirical treatment for toxoplasmosis  the most common initial treatment for aids patients with neurological symptoms stemming from mass lesions  is not likely to be successful for patients with solitary lesions on mr images  rather  early biopsy is advisable  if the presence of lymphoma is confirmed  the rapid initiation of treatment can allow prolonged high quality survival  
class10	hormonal dependency of cerebral meningiomas  part 1  female sex steroid receptors and their significance as specific markers for adjuvant medical therapy  female sex steroid receptors were examined in 50 human cerebral meningiomas  for estrogen receptors  high affinity binding sites  dissociation constant  kd   0 05 to 0 2 nm  were found in the cytosolic fraction with a capacity of less than 4 fmol mg protein in 10 meningiomas using a dextran coated charcoal  dcc  assay  in the same cytosolic fraction  the solid phase enzyme immunoassay revealed only one cytosol with a positive colorimetric reaction equal to 5 fmol mg protein  however  in the nuclear compartment  none of the tumors stained positively for estrogen receptors with immunohistochemical techniques  in addition  the most convincing evidence for the absence of estrogen receptors was obtained by in situ hybridization using an oligonucleotide probe complementary to a fraction of the human receptor messenger ribonucleic acid  mrna   in none of the 50 meningiomas was the expression of estrogen mrna coding for the estrogen receptor detected  for progesterone receptors  high affinity binding sites  kd  0 3 to 2 6 nm  were found in 49 of the 50 tumors using a dcc assay  in the same cytosols  solid phase enzyme immunoassay revealed that each tumor was positive for progesterone receptors  however  in the nuclear compartment  only five tumors had partially positive staining for progesterone receptors with immunohistochemical techniques  within the confines of this study  it is concluded that  1  the estrogen receptor is generally absent in meningioma tissue  and 2  the progesterone receptor is mainly absent in the nuclear compartment  leading to the conclusion that the cytosolic progesterone receptor may be an inactive form  this study suggests that female sex steroid receptors are not primarily involved in the proliferative rate of cerebral meningiomas and that they are of no current significance as markers for adjuvant medical therapy of most meningiomas  
class10	hormonal dependency of cerebral meningiomas  part 2  in vitro effect of steroids  bromocriptine  and epidermal growth factor on growth of meningiomas  cell culture and biochemical techniques have been employed to examine the effects of steroids  bromocriptine  and epidermal growth factor  egf  on the growth and proliferative potential of meningiomas  in cell culture  the growth of meningiomas was not altered by progestogens  antiprogestogens  or 17beta estradiol  the progestogen  norethisterone  had no effect on the uptake by meningiomas cell cultures of 3h thymidine  furthermore  cytosolic deoxyribonucleic acid  dna  polymerase activity of meningiomas did not correlate with the progesterone receptor status of the same tumors  in contrast  the androgen antagonists  cyproterone acetate and 11 alpha hydroxyprogesterone  and the dopamine agonist  bromocriptine  all inhibited the in vitro growth of meningioma cells  the growth of meningioma cell cultures was stimulated by egf  and there was a positive correlation between the egf content and dna polymerase activity in meningioma cytosols  these results demonstrate that female sex steroids do not influence growth of meningiomas in vitro  whereas antiandrogens and bromocriptine have an antiproliferative effect  consequently  bromocriptine and antiandrogens may have a role in the medical treatment of meningiomas  in addition  these results suggest that egf may be involved in the genesis and or progression of meningiomas  
class10	intracarotid hydroxyethyl methacrylate solution causing stroke in dogs  hydroxyethyl methacrylate  hema  has been advocated as a polymerizing solution with which to prevent deflation of detachable balloons in interventional neuroradiology  it is pertinent to know if unpolymerized hema would have untoward effects if accidentally released into the carotid artery by balloon rupture or deflation  seven mongrel dogs underwent transfemoral catheterization of the common carotid artery and subsequent injection of hema solution in volumes of 1 cc in five dogs  2 cc in one  and 4 cc in one  angiography performed at the time of injection revealed evidence of intravascular thrombosis as well as possible spasm  three surviving animals were sacrificed at 48 hours  the brains were fixed and examined histopathologically  one brain was normal and one was autolyzed and could not be examined  five of the seven animals had histopathologically documented cerebral infarctions of varying size  no foreign substance was seen within the blood vessels to suggest intravascular polymerization  the animals injected with 2 or 4 cc hema solution did not survive 48 hours  literature review reveals little documentation of the toxicology of intravascular hema  with its increasing popularity as a compound for polymerization in detachable balloons introduced into the brain  further investigations are warranted to understand the physical properties of the compound and potential risks of its use  
class10	hemiparkinsonism as a complication of an ommaya reservoir  case report  the authors describe the case of a 28 year old woman who developed the following symptoms in her right hand  a lasting resting tremor  transient focal rigidity  and paresthesia  these deficits occurred following treatment with intrathecal methotrexate via an ommaya reservoir which was placed too deeply  resulting in trauma to the contralateral mesencephalon  
class10	fourth ventricular schwannoma  case report  a schwannoma arising from the dorsum of the pontomedullary junction and presenting as an exophytic mass in the fourth ventricle is described  a ventricular schwannoma has not previously been reported in the literature  the presenting clinical and radiographic features and the pathology of this tumor are summarized  and an explanation is sought for its unusual location  
class10	myxomatous cyst of the brachial plexus  case report  the case of a myxomatous cyst of the brachial plexus is presented  the clinical course is reported  and the frequency of the lesion  diagnostic workup  histopathology  and surgical therapy are discussed  
class10	postlaminectomy ossified extradural pseudocyst  case report  a large ossified spurious meningocele accompanied by recurrent lumbar disc herniation occurred 7 years after posterior intervention for laminectomy and discectomy in a 53 year old man  the cyst wall  histologically composed of mature bone tissue  was sparsely covered with connective tissue and lined with fibrocyte  or fibroblast like cells on the inside  the ossified pseudocyst was presumed to have originated from a minute defect in the dura mater which occurred at the time of the first operation  
class10	intradural epithelial cyst at the craniovertebral junction  case report  a case of an intradural epithelial cyst at the craniovertebral junction is reported in a 37 year old man  the classification of these rare lesions is discussed  
class10	stereotactic investigation of limbic epilepsy using a multimodal image analysis system  technical note  a methodology has been developed for stereotactic investigation of limbic epilepsy using an image analysis system that simultaneously displays different structural and functional images of the brain  the validity and accuracy of this system were established with phantom studies  surgical planning and electrode implantation are guided by stereotactic magnetic resonance imaging  digital subtraction angiography  and position emission tomography  this methodology provides the spatiotemporal relationship of cerebral structure and function necessary to identify seizure onset and propagation in human limbic system epilepsy  
class10	disturbances in the cerebral perfusion of human immune deficiency virus 1 seropositive asymptomatic subjects  a quantitative tomography study of 18 cases  quantitative measurements of cerebral blood flow  cbf  by xenon 133  133xe  tomography  together with magnetic resonance imaging  mri   electroencephalography  eeg   psychometric tests  and laboratory analyses were performed on 18 human immunodeficiency virus 1  hiv 1  seropositive asymptomatic subjects  abnormalities of cerebral perfusion were observed in 16 cases  88    these abnormalities were particularly frequent in the frontal regions  77  of cases   mri demonstrated leucoencephalopathy in only two cases  eeg showed only induced diffuse abnormalities in two cases  psychometric tests showed restricted moderate disturbances in 55  of patients  these disturbances mostly concerned those sectors involved in cognitive functions and memorization  these results indicate that quantitative measurements of cbf by 133xe spect is capable of detecting abnormalities of cerebral perfusion at a very early stage  phase ii  of hiv 1 infection  these abnormalities are indications of disturbances resulting from unidentified metabolic or vascular lesions  this technique appears to be superior to mri at this stage of the disease s development  it could provide objective information leading to earlier treatment  and prove useful in evaluating potential antiviral chemotherapy  
class10	hmpao spect imaging resembling alzheimer type dementia in mitochondrial encephalomyopathy with lactic acidosis and stroke like episodes  melas   single photon emission computed tomography  spect  of the brain using hexamethyl propylene amine oxime  hmpao  was performed in a 37 year old patient suffering from mitochondrial encephalomyopathy with lactic acidosis and stroke like episodes  melas   reduced blood flow was observed bilaterally in the parieto occipital regions  resembling alzheimer type dementia  and in the right parietal lobe  
class10	an evaluation of sensory changes and pain relief in trigeminal neuralgia following intracranial microvascular decompression and or trigeminal glycerol rhizotomy  nineteen patients with trigeminal neuralgia were treated with either trigeminal ganglion glycerolysis or glycerolysis and intracranial microvascular decompression  all had a good degree of pain relief  of those receiving glycerol alone  group a   50  subjectively reported a mild reduction of fine tactile sensation  a similar response was reported by those treated with both glycerol and decompression  group b   the degree of sensory loss was so mild that thermal testing was useless as a discriminatory tool  the degree of sensory loss was not greater when both surgical procedures were performed than when the less invasive trigeminal ganglion glycerolysis alone was used  
class10	assessment of proplast teflon disc replacements  published erratum appears in j oral maxillofac surg 1991 feb 49 2  220  this retrospective study reports the findings in the follow up of 31 temporomandibular joints in which proplast teflon  vitek inc  houston  tx  replacements were used  among the problems noted were pain  malocclusion  restricted opening  and degenerative changes in the condyle and fossa  
class10	normalization of plasma arginine vasopressin concentrations when children with meningitis are given maintenance plus replacement fluid therapy we hypothesized that plasma arginine vasopressin  avp  concentrations in children with meningitis are appropriate for the children s degree of hypovolemia  even though the concentrations were higher than expected for the serum osmolality  a randomized study was conducted to compare the effect on plasma avp concentrations of giving maintenance fluid requirements plus replacement of any deficit versus restricting fluids to two thirds of maintenance requirements for 24 hours  plasma avp concentrations and serum osmolality were measured before fluid therapy was begun and again after 24 hours  nineteen children  2 months to 17 years of age  were studied  13 had bacterial meningitis  12 with haemophilus influenzae type b   ten children  seven with bacterial meningitis  received a mean of 1 42 times the calculated maintenance fluid requirements  and nine  six with bacterial meningitis  were restricted to a mean of 0 65 times maintenance  children in the maintenance group also received significantly more sodium  mean   6 3 meq kg 24 hr  than children in the fluid restricted group  mean   2 0 meq kg 24 hr   the two groups were comparable for plasma avp concentration and serum osmolality before fluid therapy was begun  the plasma avp concentration was significantly lower after 24 hours of maintenance plus replacement fluids than after fluid restriction  p   0 005   and the change in avp concentration correlated with the amount of sodium given  p less than 0 02   this study supports the hypothesis that serum avp concentrations are elevated in patients with meningitis because of hypovolemia and become normal when sufficient sodium is given to facilitate reabsorption of water by the proximal tubule of the kidney  patients with meningitis can be given maintenance plus replacement fluids but should be monitored for the development of the syndrome of inappropriate secretion of antidiuretic hormone  
class10	diagnosis of cerebrovascular disease in sickle cell anemia by magnetic resonance angiography the study of blood flow by means of magnetic resonance techniques has led to a noninvasive magnetic resonance angiography  mra  technique for imaging large cerebral vessels  ten children with sickle cell hemoglobinopathy and a history of acute neurologic syndromes were studied with combined parenchymal magnetic resonance imaging  mri  and mra  six had abnormal mri findings and mra defined luminal lesions in the vascular distribution of these parenchymal infarctions  the three children with previous intraarterial angiography had mra abnormalities that corresponded with vascular lesions on conventional angiograms  four had normal mri and mra findings  we conclude that a combination of mri and mra provides a noninvasive screening test for large vessel disease in this population  
class10	assessing clinical significance of apnea exceeding fifteen seconds with event recording  using event recording  we determined how often apnea exceeding 15 seconds in duration was associated with bradycardia and how often patients with apnea resumed breathing spontaneously  of 1306 documented apnea events exceeding 15 seconds  54 patients   926 lasted 16 to 20 seconds  262 lasted 21 to 25 seconds  and 118 exceeded 25 seconds  of these episodes  75 3  were isolated and 14 9  were associated with pulse deceleration  4 4  with irregular transthoracic impedance  and 5 4  with bradycardia  event recording provided data supporting discontinuation of monitoring in 50 of 54 patients  36 spontaneously resumed breathing before the auditory alarm and 14 had a decreased incidence of apnea with maturation  follow up of 51 patients  three not located  showed that none had subsequent apparent life threatening events or sudden infant death syndrome  our results in these older infants and children  median age 6 7 months  provide substantiation that such patients with apnea of less than 20 seconds without bradycardia do not require continued monitoring  further  these data suggest that in selected older infants  longer isolated apnea may be well tolerated  however  hemoglobin saturation during sleep and the ability to resume breathing after the apnea alarm delay is prolonged should be verified  our patient population had a wide age range and heterogeneity of diagnoses  and was typically free of symptoms  so these results should not be extrapolated uncritically to premature infants  infants with chronic lung disease  and patients with symptomatic apnea  
class10	measurement of progressive cerebral ventriculomegaly in infants after grades iii and iv intraventricular hemorrhages  to develop guidelines that might help predict prospectively which infants with severe intraventricular hemorrhage  ivh  would require intervention  we obtained serial cranial sonograms to measure the rate of growth of cerebral ventricular volumes in 48 preterm infants with and without ivh  the infants were divided into three groups   1  those with no ivh  22 infants    2  those with ivh with acute ventricular dilation  13 infants   and  3  those with ivh with progressive ventricular dilation requiring intervention  13 infants   the decision to intervene because of progressive ventricular dilation was based on clinical criteria and the subjective assessment of increasing ventricular size on weekly cranial sonograms  the rate of cerebral ventricular volume growth in infants with ivh who needed intervention was greater  4 2     3 3 ml day  than that in infants without ivh  0 0     0 1 ml day  p less than 0 001  and in infants with ivh and acute ventricular dilation  0 0     0 2 ml day  p less than 0 001   using these data  we generated guidelines for predicting prospectively which infants with ivh and ventricular dilation will need intervention for posthemorrhagic hydrocephalus  the guidelines were then confirmed prospectively in 10 infants  
class10	dysmorphogenesis elicited by microinjected acetaminophen analogs and metabolites in rat embryos cultured in vitro  direct additions of acetaminophen  apap   3 5 dimethylacetaminophen  3 hydroxyacetaminophen or 3 methoxyacetaminophen to the medium of cultured embryos each produced an increased incidence of morphologically similar  abnormally open anterior neuropores  approximate concentrations required to produce an equal incidence were 0 5 mm  1 0 mm  0 1 mm and 0 75 mm  respectively  in contrast  2 6 dimethylacetaminophen and n acetyl p benzoquinoneimine failed to produce elevated incidences of abnormal neurulation unaccompanied by marked growth retardation  however  with intra amniotic microinjections  3 hydroxyacetaminophen and n acetyl p benzoquinoneimine were roughly equipotent for eliciting abnormal neurulation  whereas 3 methoxyacetaminophen required greater than 30 fold higher concentrations  this suggests that n acetyl p benzoquinoneimine does not readily transit the visceral yolk sac and would likely not be a major factor in apap elicited neural tube abnormalities unless generated in target tissues  the differential effects produced by two dimethylated  2 6 and 3 5  apap analogs further suggest that sulfhydryl oxidation is associated more closely than sulfhydryl conjugation with the neurulation defect  intra amniotic microinjections of large quantities  3500 ng  of 7 hydroxy 2 acetylaminofluorene  7 oh aaf  or apap failed to produce the specific neurulation defect  microinjections of 7 oh aaf into the exocoelomic cavity effected the characteristic abnormal neurulation  conversion by conceptal homogenates of 7 oh aaf was roughly 7  to 8 fold more rapid than conversion of apap to respective catechol metabolites  and specific activities in yolk sac tissues were greater than those in the embryo  rates of conceptal conversion to the quinoneimine were approximately 2  to 3 fold lower than catechol generation  
class10	importance of a neurologic evaluation in women with lower urinary tract dysfunction  the normal coordinated functions of the bladder and urethra are controlled by a set of central and peripheral reflex mechanisms  disruptions of these neuronal reflexes may produce abnormalities in the storage and expulsion of urine  electrophysiologic testing can be employed to complement other urodynamic tests used in the evaluation of these patients and also to document that abnormalities previously thought to be anatomic in origin in reality may be secondary to neurologic dysfunction  
class10	a practical approach to the painful bladder syndrome  the painful bladder syndrome  pbs  is a progressive and painful disease of the bladder that may lead to fibrosis  contracture and reduction of bladder capacity  the usual symptoms are urinary urgency  frequency  nocturia  chronic pelvic pain and lower abdominal pain upon filling of the bladder  a retrospective analysis was performed on 21 women with pbs between march 1987 and march 1988  the patients were treated weekly with a bladder pillar block  bladder distention and dimethyl sulfoxide instillation  symptomatic relief was observed in 80  of the patients so treated  the maximum bladder volume increased from 185 to 475 ml  p less than  01   the side effects were minimal  
class10	rheumatoid arthritis and comorbidity  data collected from 288 patients with rheumatoid arthritis  ra  indicated that 54  of respondents also reported other chronic conditions  and that 20  rated at least one of these other conditions as severe  both the frequency and severity of these comorbidities affected scores on measures of depressive symptoms  social connectedness and on the arthritis impact measurement scales  these findings suggest that the absence of controls for comorbidity may bias measures of functional status among patients with ra  
class10	an unusual manifestation of paget s disease of bone  spinal epidural hematoma presenting as acute cauda equina syndrome  neurologic sequelae of paget s disease of bone include involvement of the spinal cord or cauda equina due to mechanical compression by enlarged vertebrae  ischemia caused by a spinal artery  steal syndrome or neoplasm  we describe a patient with paget s disease of bone who presented with acute cauda equina syndrome due to a spinal epidural hematoma  clinicians need to recognize this entity since surgical intervention may result in a favorable outcome  
class10	acute central nervous system symptoms caused by ibuprofen in connective tissue disease  we describe 2 cases of acute encephalopathy in patients with connective tissue disease caused by small doses of ibuprofen  in addition to aseptic meningitis  both patients had altered mental status and focal neurologic signs  ophthalmoplegia in one and hemiparesis in the other  the spectrum of neurologic manifestations of ibuprofen hypersensitivity is reviewed  
class10	recurrent thoracic outlet syndrome  recurrent symptoms develop in 15  to 20  of patients undergoing either first rib resection or scalenectomy for thoracic outlet syndrome  over the past 22 years 134 operations for recurrence were performed in 97 patients  four operations were used  transaxillary first rib resection  26   supraclavicular first rib resection with neurolysis  15   scalenectomy with neurolysis  58   and brachial plexus neurolysis  35   complications included temporary plexus injury  0 7    temporary phrenic palsy  3 7    and permanent phrenic palsy  1 4    the combined primary success rate of all four operations for recurrence was 84  in the first 3 months  this fell to 59  at 1 to 2 years  50  at 3 to 5 years  and 41  at 10 to 15 years  no significant difference was found in results between the four operations used for recurrence  when recurrence was caused by trauma the results of reoperations were better than when recurrence was spontaneous  the primary success rates of three initial operations for thoracic outlet syndrome were compared to their secondary success rates  improved after reoperation   by use of life table methods  reoperation improved the 5  to 10 year success rate of transaxillary first rib resection from 69  to 86  and for scalenectomy from 69  to 84   reoperation is successful in most cases of recurrent thoracic outlet syndrome and better when recurrence is the result of a neck injury  
class10	the influence of neutralizing heparin after carotid endarterectomy on postoperative stroke and wound hematoma  the influence of neutralizing or not neutralizing heparin after carotid endarterectomy on postoperative stroke and wound hematoma is unknown  during the past 6 years some of the authors frequently gave protamine sulfate to neutralize heparin  whereas others did not unless a patch was used or wound hemostasis was not readily obtained  to determine the influence of protamine sulfate on stroke and wound hematoma the records of 697 patients having a carotid endarterectomy from january 1984 to september 1989 were reviewed  protamine sulfate was given to 328 patients  and 369 did not receive protamine sulfate  the incidence of stroke in the two groups was 1 8   n   6  and 2 7   n   10   respectively  and the difference was not significant  p   0 6019   excluding three strokes that could not be related to neutralizing or not neutralizing heparin  the difference remained insignificant  1 5  vs 2 2   p   0 7290   the incidence of wound hematoma was 1 8   n   6  in patients given protamine sulfate and 6 5   n   24  in patients not given protamine sulfate  and this difference was significant  p   0 0044   the difference remained significant when three hematomas not related to protamine sulfate were excluded  1 2  vs 6 2   p   0 0013   in patients not given protamine sulfate draining the wound lessened the incidence of wound hematoma  4 4  vs 8 6    but this difference was not statistically significant  p   0 1475   in patients given protamine sulfate the dose of protamine sulfate  15 to 45 mg vs 50 to 75 mg  had no statistically significant effect on the incidence of stroke  0 8  vs 2 0   p   0 6530  or wound hematoma  1 6  vs 1 0   p   1 000   
class10	duplex scanning of normal or minimally diseased carotid arteries  correlation with arteriography and clinical outcome  this study evaluated the role of duplex scanning in the management of patients with normal or minimally diseases carotid arteries  carotid duplex scans were interpreted according to previously established criteria and considered normal when pulsed doppler spectral waveforms showed laminar flow or only minor flow disturbances  normal flow patterns were noted by duplex scanning in 100 carotid bifurcations of 72 patients who also underwent carotid arteriography  neurologic symptoms  amaurosis fugax  transient ischemic attack  or stroke  were present in relation to 23 arteries and absent in relation to 77 arteries  on the 23 symptomatic sides arteriography was interpreted as normal in eight  1  to 15  stenosis in 14  and 16  to 40  stenosis in one  for the 77 asymptomatic sides  arteriography showed normal vessels in 15  1  to 15  stenosis in 43  and 16  to 40  stenosis in 19  one symptomatic patient was treated by carotid endarterectomy for an irregular 1  to 15  stenosis  none of the asymptomatic lesions were in the range of 80  to 99  stenosis  which would justify endarterectomy for asymptomatic disease  clinical follow up for a mean interval of 28 months on 20 of the 22 symptomatic patients not undergoing surgery revealed no strokes and transient recurrent symptoms in two patients  assuming that the single operation in this study was indicated  duplex scanning correctly identified lesions not requiring carotid endarterectomy in 96   22 23  of the symptomatic patients  a normal duplex scan also predicted a benign clinical outcome without operation  duplex scanning can reliably exclude surgically treatable carotid bifurcation lesions in asymptomatic patients  and endarterectomy is rarely indicated in symptomatic patients with normal duplex scan results  this study supports a nonoperative therapeutic approach for most patients with neurologic symptoms and a normal carotid duplex scan on the appropriate side  
class10	changes in quality of care for five diseases measured by implicit review  1981 to 1986 we measured quality of care before and after implementation of the prospective payment system  we developed a structured implicit review form and applied it to a sample of 1366 medicare patients with congestive heart failure  acute myocardial infarction  pneumonia  cerebrovascular accident  or hip fracture who were hospitalized in 1981 1982 or 1985 1986  very poor quality of care was associated with increased death rates 30 days after admission  17  with very good care died vs 30  with very poor care   the quality of medical care improved between 1981 1982 and 1985 1986  from 25  receiving poor or very poor care to 12    although more patients were judged to have been discharged too soon and in unstable condition  7  vs 4    except for discharge planning processes  the quality of hospital care has continued to improve for medicare patients despite  or because of  the introduction of the prospective payment system with its accompanying professional review organization review  
class10	prospective payment system and impairment at discharge  the  quicker and sicker  story revisited since the introduction of the prospective payment system  pps   anecdotal evidence has accumulated that patients are leaving the hospital  quicker and sicker   we developed valid measures of discharge impairment and measured these levels in a nationally representative sample of patients with one of five conditions prior to and following the pps implementation  instability at discharge  important clinical problems usually first occurring prior to discharge  predicted the likelihood of postdischarge deaths  at 90 days postdischarge  16  of patients discharged unstable were dead vs 10  of patients discharged stable  after the pps introduction  instability increased primarily among patients discharged home  prior to the pps  10  of patients discharged home were unstable  after the pps was implemented  15  were discharged unstable  a 43  relative change  efforts to monitor the effect of this increase in discharge instability on health should be implemented  
class10	acute sensorineural deafness in lassa fever a prospective audiometric evaluation of 69 hospitalized febrile patients in sierra leone  west africa  revealed a sensorineural hearing deficit  snhd  in 14  29   of 49 confirmed cases of lassa fever and in 0 of 20 febrile controls  an snhd was present in nine  17 6   of 51 people who had evidence of previous lassa virus infection  twenty six of 32 local residents who had previously sustained a sudden deafness had antibody titers to lassa virus of 16 or greater  compared with six of 32 matched controls  lassa fever is associated with an incidence of snhd  which considerably exceeds that previously reported with any other postnatally acquired infection  and accounts for a prevalence of virus related hearing impairment in the eastern province of sierra leone that is greater than that reported from anywhere else in the world  
class10	transcranial doppler ultrasonography  clinical applications in cerebrovascular disease  transcranial doppler ultrasonography was introduced in 1982 as a noninvasive procedure for assessment of the intracranial cerebral circulation  the lightweight and portable equipment used for transcranial doppler examination facilitates its use in the bedside assessment of critically ill hospitalized patients and outpatients  clinical applications include the diagnosis of vasospasm in patients with subarachnoid hemorrhage  assessment of intracranial collateral flow in patients with extracranial arterial occlusive disease  detection of intracranial arterial stenosis  identification of the feeding arteries of arteriovenous malformations and monitoring the hemodynamic effects of their treatment  confirmation of the clinical diagnosis of brain death  intensive care unit monitoring of brain injured patients  and intraoperative and postoperative monitoring of neurosurgical patients  transcranial doppler technology is also providing new insights into the pathophysiologic mechanisms of a variety of cerebrovascular conditions  clinicians will find transcranial doppler technology most helpful if they have a specific question about the status of the intracranial circulation  further investigations may expand the clinical and research utility of this technology  
class10	arterial responses during migraine headache  the superficial temporal artery has been thought to be the main focus of pain during migraine attacks  but its diameter has never been measured directly  the use of a new  high resolution ultrasound machine to measure arterial size in 25 migraine patients with unilateral head pain showed that the lumen was wider on the painful than on the non painful side during a migraine attack  the diameters of both radial arteries and the temporal artery on the non painful side were smaller during than between attacks  the generalised vasoconstriction was not shared by the temporal artery on the affected side  which suggests a local vasodilatory response  the findings suggest that cephalic arteries may play a role in migraine pathogenesis  
class10	evoked potentials in assessment and follow up of patients with wilson s disease  treatment of 9 patients with wilson s disease was prospectively studied with evoked potentials and magnetic resonance imaging  mri   oral penicillamine therapy led to a decrease in auditory brainstem  abp  and somatosensory  sep  conduction times in 6 and 4 neurologically symptomatic patients  respectively  abp and sep were normal in 3 other symptom free patients  mri showed cerebral lesions in 4 of 7 patients  quantified indices of brain atrophy were unaffected by treatment  abp and sep may reveal a reversible component of the disease that cannot be detected by mri  and may be a more sensitive measure of treatment efficacy  
class10	neurological sequelae of cerebral malaria in children  out of 604 gambian children admitted with falciparum malaria to one hospital between september and december  1988  308 had cerebral malaria and 203 were severely anaemic  haemoglobin less than 60 g l   14  of those with cerebral malaria died  as did 7 8  of those with severe anaemia  32  12   of children surviving cerebral malaria had residual neurological deficit  69 other children were admitted with clinical features strongly suggestive of cerebral malaria but with negative blood films  16 of these died and 3 had residual neurological deficits  the commonest sequelae of cerebral malaria were hemiplegia  23 cases   cortical blindness  11   aphasia  9   and ataxia  6   factors predisposing to sequelae included prolonged coma  protracted convulsions  severe anaemia  and a biphasic clinical course characterised by recovery of consciousness followed by recurrent convulsions and coma  at follow up 1 6 months later over half these children had made a full recovery  but a quarter were left with a major residual neurological deficit  cerebral malaria in childhood may be an important cause of neurological handicap in the tropics  
class10	effects of uvulopalatopharyngoplasty on sleep architecture and patterns of obstructed breathing  in this retrospective study  72 obstructive sleep apnea patients with polysomnograms taken before and after uvulopalatopharyngoplasty were evaluated  postoperatively  there was a significant improvement of sleep architecture and respiratory indices  in addition  a second group of 17 patients also had position recordings with their polysomnograms  time spent in supine and lateral sleep positions changed postoperatively  there was significant decrease of the apnea plus hypopnea index in the lateral position  this study indicates that there is significant improvement of sleep architecture and respiratory indices in the majority of patients after uvulopalatopharyngoplasty  particularly in the lateral sleep position  
class10	mitochondrial encephalomyopathies  the mitochondrial diseases present with great heterogeneity  they are often multisystemic and vary considerably in age at onset  distribution of weakness  severity  and course  only nonthyroidal hypermetabolism has a distinctive clinical presentation  therefore  attempts at classification have generated some controversy  this article discusses the general classification that takes into account genetic and biochemical features  which has resulted from the fast pace of biochemical and molecular genetic investigations  
class10	peroxisomal disorders  although peroxisomes were once considered a vestige  their importance in cellular metabolism is clearly established by the many inherited diseases that have been described in the past two decades  unfortunately there is no definitive treatment for the various disorders  but based on the recognition of the biochemical abnormalities  prenatal testing and appropriate genetic counseling can be provided  it is essential for clinicians to be aware of this group of diseases  as diagnosis and further study of these patients are essential in understanding the basic etiologic mechanisms underlying these complex groups of disorders  clearly  there is much to be learned about the relationship between biochemical abnormalities and the phenotypic variability of the peroxisomal disorders  
class10	the molecular biology of occlusive stroke in childhood  it is very likely that many of the same factors involved in occlusive disease in the adult are operative in the child  the major difference may be in the factors that damage endothelium in these two age groups and thereby initiate this catastrophe  atherosclerosis versus  other  causes of endothelial changes   our task in this next decade is the rational exploration of the effects of endothelium mediated kinins  endothelial secretory products  angiospasm  platelet aggregration  prostaglandins  and lipoproteins on pediatric stroke  
class10	bacterial meningitis  an update  antibiotics and improvements in supportive care have greatly reduced the mortality from bacterial meningitis  nevertheless  the incidence of neurodevelopmental sequelae remains unacceptably high  ampicillin and chloramphenicol remain the standard for antimicrobial therapy against which other agents must be compared  a number of adjunct therapies are being investigated for their possible effectiveness in reducing hearing loss and other neurologic effects of this disease  there continues to be a need for carefully performed follow up studies to assess any possible benefit of these agents  a significant percentage of children surviving an episode of bacterial meningitis have obvious or subtle neurodevelopmental deficits  the role of the pediatric neurologist should not end with management of acute problems such as seizures but should be expanded to aid in close developmental monitoring of these high risk children  
class10	the classification of childhood seizures and epilepsy syndromes  the classification of seizures and the epileptic syndromes is particularly relevant to those who treat children  as most syndromes are age related  with onset between the neonatal and adolescent periods  whereas seizures are characterized by ictal behavior and eeg findings  epilepsy syndromes are defined by seizure type  etiology  age of onset  natural history  possible genetic factors  and prognosis  limitations exist  but attempts to use these classifications typically lead to a better understanding of the patient and allow for more precise evaluation and treatment  
class10	infantile spasms  infantile spasms are a seizure disorder in young infants with diverse etiologies  suggesting that they arise from any disturbance of central nervous system function during susceptible periods of development  the prognosis for normal intellectual and neurologic development parallels that of the underlying etiology  early and appropriate treatment with acth may lead to seizure control in a majority of patients  the treating physician must anticipate the side effects of this modality  
class10	status epilepticus in infancy and childhood  status epilepticus implies a prolonged seizure or recurrent seizures with persistent decreased consciousness  lasting at least 30 minutes  both convulsive and nonconvulsive forms exist  either of which may lead to death or additional neurologic deficit  therapy involves careful supportive care plus some combination of benzodiazepines  phenytoin  or phenobarbital  the outcome depends first on the etiology and second on the rapidity with which seizures are controlled  
class10	rett syndrome and the autistic disorders  rett syndrome is a disorder noted to date only in females and characterized by a pervasive developmental disability following apparently normal early infancy  in addition to gait difficulties  stereotypic hand movements  and loss of communication and purposeful hand skills  autistic like behavior is an early sign that often results in misdiagnosis  despite these significant clinical abnormalities  neuropathologic features are modest  and no consistent laboratory abnormality or diagnostic marker has been identified  the current status of research in rs is considered within the context of autism and other disorders in which autistic features may occur  such as the fragile x syndrome  the concept of autism as neurobiologically based behavior is developed  as such  autism is regarded as an umbrella category containing an ever expanding list of specific disorders  
class10	tourette syndrome  recent advances  clinical and genetic studies have allowed the limits of tourette syndrome to be broadened  there is now strong evidence that chronic motor tics and tourette syndrome are different manifestations of an autosomal dominant gene with high penetrance  a genetic link with obsessive compulsive disorder also appears to have been established  up to 10  of cases of tourette syndrome may be nongenetic phenocopies  however  there is also an association between tourette syndrome and attention deficit hyperactivity disorder  this complicates therapy  as psychostimulant drugs may precipitate or exacerbate tics in some individuals  a high proportion of patients with tourette syndrome also has neuropsychological deficits and learning disabilities  the pathophysiology is incompletely understood  the best supported hypothesis is that there is dopamine receptor supersensitivity  although there are strong suggestions of abnormalities in serotonin metabolism  the possibility of abnormalities in neuropeptide systems is being explored  treatment of tics relies primarily on neuroleptics with dopamine receptor blocking activity  clonidine may be useful in some patients  especially those with behavior problems  obsessive compulsive symptoms can be treated using appropriate pharmacologic agents  the treatment of attention deficit disorder in patients with tics should begin with behavioral strategies  clonidine can be tried as the first line drug  and psychostimulants should be used only if necessary and with great caution  in rare instances it may be necessary to combine a psychostimulant and a neuroleptic  
class10	the floppy infant  recent advances in the understanding of disorders affecting the neuromuscular junction  the clinician is often asked to evaluate the floppy infant  numerous conditions that cause hypotonia in infancy are briefly outlined in this article  these conditions may affect the brain  spinal cord  or motor unit  several disorders of neuromuscular transmission  including four distinct and recently described congenital myasthenic syndromes and infant botulism  are discussed thereafter  
class10	rehabilitation of the pediatric patient with a neuromuscular disease  a rehabilitation program for a patient with a neuromuscular disease can be developed only after an accurate diagnosis has been established  the diagnosis and its ramifications should suggest a natural course of disease which  it is hoped  can be improved upon with a rational and realistic program  the program is best developed by an interdisciplinary team  including a pediatric neurologist  who should have the greatest understanding of the patient s problem and should ultimately be responsible for the implementation and monitoring of the program  a child with cerebral palsy commonly requires the services of physical and occupational therapists as well as knowledgeable orthopedists  is the program appropriate  does it consider the child s potential as well as his limitations  a child with a traumatic brain injury requires  in addition to the above  psychological intervention and an intensive educational program  will the child and family need help from mental health professionals  a child with a motor unit disease such as duchenne s muscular dystrophy requires  in addition to the above services  a  philosophy  of care  will the child ever ambulate independently  if so  at what cost  what will be necessary for the child to reach this potential  including items such as orthoses and adaptive equipment  will respirator care become necessary  what issues must be addressed for this form of care to be established  there is no one program for all children  the programs must be individualized to meet the needs of the patient and the family  this point cannot be overemphasized  
class10	magnetic resonance in pediatric and adolescent neuroimaging  with improved availability and a practical understanding of the principles of utilization  mri will continue to replace ct and us in pediatric neuroimaging  just as it has impacted upon the more invasive modalities  in general  us remains the procedure of choice for screening of fetal and infant cns abnormalities  and ct continues as the principal screening modality beyond infancy and especially for acute  emergent presentations  mri has now emerged as a primary option for screening as well as for more definitive assessment of many intracranial and most intraspinal conditions  
class10	the use of ultrasound in evaluating neurologic diseases of childhood  real time cranial sonography  intracranial doppler  and neuromuscular sonography are the sonographic techniques that are applicable to the neurologic evaluation of infants and children  although limited by age  specificity  and operator skill and experience  the advantages of real time cranial and intracranial doppler sonography make them useful techniques in the evaluation of the young infant  particularly in the serial assessment of ventricular size and in the study of the critically ill infant  the use of neuromuscular sonography in the assessment of the floppy infant and in the guidance of biopsy makes this an increasingly valuable tool  
class10	coffee  caffeine  and cardiovascular disease in men background  for many years  an association between coffee consumption and the risk of coronary heart disease has been suspected  although based on small numbers of end points  a prospective study has suggested a particularly strong association between recent coffee drinking and the incidence of cardiovascular disease  methods  we examined prospectively the relation of coffee consumption with the risk of myocardial infarction  need for coronary artery bypass grafting or angioplasty  and risk of stroke in a cohort of 45 589 u s  men who were 40 to 75 years old in 1986 and who had no history of cardiovascular disease  results  during two years of follow up observation  221 participants had a nonfatal myocardial infarction or died of coronary heart disease  136 underwent coronary artery surgery or angioplasty  and 54 had a stroke  total coffee consumption was not associated with an increased risk of coronary heart disease or stroke  the age adjusted relative risk for all cardiovascular disease among participants who drank four or more cups of coffee per day was 1 04  95 percent confidence intervals  0 74 to 1 46   increasing levels of consumption of caffeinated coffee were not associated with higher risks of cardiovascular disease  higher consumption of decaffeinated coffee  however  was associated with a marginally significant increase in the risk of coronary heart disease  relative risk  1 63  95 percent confidence interval  1 02 to 2 60   finally  we observed no pattern of increased risk across the subgroups of participants with increasing intakes of caffeine from all sources  adjustment for major cardiovascular risk indicators  dietary intake of fats  and cholesterol intake did not materially alter these associations  conclusions  these findings do not support the hypothesis that coffee or caffeine consumption increases the risk of coronary heart disease or stroke  
class10	dwarf locus mutants lacking three pituitary cell types result from mutations in the pou domain gene pit 1  mutations at the mouse dwarf locus  dw  interrupt the normal development of the anterior pituitary gland  resulting in the loss of expression of growth hormone  prolactin and thyroid stimulating hormone  and hypoplasia of their respective cell types  disruptions in the gene encoding the pou domain transcription factor  pit 1  occur in both characterized alleles of the dwarf locus  the data indicate that pit 1 is necessary for the specification of the phenotype of three cell types in the anterior pituitary  and directly link a transcription factor to commitment and progression events in mammalian organogenesis  
class10	pre trigeminal neuralgia  eighteen patients who subsequently developed typical trigeminal neuralgia experienced a prodromal pain termed  pre trigeminal neuralgia   these patients described their prodromal pain as a toothache or sinusitis like pain lasting up to several hours  sometimes triggered by jaw movements or by drinking hot or cold liquids  typical trigeminal neuralgia developed a few days to 12 years later  and in all cases affected the same division of the trigeminal nerve  six additional patients experiencing what appeared to be pre trigeminal neuralgia became pain free when taking carbamazepine or baclofen  recognition of pretrigeminal neuralgia makes it possible to relieve the pain with appropriate medications and avoid unnecessary irreversible dental procedures  
class10	hemiplegia in posterior cerebral artery occlusion  we report 4 patients with hemiplegia due to a posterior cerebral artery occlusion  associated clinical signs were aphasia  alexia or a neglect syndrome  hemianopia  and hemisensory loss  hemiplegia was due to infarction in the lateral midbrain  the level of the occlusion in the posterior cerebral artery may be located distal to the junction with the posterior communicating artery  
class10	capsular genu syndrome  we report 5 patients with unilateral infarct and 1 with hemorrhage limited to the genu of the internal capsule  the most prominent finding was contralateral facial and lingual hemiparesis with dysarthria  three patients also showed unilateral mastication palatal pharyngeal weakness  and 1 had unilateral vocal cord paresis  mild limb involvement was limited to hand weakness in 4 patients  our findings suggest that the majority of motor corticopontine and corticocobulbar fibers are located in the genu of the internal capsule  the faciolingual syndrome and its variants are highly suggestive of capsular genu stroke  
class10	tonic contraversive ocular tilt reaction due to unilateral meso diencephalic lesion  we studied 4 patients with tonic contraversive ocular tilt reactions due to unilateral  paramedian  mesodiencephalic lesions  this is in contrast to the only 2 previously reported patients with ocular tilt reactions due to unilateral mesodiencephalic lesions  each of whom had a paroxysmal ipsiversive ocular tilt reaction  this new finding is considered in the context of previous clinical and experimental data on the various types of ocular tilt reactions that follow stimulation or destruction of the peripheral and central vestibular system  otolithic inputs to the interstitial nucleus of cajal from the contralateral vestibular nucleus and motor outputs from the interstitial nucleus of cajal to cervical and ocular motoneurons could be involved in the ocular tilt reaction  we propose that in patients with unilateral meso diencephalic lesions  a tonic contraversive ocular tilt reaction could be due to persistently decreased resting activity of ipsilateral interstitial nucleus neurons  whereas a paroxysmal ipsiversive ocular tilt reaction could be due to transiently increased activity of the same interstitial nucleus neurons  cases of ocular tilt reaction due to unilateral meso diencephalic lesion point to the existence of a crossed graviceptive pathway between the vestibular nucleus and the contralateral interstitial nucleus of cajal  
class10	acute naming deficits following dominant temporal lobectomy  prediction by age at 1st risk for seizures  age at 1st risk for seizures may predict anomia following dominant anterior temporal lobectomy  we assessed confrontation naming before and 2 to 3 weeks after surgery in 45 right handed patients grouped by side of focus and presence or absence of early  less than or equal to 5 years  risk factors  after left lobectomy  6 of 10  60   patients with no early risks demonstrated significant decline  greater than or equal to 25   in naming  but none of the patients with early risks showed this decline  after right lobectomy  there was no change  cerebral representation of naming may be atypical in patients with early risks  
class10	an estimate of the incidence of dementia in idiopathic parkinson s disease  the proportion of patients with idiopathic parkinson s disease  pd  who are considered demented ranges from 10  to 15   because dementia may affect survival in pd  the incidence rate of dementia  rather than proportion  would be a more accurate measure of disease frequency  we previously estimated the proportion of patients with pd and dementia to be 10 9  from the records of a cohort with the idiopathic form of pd in a major medical center  we reviewed the clinical records of this cohort after 4 years and 9 months to estimate the incidence rate of dementia  we identified 65 new cases of dementia from the 249 patient records available  using the number of person years of follow up for each case as the denominator  we estimated the overall incidence rate to be 69 per 1 000 person years of observation  the mean age of this cohort was 71 4 years  the cumulative incidence of dementia increased with age  by 85 years of age  over 65  of the surviving members of the cohort were demented  the age specific incidence rates for dementia in this cohort of pd were significantly greater than for a similarly aged cohort of healthy elderly people  the age specific standard morbidity ratios indicated that  compared with people of similar ages  patients with pd have the highest increase in risk for dementia between ages 65 and 75  
class10	antemortem diagnosis of diffuse lewy body disease  using the presence of widespread cortical lewy bodies  lb  as the pathologic criteria of diffuse lewy body disease  dlbd   we describe serial neurologic and mental status examinations in 6 patients with dlbd  3 patients with alzheimer s disease  ad   and 1 patient with parkinson s disease  pd   the 6 patients with dlbd included 3 with neocortical neurofibrillary tangles  nft  consistent with coincident ad  most patients with dlbd had gait impairment concurrent with mild to moderate dementia  abnormalities of tone or resting tremor were also prominent early symptoms in the subjects with dlbd  but not ad  patients with dlbd frequently had abnormal eegs with background posterior slowing and a frontally dominant burst pattern at the time of mild to moderate dementia  agitation  hallucinations  and delusions were frequent early symptoms in dlbd patients  patients with dlbd without concomitant ad had numerous alz 50 negative cortical plaques  patients with dlbd have a distinct clinical syndrome that can be differentiated from ad  pathologic features  including the absence of alz 50 immunoreactivity  also differentiate dlbd from ad  
class10	variable expression of parkinson s disease  a base line analysis of the datatop cohort  the parkinson study group  the datatop database  which includes clinical information on 800 patients with early untreated parkinson s disease  pd   is well suited to explore clinical heterogeneity in pd  patients with early onset pd  less than or equal to 40 years  n   33  reached the same level of disability as the late onset pd  greater than or equal to 70 years  n   85  group at a significantly slower rate  2 9 vs  1 7 years   early onset pd patients functioned cognitively better than late onset pd patients  bradykinesia  and postural instability and gait difficulty  pigd   were more common at onset in patients with a rapid rate of disease progression   malignant pd   duration of symptoms less than 1 year and hoehn yahr stage of 2 5  n   11  as compared with those with a relatively slow rate of progression   benign pd   duration of symptoms greater than 4 years  n   65   comparisons of tremor dominant pd  mean tremor score mean pigd score less than or equal to 1 5  n   441  with the pigd dominant type  mean tremor score mean pigd score greater than or equal to 1 0  n   233  provided support for the existence of clinical subtypes  the pigd group reported significantly greater subjective intellectual  motor  and occupational impairment than the tremor group  stage ii patients had higher depression scores than stage i patients  among the patients participating in the datatop  older age at onset with bradykinesia  or with the pigd form of pd  is associated with more functional disability than when the symptoms are dominated by tremor or begin at a younger age  
class10	chinese white differences in the distribution of occlusive cerebrovascular disease  the distribution of cerebrovascular lesions is affected by race  blacks and japanese have more intracranial occlusive cerebrovascular disease  while whites have more extracranial disease  despite a high incidence of stroke in china  there are few formal studies of the distribution of vascular occlusive disease in chinese populations  we compared clinical and angiographic features of 24 white and 24 chinese patients with symptomatic occlusive cerebrovascular disease  in symptomatic vascular territories  whites had more severe  greater than or equal to 50  stenosis  extracranial lesions  while chinese had more severe intracranial lesions  when we counted mild and severe lesions in a symptomatic territory  whites had more extracranial lesions while chinese had more intracranial lesions  when we combined symptomatic and asymptomatic territories  whites had more extracranial lesions  while chinese had more intracranial lesions  white patients reported more transient ischemic attacks  the distribution of lesions  however  was not explained by differences in incidence of transient ischemia  hypertension  diabetes  hypercholesterolemia  or ischemic heart disease between the groups  the preponderance of intracranial vascular lesions in chinese patients is similar to that seen in blacks and japanese  racial differences in the occurrence of extracranial and intracranial lesions raise the possibility of a different underlying pathophysiology for the 2 locations  
class10	abnormal pulsatile secretion of luteinizing hormone in men with epilepsy  relationship to laterality and nature of paroxysmal discharges  we compared the pulsatile secretion of luteinizing hormone  lh  between 13 men with clinically and electrographically documented temporal lobe seizures and 8 age matched controls  serum for lh measurement was drawn every 15 minutes during 8 hours of eeg telemetry in both groups  the 2 groups did not differ significantly in average mean baseline lh secretion  total lh secretion  or average pulse amplitude  the group with seizures  however  showed a significantly greater  p less than 0 05  variability of baseline lh secretion and pulse frequency  among the men with unilateral paroxysmal eeg findings  pulse frequency was significantly greater  p   0 05  with right epileptiform discharges or left slowing  6 4     0 4  than with left epileptiform discharges or right slowing  3 0     1 3   the relationship of pulse frequency to the nature and laterality of paroxysmal discharges makes it unlikely that endocrine abnormalities can be attributed to medication alone and strengthens the notion that temporal lobe epileptiform discharges may disrupt hypothalamic regulation of pituitary secretion  
class10	dystonia in parkinson s disease  multiple system atrophy  and progressive supranuclear palsy  adult onset dystonia parkinsonism is a syndrome in search of a pathology  we therefore reviewed the literature on dystonic manifestations in autopsy proven cases of multiple system atrophy  msa   progressive supranuclear palsy  psp   and idiopathic parkinson s disease  pd   only 6 of 140 autopsy reports of msa remarked on the presence of dystonia in life  but personal observations suggest prominent antecollis may develop at some stage in up to 1 2 of sufferers  similarly  very few  15 118  clinicopathologic observations on psp included convincing dystonic manifestations  in contrast to some clinical reports where blepharospasm and early limb dystonia were prominent  virtually any form of focal and segmental dystonia may sometimes occur with clinically diagnosed pd  with occasional descriptions of hemidystonia hemiparkinsonism  however  there is pathologic confirmation of this diagnosis in only 1 case  with many patients thought clinically to have pd proving pathologically to have another cause for their parkinsonism  the true frequency and the range of dystonic manifestations acceptable in pd remain unknown  
class10	neuroexcitatory plasma amino acids are elevated in migraine  to investigate the role of glutamic  glu  and aspartic acid  asp  in migraine  we measured the plasma amino acids in migraine patients with and without aura  between and during attacks  and compared the profiles with the plasma amino acid profiles of tension headache patients and healthy controls  between attacks  migraineurs  notably with aura  had substantially higher plasma glu and asp levels than did controls and tension headache patients  in addition  patients with migraine without aura showed low plasma histidine levels  during migraine attacks  glu  and to a lesser extent asp  levels were even further increased  the results suggest a defective cellular reuptake mechanism for glu and asp in migraineurs  and we hypothesize a similar defect at the neuronal glial cell level  predisposing the brain of migraineurs to develop spreading depression  
class10	borderzone hemodynamics in cerebrovascular disease  to investigate the possible existence of chronic selective hemodynamic impairment in the arterial borderzone regions of the brain  we used positron emission tomography  pet  to measure regional mean vascular transit time  rt  equal to the ratio of regional cerebral blood volume to cerebral blood flow  and regional oxygen extraction fraction  roef  in 32 patients with either severe internal carotid artery stenosis or occlusion and 11 normal controls  twenty four of the patients had had tias or amaurosis fugax from 1 to 60 days before pet  all had normal brain ct  we used a stereotactic localization method to locate the anterior and posterior borderzone regions of the middle cerebral artery  mca  territory  we then calculated ratios of each borderzone to the ipsilateral mca territory for both rt and roef  there was no significant difference from control ratios in any patient subgroup including those with greater than or equal to 75  stenosis or occlusion  those with or without contralateral greater than or equal to 50  stenosis  or those with abnormal hemodynamics in the mca territory  we therefore found no evidence for selective borderzone hemodynamic impairment in this group of patients with severe carotid artery disease  
class10	fresnel prisms improve visual perception in stroke patients with homonymous hemianopia or unilateral visual neglect  we randomly assigned 39 patients with stroke and homonymous hemianopia or unilateral visual neglect to treatment with 15 diopter plastic press on fresnel prisms  n   18  or to serve as controls  n   21   baseline evaluations of visual perception and activities of daily living  adl  function were similar for both groups  after 4 weeks  the prism treated group performed significantly better than controls on the following   1  motor free visual perception test   2  line bisection task   3  line cancellation task   4  harrington flocks visual field screener  and  5  tangent screen examination  there was no significant difference in barthel adl assessment at 4 weeks  thus  treatment with 15 diopter fresnel prisms improves visual perception test scores but not adl function in stroke patients with homonymous hemianopia or unilateral visual neglect  
class10	comparison of algorithms of testing for use in automated evaluation of sensation  estimates of vibratory detection threshold may be used to detect  characterize  and follow the course of sensory abnormality in neurologic disease  the approach is especially useful in epidemiologic and controlled clinical trials  we studied which algorithm of testing and finding threshold should be used in automatic systems by comparing among algorithms and stimulus conditions for the index finger of healthy subjects and for the great toe of patients with mild neuropathy  appearance thresholds obtained by linear ramps increasing at a rate less than 4 15 microns sec provided accurate and repeatable thresholds compared with thresholds obtained by forced choice testing  these rates would be acceptable if only sensitive sites were studied  but they were too slow for use in automatic testing of insensitive parts  appearance thresholds obtained by fast linear rates  4 15 or 16 6 microns sec  overestimated threshold  especially for sensitive parts  use of the mean of appearance and disappearance thresholds  with the stimulus increasing exponentially at rates of 0 5 or 1 0 just noticeable difference  jnd  units per second  and interspersion of null stimuli  bekesy with null stimuli  provided accurate  repeatable  and fast estimates of threshold for sensitive parts  despite the good performance of bekesy testing  we prefer forced choice for evaluation of the sensation of patients with neuropathy  
class10	gadolinium mri in acute transverse myelopathy  a patient with acute transverse myelopathy  atm  had serial magnetic resonance imaging  mri  studies before and after administration of gadolinium  gd dtpa   gd dtpa mri was useful in estimating the pathologic extent and residual deficit expected in atm  
class10	right left disorientation in dementia of the alzheimer type  we demonstrated that right left orientation  r l o  on a confronting subject is more impaired in patients with dementia of the alzheimer type than in patients with multi infarct dementia of comparable degree of dementia  the impairment in r l o is independent of aphasia and spatial disorientation  
class10	effect of plasmapheresis on serum and csf autoantibody levels in cns paraneoplastic syndromes  we compared the effect of plasmapheresis on antineuronal autoantibody titers in the serum and csf of 3 patients with cns paraneoplastic syndromes  plasmapheresis reduced the serum autoantibody titer to 20  of the initial levels in the 3 patients  but the csf autoantibody titer decreased only in the patient with severe damage of the blood brain barrier  
class10	aggravation of human and experimental myasthenia gravis by contrast media  after observing a 72 year old myasthenic patient develop an acute myasthenic exacerbation following the administration of routine diagnostic iv contrast material  an observation rarely described in the literature  we used the experimental autoimmune myasthenia gravis model in rabbits injected with a contrast agent to simulate the situation  there was significant worsening of the decremental response to 3 hz repetitive nerve stimulation from 40     29  to 55     27  following the iv administration of contrast agent at doses similar to those used in humans  iv calcium partially reversed this aggravation  caution is merited when myasthenic patients are administered contrast media  
class10	dopamine beta hydroxylase activity in cerebrospinal fluid of idiopathic torsion dystonia  since a postmortem biochemical study and a genetic linkage study of idiopathic torsion dystonia suggested possible involvement of dopamine beta hydroxylase  dbh   we determined csf dbh activities of jewish and non jewish patients with childhood onset idiopathic torsion dystonia and found no differences from a control population  
class10	inconsistent response to divalproex sodium in hemichorea hemiballism  we report 6 patients with hemichorea hemiballism of vascular origin who were treated with divalproex sodium  depakote   four of 6 responded initially  marked improvement was seen in 2 patients only and in 1 of these hemiballism recurred despite continuing therapy  divalproex sodium is not uniformly effective in the treatment of hemichorea hemiballism  
class10	oxidation reactions in parkinson s disease  free radicals generated from oxidation reactions may contribute to the pathogenesis of parkinson s disease  pd   free radicals are capable of reacting almost instantaneously with membrane lipids and causing lipid peroxidation  membrane injury  and cell death  dopamine is metabolized by oxidation reactions capable of generating free radicals  recent evidence indicates that the substantia nigra of patients with pd contains increased iron  which enhances oxidation  and decreased glutathione  which protects against the formation of free radicals  further  the end products of lipid peroxidation are increased in the substantia nigra of patients with pd  supporting the notions that free radicals are being generated and may contribute to dopamine neuronal death  this hypothesis suggests that antioxidant therapies may slow the rate of progression of pd and raises concern that metabolites of levodopa therapy may accelerate the rate of neuronal degeneration  
class10	the modified superior based pharyngeal flap  part iii  a retrospective study  a retrospective study of 31 patients who had diagnosed velopharyngeal incompetence and were surgically managed with the modified superior based pharyngeal flap was completed  the following were analyzed  age at time of operation  gender  physical status  diagnostic protocol  length of operation  length of total surgery  and length of superior based pharyngeal flap  length of postoperative hospital stay  length of total hospital stay  length of follow up  speech results  complications  patient care  and medication  the result showed that the optimal timing for correction of velopharyngeal incompetence was between 3 and 6 years of age  the mean length of total hospital stay was 2 7 days  postoperative complications were minimal  and speech results were generally good  
class10	a unique indexing splint for use in combined le fort and nasal injuries to avoid tracheostomy  midface fractures with associated displaced and or comminuted nasal fractures can require tracheostomy for a general anesthetic airway if these fractures are to be reduced simultaneously  we describe a unique indexing splint that allows oral intubation yet also allows simultaneous reduction of midface and nasal fractures under one anesthetic  furthermore  tracheostomy with its potential complications is avoided  the case report illustrates the technique  and alternative treatments for these injuries are discussed  
class10	patient compliance  a factor in facial trauma repair  the clinical records of 25 consecutive patients who were treated for facial trauma were reviewed and analyzed to ascertain what effect patient cooperation had on the outcome of facial fracture repair  the study was designed to establish the incidence of complications and to discover what factors contributed to untoward sequela in such patients  overall  15 patients  60   were noncompliant in one or more aspects of their care  six patients  24   had significant postoperative complications associated with their facial injuries  four of these patients were not fully cooperative  
class10	febrile status epilepticus as part of a study of status epilepticus in children  maytal j  shinnar s  moshe sl  alvarez la  pediatrics  1989  83 323 331   44 children with febrile convulsions lasting more than 30 minutes were followed for a mean of 28 months  range 4 to 72   thirty children were followed prospectively  children with prior afebrile seizures or evidence of acute central nervous system infection were excluded  nine  20   children had prior neurological deficits  the duration of the febrile seizure was 0 5 to 1 hour in 41 cases  85    1 to 2 hours in 5  10    and greater than 2 hours in 2 children  5    no child died or developed new neurological deficits following the seizures  the risk of recurrent seizures was increased  but only in the group with prior neurological abnormality  six  66   of these children had subsequent febrile seizures compared with 12  34   of the normal children  p    08   three  33   had recurrent febrile status epilepticus compared with only 1  3   normal child  p    023   the 2 children in the prospective arm of the study with recurrent febrile status epilepticus were both neurologically abnormal  p    035   all 3 of the children who subsequently had afebrile seizures  2 prospective  were neurologically abnormal  p    006 overall  p    035 for prospective only   it is concluded that the occurrence of febrile status epilepticus in a neurologically impaired child is a risk factor for subsequent febrile as well as afebrile seizures  the occurrence of febrile status epilepticus in an otherwise normal child does not significantly increase the risk for subsequent febrile  brief or prolonged  or afebrile seizures in the first few years following the episode  
class10	bacterial or viral meningitis  measuring lactate in csf can help you know quickly  measurement of cerebrospinal fluid  csf  lactate is a useful test when properly applied to the appropriate clinical situation and can offer information other csf parameters cannot provide  except for gram s stain of csf  lactate level is the most important csf parameter in the early differentiation of viral  aseptic  and bacterial purulent meningitis  
class10	understanding dizziness  how to decipher this nonspecific symptom  dizziness is a common but often nonspecific symptom  through careful history taking and physical examination  primary care physicians can usually determine the type of sensation  vertigo or light headedness  and its source  although most causes of dizziness are benign  disorders of the central nervous system tend to be ominous and require immediate referral to a specialist  
class10	levels of mrna for a putative kainate receptor are affected by seizures  in situ hybridization and rna blot hybridization techniques were used  i  to examine the regional distribution of mrna for a putative kainate receptor in adult rat brain and ii  to test the possibility that seizures affect expression of the receptor gene  the highest densities of hybridization were distributed within hippocampal pyramidal and granule cells  medial habenula  purkinje cells and the molecular layer of cerebellum  and olfactory bulb  recurrent limbic seizures caused a massive  delayed  and reversible reduction in levels of the kainate receptor mrna in dentate gyrus  lesser decreases were found in pyramidal cell fields of hippocampus and superficial cortex  these findings provide evidence that unusual patterns of physiological activity can alter genomic expression for a subclass of glutamate receptors in brain  
class10	immunodominant regions for t helper cell sensitization on the human nicotinic receptor alpha subunit in myasthenia gravis  in myasthenia gravis an autoimmune response against the nicotinic acetylcholine receptor  achr  occurs  the alpha subunit of the achr contains both the epitope s  that dominates the antibody response  main immunogenic region  and epitopes involved in t helper cell sensitization  in this study  overlapping synthetic peptides corresponding to the complete achr alpha subunit sequence were used to propagate polyclonal achr specific t helper cell lines from four myasthenic patients of different hla types  response of the t helper lines to the individual peptides was studied  four immunodominant sequence segments were identified  i e   residues 48 67  101 120  304 322  and 419 437  these regions did not include residues known to form the main immunogenic region or the cholinergic binding site  and they frequently contained sequence motifs that have been proposed to be related to t epitope formation  
class10	concurrent and construct validity of the pediatric evaluation of disability inventory  the purpose of this study was to determine the validity of the development edition  pilot version  of the pediatric evaluation of disability inventory  pedi  in groups of disabled and nondisabled children  the pedi is a new functional assessment instrument for the evaluation of disabled children aged 6 months to 7 years  the pedi has been developed to identify functional status and change along three dimensions  1  functional skill level  2  caregiver assistance  and 3  modifications or adaptive equipment used  the pedis were administered as a parental report questionnaire  and the results were compared with data obtained by the battelle developmental inventory screening test  bdist   the bdist is a standardized assessment with developmental and adaptive content  subjects were 20 children between the ages of 2 and 8 years with arthritic conditions and spina bifida and 20 nondisabled children matched for age and sex  all subjects  scores on the bdist cognitive domain were no greater than 1 50 standard deviations below the mean for their age group  concurrent validity was supported by moderately high pearson product moment correlations between bdist and pedi summary scores  r    70  80   construct validity was supported by significant differences between the disabled and nondisabled groups  pedi scores and by discriminant analysis identifying the pedi scores as better group discriminators than the bdist scores  results validate the developmental edition of the pedi and support the further development and standardization of the final version  use of the pedi in clinical pediatric physical therapy practice is discussed  
class10	effects of neuro developmental treatment and orthoses on knee flexion during gait  a single subject design  the interactive effects of neuro developmental treatment and inhibitive ankle height orthoses on gait were examined via a single subject research design  knee flexion during gait at initial contact  mid stance  heel off  and mid swing were measured in a 2 year old girl with diplegia by use of a goniometer and freeze frame videography  during the treatment and treatment orthoses phases  a decrease in excessive knee flexion was noted  changes in trend over time were greater in the 3 week treatment phase than in the 3 week treatment orthoses phase  changes in level at the initiation of the treatment orthoses phase were greater than in the treatment phase  the described neuro developmental treatment activities were conducted correctly 92  of the time according to an independent observer  the interrater reliability of goniometric data measured by videography was  93 using intraclass correlation coefficients  the results of this study suggest that both methods of treatment can be used to decrease excessive knee flexion during gait in a child with diplegia  
class10	conditioning of the spinal stretch reflex  implications for rehabilitation  the purpose of this article is to describe a new technique that can potentially be applied to patients with hyperactive spinal stretch reflexes  ssrs   the progression of clinical research from conditioning of individual muscles or muscle groups  electromyographic biofeedback  to conditioning ssrs is explained  research data from subhuman primates in addition to the first human experiments are reviewed  potential applications of ssr conditioning are discussed  as are the issues requiring further delineation and research before the specificity of a training effect can be ascertained  
class10	a clinicopathological study of the paraneoplastic neuromuscular syndromes associated with lung cancer  the highest incidence of remote neuromuscular disorders in cancer has previously been reported in lung carcinoma  the clinical incidence of neuromuscular disorder was estimated and correlated with muscle histology and the histological type of lung tumour in 100 patients with lung carcinoma who were studied prospectively  thirty five patients had small cell carcinoma and 65 patients non small cell lung cancer  clinically  33 patients had a polymyopathy  of whom 18 had a cachectic myopathy and 15 had a proximal myopathy  two patients had lambert eaton myasthenic syndrome  one presented with dermatomyositis and one had evidence of ectopic acth production   cachexia was more common in non small cell cancer  proximal myopathy was more common in small cell cancer  ninety nine patients had abnormal muscle histology  74 had type ii atrophy  12 had type i and ii atrophy  one had type i atrophy and 12 had necrosis  the majority of patients were affected sub clinically and the clinical entities of cachectic and proximal myopathy did not correspond to previous pathological classifications  atrophy was not related to the duration of tumour symptoms  ageing  clinical type of myopathy or histological type of lung tumour  and was statistically different from that seen in controls  qualitatively  the presence of weight loss  muscle wasting and metastatic disease were not factors in the development of atrophy  similarly  necrosis was not related to the type of lung tumour  the presence of metastases  ageing  weight loss  muscle wasting  duration of tumour symptoms or the clinical form of myopathy  this study demonstrates that lung carcinoma has a direct effect on the motor unit  including atrophy  a necrobiotic myopathy and lambert eaton myasthenic syndrome  clinical assessment does not accurately assess the  remote  neuromuscular effects of cancer on the motor unit  
class10	wilson s disease  35 years  experience  thirty seven chinese patients fulfilling the criteria for wilson s disease seen during a 35 year period were reviewed  males and females were equally affected  twenty two patients were symptomatic and 15 asymptomatic  most of them presented before the third decade  thirty one per cent of the relatives screened showed evidence of disease  and parents were rarely affected  13 per cent   half of the adult symptomatic females presented with primary amenorrhoea  liver laboratory tests were abnormal in only 50 per cent of patients  with gamma glutamyltranspeptidase being the most sensitive index  renal disease was infrequent  serum caeruloplasmin level was the single biochemical parameter of prognostic significance  p   0 0001   seventy per cent of the symptomatic patients showed an improvement after treatment with penicillamine  
class10	progression of diabetic autonomic neuropathy over a decade in insulin dependent diabetics  the prognosis for diabetics with autonomic neuropathy is little known  we therefore studied the progress of young insulin dependent diabetics  first identified as having abnormal autonomic function 10 15 years ago  we have shown that the mortality of diabetics with symptomatic autonomic neuropathy is increased  but is less than previously reported  mortality in asymptomatic diabetics with an isolated abnormality in autonomic function tests is not increased  the heart rate variability declines at 1 02     0 47  sd  per annum in diabetics with an initially normal heart rate variability  while symptoms of autonomic neuropathy do not usually remit even over a decade  they do not commonly progress  three groups of young insulin dependent diabetics had heart rate variability tested between 1972 and 1977 and have been reviewed 10 15 years later  group a  n   49  had symptomatic autonomic neuropathy and an abnormal heart rate variability  less than 12   group b  n   24  were asymptomatic yet had an abnormal heart rate variability and group c  n   38  were asymptomatic and had a normal heart rate variability  16 26   the 10 year survival in group a  73 4 per cent  was less  p less than 0 05  than in groups b  91 7 per cent  or c  89 5 per cent  which did not differ from each other  the 18 group a deaths were due predominantly to renal failure  n   4   myocardial infarction in patients with nephropathy  n   3  and sudden unexpected death  n   3   the chief symptoms of autonomic neuropathy  diarrhoea  postural hypotension and gustatory sweating  were very persistent but did not necessarily deteriorate or become disabling in the majority of patients  the development of autonomic symptoms in asymptomatic patients with abnormal heart rate variability was uncommon over a decade  
class10	hyponatraemia in patients with cirrhosis  hyponatraemia occurs in nearly half of patients in hospital with cirrhosis and ascites  and is due to the excessive retention of free water which results from the kidney s inability to excrete it normally  the morbidity and mortality associated with hyponatraemia is largely attributable to central nervous system disturbances  the degree to which brain water content increases depends on the duration of hyponatraemia and on compensatory mechanisms  altered steroid and peptide hormones in cirrhotic patients may contribute to the development of hyponatraemic encephalopathy  symptoms of which overlap with hepatic encephalopathy and uraemia  the occurrence of central pontine myelinolysis is unrelated to the rate of correction of hyponatraemia  the appearance of hyponatraemia in cirrhotic patients  long regarded as a poor prognostic sign  may be a function of unrecognized underlying impaired renal function  therapy for hyponatraemia remains suboptimal  
class10	temporal bone  three dimensional ct  part ii  pathologic alterations  three dimensional  3d  surface renderings were obtained from routine axial computed tomographic  ct  images in 15 patients with a variety of complex temporal bone abnormalities  the 3d ct reformations served as an adjunct to conventional sectional ct examination  while no diagnosis was substantially changed because of the 3d ct images  they did provide a more global perspective in cases of large tumors and fractures and at the postmastoidectomy site  three dimensional ct surface reformations are now practical and may be potentially useful for visualizing temporal bone lesions characterized by complex destructive change  
class10	unusual cerebral manifestations in hereditary fructose intolerance  five children with hereditary fructose intolerance developed symptoms of neurological impairment  in three of them  neurological involvement was related to the acute hepatic toxicity of fructose  hypoglycemia  abnormal coagulation  cardiovascular collapse   in the other two  such a relationship could not be demonstrated  neurological impairment is not classic in hereditary fructose intolerance  but its occurrence in the acute phase of the disease is possible and does not constitute an argument against the diagnosis  
class10	gynecologic cancer in patients with subacute cerebellar degeneration predicted by anti purkinje cell antibodies and limited in metastatic volume  between 1982 and 1989  19 patients with gynecologic carcinoma  paraneoplastic cerebellar degeneration  and seropositivity for anti purkinje cell cytoplasmic antibodies were identified at our institution  seven of the patients had no clinical  computed tomographic  or magnetic resonance imaging evidence of cancer but had undergone laparotomy solely because anti purkinje cell antibodies were found in their serum  all had high grade adenocarcinoma  cerebellar symptoms preceded or coincided with the initial cancer diagnosis in 15 patients and preceded the diagnosis of recurrent cancer in 4 patients  the cancers were 14 ovarian  2 fallopian tube  2 surface papillary  and 1 poorly differentiated metastatic adenocarcinoma in a periaortic lymph node  two remarkable surgical observations in patients with high grade ovarian and tubal cancers were the conspicuous lack of peritoneal implants and the small metastatic volume  a comparison of the 8 patients who had primary stage iii cancer with 24 matched control patients without paraneoplastic cerebellar degeneration revealed no difference in primary tumor volume but a significantly smaller volume of metastatic tumor in the seropositive group  p   0 05   anti purkinje cell antibodies were not detected in 111 neurologically normal patients with advanced ovarian cancer  the small metastatic volume in the face of high grade and advanced stage malignancy in seropositive patients with paraneoplastic cerebellar degeneration suggests that an immune response to the tumor  presumably cross reactive with cerebellar cells  may impair the metastatic process  earlier diagnosis and treatment of cancer  based on prompt serologic testing  may offer an improved neurologic and oncologic prognosis  
class10	selected neurologic complications of pregnancy  many neurologic disorders  such as eclampsia  pseudotumor cerebri  stroke  obstetric nerve palsies  subarachnoid hemorrhage  pituitary tumors  and choriocarcinoma  can develop in the pregnant patient  maternal mortality from eclampsia  which ranges from 0 to 14   can be due to intracerebral hemorrhage  pulmonary edema  disseminated intravascular coagulation  abruptio placentae  or failure of the liver or kidneys  associated fetal mortality ranges from 10 to 28  and is directly related to decreased placental perfusion  pseudotumor cerebri can be associated with serious visual complications  thus  the therapeutic goal is to prevent loss of vision  the risk of stroke in the pregnant patient is 13 times the risk in the nonpregnant patient of the same age  the major causes of stroke in pregnant patients are arterial occlusion and cerebral venous thrombosis  lumbar disk prolapse is common in pregnant patients  and lumbosacral plexus injuries can occur during labor or delivery  in addition  peripheral nerve compression or entrapment syndromes are thought to be caused by the retention of fluid during pregnancy  the incidence of subarachnoid hemorrhage during pregnancy is 1 in every 10 000 patients  a rate 5 times higher than in nonpregnant women  because of a proliferation of prolactin secreting cells  the pituitary gland can enlarge dramatically during pregnancy  a change that can disclose a previously unknown tumor or cause a known pituitary tumor to become symptomatic  the incidence of choriocarcinoma is 1 in 50 000 full term pregnancies but 1 in 30 molar pregnancies  this malignant tumor has a high rate of cerebral metastatic lesions  in addition to these disorders that develop during pregnancy  the pregnant state can affect numerous preexisting neurologic conditions  including epilepsy  headaches  multiple sclerosis  myasthenia gravis  spinal cord injury  and brain tumors  we discuss advice for patients with such conditions who wish to become pregnant  recommendations for medical and surgical management  and surgical considerations for neurologic complications during pregnancy  
class10	quinine induced disseminated intravascular coagulation  recurrent disseminated intravascular coagulation occurred in 3 women after ingestion of quinine tablets for cramp  all had circulating quinine dependent antibodies to platelets and in 2 there was initial evidence of antibody consumption  with low titres that rose steeply over the next few days and remained high for many months  
class10	the effect of epilepsy or diabetes mellitus on the risk of automobile accidents background  previous studies of possible associations between chronic medical conditions and traffic safety have been inconsistent and subject to bias because of the incomplete identification of affected persons  recent advances in the diagnosis and management of epilepsy and diabetes mellitus have improved the control of these disorders and suggest a need to reexamine the risk of traffic mishaps among patients with these conditions  methods  we conducted a population based retrospective cohort study of 30 420 subjects 16 to 90 years of age  with and without epilepsy or diabetes mellitus  subjects included all the licensed drivers in seven contiguous zip code areas in which the marshfield clinic and st  joseph s hospital  marshfield  wisconsin  are the primary sources of medical care  standardized rates of moving violations and accidents over a four year period  1985 through 1988  were compared in affected and unaffected cohorts  results  standardized mishap ratios for subjects with diabetes were 1 14 for all moving violations  p   0 23  and 1 32 for accidents  p   0 01   for subjects with epilepsy the ratios were 1 13 for moving violations  p   0 26  and 1 33 for accidents  p   0 04   conclusions  we conclude that drivers with epilepsy or diabetes mellitus have slightly increased risks of traffic accidents as compared with unaffected persons  the increases in risk observed in our study were generally smaller than those in previous studies  and we believe they are not great enough to warrant further restrictions on driving privileges  
class10	imaging the fetal brain in the second and third trimesters using transvaginal sonography  high frequency transvaginal probes were used at 20 40 weeks  gestation to develop a systematic examination of the fetal brain  modeling the procedure after the standard neonatal neurosonographic examination  we attempted to obtain three coronal sections  anterior  midline  posterior  and two sagittal sections  midsagittal  right or left parasagittal   in 70 normal patients  all planes were imaged with a similar frequency  74 76   except for the posterior coronal plane  which was imaged 59  of the time  among the first 35 cases  17  had a complete study  compared with 71  of the second 35 cases  transvaginal sonography established or changed the diagnosis in five of the 13 cases with central nervous system or other abnormalities  we recommend that a complete fetal neurosonographic examination include transvaginal sonography to complement and enhance the transabdominal examination  especially for cases in which a fetal abnormality is suspected  
class10	botulinum treatment of childhood strabismus  four hundred thirteen children ranging in age from 2 months to 12 years were treated for strabismus by botulinum injection of extraocular muscles  an average of 1 7 injections per patient was given  follow up at an average of 26 months after the last injection  minimum  6 months  was available on 362 children  88    the frequency of correction of 10 prism diopters  pd  or less in various groups of strabismus cases was  all 362 cases  61   all esotropia  66   infantile esotropia  65   and exotropia  45   smaller deviations  10 20 pd  were more frequently corrected  73   than were larger deviations  20 110 pd  54    the frequency of correction to 10 pd or less of previously operated cases was not different from that of unoperated cases  there was no globe perforation  amblyopia  or visual loss produced by the injection treatment in this series  
class10	bicarbonate buffered lidocaine epinephrine hyaluronidase for eyelid anesthesia  a double masked  randomized clinical trial was conducted to determine if subcutaneous eyelid injections of a bicarbonate buffered lidocaine epinephrine hyaluronidase mixture were less painful than unbuffered injections  twenty one patients received both buffered  ph   7 4  and unbuffered  ph   4 6  injections  after each injection  patients recorded pain on a scale of 0   no pain   to 10   severe pain   mean pain score for buffered injections was 2 0 versus 4 1 for unbuffered injections  p   0 0003   seventeen  81   of 21 patients ranked the buffered injection less painful  use of a bicarbonate buffered lidocaine epinephrine hyaluronidase mixture is effective in making ophthalmic anesthesia less painful  
class10	optic nerve sheath meningoceles  clinical and radiographic features in 13 cases with a review of the literature thirteen patients with dilated intraorbital optic nerve sheaths with an expanded  patulous cerebrospinal fluid  csf  space were studied with high resolution computed tomography  ct  or magnetic resonance imaging  mri   eleven patients had bilateral findings  headache or visual complaints  or both  were present in all patients  signs of optic nerve dysfunction were present in eight patients  three patients had visual acuity worse than 20 200  cerebrospinal fluid pressure was mildly elevated in two patients  three patients underwent a surgical procedure  visual acuity improved in one  the authors propose the term meningocele for this condition and suggest mri with fat suppression techniques and off axis sagittal views as the radiographic procedure of choice  
class10	long term visual outcome in patients with optic nerve pit and serous retinal detachment of the macula serous detachment of the macula is a well known complication in patients with an optic nerve pit  despite the many descriptions of this condition and possible treatment options  the long term natural history is not well known  the authors identified 15 eyes of 15 consecutive patients seen over 21 years who were diagnosed with a serous detachment of the macula arising from an optic nerve pit  average length of follow up was 9 years  twelve eyes lost three or more lines of vision  two eyes remained unchanged  and only one eye improved  all of the 12 eyes losing three or more lines of vision experienced this decrease within the first 6 months of follow up  although only two patients had a visual acuity of 20 200 or less initially  12 of 15 patients had a visual acuity of 20 200 or less at the time of their last examination  the appearance of the macula at last examination included cystic changes of the neurosensory retina  full thickness hole formation  retinal pigment epithelial mottling  and lamellar hole formation in the outer retinal layer  the long term visual prognosis in patients with optic nerve pit and untreated serous retinal detachment of the macula is poor  and visual loss occurs within 6 months of the serous detachment  
class10	the risk for systemic vascular diseases and mortality in patients with central retinal vein occlusion  in this cross sectional study  the authors evaluated 197 patients diagnosed with central retinal vein occlusion  crvo  at the wilmer ophthalmological institute between 1980 and 1985 to determine the risk of systemic disease and mortality  complete follow up information for mortality was obtained in 191  97    national health interview survey  nhis  patients and wilmer cataract patients formed two comparison groups  the prevalence of hypertension was significantly elevated in the crvo cases when compared with both comparison groups  p less than 0 03  0 005   the prevalence of diabetes mellitus was increased in crvo cases in comparison with the nhis group  p less than 0 005   the prevalence of cerebrovascular or cardiovascular disease was the same for all three groups  as was overall mortality  mortality was not increased in crvo cases as compared with united states mortality rates  
class10	strategies underlying the control of disordered movement  the purpose of this article is fourfold  first  a theory of motor control  the dual strategy hypothesis  is outlined  second  the methodologies and theoretical framework that are used to develop this theory are examined  third  motor dysfunction is discussed in the context of this theory  in particular  down syndrome  parkinson s disease  cardiovascular accidents  and spasticity are discussed  finally  potential applications of the theory to physical therapy are considered  
class10	a new challenge  robotics in the rehabilitation of the neurologically motor impaired  rehabilitation robotics is a research area  originating in engineering  that has emerged in the last decade  its broad aim is to use robot technology to assist people with movement dysfunction  the neurologically impaired population might gain considerably from the provision of robots as  assistants  or  therapy aides   but the interface with the machine must match both the physical and intellectual abilities of the user  we therefore consider a multidisciplinary approach  encompassing both behavioral and engineering perspectives  to be essential in achieving this aim  however  to date  published reports have been largely restricted to engineering journals or conference reports  and relatively little has appeared in the therapy literature  this article seeks to introduce physical therapists to robotics  describe possible applications to the rehabilitation of neurologically impaired patients  and suggest issues deserving further investigation  
class10	brain potentials associated with movement in traumatic brain injury  brain potentials may be used to assess the functional abnormalities that underlie impairments of movement  the purpose of this article is to illustrate the usefulness of examining these potentials  in addition to an overview of the topic  the article includes a report of a study demonstrating that there were differences between the brain potentials of five patients with traumatic brain injury and those of four healthy control subjects  all five patients were in the postacute phase of hemiplegia  slow cortical potentials associated with simple goal directed forearm and finger movements were recorded from frontal and parietal electrodes  two seconds of movement related electroencephalographic activity  movement related potential  were recorded  the patients showed reduced brain potentials for movements associated with their paretic limb and  to a lesser extent  reduced brain potentials for movements associated with their nonparetic limb  the waveforms obtained from the patients were unusual  with uncharacteristic cross cortical movement related potential correlations associated with specific electrode configurations  as well as with specific movement conditions  brain potentials associated with the fore period interval of a simple reaction time paradigm were later recorded in two of the patients with traumatic brain injury and in a control subject to help determine the functional significance of the relative positivity apparent in their movement related potential data  this preliminary study indicates that electroencephalographic potentials obtained during the preparation for and execution of movement can provide information regarding the basis for motor dysfunction  
class10	movement disorders  limb movement and the basal ganglia  the primary concern of this article is to review experimental methods that may lead to a better understanding of the functional role of the basal ganglia in the control of movement  two models of basal ganglia impairment are considered  parkinson s disease and huntington s disease  the review focuses primarily on akinesia and bradykinesia because they are key abnormalities of basal ganglia dysfunction  in general  through electromyography and kinematic analysis of movement  it may be possible to characterize specific movement disorders  specifically  if damage sustained by the central nervous system is traced to a certain structure  it may provide insight on the extent of involvement and functional role of that structure in the control of movement  much of the data reviewed suggests that the basal ganglia may play a specific role in the initiation and regulation of force control  
class10	three dimensional reconstructed mr imaging of the inner ear  the three dimensional fourier transform fast imaging with steady precession  fisp  technique was used to obtain high resolution magnetic resonance  mr  images of the temporal bone region and to generate three dimensional reconstructed images of the inner ear  the three dimensional reconstructed images of the inner ear were directly synthesized from two dimensional images of the temporal bone region by means of an external processing computer  with use of three dimensional reconstructed images and stereoscopic observations  structures inside the temporal bone region and the positional relationship among them were easily recognized  these structures are difficult to demonstrate with two dimensional images  this three dimensional method was also shown to be useful for recognition of disease and anatomic malformations in the temporal bone region  
class10	neuroophthalmologic effects of intravenous magnesium sulfate  to test the hypothesis that visual disturbances are more common during intravenous magnesium sulfate administration than at 1 to 4 days after discontinuation of the drug  13 women underwent bedside neuroophthalmologic examinations during intravenous magnesium sulfate tocolysis at 2 0 to 3 0 gm hr and again at 1 to 4 days after cessation of therapy  visual symptoms were common during intravenous magnesium sulfate administration  blurred vision was present in 12 of 13 patients and diplopia was present in 10 of 13 patients  abnormal findings during neuroophthalmologic examination occurred in all patients during intravenous magnesium sulfate administration  findings included ptosis  accommodative and convergence insufficiency  and abnormal pupillary responsiveness to light and near  all patients were symptom free and had normal examinations after magnesium sulfate was discontinued  these findings suggest that visual disturbances with therapeutic magnesium sulfate are common  
class10	oral contraception in disease states  oral contraceptives are clearly contraindicated in patients with a history of thromboembolic disease  ischemic heart attack  or cerebral stroke  patients requiring long term anticoagulant treatment can be treated with gonadotropin releasing hormone analogs to prevent ovulation  because ruptured follicles can cause massive intraperitoneal bleeding  patients with essential hypertension and severe liver diseases should also discontinue treatment 4 weeks before major elective surgery  migraine and diabetes mellitus are regarded as relative contraindications  depending on the individual situation  long term diseases  such as crohn s disease  epilepsy  and sickle cell anemia  also require individualized consultation  
class10	treatment of patients with aortic dissection presenting with peripheral vascular complications  the incidence of peripheral vascular complications in 272 patients with aortic dissection during a 25 year span was determined  as was outcome after a uniform  aggressive surgical approach directed at repair of the thoracic aorta  one hundred twenty eight patients  47   presented with acute type a dissection  70  26   with chronic type a  40  15   with acute type b  and 34  12   with chronic type b dissections  eighty five patients  31   sustained one or more peripheral vascular complications  seven  3   had a stroke  nine  3   had paraplegia  66  24   sustained loss of a peripheral pulse  22  8   had impaired renal perfusion  and 14 patients  5   had compromised visceral perfusion  following repair of the thoracic aorta  local peripheral vascular procedures were unnecessary in 92  of patients who presented with absence of a peripheral pulse  the operative mortality rate for all patients was 25      3   68 of 272 patients   for the subsets of individuals with paraplegia  loss of renal perfusion  and compromised visceral perfusion  the operative mortality rates      70  confidence limits  were high  44      17   4 of 9 patients   50      11   11 of 22 patients   and 43      14   6 of 14 patients   respectively  the mortality rates were lower for patients presenting with stroke  14      14   1 of 7 patients   or loss of peripheral pulse  27      6   18 of 66 patients    multivariate analysis revealed that impaired renal perfusion was the only peripheral vascular complication that was a significant independent predictor of increased operative mortality risk  p   0 024   earlier surgical referral  replacement of the appropriate section of the thoracic aorta  or more expeditious diagnosis followed by surgical renal artery revascularization after a thoracic procedure may represent the only way to improve outcome in this high risk patient subset  early  aggressive thoracic aortic repair  followed by aortic fenestration and or abdominal exploration with or without direct visceral or renal vascular reconstruction when necessary  can save some patients with compromised visceral perfusion  however  once visceral infarction develops the prognosis is also poor  increased awareness of these devastating complications of aortic dissection and the availability of better diagnostic tools today may improve the survival rate for these patients in the future  the initial surgical procedure should include repair of the thoracic aorta in most patients  
class10	return to work for persons with traumatic brain injury  a supported employment approach  supported employment was used to place 41 persons into competitive employment during 30 months  all individuals had experienced severe head injuries  almost 70  of injuries were due to motor vehicle accidents  a mean of seven years had passed since injury for all referred clients  who had been unconscious a mean of 53 days  only 36  of referred clients had achieved any competitive postinjury employment  compared with 91  of the same group who were competitively employed before injury  a job retention rate of 71  was reported  with most jobs in warehouse  clerical  and service related occupations  a mean of 291 hours of job coaching was required to place and maintain all clients in supported employment  
class10	functional evaluation of quadriplegic patients using a hand neuroprosthesis  the objective of this retrospective study was to compare the abilities of quadriplegic patients to complete activities of daily living with and without the use of a portable hand neuroprosthesis  the neuroprosthesis provided synthetic hand grasp through functional neuromuscular stimulation of paralyzed forearm and hand muscles  data were obtained from telephone interviews  patient records  and videotapes  twenty two quadriplegic patients were included in the study  15 were functional at a c5 spinal cord injury level and seven at a c6 level  the median success rate  ie  the percentage of patients who could complete each activity  across the ten activities was 89  with the hand neuroprosthesis but was only 49  without the hand neuroprosthesis  all patients could perform more tasks when the neuroprosthesis was used  although the relative improvement of c5 patients was larger than that of c6 patients  
class10	impaired awareness of behavioral limitations after traumatic brain injury  sixty four traumatically brain injured patients were divided into three groups  patients in group i overestimated their behavioral competencies  patients in group ii showed behavioral ratings similar to relatives  reports concerning behavioral competencies  patients in group iii underestimated their behavioral competencies  group i patients had greater evidence of bilateral and multiple site lesions than group ii and iii patients  speed of left hand finger tapping was also worse in group i than groups ii and iii  but other standard neuropsychologic test findings failed to separate the groups  specific brain lesion sites were not related to group membership  impaired awareness of behavioral limitations after traumatic brain injury may be related to neuropsychologic changes not measured by standard tests  bilateral impairment of heteromodal cortex may be important to this phenomenon when it exists several months or years postinjury  
class10	maximal exercise testing of mentally retarded adolescents and adults  reliability study  few data are available regarding maximal exercise testing of mentally retarded individuals  no data are available on the reliability of maximal exercise testing of mentally retarded individuals  the purpose of this study was to determine the reliability of graded exercise testing of mentally retarded adolescents and adults  the testing was conducted at two geographically different centers  at center a  14 mentally retarded adolescents  11 boys  three girls  with down syndrome  who were educable or trainable  were recruited from a nonresidential school  the subjects completed two balke ware treadmill protocols until exhaustion  the treadmill time and heart rate  hr  were recorded  the time between tests was approximately one week  at center b  21 mentally retarded adults  14 women  seven men means iq   56  were recruited from local workshops and group homes  these subjects completed a treadmill walking protocol  with metabolic measurements  until exhaustion  the time between tests varied from one to four months  at center a  the subjects achieved a mean treadmill time of 8 72min on test one and 8 84min on test two  means hr   174 and 175bpm  respectively   the reliability coefficient between the two tests was  94  at center b  the subjects achieved a mean v0 2 max of 27 2ml kg 1 min 1 on test one and 26 9ml kg 1 min 1 on test two  the reliability coefficient was  93  these data show that maximal exercise testing is reliable for these populations of mentally retarded individuals  exhibiting similar values to their nonretarded peers  
class10	recovery from vegetative state of six months  duration associated with sinemet  levodopa carbidopa   certain pharmacologic interventions may improve outcome for brain injury in animals and humans  medications affecting the dopaminergic pathway appear to be important  we present the case of a 24 year old man with traumatic brain injury who remained unresponsive to commands and unchanged for six months despite periodic aggressive therapy  within days of beginning sinemet  levodopa carbidopa   the patient became conversant and responsive  the reported low likelihood of spontaneous recovery of cognition in patients who are vegetative for six months suggests that sinemet was responsible for this patient s recovery  in this case  the relatively small risk of side effects from sinemet was greatly outweighed by the change in functional outcome  
class10	threshold perimetry in tilted disc syndrome  twelve consecutive patients  17 eyes  with tilted disc syndrome underwent quantified visual field examination with the g1 octopus program  interzeag ag  schlieren  switzerland   visual fields were abnormal in all cases  although field loss was more pronounced in the superotemporal quadrant  p less than  001   it also involved the other three quadrants  thus demonstrating that optic nerve hypoplasia in tilted disc syndrome is apparently not entirely sectorial  linear regression analysis showed that an increase in mean defect correlated with increase in myopic refractive error  p less than  05   however  the increase in myopic refractive error was found to be related to a decrease in corrected loss variance  p less than  05   indicating that in tilted discs with higher myopia  field loss is more homogeneous  with this series of patients  short term fluctuation was within normal ranges in all visual fields  showing that this may be an additional clue for differential diagnosis from acquired disorders  
class10	familial trigeminal anesthesia  familial congenital trigeminal anesthesia as an isolated abnormality is an unusual disorder  to our knowledge  only one family has previously been reported  we report here a family with three affected members demonstrating facial anesthesia  bilateral corneal changes  and nasal septal damage secondary to self traumatization  magnetic resonance imaging demonstrated hypoplasia of gasserian ganglia and trigeminal nerves in the affected father of two affected sons  the pathogenesis of this disorder appears to be congenital hypoplasia of the trigeminal nerves and gasserian ganglia that is inherited in a dominant fashion  
class10	tumor necrosis factor and severe malaria  to investigate the relation of tumor necrosis factor alpha  tnf alpha  to plasmodium falciparum infection  plasma tnf alpha concentrations were measured in zairian children with severe malaria  mild malaria  or other illnesses  the initial geometric mean plasma concentration of tnf alpha among 61 children with p  falciparum infection   71 pg ml  was higher than the level in 26 severely ill  aparasitemic children  10 pg ml  p less than  001   among 29 parasitemic children  initial geometric mean tnf alpha levels decreased from 77 to 5 pg ml  p less than  001  at day 7  tnf alpha levels increased with parasite density and were associated with hyperparasitemia  severe anemia  hypoglycemia  and young age but not with cerebral malaria or fatal outcome  however  tnf alpha levels were elevated equally in children with cerebral malaria and with other signs of severe malaria  with multiple linear regression  tnf alpha levels were elevated independently in children with hyperparasitemia  p    001  and severe anemia  p    04   in this study  high tnf alpha levels were associated with several manifestations of severe malaria and were not specific to cerebral malaria  
class10	tumor associated neurological dysfunction prevented by lazaroids in rats  the efficacy of u 74006f and u 78517f in the treatment of blood tumor barrier permeability and tumor associated neurological dysfunction was evaluated in a brain tumor model in rats  u 74006f is a 21 aminosteroid and u 78517f is a 2 methylamino chroman  rats with stereotactically implanted walker 256 tumors were treated with methylprednisolone  u 74006f  u 78517f  or vehicle  0 05 n hcl  on days 6 through 10 following implantation  neurological function and vascular permeability were assessed on day 10  methylprednisolone and u 74006f were equally effective at preventing neurological dysfunction compared to the control group  p less than 0 01   u 78517f was slightly less effective than u 74006f and methylprednisolone but was significantly better than vehicle in preventing neurological dysfunction  delivery of methylprednisolone resulted in a significant decrease in tumor vascular permeability  p less than 0 006  while u 74006f and u 78517f had no effect on permeability  this suggests that u 74006f and u 78517f prevented tumor associated neurological dysfunction by a mechanism other than decreasing permeability in tumor capillaries  and that u 74006f or u 78517f could prove useful in the treatment of brain tumors  
class10	enhanced in vitro uptake and retention of 3h tetraphenylphosphonium by nervous system tumor cells  photodynamic therapy is a promising treatment for human brain tumors because of the selective retention of certain compounds by tumor cells  certain lipophilic cationic compounds  such as tetraphenylphosphonium  tpp   are selectively taken up by a variety of carcinomas  although preferential retention of tpp has been demonstrated for the breast carcinoma cell line mcf 7  this compound had not been tested previously on cells derived from nervous system tumors  in the present study  tritiated tpp  3h tpp  uptake and retention for eight different cell cultures of three histologically different types of nervous system tumors was measured and the data were compared to a positive control  mcf 7  and negative controls  normal african green monkey kidney epithelium  cv 1  and the normal human fibroblast  wi 38  cell lines   uptake and retention characteristics could be grouped by specific pathological tumor types  but individual tumor variability was notable  malignant astrocytoma  grade iii iii glioblastoma  and malignant neurofibrosarcoma cells showed preferential uptake and retention of 3h tpp relative to meningioma cells and normal controls  a clonogenic assay utilizing the cytotoxic lipophilic cationic compound dequalinium showed strong retainers of 3h tpp to be more susceptible to the effects of dequalinium than weak retainers  these data demonstrate that certain human and experimental animal nervous system tumor cell lines retain lipophilic compounds possessing a delocalized positive charge  lipophilic cationic compounds may be useful in the intraoperative delineation of tumor margins and in the photodynamic therapy of certain nervous system tumors  
class10	epidermoid cysts of the brain stem  report of three cases  the authors report the cases of three patients with epidermoid cysts which insinuated themselves into the brain stem  in all three patients  the tumor occupied the pons  although in one it was predominantly located in the medulla  the cyst contents and nonadherent tumor capsule were removed in all three patients  but no attempt was made to remove tumor densely adherent to the brain stem  one patient s cyst was removed in one operation  but maximal resection in the other two required two operations  after surgery  sixth nerve function completely returned in one patient  another patient had a stable pontine gaze palsy but developed new facial weakness  and the third patient had stable cranial nerve deficits with a diminished hemiparesis  the last patient developed a pseudomeningocele and communicating hydrocephalus  and required a lumboperitoneal shunt  in all three patients  computerized tomography scans demonstrated hypodense tumors not enhanced by contrast material  magnetic resonance imaging was performed on two patients  in both  the tumors showed increased signal intensity relative to brain on t1 weighted images and decreased signal intensity relative to brain on t2 weighted studies  magnetic resonance imaging  the most accurate modality for localizing these lesions and determining their extent  was also invaluable for postoperative monitoring and follow up evaluation  safe and adequate resection includes decompression of cyst contents and removal of nonadherent portions of the cyst capsule  cyst wall adherent to the brain stem  however  should not be removed  
class10	pseudopsammomatous meningioma with elevated serum carcinoembryonic antigen  a true secretory meningioma  case report  a sphenoid wing meningioma in a 60 year old woman was accompanied by elevated serum carcinoembryonic antigen  cea  levels  which returned to normal after removal of the tumor  light microscopic examination revealed a secretory meningioma containing numerous pseudopsammoma bodies and a prominent vascular pattern  immunohistochemical analysis showed the tumor cells and pseudopsammoma bodies to be cea positive  this case illustrates the possibility that secretory meningioma may be associated with clinically detectable secretion of cea  the report also documents the rare occurrence of elevated serum cea in a primary benign intracranial tumor  
class10	tension pneumocephalus  treatment with controlled decompression via a closed water seal drainage system  case report  the successful treatment of a patient with tension pneumocephalus by controlled decompression via external drainage is described  the advantage of the technique includes the immediate release of high pressure and the capability of maintaining constant low pressure to enable and facilitate sealing of dural tears  the method has been used in three other patients  leading to resolution of the tension pneumocephalus without recurrence or other complications  
class10	risks factors for cerebral infarction in good grade patients after aneurysmal subarachnoid hemorrhage and surgery  a prospective study  a prospective series of 265 patients with aneurysmal subarachnoid hemorrhage  sah  of grades i to iii  hunt and hess classification  upon admission were evaluated as to neurological outcome and computerized tomography  ct  findings 1 to 3 years  mean 1 4 years  after the sah and surgery  a total of 73 patients underwent acute surgery  within 72 hours after the bleed  days 0 to 3   86 were operated on subacutely  between days 4 and 7   and 91 had late surgery  on day 8 or later   fifteen patients died before surgery was undertaken and another 20 patients died during the follow up period  a total of 104 patients received nimodipine and the rest of the patients received either placebo  109 patients  or no medication  52 patients   a logistical regression analysis revealed the following prognostic factors for cerebral infarction  in order of importance  the amount of blood on the primary ct scan  postoperative angiographic vasospasm  the timing of the operation  and a history of hypertension  the use of nimodipine was associated with a significant reduction of cerebral infarcts visualized by ct scanning in patients who received intermediate or late surgery  in patients who underwent acute surgery no significant difference between the incidence of cerebral infarcts was observed  
class10	cerebrospinal fluid rhinorrhea following acoustic neurinoma surgery  technical note  the authors describe a method of preventing cerebrospinal fluid  csf  rhinorrhea following surgery for acoustic neurinoma  mastoid air cells exposed during craniectomy are skeletonized and packed with bone dust  then covered with surgicel soaked with tisseel fibrin glue  the use of this technique has reduced the number of acoustic neurinoma cases requiring secondary mastoidectomy for csf leakage from 16  to 5   
class10	the effect of glucose administration on carbohydrate metabolism after head injury  the role of intravenous infusion of glucose in limiting ketogenesis and the effect of glucose on cerebral metabolism following severe head injury were studied in 21 comatose patients  the patients were randomly assigned to alimentation with or without glucose  systemic protein wasting  arterial concentrations of energy substrates  and cerebral metabolism of these energy substrates were monitored for 5 days postinjury  both groups were in negative nitrogen balance  and had wasting of systemic proteins despite substantial protein intake  blood and cerebrospinal fluid  csf  glucose concentrations were highest on day 1  but remained higher than normal fasting levels on all days of study  even in the patients who received no exogenous glucose  although there were no differences in blood or csf glucose concentrations in the two groups of patients  the glucose group had higher plasma insulin levels  with a mean     standard deviation of 14 8     7 3 microu ml compared to 10 3     4 2 microu ml in the saline group  the blood concentrations of beta hydroxybutyrate  acetoacetate  pyruvate  glycerol  and the free fatty acids were higher in the saline group than in the glucose group  cerebral oxygen consumption was similar in the two groups  while the cerebral metabolism of glucose and of the ketone bodies was dependent on whether glucose was administered  in the glucose group  glucose was the only energy substrate utilized by the brain  in the saline group  the ketone bodies beta hydroxybutyrate and acetoacetate replaced glucose to the extent of 16  of the brain s total energy production  cerebral lactate production and csf lactate concentration were lower in the saline group  these studies suggest that administration of glucose during the early recovery period of severe head injury is a major cause of suppressed ketogenesis  and may increase production of lactic acid by the traumatized brain by limiting the availability of nonglycolytic energy substrates  
class10	shunt surgery for hydrocephalus in tuberculous meningitis  a long term follow up study  hydrocephalus is a common complication of tuberculous meningitis  case studies of 114 patients with tuberculous meningitis and hydrocephalus  who underwent shunt surgery between july  1975  and june  1986  were reviewed to evaluate the long term outcome and to outline a management protocol for these patients based on the results  seven factors were studied in each case  1  age at admission  2  grade on admission  i to iv  classified by the authors  grade i being the best and grade iv being the worst   3  duration of alteration of sensorium  4  cerebrospinal fluid  csf  cell content at initial examination  5  csf protein levels at initial examination  6  number of shunt revisions required  and 7  the necessity for bilateral shunts  during a long term follow up period ranging from 6 months to 13 years  mean 45 6 months   the mortality rate was 20  for patients in grade i  34 7  for patients in grade ii  51 9  for patients in grade iii  and 100  for patients in grade iv  only the grade at the time of admission was found to be statistically significant in determining final outcome  p less than 0 001   based on these results  the authors advocate early shunt surgery for grade i and ii patients  for patients in grade iii  surgery may be performed either if external ventricular drainage causes an improvement in sensorium or without selection  all patients in grade iv should undergo external ventricular drainage and only those who show a significant change in their neurological status within 24 to 48 hours of drainage  should have shunt surgery  
class10	management of meralgia paresthetica meralgia paresthetica is a syndrome of pain or dysesthesia  or both  in the anterolateral thigh caused by entrapment or neurinoma formation of the lateral femoral cutaneous nerve  conservative treatment was successful in relieving symptoms in 91  of 277 patients with this syndrome  however  24 patients required surgical treatment for intractable symptoms  although neurolysis with transposition is the most common procedure  sectioning of the lateral femoral cutaneous nerve was performed in 24 cases and was successful in 23  one patient had early symptomatic relief  but subsequently developed different neurological signs and symptoms because of an undetected pelvic neoplasm  anatomical variations of the nerve and neurinomas  which occur frequently  are easily handled with sectioning but may lead to recurrence with neurolysis and transposition  
class10	long term effects of nimodipine on cerebral infarcts and outcome after aneurysmal subarachnoid hemorrhage and surgery  a total of 213 patients with verified aneurysmal subarachnoid hemorrhage  sah  of grades i to iii  hunt and hess classification  were enrolled in a double blind placebo controlled trial to determine the effect of intravenous nimodipine on delayed ischemic deterioration and computerized tomography  ct  visualized infarcts after sah and surgery  the administration of the drug or matching placebo was started immediately after the radiological diagnosis of a ruptured aneurysm had been made  of the 213 patients enrolled in the study  58 were operated on early  within 72 hours after the bleed  days 0 to 3   69 were operated on subacutely  between days 4 and 7   and 74 had late surgery  on day 8 or later   eleven patients died before surgery was undertaken and one was not operated on  a follow up examination with ct scanning  performed 1 to 3 years after the sah  mean 1 4 years   revealed no significant differences in the overall outcome between the groups  however  nimodipine treatment was associated with a significantly lower incidence of deaths caused by delayed cerebral ischemia  p   0 01  and significantly lower occurrence of cerebral infarcts visualized by ct scanning in the whole population  p   0 05   especially in patients without an associated intracerebral hemorrhage on admission ct scan  p   0 03   
class10	effects of tromethamine and hyperventilation on brain injury in the cat  the metabolic brain acidosis after trauma has been thought to be harmful and to contribute to neurological deterioration  amelioration of the brain acidosis either by systemic buffering agents or by hyperventilation has been proposed as a method of treatment  the objective of this study was to explore with magnetic resonance  mr  spectroscopy the metabolic changes in brain that occur with the use of hyperventilation  tham  tromethamine  tris hydroxymethyl aminomethane   and a combination  tham and hyperventilation  therapy in experimental fluid percussion injury  brain lactate  brain ph  inorganic phosphate  pi   and adenosine triphosphate levels were measured by 1h and 31p mr spectroscopy  arterial and cerebrovenous lactate and water content in brain tissue was determined in 29 cats using the specific gravimetric technique  following injury  the phosphocreatine  pcr  pi ratio  which is an index of cerebral energy depletion  decreased to 76  in four untreated animals  to 79  in 11 tham treated animals  to 68  in seven animals receiving hyperventilation  and to 66  in seven animals with combination tham and hyperventilation therapy  the pcr pi ratio returned to a normal level in 8 hours in animals treated with tham and tham in combination with hyperventilation  the brain lactate index increased to 157  in the hyperventilation group after trauma  in cats receiving tham plus hyperventilation  the brain lactate index was reduced to 142   while the minimum rise of 126  was associated with treatment of tham alone  in the tham treatment and combination treatment groups  the water content of the white and gray matter was significantly decreased compared with that in untreated cat brains  prolonged hyperventilation provided relative ischemia in brain tissue and promoted more production of brain lactate  no recovery of the pcr pi ratio  and no decrease in brain edema  on the other hand  administration of tham decreased production of brain lactate and brain edema and promoted the recovery of cerebral energy dysfunction  it was found that tham ameliorates the deleterious effects of hyperventilation by minimizing energy disturbance and that it also decreases brain edema  the authors conclude that tham may be effective in reducing brain tissue acidosis and helpful as a metabolic stabilizing agent following severe head injury  
class10	post traumatic intracerebral pneumatocele  case report  pneumocephalus occurs in 0 5 to 1 0  of head trauma  but may also occur after neurologic surgery  or as a result of eroding infection or neoplasm  the pathophysiology involves the presence of craniodural fistula allowing ingress of air  a ball valve mechanism may allow air to enter but not exit the cranium  or csf leak permits air entrance as fluid leaves the intracranial space  while a  succession splash  is considered diagnostic of pneumocephalus  most patients have nonspecific signs and symptoms such as headache  therefore  a high index of suspicion in a patient with recent head trauma is necessary  the diagnosis is made radiographically by ct scan  this is generally performed to rule out intracranial hematoma or cerebral contusion in head trauma  but will reveal even very small quantities of air to the unsuspecting physician  therapy is often noninvasive  allowing the craniodural defect to heal spontaneously  selected situations require immediate operative repair of the fistula  
class10	fracture dislocation of the base of the fifth metacarpal with an ulnar motor nerve lesion  case report  we report a case of delayed diagnosis of a fracture dislocation of the base of the fifth metacarpal with a resultant ulnar motor nerve lesion  the patient achieved marked improvement after fracture reduction and ulnar neurolysis  
class10	otolaryngologic management of patients with subdural empyema  from 1979 to 1988  17 patients presented to duke university medical center for treatment of subdural empyema  empyemas were caused by sinusitis in 53  of the patients and by otitis media in 12   none of those with otologic causes required mastoid drainage  while all patients with sinus infections required sinus drainage  external frontoethmoidectomies were associated with a lower incidence of frontoethmoid re exploration  p   0 048   and antrostomies with a lower incidence of maxillary re exploration  p   0 111   than were more limited drainage procedures  sinus drainage performed simultaneously with neurosurgical drainage reduced the incidence of sinus re exploration  p   0 167   neurosurgical reexploration  p   0 048   and length of hospitalization  p   0 020   
class10	magnetic resonance imaging of facial nerve neuromas  facial nerve neuromas are uncommon tumors often confused with other tumors of the temporal bone and cerebellopontine angle  radiologically  it may be impossible to differentiate an intracanalicular facial nerve neuroma from an acoustic neuroma  we present three case reports of facial nerve neuromas arising within the internal auditory canal to show the important magnetic resonance imaging features of these tumors  one tumor extended into the cerebellopontine angle  middle cranial fossa  and middle ear  another filled the internal auditory canal and extended through the cerebellopontine angle to the brain stem  the third occurred in a patient who had neurofibromatosis as well as numerous other intracranial tumors  we feel that gadolinium enhanced magnetic resonance imaging provides the most useful information in the preoperative assessment of this disorder  
class10	sternocleidomastoid muscle transfer and superficial musculoaponeurotic system plication in the prevention of frey s syndrome parotidectomy may be associated with a significant depression in the retromandibular region and a significant incidence of gustatory sweating  frey s syndrome   superiorly and inferiorly based sternocleidomastoid flaps and posterior plication of the superficial musculoaponeurotic system were evaluated for their ability to ameliorate both consequences  sixteen patients with sternocleidomastoid flaps and 16 patients with superficial musculoaponeurotic system plication were compared to a control group of 104 patients  the incidence of frey s syndrome was 47 1  in the control group  12 5   p   0 025  in the sternocleidomastoid flap group  and 0   p   0 005  in the superficial musculoaponeurotic system plication group  the surgical techniques are described  the prevalence of frey s syndrome is discussed with respect to age  sex  radiation therapy  and the type of parotidectomy performed  the indications and contraindications of the three surgical techniques are described  
class10	neurotologic findings in basilar migraine  treatment of a patient with otologic symptoms and associated migraine like headache presents the otolaryngologist with formidable problems  although clinical practice and scientific publications recognize their frequent association  relationships have yet to be well defined  this study seeks to add order to disarray by delineating symptoms and signs of a clearly identified group of migraine patients  fifty patients with well defined basilar migraine underwent a thorough neurotologic examination  as well as comprehensive auditory and vestibular testing  patients were selected from 5880 patients seen over a 2 year period and were prospectively entered into the study after detailed questionnaires and testing were completed for each patient  the most common symptoms found were dysequilibrium  phonophobia  and head pressure  the most common signs were positional nystagmus  low frequency hearing loss  abnormal loudness discomfort level  and an abnormality on caloric examination  advanced vestibular testing showed abnormal amplitude scaling  abnormal toes down pertubation  and an abnormal sway  condition 6  on dynamic posturography  there was frequently an asymmetry on computerized rotation  the author concludes that the majority of patients have subtle findings on testing  but a few have severe peripheral injury due to the basilar migraine  findings are consistent with the theory that basilar migraine is a central nervous system maladaptation syndrome which creates otoneurologic symptoms and  in a small percentage of cases  may injure the peripheral end organ  
class10	headache  public health problem  headache is  and apparently always has been  a frequent pain syndrome  it is reported in american and western european societies in very high percentages of the population  headache  and specifically severe headache  have also been reported as prevalent from a variety of societies worldwide  although prevalence rates have varied  they are very low  for example  in the people s republic of china   whether prevalence varies with different socioeconomic groups remains uncertain  severe headache and specifically migraine is  for reasons still unknown  much more common in women  and  in most studies  is reported to decrease in prevalence in older age groups  positive family histories are common  but the precise role of genetics is unknown  a major problem in the epidemiologic studies remains the difficulty of uniform definition of headache syndromes  
class10	the classification and diagnosis of headache disorders  headache disorders recently have been reclassified  and new operational diagnostic criteria assist in making the correct diagnosis  these diagnostic criteria have been accepted worldwide  
class10	basic mechanisms in vascular headache  to better understand and treat painful conditions  one needs to identify the cause  discover the source  and develop knowledge of peripheral and central pain transmission  headaches are no exception  the development of appropriate animal models is important  accordingly  we have reviewed the anatomy  neurochemistry  electrophysiology  and pharmacology of the trigeminovascular system in experimental animals and emphasized whenever possible the relevance of this final common pathway to migraine  cluster  and other headache syndromes in humans  for example  based on recent anatomic dissections  the pericarotid cavernous sinus plexus was suggested as an important focus to investigate cluster headache pathophysiology  this plexus is an anatomic point of convergence for the nerves giving rise to the signs of sympathetic and parasympathetic activity and sensory symptoms that develop in cluster patients  as in other nociceptive systems  trigeminovascular axons assume at least two important roles  one concerns the transmission of nociceptive information  electrophysiologic evidence supports the trigeminal nucleus caudalis as an important site for the convergence of visceral  vessel  and somatic  forehead  inputs to mediate the referral of vascular pain to superficial tissues  a second important role concerns the initiation of local increases in blood flow and enhanced protein permeability  sterile inflammation  via the axonal release of vasoactive neuropeptides  plasma extravasation develops within the dura mater following trigeminal stimulation  extravasation can be blocked by the administration of ergot alkaloids or sumatriptan  a new serotonin like agonist  and a prejunctional  neuronal  mechanism of action for these drugs  such as blockade of release  was suggested based on experimental evidence  whether vasoconstriction also relates to the therapeutic efficacy remains to be determined  as in other organ systems  real or threatened tissue injury provides an important stimulus for depolarizing sensory fibers  the stimulus may come from external conditions such as reduced blood flow or hypoglycemia  the brain may also possess intrinsic neuronal mechanisms by which nociceptors may be synthesized  e g   glutamate induced neurotoxicity  seizures   molecules of relevance include bradykinin  prostaglandins  leukotrienes  and potassium  experimental evidence was presented demonstrating that the trigeminal nerve mediates hyperemia within cortical gray matter by axon reflex like mechanisms  an important role for this nerve was established during the hyperemic period of recirculation after ischemia or during severe hypertension above the limits of autoregulation  abstract truncated at 400 words   
class10	the concept of migraine as a state of central neuronal hyperexcitability  this article explores the hypothesis that migraine with aura is associated with a state of central neuronal hyperexcitability  the authors propose that this central neuronal hyperexcitability involves overactivity of the excitatory amino acids  glutamate  and possibly aspartate  stimuli that activate the migraine attack evoke neuronal depolarization  slow depolarization shifts  and spreading suppression of spontaneous neuronal activity possible by glutamate and k  dependent mechanisms  a low brain mg2  and consequent reduced gating of glutamatergic receptors may provide the link between the physiologic threshold for a migraine attack and the mechanisms of the attack itself by promoting glutamate hyperactivity  neuronal hyperexcitability  and susceptibility to glutamate dependent spreading depression  
class10	developments in 5 hydroxytryptamine receptor pharmacology in migraine  because a satisfactory animal model for migraine does not exist  attempts to determine a common mechanism of action for effective antimigraine agents may be of benefit in elucidating the pathogenesis of this neurologic syndrome  the present review demonstrates that the clinical data that has developed over the past 30 years may allow for the elucidation of the role of specific 5 ht receptor subtypes in the pathophysiology of migraine  a large number of both acute and prophylactic antimigraine agents share an ability to interact with 5 ht receptor subtypes in human brain  as summarized in table 3  acute antimigraine drugs  e g   ergots  sumatriptan  share high affinity for 5 htid receptors and somewhat lower affinity for 5 ht1a receptors  these receptors are present in certain intracranial blood vessels  5 ht1d receptors are also located on nerve terminals where they act to inhibit the release of 5 ht and other neurotransmitters  theoretically  5 htid receptor agonists may acutely inhibit the release of vasoactive or pain inducing substances in the perivascular space  conceivably  drugs acting at this receptor would stop the progression of this perivascular process  in addition  a number of prophylactic antimigraine drugs display a relatively high affinity for both 5 ht2 and 5 ht1c receptors in human brain  although these receptors are also found in certain blood vessels  they are present throughout the nervous system  the receptors appear to mediate neuronal depolarizations at the cellular level  moreover  the 5 ht2 receptor appears to play a key role in the development of inflammation in certain smooth muscle systems  theoretically  the ability of 5 ht2 antagonists to protect perivascular inflammation may account for their efficacy in the prophylactic treatment of migraine  these data offer a novel approach to the analysis of antimigraine agents  drugs could be selected for use in clinical migraine studies based on their selectivity for a specific 5 ht receptor subtype  for example  an agent that displays both high affinity and selectivity for 5 ht1d receptors could be clinically evaluated  its effectiveness  or lack thereof  would indicate the importance of this specific 5 ht receptor site in the pathogenesis of migraine  future attempts to determine a common mechanism of action for effective antimigraine agents should facilitate the elucidation of the pathogenesis of this neurologic syndrome  
class10	manifestations of migraine  migraine is a disorder with multiple manifestations affecting the circulation  gastrointestinal tract  and the central nervous system  involvement of the autonomic nervous system is responsible for many of the clinical features  an attack of migraine can vary from a fragment of the clinical spectrum to one with several phases and potentially permanent sequelae  
class10	modern pharmacotherapy of migraine  rectal ergotamine and naproxen are the major candidates for the ad hoc treatment of migraine attacks  for particularly dramatic episodes  intravenous dhe with prochlorperazine is the author s preference  for long term stabilization  after simpler measures fail  valproate appears to be a major addition to migraine therapy  
class10	advances in cluster headache  the physician may have to combine the art and science of medicine in the management of this most fascinating of human ailments  the choice of drugs and the length of treatment prescribed are greatly influenced by the individual physician s experience  convictions  and reasoning  needless to say  chronic use of narcotics should be avoided  the author s own regimen is to use combinations of ergotamine prophylaxis with either verapamil or prednisone in episodic cluster headache and with lithium for chronic cluster headache  management of the treatment resistant patient remains problematic  but a carefully performed trigeminal radiofrequency thermocoagulation procedure may be worthwhile  
class10	drug induced headache  headache induced by medications used for nonheadache conditions  and more importantly  headache perpetuated by symptomatic medications used for primary headache disorders are discussed in detail in this article  the clinical features and mechanisms of drug induced headaches are reviewed  ergotamine and analgesic rebound phenomena are described  management strategies for drug induced headaches are outlined  
class10	oromandibular disorders and headache  a critical appraisal  oromandibular disorders are functional disorders and associated pains in the anatomic region of the temporomandibular joint  their diagnosis and treatment are controversial because of the lack of conformity concerning these disorders among health care providers  this article provides a clear classification of these disorders and critically reviews their evaluation and treatment  
class10	headache and acquired immunodeficiency syndrome  because the acquired immunodeficiency syndrome  aids  virus is neurotropic  physicians will continue to see a rise in the number of neurologic complications of this syndrome  much of this increase will be accompanied by headache  not only as a primary symptom of hiv infection or opportunistic disease but also as a result of diagnostic tests and therapeutic efforts  complete understanding of the ramifications of headache in aids will be important in the 1990s as we continue to treat a younger population  usually affected by benign vascular and muscle contraction type headache  
class10	psychologic and behavioral aspects of chronic headache  it is important for physicians to be aware of the expectations and psychologic needs patients have  to understand how psychologic and personality variables can impact care  to realize the importance of patient education  and to be cognizant of how environmental factors can influence headache pain behaviors  empirical data indicate that the nonpharmacologic treatments of biofeedback  relaxation  and stress coping training can serve as useful adjunctive or alternative procedures  and that the combined use of medication and nonpharmacologic treatments yields the greatest clinical outcome  certain headache types show minimal response to nondrug therapies alone  cluster  menstrual  and post traumatic headache   age and personality variables have a bearing on nondrug treatment outcome as well  
class10	development of a traumatic intracranial hematoma after a  minor  head injury  we have analyzed features of patients who had what appeared initially to be a minor head injury but who developed an acute traumatic intracranial hematoma  over a 10 year period  183 patients who were able to open their eyes spontaneously  were oriented to person  place  and time  and who obeyed commands when they were first seen at a hospital subsequently underwent operation for an acute intracranial hematoma  the hematoma was extradural in 54  of these patients  a history of altered consciousness or symptoms of headache and vomiting were present in 61  of the patients  33  had a focal neurological deficit  and 43  had either focal deficit or signs of a basal skull fracture  a skull fracture was shown radiologically in 60  of patients  including 52  of those not clinically suspected of having an intracranial lesion  six months after injury  77  of the patients had made a moderate or good recovery  the possibility that a patient who has recently sustained a head injury might develop an acute intracranial hematoma can never be completely discounted  even when there are no abnormal clinical signs  and a skull x ray retains a useful place in the investigation of selected patients with a minor head injury  
class10	experimental intracerebral hemorrhage  early removal of a spontaneous mass lesion improves late outcome  the purpose of the present study was to determine whether early removal of an experimental intracerebral mass altered cerebral blood flow  brain water content  neuropathological findings  or neurological function 24 hours later  in three experimental series  a 50 microliter balloon was inflated within the right caudate nucleus in rats  at 24 hours after inflation  we studied cerebral blood flow by quantitative autoradiography  brain specific gravity  and qualitative histopathology by light microscopy  the animals were also assessed using a simple neurological deficit scale  in each series  half of the animals had the balloon inflated for 10 minutes  group 1   and half had the balloon inflated permanently  group 2   after transient inflation  there were surprisingly small differences in the blood flow between the two cerebral hemispheres at 24 hours  by contrast  in animals with permanent inflation  several indices of blood flow were significantly worse in the hemisphere ipsilateral to the balloon  the mean and median blood flow levels in the caudate nucleus  the mean blood flow in the cerebral cortex  and the area of cortex with ischemic levels of blood flow  the specific gravity was reduced in areas surrounding the site of balloon insertion after either transient or permanent inflation  and there was evidence of ischemic cell damage in all animals studied  these changes were more severe after permanent inflation  but the differences were not significant  neurological outcome was significantly better after transient as compared with permanent inflation  the present findings contradict previous results and suggest that early removal of an intracerebral mass may have subsequent benefits  
class10	the children s orientation and amnesia test  relationship to severity of acute head injury and to recovery of memory  the children s orientation and amnesia test  coat  was developed to assess cognition serially during the early stage of recovery from traumatic brain injury in children and adolescents  the norms for the coat  which is composed of 16 items evaluating general orientation  temporal orientation  and memory  were defined from data obtained from 146 children aged 3 to 15 years  in 37 patients with head injuries  the duration of posttraumatic amnesia  as indicated by the number of days coat scores were in the impaired range  was significantly related to both verbal and nonverbal memory at the baseline and 6 and 12 months after injury  coat scores were a better predictor of verbal and nonverbal memory performance than the glasgow coma scale score at 6 and 12 months after the injury  this study shows that the coat has adequate reliability and validity as a measure of the duration of posttraumatic amnesia in children and adolescents  
class10	surgical decompression without transposition for ulnar neuropathy  factors determining outcome  fifty one surgical decompressions without nerve transposition for ulnar neuropathy were performed in 46 patients  all of the patients were men with an average age of 59 years at the time of surgery  the follow up range was between 5 and 32 months  average  17 8 months   the disease involved the nondominant arm in 24 patients  52   and was bilateral in 5  11    in 23 cases  50    no predisposing condition could be identified  whereas 15 patients  33   abused alcohol and 8 patients  17   had diabetes mellitus  fifty seven percent of the patients helped by surgery had symptoms for less than 1 year  whereas only 30  of patients with symptoms for more than 1 year had symptomatic improvement  the relative magnitude of the slowing of ulnar nerve conduction velocity across the elbow was not significantly correlated with the success of decompression in relieving symptoms  ulnar nerve conduction velocities across the elbow were 36 13     11 76 m s in those responding to surgery and 38 97     13 91 m s in those not responding  c   0 06  df   50  p less than 0 3   a total of 37 patients showed symptomatic improvement after decompression  simple decompression of the ulnar nerve was performed under local anesthesia without transposition of the nerve  in all of these cases  compression of the nerve occurred predominantly in the epicondylar groove  narrowing of the nerve in the groove was present in 28 cases  55    scar tissue was found adhering to the nerve in 21 cases  41    and two pseudoneuromas were found  4    forty one operations  80   resulted in symptomatic improvement  typically noted by the patient within the first month postoperatively  
class10	hemorrhagic pituitary adenomas  clinicopathological features and surgical treatment  forty five  9 9   of 453 pituitary adenomas operated on between january 1973 and november 1988 demonstrated hemorrhagic changes at surgery  24 had a blood collection  12 had a blood collection associated with hemorrhagic necrosis  and 9 had hemorrhagic necrosis  thirteen patients  28 9   experienced the acute symptoms of pituitary apoplexy  whereas another 32 had an  asymptomatic  hemorrhage  that is  the clinical course was comparable to an uncomplicated adenoma  nineteen tumors  42 2   showed marked suprasellar extension  8  17 8   showed moderate extension  and 11  24 5   showed slight extension  another 2  4 4   were laterosellar and 5  11 1   were intrasellar  invasive behavior was present in 32 cases  71 1   and this may suggest another hypothesis to explain the pathogenesis of tumoral hemorrhage  the incidence of hemorrhagic complications in invasive adenomas with marked suprasellar extension was particularly impressive  therefore  we do not suggest preoperative bromocriptine treatment in this type of tumor  two of 14 patients operated on by the transcranial route died after surgery  whereas there was no operative mortality in the 31 patients operated on by the transsphenoidal route  it proved advantageous to operate as early as possible  even during the acute phase of pituitary apoplexy  the transsphenoidal approach gave the best results  but to achieve satisfactory late results multidisciplinary treatment was necessary  namely  postoperative radiotherapy in 23 patients  bromocriptine in 12  and endocrine replacement therapy in almost all  in an average follow up period of 6 2 years  5  11 1   symptomatic recurrences were observed  
class10	the association of hydrocephalus with intramedullary spinal cord tumors  a series of 25 patients  171 patients with intramedullary spinal cord tumors were operated on  of which 25 patients  15    mostly children  developed symptomatic hydrocephalus  twenty patients  12   had malignant tumors  with 13 of the 20 cases  63   complicated by increased intracranial pressure and ventriculomegaly  of the remaining 151 patients with benign tumors  89    only 12  8   developed symptomatic hydrocephalus  in an effort to understand the relationship between hydrocephalus and intramedullary spinal cord tumor  the authors analyze the level and histology of the neoplasm  as well as its association with spinal cysts  a review of the neurosurgical literature reveals that 34 similar cases of hydrocephalus associated with intramedullary spinal cord tumors have been reported to date  the authors note that the presence of hydrocephalus in patients with malignant intramedullary astrocytomas is associated with a shorter rate of survival than in those patients with high grade lesions but without hydrocephalus  apparently due to rapid tumor progression  the ventriculomegaly seen with benign spinal cord gliomas has no statistically significant effect upon long term prognosis  
class10	antimigraine treatment for slit ventricle syndrome  slit ventricle syndrome is characterized by chronic or recurring headaches associated with subnormal ventricular volume in patients who have undergone shunt treatment for hydrocephalus  there appear to be at least three pathophysiological mechanisms that cause this syndrome  1  intermittent shunt malfunction  2  intracranial hypotension  and 3  paroxysms of increased intracranial pressure in the presence of normal shunt function  to treat seven patients with slit ventricle syndrome caused by paroxysms of elevated intracranial pressure  we successfully used antimigraine therapy rather than standard calvarial expansion procedures  none of these patients has required shunt revision or calvarial expansion during a mean follow up period of 2 years  the symptoms of slit ventricle syndrome may be a form of  acquired  migraine in shunt patients  we suggest that  in clinically stable patients with normal shunt function  treatment against migraine may stabilize symptoms resulting from paroxysms of increased intracranial pressure  such treatment may prevent unnecessary shunt revisions and or calvarial expansion procedures  
class10	meningiomas involving the clivus  a six year experience with 41 patients  a series of 41 meningiomas involving the clivus operated on from july 1983 to january 1990 is reported  the presenting symptoms and signs of these patients were similar to those reported previously  all the patients were evaluated by pre  and postoperative thin section  high resolution computed tomography using soft tissue and bone algorithms  most of the patients also underwent magnetic resonance imaging  the regions of the clivus involved by tumor were divided into upper  middle  or lower regions on the basis of anatomical landmarks  the diameter of the tumor was measured in three axes  and a tumor volume and a tumor equivalent diameter were computed to categorize tumors as small  medium  large  or giant types  there were 9 medium  27 large  and 5 giant tumors in this series  some simple and some complex operative approaches were employed to effect tumor removal  large and giant tumors often required more than one operative approach to remove the tumor  intraoperative technical difficulties included tumor consistency  vascularity  dissection from the brain stem  and vascular and cranial nerve encasement  postoperative computed tomographic scans documented total excision in 32 patients  78    residual tumor remained in the clival or cavernous sinus areas  these patients were either being observed  or were treated with gamma knife radiosurgery  there was one operative death due to pneumonia  2    and three patients  7   suffered permanent major neurological changes  presumably due to vascular occlusions in the posterior circulation  in the follow up period  which ranged from 3 to 76 months  2 patients  6   with tumors that had appeared to be totally excised experienced recurrence  these patients were treated by a second operation  alone or in combination with radiation therapy  two patients who had subtotal excisions  25   had evidence of regrowth  in 2 patients  tumor growth continued despite gamma knife radiosurgery or external beam radiotherapy  
class10	entrapment neuropathy of the median nerve at the level of the ligament of struthers  the presence of a supracondylar process and struthers  ligament is a rare congenital anomaly that may cause compression of either the median nerve  the brachial artery  or both  the authors present a case in which the supracondylar process and struthers  ligament compressed both the median nerve and the brachial artery  this case is unusual  in that the symptoms of compression of the brachial artery increased  namely  the pulse intensity decreased and the pain increased with elbow flexion  
class10	spinal hemangioblastoma  syrinx  and hydrocephalus in a two year old child  a two year old child presented with an acute inability to bear weight  radiological investigation revealed a large cervicothoracolumbar syrinx of no known cause  during investigation  acute communicating hydrocephalus developed  which required a shunt  at surgery  a small thoracic spinal cord hemangioblastoma was discovered and excised  complete recovery with collapse of the syrinx followed  the clinical features of this rare childhood tumor and its associated effects are discussed  
class10	an intracranial mass lesion in systemic xanthogranulomatosis  case report  the authors describe a 42 year old woman with systemic xanthogranulomatosis and bilateral intraorbital tumors  who subsequently developed multiple lesions of the intracranial dura mater  spinal cord  retroperitoneum  pericardium  and mediastinum  systemic xanthogranulomatosis is histologically similar to systemic weber christian disease  except for the absence of subcutaneous panniculitis  immunohistochemical studies suggest that this clinical entity can be differentiated from histiocytosis x  because foamy cells in systemic xanthogranulomatosis demonstrate macrophages but not t zone histiocyte markers  differentiation of this disease from other intracranial xanthogranulomas and treatment are discussed  
class10	fine surface structure of an intraspinal neurenteric cyst  a scanning and transmission electron microscopy study  the case of an 11 year old boy with an intraspinal neurenteric cyst  which recurred 8 years and 3 months after surgery  is presented  scanning and transmission electron microscopy of the cyst epithelium revealed marked resemblance to that of the respiratory tract  despite the presence of numerous goblet cells mimicking intestine on light microscopy study  detailed ultrastructural findings are described  
class10	syringomyelia secondary to compression of the cervical spinal cord by an extramedullary lymphoma  a case of syringomyelia secondary to an extramedullary cervical spinal cord compression by a non hodgkin s lymphoma is described  after radiotherapy  the syrinx was no longer seen  the pathogenesis of this type of syrinx is discussed  and the potential benefit of radiotherapy in these cases is suggested  
class10	stridor  intracranial pathology causing postextubation vocal cord paralysis  during an 18 month period in a pediatric intensive care unit  nine patients with vocal cord paralysis were identified using flexible bronchoscopy  when tracheally extubated  each child was found to have stridor  the children ranged in age from 17 days to 5 1 2 years  two patients had unilateral paralysis  but neither required tracheostomy  seven patients displayed bilateral abductor vocal cord paralysis  of these  six patients required tracheostomy  surgical injury to the recurrent laryngeal nerve was the probable cause in two patients  the other seven patients had neurologic disorders with documented or suspected increases of intracranial pressure  four of the seven patients with bilateral abductor vocal cord paralysis regained cord mobility within 4 months  both children with unilateral cord paralysis have no stridor and vocalize well 1 year later  cord paralysis in the setting of intracranial hypertension probably results from compression or ischemia of the vagus nerve before it exits the skull  early visualization of the larynx should be done in patients who become stridulous when extubated  especially those with prior thoracic procedures or with neurologic disorders associated with intracranial hypertension  
class10	relationship between duration of spinal cord ischemia and postoperative neurologic deficits in animals  stagnara wake up tests  blood flow measures  somatosensory evoked potentials  seps   and neurogenic motor evoked potentials  nmeps  were elicited from 20 hogs before and after spinal cord overdistraction at l3 l4  overdistraction was maintained from 5 to 30 minutes after loss of nmeps  results suggest that the longer the duration of overdistraction the greater the likelihood of paraplegia  blood flow measures indicated that reduced perfusion was greatest at the distraction site but extended proximally and distally  finally  nmeps were more sensitive to onset of overdistraction and a more valid indicator of paraplegia than seps  nmeps should provide the surgeon with more time for initiation of intervention techniques than seps  because nmeps and seps provide information regarding different spinal cord tracts  the authors continue to use both methods for monitoring the functional integrity of the human spinal cord during corrective spine surgery  
class10	urologic function after experimental cauda equina compression  cystometrograms versus cortical evoked potentials  twenty female beagle dogs underwent an l6 7 laminectomy and six dogs each had 25  50 or 75  constriction of the cauda equina and 2 control dogs had laminectomy only  cystometrograms were performed pre  and post operatively and three months after constriction  cortical evoked potentials were monitored pre  and post operatively and monthly for three months  after three months of constriction  the cauda equina of these dogs in each group was examined histologically and vascular circulation was examined by latex and india ink injection  spalteholz technique   the control dogs had normal cmgs and ceps  twenty five percent constriction caused no cmg changes and mild cep changes  fifty percent constriction caused no statistically significant cmg changes  major cep changes and venous congestion of the nerve roots and dorsal root ganglia  seventy five percent constriction produced severe cmg changes with detrusor areflexia  increased bladder capacity and clinical incontinence  ceps also had marked deterioration  vascular analysis revealed severe arterial narrowing at the level of constriction and venous congestion of the nerve roots and dorsal root ganglia  blockage of axoplasmic flow and nerve root atrophy was seen in all dogs with 75  constriction  cortical evoked potentials were the most sensitive predictor of neural compression  cmgs were not sensitive until severe compression was achieved  bladder dysfunction  i e   detrusor areflexia  appears to occur with blockage of axoplasmic flow and early sensory changes occur with neurovenous congestion  
class10	delayed anterior decompression in patients with spinal cord and cauda equina injuries of the thoracolumbar spine  forty nine patients with complete and incomplete injuries of the spinal cord or cauda equina who had undergone anterior decompression at a minimum of 3 months after injury were examined  follow up was from 12 months to 19 years  postoperative neurologic improvement occurred in 46 5  of patients with incomplete injuries  if the surgery was performed less than 2 years after injury  neurologic improvement occurred in 68  with an improvement in frankel grade of 32   bladder function improved in 27  of patients and if operated on less than 2 years after injury improvement occurred in 43   conus medullaris decompression resulted in a 50  improvement  there was an 83  improvement in the pattern of pain after decompression  of 23 patients with preoperative spasticity  10 improved but 6 were worse after surgery  
class10	blood flow direction in the lumbar nerve root  the effect of clipping on lumbar nerve root blood flow rates in the region of the nerve root canal was studied experimentally in the hog  blood flow rate was measured using the hydrogen washout technique  when the entrance zone was clipped with a microvascular clip  blood flow rate of the nerve root was decreased by 37  in comparison with the initial control rate  clipping at the exit zone reduced blood flow rate by 69   blood flow direction in the lumbar nerve root within the nerve root canal was found to be predominantly proximal  the current data indicate that the more lateral the impingement of the nerve root occurs  the more ischemic changes are induced  
class10	therapy of diseased stroke prone spontaneously hypertensive rats with nimodipine  we investigated the therapeutic effect of nimodipine or parathyroidectomy in old  diseased stroke prone spontaneously hypertensive rats by observing 98 male 1 year old rats over 5 months  after stroke had occurred  the rats were divided into three groups  1  parathyroidectomy  2  nimodipine  and 3  controls  in the nimodipine group  the rats survived longer than those in the other groups  blood pressure of the controls did not differ from the nimodipine treated and parathyroidectomy animals  the increase in calcium content of brain and kidney tissues and of plasma renin activity  urea  and creatinine was attenuated by nimodipine or parathyroidectomy  the histology of the kidneys revealed widespread fibrinoid necrosis of arteries in all rats  in the nimodipine treated or parathyroidectomy groups  healing of the lesions was detectable  cerebral lesions were mainly characterized by fibrinoid necrosis  nimodipine treated as well as parathyroidectomied animals showed significantly fewer hypertensive cerebral lesions  in old  diseased stroke prone spontaneously hypertensive rats  therapy with nimodipine or parathyroidectomy increased their survival rate  the cerebrovascular and renovascular lesions of treated animals were attenuated  and morphologic signs of healing were observed  reduction of calcium overload by nimodipine or parathyroidectomy  even in an advanced stage of disease  had a therapeutic effect  
class10	preventing stroke by the modification of risk factors  epidemiologic research has revealed the major risk factors in cerebrovascular disease  this review will concentrate on three important risk factors  elevated blood pressure  the most common and important  since it is responsible for up to 70  of all strokes  raised cholesterol  and smoking  these factors are important not only because they increase the risk of stroke  but also because they are amenable to modification by drugs  diet  or other interventions  strategies to avoid stroke can either 1  try to produce substantial reductions  usually with drugs  in the level of the risk factor in the few individuals in the population with high levels  the  high risk  approach   or 2  try to produce modest reductions in the level of the risk factor in every individual in the population  usually not with drugs but with lifestyle modification  the  mass  approach   the prevention of stroke could best be achieved through continuing medical efforts to deal with high risk individuals and through political strategies to encourage a healthier lifestyle in the population as a whole  
class10	cytosolic free calcium during focal cerebral ischemia and the effects of nimodipine on calcium and histologic damage  the role of calcium as a mediator in neuronal death during ischemia is now quite strong  evidence supporting this link includes studies in cell cultures and measurements of calcium accumulation in the mitochondria during ischemia  as well as direct measurements of shifts in extracellular calcium using microelectrodes  since it is dangerously high concentrations of the intracellular free calcium that have been hypothesized to lead to neuronal damage  direct in vivo measurements of this parameter in ischemia are important  a technique for the measurement of intracellular free calcium is described  along with data from studies that dramatically demonstrate the time course of changes in intracellular free calcium induced by focal ischemia  additional data are also presented that indicate that cellular damage can be attenuated by the use of agents that block calcium channels  nimodipine  which blocks voltage sensitive calcium channels  and mk 801  which blocks receptor operated channels  and support the concept that these agents owe their beneficial effects to their ability to reduce the accumulation of intracellular calcium  
class10	effect of nimodipine on acute ischemic stroke  pooled results from five randomized trials  in a review of pooled data from five double blind  placebo controlled studies of nimodipine in acute ischemic stroke  we compared the effect of 120 mg nimodipine given orally with that of placebo  in the five studies  871 patients were followed  and 781 adhered to entry and inclusion criteria  end points were mortality and outcome at the end of the treatment period  21 or 28 days   outcome was assessed with mathew s scale and the physician s clinical judgement  the treatment and control groups were well matched with respect to demographic data  risk factors  and baseline mathew scores  in the treatment group  34 patients  7 9   died during the treatment period  whereas 54  12 3   in the control group died  corresponding with a mortality reduction of 36   significantly less neurologic impairment at the end of the treatment period was documented under nimodipine treatment  and this impairment improved more in patients with moderate to severe stroke  baseline mathew score less than 66  if administration of nimodipine occurred within 12 hours after stroke onset or if the patient was more than 65 years old  the overall incidence of adverse reactions was relatively modest  and these were of minor severity  only a few appeared to have more than a remote relation to the study medication  
class10	effects of nimodipine on infarct size and cerebral acidosis after middle cerebral artery occlusion in the rat  the objective of this study was to determine the effect of nimodipine on infarct development and local brain ph after middle cerebral artery occlusion in the rat  female fischer 344 rats were subjected to permanent occlusion of the left middle cerebral artery by electrocoagulation  after 6  12  or 24 hours  brains were frozen  and infarct size  degree of edema formation  and local brain ph were quantified by standard histology or the umbelliferone technique  respectively  in control rats  cortical infarct size was increased from 29 5 microliters at 6 hours to 72 5 microliters at 24 hours after vessel occlusion  in striatum only  an insignificant increase from 15 2 to 24 7 microliters in infarct volume was observed during this period  edema increased from 7  to 22  in cortical and from 4  to 39  in the striatal infarct areas during this time  nimodipine  0 1 mg kg s c    given 45 minutes before and again 8 and 16 hours after middle cerebral artery occlusion  did not alter infarct size at 6 hours but considerably improved outcome at later times  edema formation was lower at 12 hours in the group treated with the calcium antagonist  p less than 0 05   by contrast  effects on local brain ph were seen as early as 6 hours after the vessel occlusion  nimodipine greatly reduced the areas exhibiting the lowest ph values beyond ph 6 0  p less than 0 05   similar effects by nimodipine on brain ph were observed in the 12 hour series  whereas at 24 hours after middle cerebral artery occlusion  a shift to more alkalotic values was noted with no overt differences between control and drug treated groups  
class10	effects of dietary calcium on nimodipine sensitive calcium channel function in stroke prone spontaneously hypertensive rats  we studied the effects of dietary ca2  on blood pressure  survival  and calcium channel function to investigate cardiovascular disease mechanisms in stroke prone spontaneously hypertensive rats  beginning at 3 weeks of age  rats were fed high sodium chloride diets  8 0   in combination with either high  2 0   or low  0 2   ca2  diets for 8 weeks  at 12 weeks of age  survival was 90  in the high ca2  group and 30  in the low ca2  group  the higher blood pressure and lower survival in the low ca2  group suggest an intensification of altered vascular muscle cell mechanisms by a dietary ca2  deficit  nimodipine  1 10 nm  effectively blocked l type ca2  currents in isolated vascular muscle cells from both groups  contraction of isolated cells that were not patch clamped to high potassium solutions were also blocked by 1 nm nimodipine  disappearance of the l type ca2  channel current was accelerated by holding at depolarizing potentials  positive to  50 mv  and by depolarizing steps to 0 mv  nimodipine block of the l type ca2  currents in vascular muscle is believed to contribute substantially to antihypertensive properties and stroke prevention  actions that may develop fully only in stroke prone spontaneously hypertensive rats on a diet of at least normal ca2   
class10	tardive dyskinesia  tardive dyskinesia is a potentially irreversible syndrome of involuntary hyperkinetic movements that occur in predisposed persons receiving extended neuroleptic  antipsychotic  drug therapy  it is usually characterized by choreoathetoid dyskinesias in the orofacial  limb  and truncal regions  but subtypes of this syndrome may include tardive dystonia and tardive akathisia  although the mechanisms underlying the pathogenesis and pathophysiology of this disorder are unproven  altered dopaminergic functions will likely play a role in any explanation of it  tardive dyskinesia develops in 20  of neuroleptic treated patients  but high risk groups such as the elderly have substantially higher rates  risk factors include age  female sex  affective disorders  and probably those without psychotic diagnoses  including patients receiving drugs with antidopaminergic activity for nausea or gastrointestinal dysfunction for extended periods  total drug exposure is positively correlated with tardive dyskinesia risk  management strategies include a careful evaluation of both the psychiatric and neurologic states  a broad differential diagnosis  and adjustment of neuroleptic agents to the lowest effective dose that controls psychosis and minimizes motor side effects  no drug therapy is uniformly safe and effective for treating this disorder  a favorable long term outcome of improvement or resolution correlates with younger age  early detection  lower drug exposure  and duration of follow up  
class10	cerebellar syndrome caused by isoniazid  treatment of tuberculosis in a hemodialysis patient with isoniazid  rifampin  and pyrazinamide resulted in the development of acute cerebellar dysfunction  this resolved rapidly following the discontinuation of isoniazid and pyrazinamide  reinstitution of isoniazid at a lower dose  and addition of pyridoxine  we discuss why we believe this syndrome was caused by isoniazid  patients with renal failure who undergo antituberculous therapy with isoniazid should receive supplemental pyridoxine to reduce the likelihood of isoniazid related neurotoxicity  
class10	excipients in valproic acid syrup may cause diarrhea  a case report  a 5 year old child receiving valproic acid syrup for seizure control developed diarrhea probably from the excipient ingredients  each 5 ml of valproic acid syrup contains sucrose 3 g  glycerin 0 75 g  and sorbitol 0 75 g  providing daily amounts of 36  9  and 9 g of sucrose  glycerin  and sorbitol  respectively  the diarrhea resolved when the child was switched to another valproic acid product  clinicians should be aware of potential problems that may occur from excipient ingredients in pharmaceutical products when evaluating adverse effects of medications  
class10	the relationship between viral rna  myelin specific mrnas  and demyelination in central nervous system disease during theiler s virus infection  the da strain of theiler s murine encephalomyelitis virus  dav  causes a chronic demyelinating disease in susceptible mouse strains  to elucidate the pathogenesis of dav induced demyelination  the authors investigated the spatial and chronologic relationship between virus  antigen and rna   myelin specific mrnas  and demyelination in dav infected mice using immunohistochemistry  in situ hybridization  and slot blot hybridization analyses  in spinal cord white matter  viral rna was detected easily in ventral root entry zones 1 to 2 weeks after infection  viral rna increased to maximum levels by 4 weeks after infection  which was associated with inflammation and mild demyelination  at 8 to 12 weeks after infection  when demyelination became most extensive  viral rna was significantly decreased  demyelination did not chronologically or spatially parallel the presence of viral rna within the spinal cord  decrease of myelin specific mrnas  including myelin basic protein and proteolipid protein mrnas  was observed within the demyelinating lesions with or without detectable viral rna  these results indicate that a viral infection of white matter in the early phase of the infection initiates spinal cord disease leading to demyelination  but later an ongoing immunopathologic process contributes to the presence of extensive demyelination  
class10	sleep disturbances in survivors of the nazi holocaust  objective and method  sleep disturbances are commonly reported by victims of extraordinary stress and can persist for decades  this study was designed to test the hypothesis that survivors of the nazi holocaust would have significantly more and different sleep problems than depressed and healthy comparison subjects and that the severity of the survivors  problems would be correlated with length of time spent in a concentration camp  forty two survivors  37 depressed patients  and 54 healthy subjects of about the same age  all living in the community  described their sleep patterns over the preceding month on the pittsburgh sleep quality index  a self rating instrument that inquires about quality  latency  duration  efficiency  and disturbances of sleep  use of sleep medication  and daytime dysfunction  results  the survivors had significantly greater sleep impairment than the healthy comparison subjects  as measured by all subscales of the index  but had less impairment than the depressed patients except on the sleep disturbances and daytime dysfunction subscales  however  for specific items within these subscales  survivors had significantly more frequent awakenings due to bad dreams and had less loss of enthusiasm than the depressed subjects  sleep disturbances and frequency of nightmares were significantly and positively correlated with the duration of the survivors  internment in concentration camps  conclusions  these findings suggest that for some holocaust survivors  impaired sleep and frequent nightmares are considerable problems even 45 years after liberation  
class10	use of neuroleptic induced extrapyramidal symptoms to predict future vulnerability to side effects  objective  susceptibility to neuroleptic induced extrapyramidal syndromes varies widely  even within age and sex subgroups  individual vulnerability to extrapyramidal syndromes has been assumed to explain this  but the utility of past history for predicting future occurrence of extrapyramidal syndromes has not been studied extensively  this investigation was undertaken to determine whether patients  previous histories of extrapyramidal syndromes predict future episodes of extrapyramidal syndromes and to compare the importance of this predictive factor with patient age  sex  neuroleptic dose  and anticholinergic dose as predictors of extrapyramidal syndromes  methods  the charts of 62 schizophrenic patients with multiple neuroleptic treatment episodes were reviewed  extrapyramidal syndromes  neuroleptic drug doses  and anticholinergic drug doses during the first 21 days of each treatment episode were recorded  results  previous extrapyramidal syndromes correctly predicted extrapyramidal syndromes in subsequent treatments for 84  of the patients  variations in neuroleptic potency  neuroleptic dose  and anticholinergic dose partially explained incorrect predictions  conclusions  these results support the hypothesis that patients with a history of extrapyramidal syndromes are at greater risk for future extrapyramidal syndromes  if confirmed  these results strongly support individual susceptibility as a major predictor of extrapyramidal syndromes and indicate that prophylaxis of extrapyramidal syndromes should be considered for patients who have previously suffered extrapyramidal syndromes from similarly prescribed neuroleptic therapy  
class10	acute phase reactants and risk of bacterial meningitis among febrile infants and children  study objective  to test the hypothesis that quantitation of either c reactive protein  crp  or the total peripheral wbc count can improve clinical detection of underlying bacterial meningitis among young febrile children  design  cross sectional survey of selected symptoms of central nervous system infection  signs of meningeal irritation and or elevated intracranial pressure  levels of crp in serum  and total peripheral wbc counts among unselected pediatric patients undergoing lumbar punctures for evaluation of acute febrile illnesses  setting  emergency department and acute care  walk in  clinic of an urban  university affiliated general hospital  participants  160 previously well  acutely febrile infants and children  median age  6 months   results  the prevalence of bacterial meningitis was 6   sensitivity of symptoms was 1 00 and specificity was 0 17  sensitivity of signs was 0 70 and specificity was 0 81  of the acute phase reactants  sensitivity of a crp level of more than 1 0 mg dl was 0 80  while that of a total peripheral wbc count of more than 15 000 mm3 was 0 40  the presence of signs and or a crp level of more than 1 0 mg dl correctly identified all children with bacterial meningitis  sensitivity  1 00   the absence of signs and a crp level of 1 0 mg dl or less correctly identified 71 of 150 children without bacterial meningitis  specificity  0 47   of 125 children without meningeal signs  the combination of symptoms and a crp level of more than 1 0 mg dl correctly identified all three children with bacterial meningitis  sensitivity  1 00   the absence of these symptoms and or a crp level of 1 0 mg dl or less correctly identified 80 of 122 children without bacterial meningitis  specificity  0 66   conclusion  quantitation of crp but not the total peripheral wbc count can increase the sensitivity of physical examination findings and the specificity of symptoms for the diagnosis of bacterial meningitis  measurement of crp in serum is useful as an adjunct to history and physical examination for the detection of acute bacterial meningitis in the acutely febrile child  
class10	emergency department approach to managing seizures in pregnancy  seizures in pregnancy pose risks for both the mother and the fetus and must be managed aggressively  antiepileptic drugs have some teratogenic potential  but the risks are not as profound as reported in earlier literature  there is definitely less risk to the fetus from anticonvulsant exposure than from uncontrolled seizures  the evaluation of a pregnant woman with new onset seizures is the same as for the nonpregnant patient  including head computed tomography with appropriate abdominal shielding  status epilepticus management is based on iv benzodiazepines  phenytoin  or phenobarbital  good fetal outcome is dependent on rapid seizure control  management of eclampsia is controversial  there is little evidence that magnesium sulfate has anticonvulsant properties  and its use as such will probably decline steadily in the future  at present  it is reasonable to manage eclamptic seizures in the same way that status epilepticus is managed  
class10	large scale neurocognitive networks and distributed processing for attention  language  and memory  cognition and comportment are subserved by interconnected neural networks that allow high level computational architectures including parallel distributed processing  cognitive problems are not resolved by a sequential and hierarchical progression toward predetermined goals but instead by a simultaneous and interactive consideration of multiple possibilities and constraints until a satisfactory fit is achieved  the resultant texture of mental activity is characterized by almost infinite richness and flexibility  according to this model  complex behavior is mapped at the level of multifocal neural systems rather than specific anatomical sites  giving rise to brain behavior relationships that are both localized and distributed  each network contains anatomically addressed channels for transferring information content and chemically addressed pathways for modulating behavioral tone  this approach provides a blueprint for reexploring the neurological foundations of attention  language  memory  and frontal lobe function  
class10	impairment of sequences of memory guided saccades after supplementary motor area lesions  different paradigms of saccades were recorded electro oculographically in 2 patients with infarction affecting the left supplementary motor area  saccades made toward visual targets  visually guided saccades  or away from them  antisaccades  were normal in both patients  memory guided saccades  made to the remembered position of a flash occurring 2 seconds before  were preserved in 1 patient and only slightly impaired in the other  however  sequences of two or three memory guided saccades were severely impaired in both patients  it has previously been reported that the supplementary motor area plays an important role in programming sequential limb movements  our data suggest that this area plays a similar role in the control of sequential eye movements  
class10	brain ph in head injury  an image guided 31p magnetic resonance spectroscopy study  it has been suggested that brain acidosis may follow head trauma  and therapies aimed at correcting acidosis have been proposed  direct measurements of intracellular ph  however  have thus far not been possible in clinical situations  we have studied the intracellular brain ph in 22 patients after head injury  mean glasgow coma score 6 1   patients were investigated by a combined approach of phosphorus 31 magnetic resonance spectroscopy and magnetic resonance imaging  overall examination time 50 75 min  at a mean time of 11 days after injury  36 hours to 24 days   31p spectra were obtained in 11 patients on assisted ventilation and in 11 patients on spontaneous ventilation  these spectra were analyzed to yield the ph in the regions studied in all the patients  all ph values were in the normal or alkalotic range when compared with 6 age matched normal controls  no differences were found between patients on assisted ventilation and patients on spontaneous ventilation  when analyzed as a group  the brain ph in the focal lesions appeared to increase in the first days  to reach a peak in the alkalotic range in the second week  and to return toward normal within 3 weeks from acute injury  our results suggest that there is no evidence of posttraumatic intracellular brain acidosis in recent human head injury  and therefore  therapies aimed at alkalinizing brain cells need to be reconsidered  
class10	respiratory failure and unilateral caudal brainstem infarction  we report clinicotopographic correlations in 2 patients with central hypoventilation and unilateral infarct in the caudal brainstem  one patient had nearly complete loss of ventilation involving both automatic and voluntary components  he showed no ventilator response during a co2 retention test  paco2 62 mm hg  pao2 82 mm hg   while consciousness was preserved until death  the infarct involved the reticular formation  nucleus tractus solitarius  nucleus ambiguus  and nucleus retroambiguus on the right but spared the dorsal motor nucleus of the tenth cranial nerve  and sensory and corticospinal tracts  the second patient showed hypoventilation more selectively involving automatic responses  ondine s curse   the infarct involved the medullary reticular formation and nucleus ambiguus but spared the nucleus tractus solitarius  we suggest that unilateral involvement of pontomedullary reticular formation and nucleus ambiguus is sufficient for generating loss of automatic respiration  while associated lesion of the nucleus tractus solitarius may lead to more severe respiratory failure involving both automatic and voluntary responses  
class10	magnetic motor evoked potentials in epilepsy  effects of the disease and of anticonvulsant medication  magnetic motor evoked potentials were recorded in 53 patients with medically intractable  mainly temporal lobe epilepsy and compared with potentials of 110 healthy volunteers  the motor evoked potentials were reevaluated in 16 of the 53 patients after substantial reduction of antiepileptic drug doses  the objective was to assess the effect of epilepsy and of anticonvulsant medication on the central motor system  in subjects receiving antiepileptic treatment  cortical threshold intensities were markedly elevated and peripheral latencies were prolonged  cortical threshold intensities and peripheral latencies decreased to approach control values after anticonvulsant medication was reduced but were increased in patients treated with 2 or 3 anticonvulsant agents instead of 1  additionally  high levels of interictal epileptiform activity and a high frequency of seizures significantly decreased the central motor conduction time and  in part  threshold intensities  the central motor conduction time was further diminished after reduction of anticonvulsant treatment and increased when several drugs were administered  the duration of epilepsy  the location of the epileptic focus  and the type of the epileptic seizure did not affect motor evoked potentials  conclusively  central motor pathways are endogenously facilitated by epileptiform activity even if clinical signs of their involvement are absent  anticonvulsant medication exerts major reversible effects on magnetic motor evoked potentials  
class10	isolation of a complementary dna clone encoding an autoantigen recognized by an anti neuronal cell antibody from a patient with paraneoplastic cerebellar degeneration  we isolated a complementary dna clone encoding a 52 kd protein recognized by an anti neuronal cell antibody in serum from a patient with paraneoplastic cerebellar degeneration associated with uterine carcinoma  the recombinant protein expressed in prokaryotic cells was specifically recognized by the anti neuronal cell antibody from the patient  and its molecular weight was identical to that of antigenic proteins in the cerebellum  the deduced protein consisted of 450 amino acids dominated by hydrophilic residues  the calculated relative molecular mass was 51 238  and the predicted value of the isoelectric point was 4 99  this complementary dna sequence and the deduced protein sequence have not been reported previously  and the sequences showed no homologies with the complimentary dna or the amino acid sequences in the genbank  embl  or nbrf databases  including the complementary dna for a 34 kd cerebellar protein  cdr34  that is recognized by an anti purkinje cell antibody  unexpectedly  the transcript of this gene was detected not only in the cerebellum and the brain stem but also in an extraneural tissue  the intestine  
class10	a follow up study of intractable seizures in childhood  one hundred forty five children with seizures that were refractory to medical therapy for at least 2 years were followed 5 to 20 years after onset  the majority of children with uncontrollable seizures  61   were mentally retarded  and most of these  73   had onset of seizures at younger than 2 years of age  age of onset was significantly later  mean 5 0     0 5 yr  sem   in the group of children with borderline to normal intelligence  follow up data showed remission of seizures in a significant proportion of children with borderline or normal intelligence  with a linear decrease of the percentage with persistent seizures at a rate of about 4  per year  remission of seizures was much less frequent  1 5  yr  in the group with mental retardation  seizure type had some effects on outcome  children with focal atrophic brain lesions did no worse than those without definable pathology on brain imaging studies  
class10	stiff man syndrome  a gabaergic autoimmune disorder with autoantigenic heterogeneity  autoantibodies that reacted with cell bodies and axon terminals of gamma aminobutyric acid  gaba ergic neurons were present in the serum and cerebrospinal fluid in a patient with stiff man syndrome with type i diabetes  immunoblot experiments using this patient s serum and cerebrospinal fluid did not corroborate an earlier observation that these autoantibodies are directed against the gabaergic cytosolic enzyme  l glutamic acid decarboxylase  while l glutamic acid decarboxylase autoantibodies may be associated with this syndrome  they do not appear to be easily demonstrated  
class10	relationship of clinical features with psychological status in primary fibromyalgia  clinical features and psychological status determined by the minnesota multiphasic personality inventory  mmpi  in 103 patients with primary fibromyalgia syndrome  pfs  were analyzed by univariate and multivariate techniques to determine if clinical features were related to psychological status or were intrinsic to pfs per se  the central features of pfs  e g   number of pain sites  number of tender points  fatigue  and poor sleep  were independent of psychological status  however  discriminant analysis identified 4 variables  patient reported depression  anxiety  stress  and pain severity  which together predicted 3 mmpi subgroups with an accuracy of 55   p less than 0 001   the only musculoskeletal feature  pain severity  alone provided an accuracy of only 34   p greater than 0 05   these data suggest a new concept  that the central features of fibromyalgia are independent of the psychological status and are more likely related to the pfs itself  however  pain severity may be influenced by psychological factors  
class10	septic arthritis of the c1 c2 lateral facet joint and torticollis  pseudo grisel s syndrome  we present the case of a 76 year old man who experienced the sudden development of fever  rightsided neck pain and stiffness  and torticollis  a soft tissue mass was noted on the right side of his neck  but his head was tilted to the left  computed tomography scans  with reformatted sagittal and coronal images  of the patient s cervical spine revealed destructive changes of the right lateral masses of c1 and c2 and the clivus  and a well delineated peridontoid soft tissue mass  confirmed by magnetic resonance imaging   after the second episode of right sided hemiparesis  he underwent transoral surgical exploration  with anterior decompression and odontoidectomy  histologic examination of the surgical material revealed granulation tissue  fibrosis  and chronic inflammation  consistent with abscess formation with invasion and compression of the spinal cord and bone  this case suggests that nonreducible rotational head tilt to the side opposite the side of lateral mass collapse should raise the suspicion of a possible infection  
class10	sleep disturbances in hiv infected homosexual men  to provide a better understanding of the etiology of subjective sleep complaints in hiv infected individuals  a study to evaluate sleep wake disturbances in 10 healthy hiv infected male volunteers was performed  all subjects were hiv infected but had no history of aids related infections  and considered clinically asymptomatic  interviews and sleep questionnaires revealed sleep complaints in nine subjects  five healthy hiv seronegative male subjects  with no history of sleep complaints  were also evaluated  sleep architecture analyses detected that  in comparison to published normative data and to negative controls  there was a significant increase in the total percentage of slow wave sleep  sws  and an increase in the percentage of sws in the later sleep cycles  when compared with normative data  an increase in stage 1 shifts  rapid eye movement  rem  periods  and arousals were also observed in the hiv infected group  significant decreases in sleep latency  total percentage stage 2 sleep  and average rem durations were also observed in the hiv infected group compared with normative data  these sleep architecture abnormalities could not be attributed to known sole primary sleep disorders  first night effect  medications  anxiety or depression  this study indicates that sleep disturbances occur early in the course of hiv infection and suggests that the observed alterations of sleep physiology may be a consequence of central nervous system involvement and or immune defense mobilization in the early phases of hiv infection  
class10	new angiotensin converting enzyme inhibitors  their role in the management of hypertension  the introduction of orally active angiotensin converting enzyme  ace  inhibitors has revolutionized the treatment of hypertensive disorders and provided an effective alternative for the management of congestive heart failure  chf   by interfering with the formation of angiotensin ii  the active agent of the renin system  ace inhibitors block the system s vasoconstrictive and sodium retaining effects  with a consequent reduction in systemic blood pressure  the net effect is improved blood flow and reduced cardiac work  thus  ace inhibitors are likely to improve cardiac work capacity and quality of life  their mechanism of action differs markedly from that of traditional antihypertensive agents which lower blood pressure while reducing cardiac output and blood flow  since the primary action of ace inhibitors is to block the renin system  a dramatic response to monotherapy suggests a large renin factor while the lack of a response suggests a low renin state more amenable to treatment with a diuretic or calcium antagonist  because of their many attributes  ace inhibitors are increasingly used as first line therapy for the treatment of hypertension or chf  the prototype orally active ace inhibitor  captopril  is a sulfhydryl compound with a good safety profile at the recommended dosages but reported toxicity at higher dosages  second generation ace inhibitors  eg  enalapril and quinapril  are more potent sulfhydryl free esters with a greater affinity for the converting enzyme  these newer agents are pro drugs requiring ester hydrolysis to form the active free acid compound  
class10	brain death and organ donation in a neurosurgical unit  audit of recent practice objective  to assess the potential for increasing the yield of donors by comparing the current pattern of brain death and organ donation in a neurosurgical unit with that reported in 1981 and with a recent national audit  design  retrospective review of all deaths for 1986  1987  and 1988 and prospective data for 1989  setting  a regional neurosurgical unit serving 2 7 million population  results  of 553 deaths  35   191  patients died while on a ventilator and 17   92  after discontinuation of ventilation  medical contraindications to donation were found in 23   32  of 141 patients tested for brain death  in 38   19  of 50 patients who died while being ventilated who were not tested  and in 12   11  of 92 patients no longer being ventilated  consent for donation was sought in 88   96  of 109 medically suitable brain dead patients and granted in 70   67  of these  half those with permission for multiorgan donation had only the kidneys removed  conclusions  more organs may be lost owing to transplant team logistics than by failure to seek consent from relatives of brain dead patients  the estimated size of the pool of potential donors depends on what types of patients might be considered  ensuring that all who die while being ventilated are tested for brain death and considering the potential for donation before withdrawing ventilation could yield more donors  ventilating more patients who are hopelessly brain damaged to secure more donors raises ethical and economic issues  
class10	the appearance of the piriformis muscle syndrome in computed tomography and magnetic resonance imaging  a case report and review of the literature  the piriformis syndrome  ps  is a controversial cause of hip pain because of the lack of objective findings to support the diagnosis  computed tomography  ct  and magnetic resonance  mr  imaging revealed ps in a 27 year old woman  this case may be one of the first reports in the literature on a piriformis muscle enlargement documented by ct and mr imaging  
class10	noncardiogenic pulmonary edema complicating massive diltiazem overdose  non cardiogenic pulmonary edema has not been previously described in calcium channel blocker overdose  we describe a case of non cardiogenic pulmonary edema occurring during the course of therapy for massive diltiazem overdose in a young patient with anorexia nervosa  review of the current literature suggests that major and minor pulmonary complications occur with some frequency in the setting of calcium channel blocker overdose although their exact incidence remains unclear  
class10	visceral perception in health and functional dyspepsia  crossover study of gastric distension with placebo and domperidone  the symptoms of functional dyspepsia are still unexplained  to evaluate the possible role of abnormal visceral perception  we studied the symptomatic responses and the pressure variations during progressive gastric distension in 10 female healthy control subjects  mean age 33 6 years  and in 10 female patients with functional dyspepsia  mean age 35 2 years   a rubber balloon was positioned 4 cm below the lower esophageal sphincter  les  and inflated with progressively larger volumes of air by steps of 50 ml  pressures at the gastric fundus and at the les were continuously recorded by perfused manometric catheters  each subject was studied on two separate occasions after randomized double blind administration of either placebo or 20 mg of domperidone  symptomatic responses and the manometric data were analyzed at the time of the initial recognition of distension  bloating step  and at the time of reporting pain or up to a maximum of 700 ml of balloon inflation  pain or 700 ml step   on placebo  the volumes of gastric distension were more than two times lower in patients than in control subjects at the bloating step  185     32 ml vs 470     40 ml  p   0 001  and at the pain or 700 ml step  265     54 ml vs 600     34 ml  p less than 0 005   while the pressure gradients  pressure at inflation steps minus baseline pressure before beginning inflation  were not statistically different between the two groups  
class10	bowel dysfunction in fibromyalgia syndrome  fibromyalgia and irritable bowel syndrome frequently coexist  in this study  we utilized a previously validated self administered questionnaire to assess the prevalence of symptoms of bowel dysfunction and irritable bowel syndrome in 123 patients with fibromyalgia as compared to 54 patients with degenerative joint disease  djd  and 46 normal controls  ninety  73   of the fibromyalgia patients reported altered bowel function as compared to 20  37   djd patients and none of the normal controls  p less than 0 001   ninety nine patients  81   reported normal alternating with irregular bowel pattern  and 77  63   had alternating diarrhea and constipation  in contrast  only 24  44   of djd patients and six  13   of controls had regular alternating with irregular bowel pattern and only 12  22   of the djd patients and none of the healthy controls had alternating constipation and diarrhea  p less than 0 01   other bowel dysfunction complaints noted in the fibromyalgia group were abdominal gas  59    nausea  21    diarrhea  9    and constipation  12    seventy nine  64   fibromyalgia patients reported frequent abdominal pain that was stress related 47  of the time  laxative use was frequent in the fibromyalgia group  19   and absent in the other two groups  fifty percent of fibromyalgia patients  compared to 28  of djd patients  felt that their bowel complaints were worse during exacerbations of their joint disease  p less than 0 05   in conclusion  patients with fibromyalgia have a high prevalence of gastrointestinal complaints that should be carefully assessed  if the diagnosis of ibs is confirmed  appropriate treatment may improve patients  symptoms  although this approach requires further study  
class10	treatment of fulminant hepatic failure with insulin and glucagon  a randomized  controlled trial  insulin and glucagon are among the therapeutic modalities that have been investigated in the treatment of fulminant hepatic failure  fhf   we have completed a randomized  controlled trial of insulin and glucagon in 38 patients with fhf from either viral or toxin exposure  the control and treatment groups consisted of 21 and 17 patients  respectively  and did not differ significantly in etiology or admission laboratory values  mortality was not significantly different between control and treatment groups and was 67  and 82   respectively  time from randomization to death or discharge was not significantly different between the two groups  peak levels of alpha fetoprotein were statistically higher in survivors than in nonsurvivors  p less than 0 01   we conclude that even though a type 2 error may exist  the combination of insulin and glucagon is not useful in the treatment of fhf  
class10	analgesic use  a study of treatments used by patients for migraine prior to attending the city of london migraine clinic  eighty three unselected patients attending the city of london migraine clinic for the first time were asked about their drug intake and use of alternative treatment  thirty one of those questioned took regular daily doses of medication  fifteen were taking a combination of drugs bought  over the counter   otc  and drugs prescribed by their gp  eleven took otc drugs only  and 5 took prescription drugs only  it was noticeable that those taking drugs prescribed both by the gp and obtainable over the counter were more likely than the other groups to be taking several drugs rather than a single type  thirty five of the 83  42 2   had tried alternative treatments for their attacks  
class10	vasospasm contributes to monosodium glutamate induced headache  consumption of monosodium glutamate has long been considered to precipitate headaches in susceptible patients  in this study the direct effects of glutamate and its metabolite  glutamine  on arterial contractility were examined using rings of rabbit aorta  in a high concentration glutamate caused significant concentration dependent contractions  ec50  10  1 m  maximum tension  188 4     33 3 mg wt tension mg tissue   agonists and antagonists for alpha adrenergic  histaminergic  serotonergic  cholinergic  and gaba nergic receptors as well as inhibition of prostaglandin synthesis failed to influence glutamate contractions  at high concentrations  10  5 m  the calcium channel blocker  verapamil  inhibited the glutamate response  glutamate and glutamine both exhibited concentration dependent relaxation of norepinephrine  ne   phenylephrine  pe   histamine  serotonin  5 ht   and prostaglandin f2 alpha  pgf2 alpha  induced contractions  kainic acid  10  4 m   an agonist of one subpopulation of central glutamate receptor  potentiated glutamate induced vasoconstriction  a higher concentration  10  3 m  produced an irreversible inhibition of glutamate contractility  only the central glutamate receptor antagonist  ketamine  10  4  10  2 m   induced a reversible  concentration dependent inhibition of glutamate induced contractions  glutamate contractility was not dependent on extracellular calcium  an intact endothelium or neuronal function  these results demonstrate a direct effect of glutamate on peripheral arterial tone  dietary consumption of large quantities of msg may represent a serious health hazard to certain individuals with pre existing vascular disease  
class10	alteration of platelet serotonin in patients with chronic tension type headache during cold pressor test  change of 5 hydroxytryptamine  5 ht  concentrations in platelets from patients with chronic tension type headache  th  and controls were observed during cold pressor test  cpt   before cold stimulation  5 ht concentrations in platelets from patients with th were significantly lower than those found in controls  one minute after the start of cold stimulation  5 ht levels in platelets from patients with th were significantly much lower than in the controls  as control levels rose and th levels fell  the results show that  under stress  the absorbance of 5 ht into the platelets in patients with th is reduced  it is suggested that  in patients with th  there are abnormalities of 5 ht uptake into platelets and factors which cause release of 5 ht from platelets  
class10	the blink reflex in cluster headache  to investigate the involvement of the trigeminal system in cluster headache  in twelve subjects the electrically elicited blink reflex during a symptomatic period was examined  in eleven cases  the amplitude of the contralateral r2 response on the symptomatic side was significantly lower  at the same stimulus intensity  than on the asymptomatic side  p   0 005   the blink reflex can be useful to evaluate biological and drug induced phenomena in cluster headache  
class10	assessment and treatment of children s headaches from a developmental perspective  childhood headache is a common pediatric problem  clinical researchers have evaluated several behavioral treatment  such as biofeedback and relaxation training  that may be viable interventions  adding a developmental perspective to the evaluation and treatment of childhood headache is a likely way to increase the effectiveness of these strategies  this paper presents developmental issues related to the assessment and treatment of childhood headache  three major areas of development are examined and the impact of these areas on the treatment and assessment of headache are discussed  the three major areas are cognitive development  self regulation and psychosocial development  provided are practical suggestions for the application of child development principles to assessment and intervention practices that may be more developmentally appropriate  
class10	health status in patients with tension headache treated with acupuncture or physiotherapy  sixty two female patients with chronic tension headache were randomly divided into two treatment groups  acupuncture and physiotherapy  their overall function  sickness impact profile   and mental well being  mood adjective check list  and the intensity and frequency of headache were assessed before and after treatment  before treatment the patients showed significantly more dysfunction and less positive mental well being than a general population sample  both treatment groups improved in overall function  the physiotherapy group somewhat more  the mental well being increased only in the physiotherapy group  the intensity and frequency of headache was significantly reduced in both the physiotherapy group and the acupuncture group  the intensity of headache was significantly more improved in the physiotherapy group  the improvement of headache intensity persisted unchanged 7 12 months after treatment  
class10	nocturnal sleep recording with cassette eeg in chronic headaches  many headache patients complain of poor sleep  and sleep disturbance has been shown to play a role in chronic pain  we recorded nocturnal sleep with a 4 channel cassette eeg monitoring device in 10 common migraine patients  10 individuals with muscle contraction  tension  headache  and 10 chronic tension vascular headache sufferers  migraine patients had essentially normal sleep  although rapid eye movement  rem  sleep and rem latency were increased  patients with tension headache had reduced sleep time and sleep efficiency  decreased sleep latency but frequent awakenings  increased nocturnal movements  and marked reduction in slow wave sleep  without change in rem sleep or latency  mixed element headaches with both tension and vascular features were associated with reduced sleep  increased awakening  diminished slow wave sleep  and rem sleep that was decreased in amount and reduced in latency  the findings suggest that patients with intermittent migraine may have minimal sleep disturbance  while chronic headache may be worsened by chronically poor sleep  muscle contraction headache may be associated with frequent awakenings and decreased slow wave sleep similar to the sleep changes of fibrositis  while chronic tension vascular headache may have a depressive substrate  four channel sleep recording may miss contributory sleep apnea  but nonetheless cassette eeg may facilitate outpatient evaluation of refractory headaches  
class10	contingent negative variation in migraine  the contingent negative variation  cnv  is an event related slow potential  it was recorded in healthy volunteers  n   8  and in patients suffering from migraine without  n   12  or with  n   5  aura  during one  cnv1  and three second  cnv3  foreperiods in a forewarned reaction time task  cnv1 was recorded at the vertex while cnv3 was recorded at multiple electrode sites to assess topographical differences  seven out of twelve migraine patients without aura had increased cnv1 amplitudes  cnv3 amplitudes were increased as well  but only at electrode positions c3 and c4 and not at fz  cnv3  which allows for analysis of both an early and a late cnv component  could improve the discrimination of migraine without aura beyond that of cnv1  in migraine with aura all cnv parameters were at control levels  confirming previous results  the data obtained are discussed in terms of arousal  activation and stress and the  biobehavioral model of migraine   welch  1986   
class10	centrifugal intensity and duration as countermeasures to soleus muscle atrophy  mechanical acceleration is a countermeasure that may be employed to prevent atrophy of slow twitch muscle during non weight bearing  in the present study  daily centrifugation of rats for different durations  1 or 2 h  and at different gravitational intensities  1 5 or 2 6 g  was used to test whether mechanical acceleration could ameliorate the atrophy of the soleus muscle induced by non weight bearing  tail traction model   the soleus muscle atrophied 32  during 7 days of non weight bearing without countermeasures  centrifugation treatment did not completely prevent atrophy relative to precontrol wet weight of the soleus muscle  non weight bearing groups receiving 2 h daily treatments of 1  1 5  or 2 6 g had 48  56  and 65   respectively  of the atrophy observed in the non weight bearing only group compared with the precontrol group  no evidence was obtained that centrifugation at 2 6 g was more effective than exposure to 1 or 1 5 g as a countermeasure to non weight bearing induced atrophy of the soleus muscle  
class10	effects of carotid denervation and decerebration on ventilatory response to co  to clarify the mechanisms involved in the ventilatory response to the inhalation of low concentrations of co  0 18 0 22  in air   the roles of the arterial chemoreceptors and the forebrain structures have been investigated in unanesthetized adult cats  the ventilatory response was observed in conscious animals intact  after carotid denervation  cd   and after midcollicular decerebration  the results show that the initial small ventilatory depression was unaffected by cd but that the subsequent characteristic tachypnea was blunted after cd even after more prolonged exposure to co  the co tachypnea was not observed after decerebration  but a residual hyperventilation was noted with the higher concentration used  it may be concluded that carotid chemoreceptors do not mediate the co tachypnea  which may then originate in suprapontine structures as shown by comparison of intact and decerebrate animals  the blunting of the tachypnea after cd may be caused by the relative hypercapnia observed in cd animals  the residual hyperventilation observed in decerebrate animals may be caused by central acidosis and or some peripheral potentiation of chemoreceptor activity resulting from the decrease in arterial blood pressure that accompanied co inhalation in decerebrate animals  
class10	the association of carotid artery stenosis with carotid sinus hypersensitivity  transitory cerebral ischaemic attack provoked by carotid sinus reflex the association of internal carotid stenosis with the carotid sinus syndrome represents a special clinical entity  transitory cerebral ischaemic attack  tia  will usually be manifested by activation of carotid sinus reflex  eighteen patients were observed suffering from both carotid sinus hypersensitivity and tia  the patients had had tia s for many years  unilateral internal carotid stenosis was detected in 15 cases  while 3 patients had bilateral carotid stenosis  on carotid sinus stimulation  syncope appeared and a tia could be provoked  the mean duration of the syncopic attack was 5500 ms and was based on sinus arrest in 14 cases and on third degree av block in 4 cases  in all patients carotid artery disobliteration was performed  in 14 patients pacemaker implantation was necessary  while 4 patients could be treated by atropine medication  the development of a tia could be abolished in every patient and 14 patients remained totally symptom free  
class10	elevated serum concentrations of ige antibodies to environmental antigens in hiv seropositive male homosexuals  forty five homosexual male subjects with human immunodeficiency virus  hiv  infection  who received care during a 4 month period in an ambulatory center for acquired immunodeficiency syndrome  aids   were classified according to their principal presentation with characteristic secondary infections  cdc group iv c  n   28   cancers  iv d  n   10   or limited or no symptoms  groups ii  iii  iv a  or iv b  n   7   the incidence of allergic rhinitis and conjunctivitis increased after hiv seroconversion by approximately twofold in patients of groups iv c and iv d  the mean serum concentration of ige was significantly higher for group iv c than for the other hiv seropositive groups and for a control group of 45 hiv seronegative homosexual male subjects from the same community who were studied concurrently  more patients in groups iv c and iv d had positive rasts for a panel of environmental antigens than patients in the other hiv seropositive groups and the hiv seronegative control group  patients with aids presenting with typical secondary infections thus have a high frequency of some clinical and laboratory manifestations of allergic diseases  
class10	florid refractory schizophrenias that turn out to be treatable variants of hla associated narcolepsy  narcolepsy in which the hallucinatory component is unusually prominent may lead to the development of an illness indistinguishable from the schizophrenic syndrome  psychotic symptoms dominate the symptomatology  so that the primary illness is obscured  five patients are described for whom conventional antipsychotic drugs were ineffectual  but for whom treatment with stimulants produced substantial improvement  the diagnosis of narcolepsy was confirmed by human leukocyte antigen typing and sleep laboratory testing  these results support the  rem intrusion  hypothesis of the causation of schizophrenia in as many as 7  of a series of schizophrenic patients  implications for diagnosis and treatment are discussed  
class10	the long distance effects of brain lesions  visualization of myelinated pathways in the human brain using polarizing and fluorescence microscopy  we describe several new possibilities for the study of degenerated myelinated tracts in the human central nervous system  cns   the methods are based on the visualization of myelin breakdown products that show birefringence in polarized light and  when stained with nile blue and benzpyrene 3 4  exhibit fluorescence  even after lengthy formalin fixation  the methods permit the localization of anterogradely degenerated tracts in a variety of fiber systems in the brains of patients who died between five and 20 months after the onset of neurological symptoms  particularly the polarizing technique  because of its simplicity  can be added to the usual neuropathological methods for demonstrating the long distance effects of a brain lesion  as research tools  these methods would also aid in the study of the anatomical substrate of human neurological symptomatology  
class10	the neuromuscular pathology of the eosinophilia myalgia syndrome  the eosinophilia myalgia syndrome  ems  is a recently reorganized disorder in patients ingesting pharmacologic doses of l tryptophan  we studied the lesions of skeletal muscle  peripheral nerve and skin in 12 cases of ems  perimyositis was severe in four  moderate in two  mild in three and absent in three cases  the lesions contained many eosinophils  t helper cells  mast cells and activated macrophages  type 2 myofiber atrophy was present in five cases and in one  this was the only pathologic finding  severe epineurial inflammation was seen in the three sural nerve biopsies  indirect evidence for peripheral neurologic involvement in three other cases consisted of inflammation surrounding intramuscular nerve twigs  two cases  and neurogenic atrophy  one case   phlebitis accompanied the connective tissue inflammation in five cases and endarteritis in one  fasciitis was present in three of four skin biopsies and dermal fibrosis in one  
class10	magnetic resonance imaging and tomographic evaluation of occlusal appliance treatment for advanced internal derangement of the temporomandibular joint  this study evaluates the positional relationship of the disc and mandibular condyle in patients with late opening clicks treated with appliance therapy  a total of 30 joints  18 patients  were studied  twenty seven of these 30 joints were treated with the appliance until the joints were silent to auscultation  the patients were then evaluated with axial corrected tomography and magnetic resonance imaging  mri  in the centric occlusion position and with their bite appliance  sved type  in place  comparisons were made between condyle position in centric occlusion and with the appliance in place  magnetic resonance imaging was then used to evaluate disc positional changes  each imaging procedure was made in the same sagittal plane  only changes in condyle positioning could be identified  evidence of disc repositioning with the appliance in place was seen in only three mri examinations  the remaining 27 joints continued to exhibit disc displacement with various changes in disc morphology  it is concluded that the concept of  disc capture  is a clinical term only  and that such perceived clinical success should not lead to the assumption that an actual change in intra articular anatomic relationships has occurred  joint noises may decrease because joint space is increased  allowing smoother condylar translation beyond disc surface irregularities and positional abnormalities  
class10	neurotoxic action of veratridine in rat brain neuronal cultures  mechanism of neuroprotection by ca   antagonists nonselective for slow ca   channels  the effect of various ca   antagonists and local anesthetics on neuronal cell degeneration induced by veratridine was studied in primary rat brain neuronal cultures  cell death was quantified by measuring lactate dehydrogenase  ldh  released in the culture medium  the neuronal cell degeneration was ca     dependent because  in the absence of extracellular ca    16 hr of exposure to 30 microm veratridine failed to produce release of ldh  ca   antagonists  nonselective for slow ca   channels  flunarizine  cinnarizine  lidoflazine  prenylamine and bepridil  inhibited veratridine induced release of ldh with ic50 values between 0 11 and 0 47 microm  ca   antagonists selective for slow ca   channels were less potent and inhibited veratridine induced release of ldh at concentrations in the following order of potency  nicardipine greater than gallopamil and verapamil greater than niludipine greater than nitrendipine greater than nifedipine greater than nimodipine greater than diltiazem  tested local anesthetics were incomplete inhibitors of veratridine induced release of ldh  a good correlation was found between the potency of the drugs to inhibit released ldh induced by 30 microm veratridine in neuronal cultures and their binding affinity for the batrachotoxin binding site of na  channels in rat cortex synaptosomal preparation  it is concluded that protection against veratridine induced neurotoxicity can be mediated by blocking a veratridine sensitive na  channel  it is a property of certain nonselective ca   antagonists  there is apparently no direct relationship with ca   antagonistic activity  the effect is unrelated to local anesthetic activity  
class10	the cholecystokinin receptor antagonist devazepide enhances morphine induced analgesia but not morphine induced respiratory depression in the squirrel monkey  the effects of the cholecystokinin antagonist devazepide on analgesia and respiratory depression induced by morphine in squirrel monkeys were examined  pain thresholds were determined using the tail withdrawal procedure  in which monkeys restrained in chairs kept their tails in cool  35 degrees c  water for at least 20 sec  but withdrew them from warm  55 degrees c  water in less than 4 sec  morphine produced a dose related increase in tail withdrawal latencies from warm water  devazepide  injected i p  or p o   had no effect on tail withdrawal latencies when given alone but enhanced the analgesic effects of morphine  the devazepide dose response curve for morphine enhancement was bell shaped with doses of 3  10  30 and 100 micrograms kg injected i p  increasing morphine analgesia whereas higher and lower dose did not  in a separate group of monkeys  morphine produced dose dependent decreases in respiratory rate and oxygen tension and increases in carbon dioxide tension  in contrast to its effects on morphine analgesia  devazepide had no effect on the various indices of morphine induced respiratory depression  these data suggest that devazepide may have therapeutic utility as an adjuvant to morphine analgesia allowing lower dose of the opiate to be used to relieve pain and reducing the risk of opiate induced respiratory depression  
class10	central adenosinergic system involvement in ethanol induced motor incoordination in mice  to clarify if the behavioral interaction between ethanol and adenosine reported previously occur centrally or due to a peripheral hemodynamic change  the effect of i c v  adenosine agonists  n6  r phenylisopropyl adenosine  r pia   n6  s phenylisopropyl adenosine  5   n cyclopropyl  carboxamidoadenosine  antagonists  theophylline and 8 p  sulfophenyl theophylline as well as enprofylline on ethanol  i p   induced motor incoordination was evaluated by rotorod  adenosine agonists and antagonists dose dependently accentuated and attenuated  respectively  ethanol induced motor incoordination  thereby suggesting a central mechanism of adenosine modulation of this effect of ethanol and confirmed our previous reports in which adenosine agonists and antagonists were given i p  enprofylline  a weak adenosine antagonist but potent inhibitor of cyclic amp phosphodiesterase  did not alter ethanol s motor incoordination  further supporting involvement of brain adenosine receptor mechanism s  in ethanol adenosine interactions  results from r pia and n6  s phenylisopropyl adenosine experiments showed nearly a 40 fold greater potency of r vs  s diastereoisomer  suggesting predominance of adenosine a1 subtype  however  5   n cyclopropyl  carboxamidoadenosine data indicate complexity of the mechanism s  and point toward an additional involvement of a yet unknown subtype of adenosine a2  no effect of ethanol on blood or brain levels of  3h r pia was noted and sufficient amount of the latter entered the brain to suggest adenosine receptor activation adequate to produce behavioral interaction with ethanol  there was no escape of i c v  administered  3h r pia from brain to the peripheral circulation ruling out a peripheral and supporting a central mechanism of ethanol adenosine interaction  
class10	interactions between n methyl d aspartate and cgs 19755 administered intramuscularly and intracerebroventricularly in pigeons  behavioral effects of n methyl d aspartate  nmda  and the competitive nmda antagonist cis 4 phosphonomethyl 2 piperidine carboxylic acid  cgs 19755  were studied in pigeons  nmda decreased responding under a fixed ratio schedule of food presentation and was 8000 times more potent administered intracerebroventricularly  i c v   as compared to intramuscularly  i m    cgs 19755 was 870 times more potent in producing catalepsy when administered i c v   however  the duration of catalepsy was similar by the two routes of administration  administered i m  cgs 19755 decreased response rates only at doses that also produced catalepsy  administered i c v  some doses of cgs 19755 decreased responding without producing other behavioral effects  rate decreasing effects of i m  nmda were attenuated by i m  cgs 19755  however  when cgs 19755 was administered i c v   there was little or no antagonism of nmda  rate decreasing effects of i c v  nmda were not attenuated by i m  or i c v  cgs 19755 up to doses that produced catalepsy or eliminated responding  the large difference in potency between i m  and i c v  administration for nmda and for cgs 19755  as well as the slower onset of catalepsy when cgs 19755 was administered i m   suggests these compounds do not readily cross the blood brain barrier when administered parenterally  the inability of cgs 19755 to attenuate the rate decreasing effects of nmda when cgs 19755 or nmda was administered i c v  suggests nmda might decrease responding by different mechanisms when administered i m  or i c v  in pigeons  together these results indicate antagonism of nmda in this study  and perhaps in other studies  when both nmda and cgs 19755 were administered parenterally  might result from a peripherally mediated interaction  moreover  this agonist antagonist interaction is not a simple  competitive antagonism  
class10	mechanical restraint use among residents of skilled nursing facilities  prevalence  patterns  and predictors the patterns of and risk factors for mechanical restraint use were determined in 12 skilled nursing facilities  restraints were being used for 59  of residents at the beginning of the study  31  of remaining residents were restrained during the follow up year  no facility characteristic was associated with restraint use  the resident characteristics independently associated with initiation of restraints were older age  disorientation  dependence in dressing  greater participation in social activities  and nonuse of antidepressants  unsteadiness  72    disruptive behavior such as agitation  41    and wandering  20   were the most frequently cited reasons for initiation of restraints  
class10	the j curve phenomenon and the treatment of hypertension  is there a point beyond which pressure reduction is dangerous  we critically appraised the medical literature to evaluate whether there is a point beyond which blood pressure reduction in hypertensive subjects is no longer beneficial and possibly even deleterious  thirteen studies that stratified cardiovascular outcomes by level of achieved blood pressure in treated hypertensive subjects who had been followed up for at least 1 year were critiqued by four independent reviewers  data addressing population  protocol  and methodological characteristics were evaluated  studies did not show a consistent j shaped relationship between treated blood pressure and stroke  but they did demonstrate a consistent j shaped relationship for cardiac events and diastolic blood pressure  the beneficial therapeutic threshold point was 85 mm hg  we conclude that low treated diastolic blood pressure levels  ie  below 85 mm hg  are associated with increased risk of cardiac events  
class10	response to treatment with antihistamines in a family with myotonia congenita  in a family in which myotonia congenita was found in five generations  both great grandparents of the index case were affected  in subsequent generations mild and severely affected cases were clearly segregated down parallel lines of this family  the grandmother of the index case had noted improvement with an antihistamine  when the index case was prescribed trimeprazine  she showed a striking reduction in severity of symptoms  antihistamines seem to deserve further evaluation as a safe and effective treatment for myotonia congenita  
class10	nd yag laser in the microsurgery of frontobasal meningiomas  forty three patients with big frontobasal meningiomas underwent a microsurgical removal of the tumor  the 1 32 microns nd yag laser has proved useful in this prospective series particularly with the contactless shrinkage of the tumors and the necrotization of the dural and bony attachments  tumor shrinkage was achieved by radiating the tumor surface with the nd yag laser  this technique facilitated the microsurgical dissection and reduced the blood loss by half  the nd yag laser necrotization of the dural and bony attachments reduced the recurrence rate following grade two resections from 20  to zero  the postoperative quality of life was excellent with a complete rehabilitation in 76  of the patients  the use of the 1 32 microns nd yag laser improved significantly the results of microsurgery for frontobasal meningioma  
class10	fulminating multiple sclerosis like leukoencephalopathy revealing human immunodeficiency virus infection  a 66 year old french homosexual man and a 42 year old brazilian man with no known risk factors for hiv infection developed headaches  asthenia  and neurologic episodes of abrupt onset  ct showed multiple hypodense  nonenhancing lesions  serology for hiv was positive  they died respectively 2 months and 1 month after onset of the illnesses  autopsy in both cases showed multiple  well demarcated  demyelinating foci in the white matter of the cerebral hemispheres  brainstem  and cerebellum with histologic features characteristic of recent plaques of multiple sclerosis  there were no multinucleated giant cells or microglial nodules  immunostaining for hiv was negative  although a random coincidence of ms and hiv infection cannot be ruled out  the close temporal relationship between the 2 disorders suggests a possible etiologic association  
class10	transcranial doppler in acute hemispheric brain infarction  we studied cerebrovascular anatomy using intra arterial digital angiography  and blood flow velocity in the middle cerebral artery  mca  using transcranial doppler  tcd  ultrasonography in 42 patients with acute hemispheric ischemic brain infarction  we compared angiography with tcd and the clinical findings within 6 hours of the onset of symptoms  the location and extent of the chronic ischemic brain damage was assessed by ct performed 1 to 3 months after the ictus  abnormal tcd  as manifested by either an unobtainable mca flow signal or a significantly depressed mca flow velocity  was highly associated with proximal mca occlusions demonstrated by angiography  abnormal tcd predicted both larger chronic ct lesions and more extensive ischemic change within the mca territory  these data demonstrate that early tcd conveys useful information concerning cerebral tissue prognosis following hemispheric ischemia  
class10	serum and csf levels of il 2  sil 2r  tnf alpha  and il 1 beta in chronic progressive multiple sclerosis  expected lack of clinical utility  we measured interleukin 2  il 2   soluble il 2 receptor  sil 2r   tumor necrosis factor alpha  tnf alpha   and interleukin 1 beta  il 1 beta  by elisa in paired sera and csf from 50 chronic progressive multiple sclerosis  cpms  patients during worsening disability  19 patients with other neurologic diseases  ond   and in sera from 40 healthy volunteers  in the cpms patients  28   14 50   10   5 50   16   8 50   and 6   3 50  had elevated serum levels of il 2  sil 2r  tnf alpha and il 1 beta  respectively  compared with healthy controls  the only analyte we detected in the csf was il 2 in 1 cpms patient  1 50  2    we also saw elevated serum sil 2r in 16   3 19  of ond patients  we found no significant difference in mean levels of serum sil 2r between the 3 groups  our study  the largest to date of cpms patients  shows that serum and csf levels of il 2  sil 2r  tnf alpha  or il 1 beta are not sensitive for  and the serum sil 2r level is not specific for  cpms  therefore  measurement of these analytes will not be clinically useful for therapeutic or prognostic purposes in the majority of cpms patients  
class10	neonatal subependymal giant cell astrocytoma associated with tuberous sclerosis  mri  ct  and ultrasound correlation  we describe a term newborn with tuberous sclerosis who presented with a neonatal brain tumor  diagnosed as a subependymal giant cell astrocytoma  we compare the various imaging modalities used in the diagnosis of this tumor  
class10	absence of acetylcholine induced current in epithelial cells from thymus glands and thymomas of myasthenia gravis patients  we investigated the activity of ion channels in epithelial cells from human thymus glands and thymomas kept in short term cell culture by clamping the membrane potential of the cells at  85 mv and determining the membrane current flowing on application of acetylcholine  glycine  or gamma aminobutyric acid  in concentrations of up to 10  3  m  none of the neurotransmitters induced any detectable current  this suggests  1  that there are no acetylcholine receptors  achrs  or other products of the achr gene family having ion channel properties in the membranes of these epithelial cells  and  2  that the alpha bungarotoxin binding protein of thymus and thymoma has no achr like ion channel property  these results support the hypothesis that the cross reacting structures that elicit the anti achr autoimmune response in thymoma associated myasthenia gravis are antigens having only limited homology with the achr  myasthenia gravis not associated with thymoma might have a different pathogenesis  
class10	 pseudospasticity  in guillain barre syndrome  we report a woman with guillain barre syndrome who developed a flexion posture of the right arm and hand resembling upper motor neuron dysfunction  emg demonstrated that involuntary peripherally generated continuous motor unit discharges caused the posture  
class10	suppression of carbamazepine induced rash with prednisone  we report our experience with 20 patients who developed a rash shortly after the introduction of carbamazepine and were treated with prednisone and an antihistamine  sixteen patients were successfully continued on carbamazepine while 4 had to discontinue the drug  
class10	handcuff neuropathies compressive neuropathy due to tight application of handcuffs occurred in 5 patients  the superficial radial nerve was affected in 8 hands and the median nerve in two  neurologic deficits persisted as long as 3 years after handcuffing  nerve conduction studies helped to exclude malingering and other diagnoses  all patients had been intoxicated when handcuffed or had been arrested with force  the handcuff mechanism  which allows accidental overtightening after application  is an unrecognized factor in these neuropathies  
class10	brain and spinal cord hemorrhage in long term survivors of malignant pediatric brain tumors  a possible late effect of therapy  three children with malignant primary cns tumors treated with craniospinal radiotherapy developed intraparenchymal hemorrhages a median of 5 years following therapy in sites distant from the primary tumor  radical surgical procedures disclosed fresh and old hematoma  gliosis  and necrosis in all 3 patients and an aggregation of abnormal microscopic blood vessels in two  no tumor was found  all 3 patients remain in long term  greater than 10 years  continuous remission  
class10	myelopathic neurosarcoidosis  diagnostic value of enhanced mri  neurosarcoidosis is an underdiagnosed variant of the systemic disease  we report a case of myelopathic neurosarcoidosis  noting the contribution made by mri in establishing the diagnosis  and we discuss the possibility that the disease is differentially responsive to various steroid formulations  
class10	mesencephalic cholinergic nuclei in progressive supranuclear palsy  using an antibody against choline acetyltransferase  chat   mesencephalic cholinergic cell nuclei were studied in autopsy material from 3 cases of progressive supranuclear palsy  psp  and 4 controls  chat immunoreactive neurons were quantified in sections that spanned the rostrocaudal extent of each nucleus  in psp  there was a significant decrease in the number of neurons with detectable immunoreactivity for chat in and adjacent to the central gray substance in the following nuclei  the nucleus of edinger westphal  69    the rostral interstitial nucleus of the medial longitudinal fasciculus  97    the interstitial nucleus of cajal  78    a cell loss was also evident in a group of neurons found in the deep layers of the superior colliculus  93    in contrast  the estimated number of chat immunoreactive cell bodies in cranial nerves iii and iv  in the mesencephalic reticular formation  and in the parabigeminal nucleus was not different from that of controls  the results are compatible with the notion that  in psp  there is a regionally selective destruction of cholinergic neurons  
class10	cerebral atrophy in habitual cocaine abusers  a planimetric ct study  we compared cranial cts of 35 habitual cocaine abusers  16 self reported 1st time users  and 54 headache patients using linear planimetric measures  all patients met the following criteria  age 20 to 40 years  no polydrug abuse  including alcohol   hiv seronegativity  normal albumin level  and no history of any other neurologic disease  the sex ratios and ages were not significantly different in the 3 groups  the planimetric measurements and calculated indices of cerebral atrophy were significantly different in the habitual cocaine abusers compared with the 2 other groups of patients  there were no differences between 1st time cocaine users and controls  among the habitual cocaine abusers there was a positive correlation between the approximate duration of cocaine abuse and the calculated atrophy indices  the findings suggest that cerebral atrophy develops in chronic cocaine abusers  and the severity correlates with the duration of abuse  
class10	central nervous system involvement in von hippel lindau disease  fifty individuals with von hippel lindau disease  vhl  were studied with gadolinium enhanced magnetic resonance imaging  mri  to determine the frequency and distribution of cns lesions  the associated clinical features were also reviewed  thirty six  72   of the 50 had 1 or more cns tumors  the most frequently affected sites in the cns excluding the retina were the cerebellum  52    spinal cord  44    and brainstem  18    new regional predilections for the craniocervical junction and conus medullaris were demonstrated by this study  forty one percent of all vhl patients with cns tumors were neurologically asymptomatic  cerebellar tumors  50    spinal cord tumors  50    and brainstem tumors  44   were often without clinical signs or symptoms  multiple lesions were common  the mean age of all vhl patients  34 5 years  was similar to the mean age of all cns vhl patients  34 4 years   suggesting a lack of age association  cns lesions commonly occurred in the 2nd decade of life  all patients at risk for vhl should be evaluated using gadolinium enhanced mri after 10 years of age  although ophthalmic examination should be initiated within the 1st 2 years of life  enhanced mri is particularly useful in the detection of cns tumors in patients with the vhl gene  
class10	migraine and vertebrobasilar ischemia  i studied 9 patients with migraine and posterior circulation ischemia  inclusion criteria were  1  brainstem or cerebellar infarcts or transient ischemic attacks   2  satisfactory vertebrobasilar angiograms  and  3  migraine  excluded were patients with only occipital lobe ischemia  known arteriosclerosis  or other nonmigrainous vascular disease  two women and 7 men  ages 6 to 58 years  mean  34 7   had transient attacks only  2   single strokes  4   single stroke followed by attacks  1   or multiple strokes  2   five had antecedent classic  2 common migraine  and classic migraine began only after the initial ischemic event in the other two  the 7 stroke patients all had ct  or mri documented brainstem  4  or cerebellar  6  infarcts  angiography was normal  3  or demonstrated basilar artery  ba  narrowing  2  or occlusion  4   or branch occlusion  1   in 3 patients the initially occluded ba later reopened  at follow up  average 4 3 years  range 1 to 9 years   5 were normal and 4 had important clinical deficits  i conclude that  1   basilar migraine  is not always benign  it affects both sexes and a wide age range   2  the pattern of headaches  attacks  and strokes varies   3  migraine may appear only after ischemia   4  some patients have ba occlusion or diffuse narrowing  and  5  ba occlusion can be temporary  
class10	primary leptomeningeal lymphoma  report of 9 cases  diagnosis with immunocytochemical analysis  and review of the literature  we describe 9 patients who presented with a neoplastic meningitis of lymphomatous origin  no evidence of parenchymal central nervous system or systemic tumor was identified either at the time of presentation or throughout the course of their disease  we have chosen to call this entity  primary leptomeningeal lymphoma   plml   this unusual form of neurologic lymphoma must be differentiated from the more common clinical situations of primary parenchymal lymphoma with meningeal involvement and systemic lymphoma complicated by lymphomatous meningitis  
class10	dysgeusia  gustatory sweating  and crocodile tears syndrome induced by a cerebellopontine angle meningioma  facial nerve involvement in cerebellopontine angle tumors  both during their development and after excision  may be expressed in irreversible dysfunction of the parasympathetic pathways  the exact location of the lesion along the efferent nerve fibers can be established through evaluation of the functional level of those organs supplied by the cholinergic motor secretory components  this report deals with a female patient in whom peripheral facial palsy developed shortly after removal of a right cerebellopontine angle meningioma  she had slight facial asymmetry and deafness in the right ear and complained of prandial flush and sweating of the right malar area  occult ipsilateral hyposalivation and hypolacrimation were diagnosed  in patients with seventh and ninth cranial nerve pathoses  evaluation of the end organs that are supplied by their associated autonomous nerve fibers is mandatory to prevent late ocular and oral sequelae  
class10	cefotaxime and aminoglycoside treatment of meningitis caused by gram negative enteric organisms  we reviewed cases of gram negative enteric bacillary meningitis in infants and children treated with cefotaxime at texas children s hospital from january  1984  through june  1989  seventeen of 20 children had an underlying condition predisposing to the development of meningitis  the etiologic organisms in these 20 children  2 days to 12 years old  median  12 days old  were klebsiella sp  9  escherichia coli  4  enterobacter cloacae  3  citrobacter diversus  2  other  2  with the exception of one isolate of acinetobacter  all isolates were susceptible to cefotaxime  in addition to cefotaxime 17 children received an aminoglycoside intravenously  children with meningitis caused by klebsiella sp  or non klebsiella organisms received cefotaxime for 31     14 and 37     17 days  respectively  aminoglycosides were administered for 16     10 days in both groups  five children in each group also received intraventricular doses  1 to 25  of an aminoglycoside  9  or colistimethate  1   the mean durations of positive lumbar  ventricular cerebrospinal fluid or brain abscess cultures were 5 8     4 7 and 7 2     5 0 days after start of therapy in the klebsiella and non klebsiella meningitis patients  respectively  only three children were normal at the time of discharge or follow up  gram negative enteric meningitis remains difficult to treat despite the excellent in vitro activity of cefotaxime against gram negative enterics  in part as a result of the predisposing conditions resulting in the development of this infection  
class10	beneficial effects of x irradiation on recovery of lesioned mammalian central nervous tissue  we examined the potential of x irradiation  at clinical dose levels  to manipulate the cellular constituents and thereby change the consequences of transection injury to adult mammalian central nervous tissue  rat olfactory bulb   irradiation resulted in reduction or elimination of reactive astrocytes at the site of incision provided that it was delivered within a defined time window postinjury  under conditions optimal for the elimination of gliosis  15 18 days postinjury   irradiation of severed olfactory bulbs averted some of the degenerative consequences of lesion  we observed that irradiation was accompanied by prevention of tissue degeneration around the site of lesion  structural healing with maintenance of the typical cell lamination  and rescue of some axotomized mitral cells  principal bulb neurons   thus radiation resulted in partial preservation of normal tissue morphology  it is postulated that intrusive cell populations are generated in response to injury and reactive astrocytes are one such group  our results suggest that selective elimination of these cells by irradiation enabled some of the regenerative processes that are necessary for full recovery to maintain their courses  the cellular targets of these cells  their modes of intervention in recovery  and the potential role of irradiation as a therapeutic modality for injured central nervous system are discussed  
class10	neuropathological changes in transgenic mice carrying copies of a transcriptionally activated mos protooncogene  published erratum appears in proc natl acad sci u s a 1991 may 1 88 9  4060  independent transgenic mouse lines carrying the mouse mos protooncogene linked to a retroviral transcriptional control sequence display behavioral abnormalities including circling  head tilting  and head bobbing  this dominant phenotype shows various degrees of penetrance in different transgenic founder animals and lines  neuronal and axonal degeneration  gliosis  and inflammatory infiltrates are found in all transgenic mouse lines in which behavioral traits are present  recordings of auditory evoked potentials in mice of one of these lines demonstrate that transgenic mice are deaf  in these mice spiral ganglia degenerate and most of the cochlear hair cells are absent  by using an s1 nuclease protection assay  we have detected rna expression of the transgene in all tissues examined and  in particular  at high levels in brain  in situ hybridization experiments show that mos expression can be detected in specific areas of the central nervous system  lesions are present in areas with demonstrable overexpression of mos  
class10	structural alterations of nerve during cuff compression  whether compression nerve injury is due to ischemia  direct mechanical injury  or both remains unsettled  to assess structural changes of nerve during compression  peroneal nerves of rats were compressed at various pressures for different times  and the structural alterations were stopped by simultaneous in situ and perfusion fixation  the structural changes observed during a few minutes of compression cannot be explained by ischemic injury because the pathologic alterations characteristic of ischemia take many hours to develop and in any case are different from the ones found here  the pressure  and time related structural changes observed in the present study under the cuff were  i  decrease in fascicular area and increase in fiber density due to expression of endoneurial fluid   ii  compression and expression of axoplasm  sometimes to the point of fiber transection   iii  lengthening of internodes  and  iv  obscuration of nodes of ranvier due to cleavage and displacement of myelin and overlapping of nodes by displaced loops of myelin  at the edges of the cuff the changes were  i  increase of fascicular area probably from expressed endoneurial fluid   ii  widening of nodal gaps  perhaps mainly from translocated axonal fluid  and  iii  disordered structure of axoplasm  we suggest that the process of paranodal demyelination and axonal transection are linked  occur during the act of compression  and are due to shear forces  the initial event is expression of endoneurial fluid  followed by compression and expression of axoplasm and cleavage and displacement of layers of myelin  conceivably  with prolonged cuff compression ischemic injury might be found to be superimposed on mechanical injury  
class10	cervical muscle myoelectric response to acute experimental sternocleidomastoid pain  a method is presented for investigating the response of passive and active muscle to experimentally induced deep muscle pain  ten healthy adult males performed multiple  submaximal isometric neck flexion tasks before and after pain had been induced in the sternocleidomastoid  scm  muscle by injecting 5 ml of a hypertonic  5   saline solution  a similar volume of isotonic saline was injected into the contralateral muscle as a control  cervical myoelectric signal  mes  root mean square  rms  response to each injection was recorded from eight neck muscles over 8 minutes  the subject rated perceived pain at regular intervals using a visual analog scale  vas   sternocleidomastoid pain  which reached a mean of 36 mm on the 100 mm vas 2 minutes after the injection  resulted in significantly increased  1 2 microv  p less than 0 05  rms mes in the otherwise relaxed scm muscle during the first 2 minutes  this was followed by a gradual return to control values after 5 minutes  a similar trend in mes was found for the active scm muscle during a 10  maximum voluntary contraction  mvc  isometric neck flexion effort  thus  acute deep muscle pain caused subtle  yet systematic  changes in motor output in both the relaxed and active painful muscle  and its synergists and antagonists  
class10	the neurologic workup in patients with cervical spine disorders  care must be exercised in interpreting the clinical and radiologic findings when assessing patients with cervical spondylosis and involvement of neural structures for surgery  if the clinical picture cannot logically be explained by the radiologic findings  further investigation is indicated to exclude a coexistent disorder  investigations may include electrophysiologic tests  transcranial magnetic stimulation  cerebrospinal fluid  csf  analysis  and magnetic resonance imaging  mri   only then can the indication for surgical intervention be properly determined  
class10	prognosticating study for cervical myelopathy using evoked spinal cord potentials  one hundred twenty three cases of cervical spondylotic and ossification of the posterior longitudinal ligament  opll  myelopathy cases with long tract signs subjected to surgical treatment were studied to identify the most important factors having an influence on postoperative outcome using evoked spinal cord potentials  escp   disappearance and positive wave changes of these potentials at the level of responsible lesions and slow conduction velocity under 40 m indicated an unsatisfactory outcome  localized lesion cases diagnosed by escps had excellent results  significantly more so than extensive lesion cases  regardless of operative methods  in 123 cases  76  were found to have localized lesions  while the other 24  showed extensive lesions  concerning the difference between csm and opll  54  of opll and only 14  of csm demonstrated extensive lesions  
class10	gunshot wounds to the cervical spine  a retrospective review was performed on 28 patients with low velocity gunshot wounds to the cervical spine  these composed 31  of all spinal gunshot wounds seen during the study period between 1979 and 1988  surgical decompression did not seem to improve neurologic recovery in either the incomplete or complete patients  neurologic recovery also appeared to be unaffected by the presence of retained intracanal bullet fragments  the authors found no advantage to routine neck exploration of this penetrating injury  complications were seen in 93  of the patients  most complications were thromboembolic  pulmonary  and urinary tract infections  no cases of instability occurred as a direct result of the gunshot wound  no deaths occurred in this series  two cases of posttraumatic syrinxes were diagnosed  the authors  current treatment recommendations for these patients include selective wound management and observation of retained intracanal bullet fragments in patients with complete lesions  surgical decompression after this injury is not recommended  
class10	natural history of progressive ischemic stroke in a population treated with heparin data on the acute natural history of progressive stroke with or without heparin treatment are limited  to define the acute course of patients treated with heparin for progressive stroke  we examined the charts of 69 such patients identified through the cornell neurology database from october 1979 to june 1985  analysis included determining whether further clinical deterioration or hemorrhagic complications were associated with readily identifiable clinical or laboratory variables  twenty five patients  36   continued to deteriorate while receiving heparin  another two  3   worsened due to intracerebral hemorrhage  and a total of 10 patients  14   had bleeding complications  no clinical features or heparin dosing regimens distinguished the patients likely to benefit from heparin  clinical progression or hemorrhage did not correlate with the level of anticoagulation as measured by the average heparin dose per day or the mean partial thromboplastin time  without unequivocal evidence demonstrating heparin s ineffectiveness for progressive stroke  many clinicians managing such patients will continue to use heparin  our results suggest that this decision should not be governed by such clinical features as a patient s age or sex or by the vascular distribution of the stroke  furthermore  frequent measurement of and overzealous efforts to adjust the partial thromboplastin time may be unnecessary since it does not correlate with outcome  
class10	coagulation fibrinolysis abnormalities in acute and chronic phases of cerebral thrombosis and embolism  we assayed plasma concentrations of fibrinogen  fibrinopeptide a  plasmin alpha 2 plasmin inhibitor complex  d dimer  and antithrombin iii activity in 40 patients with cerebral thrombosis and nine patients with cerebral embolism during the acute  less than 7 days   subacute  7 27 days   and chronic  greater than or equal to 28 days  periods and compared these with 69 controls  in cerebral thrombosis  fibrinogen and fibrinopeptide a levels were elevated significantly in all stages  p less than 0 001   whereas plasmin alpha 2 plasmin inhibitor complex and d dimer levels were elevated significantly in the subacute and chronic periods  the antithrombin iii activity was significantly decreased in the acute stage  the elevation of fibrinogen and plasmin alpha 2 plasmin inhibitor complex levels in the acute stage was significantly greater in patients with an infarct size greater than 10 mm2 compared to patients with an infarct size less than 10 mm2  we observed similar changes in patients with cerebral embolism  these results suggest that enhanced coagulation exists at all stages and endogenous fibrinolysis is activated in the subacute and chronic periods in a large proportion of patients with cerebral thrombosis and embolism  
class10	diagnostic significance of flow separation within the carotid bifurcation demonstrated by digital subtraction angiography  the presence of an area of reversed blood flow due to flow separation in the interval carotid artery is a normal finding in doppler ultrasound studies in vivo as well as in model carotid bifurcations  this flow separation phenomenon is caused by the geometry of the carotid bifurcation and the fluid dynamics of blood  we demonstrated the flow separation phenomenon on lateral projection intra arterial digital subtraction angiograms in 99 of 100 carotid bifurcations  the mean duration of flow separation was 5 8 seconds  with values up to 14 seconds in normal carotid bifurcations  the presence of this flow separation phenomenon is almost independent of atherosclerotic lesions and is not correlated with cerebral ischemia  therefore  the angiographic finding of a flow separation has no diagnostic value  however  our results refer to a factor that may be important in the genesis of atherosclerosis at the carotid bifurcation  namely the duration of the stay of blood and its components within the area of flow separation  
class10	cerebral blood flow and oxygen metabolism in patients with vascular dementia of the binswanger type  we performed clinical and neuroradiologic studies  including positron emission tomography  in five patients with vascular dementia of the binswanger type  the clinical features of these cases consisted of slowly progressive dementia  together with vascular risk factors such as hypertension and often a history of minor stroke  and characteristic white matter lesions on brain computed tomograms or magnetic resonance images  digital subtraction angiography of the cervical and intracranial arteries demonstrated no occlusive lesion in any patient  both cerebral blood flow and the cerebral metabolic rate for oxygen were markedly reduced in the white matter  54 77  of control values   and both were decreased in the parietal  73  of control   frontal  74 80    and temporal  74 83   cortices  where no abnormalities were detected by brain computed tomography or magnetic resonance imaging  we conclude that vascular dementia of the binswanger type may be caused by disconnection between the cerebral cortex and subcortical structures due to ischemic damage in the white matter  
class10	denervation in hemiplegic muscles  this study examined the frequency of denervation activity in hemiplegic muscles in relation to the size and location of the central lesion  we studied 20 patients  14 with major unilateral cerebral infarctions in the middle cerebral or internal carotid territories  four with a single lacune in the pons  internal capsule  or thalamus  and two with precentral infarcts  using somatosensory evoked potentials  motor conduction studies  and assessments of conduction across the plexus and roots  we detected no conduction abnormalities on the affected side  fibrillation was common in both groups  especially in distal and intermediate muscles  the distribution of the fibrillation and the normal conduction studies suggested that trauma of peripheral nerves was not a factor  although the normal conduction studies and pattern of fibrillation activity do not exclude peripheral nerve trauma as the cause of the fibrillation  we suggest that transsynaptic degeneration is a reasonable alternative explanation  
class10	rupture of atheromatous plaque as a cause of thrombotic occlusion of stenotic internal carotid artery  we analyzed the clinical profiles and autopsy findings of five patients who died shortly after developing cerebral infarction following thrombotic occlusion of the internal carotid artery  in all five cases  thrombotic occlusion was caused by rupture of the fibrous lining over the gruel of atheroma at the origin of the internal carotid artery showing tight stenosis of the lumen  the mean     sd shorter diameter of the lumen at the site of occlusion was 1 5     0 4 mm  our results show that an internal carotid artery with tight stenosis of the lumen by atheroma containing gruel harbors a risk of thrombotic occlusion  which may give rise to cerebral infarction by artery to artery embolism or by reduced cerebral perfusion  
class10	sensory ataxic hemiparesis in thalamic hemorrhage  ataxic hemiparesis with cerebellar like features has been reported following infarction or hemorrhage of the thalamus  we describe five patients with incoordination and corticospinal tract signs in the limbs opposite a dorsolateral thalamic hemorrhage  in four patients the hemorrhage extended superiorly into the lateral ventricle  the adjacent paraventricular region  and the upper and medial parts of the posterior limb of the internal capsule  instead of cerebellar dysfunction  these patients exhibited directional errors of movement that improved distinctly when performed under visual guidance  we explain the incoordination on the basis of conscious deep sensory loss in the involved limbs  perception of light touch  painful pinprick  and temperature were preserved in all patients  we use the term  sensory ataxic hemiparesis  to distinguish these patients from those with  classic  ataxic hemiparesis and cerebellar like features  a distinction that may be important when planning functional rehabilitation  
class10	pontine supranuclear facial palsy  two patients presented with a unilateral supranuclear facial palsy  additional dysarthria was attributed to the pontine origin documented by magnetic resonance imaging on the contralateral side  the pontine disorder also was indicated by an isolated delay of the blink reflex r1 component or of the masseter reflex  we attribute the facial palsy to a lesion of a supranuclear fiber bundle supplying the facial nucleus  the location of the lesions favors these fibers taking a separate course from the main pyramidal tract at the mid  to upper pontine level  
class10	syncope of unknown origin  clinical  noninvasive  and electrophysiologic determinants of arrhythmia induction and symptom recurrence during long term follow up  ninety one consecutive patients with syncope of unknown origin underwent electrophysiologic studies  eps   univariate analysis identified the following variables  age    signal averaged ecg  saecg   left ventricular ejection fraction  lvef   history of myocardial infarction  coronary artery disease  left ventricular aneurysm  and history of sustained monomorphic ventricular tachycardia  smvt  on holter  multivariate analysis identified  saecg  lvef  and history of smvt as risk factors for induction of smvt at eps  all patients were followed up for 19 0     8 3 months and 17 had recurrence of syncope  patients were divided into empiric  ep guided  and no therapy groups  the ep guided therapy group included all patients with smvt at eps  recurrence rates among all three groups were similar  we conclude that   1  patients who have inducible smvt at eps can be identified using certain clinical and noninvasive variables  when these patients undergo ep guided therapy  their rate of recurrence of syncope becomes compatible with that of patients who had no arrhythmia induced at eps   2  empiric therapy does not offer any benefit over no therapy in reducing the rate of recurrent of scope  
class10	an open trial of high dosage antioxidants in early parkinson s disease  high dosages of tocopherol and ascorbate were administered to patients with early parkinson s disease as a preliminary open labeled trial for the eventual controlled double blind study evaluating antioxidants as a test of the endogenous toxin hypothesis of the etiology of parkinson s disease  the primary endpoint of the trial was the need to treat patients with levodopa  the time when levodopa became necessary in the treated patients was compared with another group of patients followed elsewhere and not taking antioxidants  the time when levodopa became necessary was extended by 2 5 y in the group taking antioxidants  the results of this pilot study suggest that the progression of parkinson s disease may be slowed by the administration of these antioxidants  a large multicenter  controlled clinical trial currently underway in north america evaluating tocopherol and deprenyl has the potential to confirm these results  
class10	lumbar puncture frequency and cerebrospinal fluid analysis in the neonate  a prospective study was performed to assess the frequency and diagnostic utility of lumbar punctures in neonates both during their first week of life and thereafter  during the two 6 month periods from january 1  1985 to june 30  1985  and february 1  1986 to july 31  1986  712 neonates underwent 728 lumbar punctures during their first week of life primarily as part of the evaluation for suspected infection  either congenital or postnatal  there were eight patients with positive spinal fluid cultures in the first week of life  but only one patient simultaneously had a positive blood culture and a clinical course consistent with meningitis  in contrast  a considerably higher yield  approximating five times that of the first week of life  was obtained in patients undergoing a lumbar puncture after the first week of life  
class10	cat scratch disease  acute encephalopathy and other neurologic manifestations  seventy six patients with neurologic complications of cat scratch disease are discussed  encephalopathy occurred in 61  while 15 had either cranial or peripheral nerve involvement  the average age of the patients with encephalopathy was 10 6 years  range  1 to 66 years   and almost twice as many males as females were affected in contrast to patients with uncomplicated cat scratch disease  in which the ratio was almost equal  fever was not documented in 50  of patients with encephalopathy and only 26  had temperatures higher than 39 degrees c  convulsions occurred in 46  and combative behavior in 40   lethargy with or without coma was accompanied by variable neurologic signs  results of laboratory studies  including imaging of the central nervous system  were inconsistent and nondiagnostic  biopsy tissue from 14 patients showed histopathologic findings compatible with cat scratch disease  the  english wear bacillus  was demonstrated by the warthin starry stain in 10 of 14 skin or lymph node specimens  of the 15 patients without encephalopathy  two children with facial nerve paresis displayed cranial nerve symptoms and or signs  10 patients had cat scratch disease neuroretinitis  and three women had peripheral neuritis  all 76 patients recovered within 12 months  78  recovered within 1 to 12 weeks  there were no neurologic sequelae  treatment consisted of control of convulsions and supportive measures  commonly used antibiotics administered to more than half of the patients were apparently ineffective  
class10	four chromosomal breakpoints and four new probes mark out a 10 cm region encompassing the fragile x locus  fraxa   we report the validation and use of a cell hybrid panel which allowed us a rapid physical localization of new dna probes in the vicinity of the fragile x locus  fraxa   seven regions are defined by this panel  two of which lie between dxs369 and dxs296  until now the closest genetic markers that flank fraxa  of those two interesting regions  one is just distal to dxs369 and defined by probe 2 71  dxs476   which is not polymorphic  the next one contains probes st677  dxs463  and 2 34  dxs477   which are within 130 kb and both detect taqi rflps  the combined informativeness of these two probes is 30   we cloned from an irradiation reduced hybrid line another new polymorphic probe  do33  dxs465  42  heterozygosity   this probe maps to the dxs296 region  proximal to a chromosomal breakpoint that corresponds to the hunter syndrome locus  ids   the physical order is thus cen dxs369 dxs476  dxs463 dxs477   dxs296  dxs465  ids dxs304 tel  we performed a linkage analysis for five of these markers in both the centre d etude du polymorphisme humain families and in a large set of fragile x families  this establishes that dxs296 is distal to fraxa  the relative position of dxs463 and dxs477 with respect to fraxa remains uncertain  but our results place them genetically halfway between dxs369 and dxs304  thus the dxs463 dxs477 cluster defines presently either the closest proximal or the closest distal polymorphic marker with respect to fraxa  the three new polymorphic probes described here have a combined heterozygosity of 60  and represent a major improvement for genetic analysis of fragile x families  in particular for diagnostic applications  
class10	identification of a highly polymorphic microsatellite vntr within the argininosuccinate synthetase locus  exclusion of the dystonia gene on 9q32 34 as the cause of dopa responsive dystonia in a large kindred  dopa responsive dystonia is a clinical variant of idiopathic torsion dystonia that is distinguished from other forms of dystonia by the frequent occurrence of parkinsonism  diurnal fluctuation of symptoms  and its dramatic therapeutic response to l dopa  linkage of a gene causing classic dystonia in a large non jewish kindred  dyt1  and in a group of ashkenazi jewish families  to the gelsolin  gsn  and arginino succinate synthetase  ass  loci on chromosome 9q32 34  respectively  was recently determined  here we report the discovery of a highly informative  gt n repeat vntr polymorphism within the ass locus  analysis of a large kindred with dopa responsive dystonia  using this new polymorphism and conventional rflps for the 9q32 34 region  excludes loci in this region as a cause of this form of dystonia  this provides proof of genetic heterogeneity between classic idiopathic torsion dystonia and dopa responsive dystonia  
class10	a family study of gilles de la tourette syndrome  previous studies have demonstrated that gilles de la tourette syndrome  ts  is a familial disorder and that chronic tics  ct  and obsessive compulsive disorder  ocd  appear to be etiologically related to the syndrome  in the present study we report the results from a study of 338 biological relatives of 86 ts probands  21 biologically unrelated relatives of adopted ts probands  and 22 relatives of normal subjects  the 43 first degree relatives of the adopted ts and normal probands constituted a control sample  the rates of ts  ct  and ocd in the total sample of biological relatives of ts probands were significantly greater than in the relatives of controls  in addition  the morbid risks of ts  ocd  and ct were not significantly different in families of probands with ocd when compared to relatives of probands without ocd  these findings provide further evidence that ocd is etiologically related to ts  
class10	chromosome 15 uniparental disomy is not frequent in angelman syndrome  genetic imprinting has been implicated in the etiology of two clinically distinct but cytogenetically indistinguishable disorders  angelman syndrome  as  and prader willi syndrome  pws   this hypothesis is derived from two lines of evidence  first  while the molecular extents of de novo cytogenetic deletions of chromosome 15q11q13 in as and pws patients are the same  the deletions originate from different parental chromosomes  in as  the deletion occurs in the maternally inherited chromosome 15  while in pws the deletion is found in the paternally inherited chromosome 15  the second line of evidence comes from the deletion of an abnormal parental contribution of 15q11q13 in pws patients without a cytogenetic and molecular deletion  these patients have two maternal copies and no paternal copy of 15q11q13  maternal uniparental disomy  instead of one copy from each parent  by qualitative hybridization with chromosome 15q11q13 specific dna markers  we have now examined dna samples from 10 as patients  at least seven of which are familial cases  with no cytogenetic or molecular deletion of chromosome 15q11q13  inheritance of one maternal copy and one paternal copy of 15q11q13 was observed in each family  suggesting that paternal uniparental disomy of 15q11q13 is not responsible for expression of the as phenotype in these patients  
class10	pearson syndrome and mitochondrial encephalomyopathy in a patient with a deletion of mtdna  a patient is described who has features of pearson syndrome and who presented in the neonatal period with a hypoplastic anemia  he later developed hepatic  renal  and exocrine pancreatic dysfunction  at the age of 5 years he developed visual impairment  tremor  ataxia  proximal muscle weakness  external ophthalmoplegia  and a pigmentary retinopathy  kearns sayre syndrome   muscle biopsy confirmed the diagnosis of mitochondrial myopathy  analysis of mtdna from leukocytes and muscle showed mtdna heteroplasmy in both tissues  with one population of mtdna deleted by 4 9 kb  the deleted region was bridged by a 13 nucleotide sequence occurring as a direct repeat in normal mtdna  both pearson syndrome and kearns sayre syndrome have been noted to be associated with deletions of mtdna  they have not previously been described in the same patient  these observations indicate that the two disorders have the same molecular basis  the different phenotypes are probably determined by the initial proportion of deleted mtdnas and modified by selection against them in different tissues  
class10	surgical management of oculomotor nerve palsy we treated seven patients with unilateral oculomotor nerve palsy by transposition of the insertion of the superior oblique tendon to a point anterior and medial to the insertion of the superior rectus muscle without trochleotomy  scott procedure   additionally  large recessions of the lateral rectus muscle of involved eyes and  occasionally  recess resect procedures of horizontal recti muscles of non involved eyes were performed  all patients were followed up between one and eight years  orthophoria in the primary position was achieved and maintained with one operation in four patients  a fifth patient had only a small residual exotropia  in two patients who had aberrant regeneration of the oculomotor nerve  surgery on horizontal recti muscles of the noninvolved eye improved the eyelid position of the involved eye after three operations  
class10	neuropsychological deficits in fetal alcohol syndrome and fetal alcohol effects  a clinical sample of 19 school aged native children diagnosed with fetal alcohol syndrome  fas  or fetal alcohol effects  fae  was compared with age  and sex matched normal controls  results on a battery of intellectual and neuropsychological tests indicated large and significant differences between alcohol affected children and controls  fas differed significantly from controls on measures of intellectual abilities  while fae did not  fas mean scores on these measures were significantly lower than fae means  for neuropsychological measures  fas were significantly poorer than controls on most measures  while fae showed deficits compared with controls only on grip strength  the results suggest that neuropsychological measures would be a valuable supplement to intellectual measures for the purpose of assessing alcohol effects because they are less vulnerable than intellectual measures to the influence of cultural and educational experiences  
class10	new approaches to research on the long term consequences of prenatal exposure to alcohol  as the summary presentation of a symposium on prenatal alcohol induced brain damage and long term postnatal consequences  this paper proposes the establishment of two main research priorities  to begin to correlate long term behavioral effects with alterations in underlying neural substrates  and to explore the mechanisms of neuroteratogenicity  to reach these goals  three objectives are described  first  animal and human research must become more interrelated  second  experimental observations should be integrated into formal models that incorporate both neural structure and function  third  researchers should choose well defined dependent measures that are derived from models of brain function based on modern concepts of cognitive neuroscience  examples of neuropsychological tests that may serve as the bases for structure function relationships are presented  incorporating these objectives into future research will facilitate understanding of the fundamental issues concerning prenatal alcohol exposure and will begin to provide the bases for rational intervention or treatment  
class10	thymoma  results of 241 operated cases clinical and histopathological aspects of 241 thymomas were reviewed  one hundred sixty of the patients with thymoma had myasthenia gravis and 15 had other autoimmune diseases  55  of the thymomas were encapsulated and 45  invasive  operation was radical resection in 87 5  of the patients  subtotal resection with residual tumor in 8 7   and simple biopsy in 3 7   a tumor relapse was observed in 24 patients  10    2  1 5   of 133 with encapsulated thymomas and 22  20 4   of 108 with invasive thymomas  among these patients  a relapse was found in 20 6  of the patients who received radiotherapy postoperatively and in 24 6  who did not  adverse prognostic factors were clinical stage iva  multiple pleural nodes   not feasible resection  for technical reasons   inoperable tumor relapse  and association with one of the following autoimmune diseases  pure red cell aplasia  hypogammaglobulinemia  and lupus erythematosus  conversely  myasthenia gravis is now a curable disease  it contributes to early discovery of associated thymoma  thus allowing a better survival for patients with thymoma who have myasthenia gravis compared with patients with thymoma but without myasthenia gravis  p less than 0 05   postoperative radiotherapy does not seem necessary after removal of encapsulated thymomas  but it is advisable in case of invasive thymomas  regardless of the extent of the resection  
class10	tracheoesophageal anastomosis for intractable aspiration pneumonia  permanent tracheostomy and tracheoesophageal anastomosis were performed as a means of surgical intervention for the treatment of intractable aspiration pneumonia  conventional methods of tracheoesophageal anastomosis have entailed various problems  the improved method devised by us uses the special histological features and enables safe and reliable anastomosis  by this method  the tracheal perichondrium is retained and the strength of the anastomosed portion of the trachea is maintained  the failure of sutures due to tension on the anastomotic site being prevented  also  reanastomosis can be performed after the cure of primary disease  
class10	acute rheumatic fever in west virginia  not just a disease of children  rheumatic fever is a poststreptococcal disease that is receiving renewed attention by the medical community  we describe a recent increase in the number of observed cases of acute rheumatic fever  arf  in west virginia  this is the fifth report of a recent increase in the incidence of arf in the ohio valley area in the last 4 years  in contrast to the other reports  nearly two thirds of our cases of arf were in adults  more than half of whom had suffered previous bouts of arf  in these adults with recurrences  none was taking prophylactic penicillin at the time of presentation  carditis was present in seven adults  two without a history of carditis  arthritis was present in all adult patients  these data indicate a possible geographic phenomenon related to the increased number of observed cases of arf and document that arf is not simply a disease of childhood  furthermore  our findings highlight the need for extended penicillin prophylaxis for secondary prevention of arf  especially for those with an increased risk of acquiring a streptococcal upper respiratory tract infection  
class10	treatment of flexor tenosynovitis of the hand   trigger finger   with corticosteroids  a prospective study of the response to local injection  we developed a protocol to maximize medical therapy for  trigger finger   fifty eight patients with 77 episodes of flexor tenosynovitis of the hand that was resistant to rest  therapy with nonsteroidal anti inflammatory drugs  and or splinting were treated with single or multiple injections of depo methylprednisolone acetate or triamcinolone acetonide  patients were prospectively followed up for an average of 4 6 years  results showed that symptoms and signs resolved in 61  after a single injection  recurrent episodes  after prolonged pain free intervals  occurred in 27  and were effectively re treated with injection  in 12  of cases  either injection failed or early recurrence required surgical release  local adverse reactions to injection  including pain at the injection site  stiffness  ecchymosis  or atrophy of subcutaneous fat  were self limited  no episodes of postinjection infection or tendon rupture occurred  the medical management of flexor tenosynovitis with local corticosteroid injection s  is effective in nearly 90  of cases and is free from serious adverse reactions  
class10	spontaneous electromyographic potentials in chronic spinal cord injured patients  relation to spasticity and length of nerve  nine patients with complete cervical spinal cord injury  sci  had their vastus medialis  tibialis anterior  and gastrocnemius muscles evaluated with an electromyographic  emg  examination in the acute  four to eight weeks  and chronic  more than one year  phases  the hypothesis that spontaneous emg activity changes with time was assessed  during the chronic phase evaluation  a conduction study was performed to rule out peripheral nerve damage  and the amount of reflex activity was assessed on a scale of 0 to 5  0   areflexia  5   greater than 5 beats of clonus  to estimate the amount of spasticity  subjects demonstrated normal conduction through the sensory  sural nerve  and or motor segments of the peroneal and tibial nerves  in the acute phase  each muscle had spontaneous activity with no significant variation between different muscles of the same patient  in the chronic phase  there was a positive correlation between the degree of spontaneous activity in a muscle and the length of its axon  p less than  01  and a negative correlation between the amount of spontaneous activity and the degree of reflex activity  p less than  01   specifically  the lower motor neuron in the chronic phase of an sci seems to behave much like an axonopathy where the degree of spontaneous emg activity is dependent on the length of the axon  with the additional concept that spontaneous activity is inhibited by spasticity  
class10	multimodality evoked potential testing in acute mild closed head injury  multimodality evoked potential  mep  testing  including brainstem auditory  visual  and somatosensory evoked potentials  have been reported to be useful in predicting outcome in severe closed head injury  brainstem auditory evoked potentials have been demonstrated to be abnormal in 10  to 40  of acute mild head injury  a prospective study of 18 patients with mild closed head injury was undertaken to determine the usefulness of mep screening within two weeks of the acute event  long latency event related potentials  p300s   in response to auditory stimuli with an oddball paradigm  were included in the screening  the subjects had several symptoms consistent with the postconcussive syndrome at the time of the evoked potential testing  only one patient had an abnormal evoked potential response  greater than three standard deviations from the mean  from all the testing done  the standard methods of mep testing were insensitive to quantifying the possible physiologic changes that are associated with memory deficits  lethargy  and emotional irritability after mild closed head injury  
class10	orthostatic hypotension after spinal cord injury  treatment with fludrocortisone and ergotamine  we report a case of a 28 year old woman with c5 quadriplegia  unresponsive to conservative treatment for orthostatic hypotension  ergotamine  daily combined with fludrocortisone  successfully prevented symptomatic hypotension  in this report  neural  renal  and hormonal blood pressure regulatory mechanisms are described  experiences obtained from this case and the existing literature suggest that  1  in persons with quadriplegia  plasma catecholamine levels show little increase with sitting  indicating an inability to activate baroreceptor and chemoreceptor reflexes   2  elevated plasma aldosterone and renin levels indicate a renal compensatory response to decreased renal perfusion secondary to low plasma volume and or chronic hypotension  and  3  the net effect of ergotamine and fludrocortisone is probably a combination of plasma volume expansion and direct peripheral vasoconstriction  
class10	silent myocardial ischemia during rehabilitation for cerebrovascular disease  in asymptomatic patients the importance of silent ischemic st t wave changes on holter monitoring is known to be a significant predictive variable for one year mortality of postmyocardial infarction patients  this case report represents the uses of ambulatory ecg to detect ischemic st changes in patients who have had recent strokes  the cases reported here of silent myocardiac ischemia in stroke patients reflect previous reports in which 70  of the ischemic episodes in patients with symptomatic coronary artery disease are not associated with angina and in which approximately 10  to 15  of acute myocardial infarctions are silent  we now believe that the incidence of  silent  ischemia may be precipitated in poststroke patients during their rehabilitation program  this belief is supported by two main factors  first  a high level of personally relevant mental stress exists which activates the sympathoadrenal system  which may lead to myocardial ischemia  second  some stroke patients become aphasic and are unable to communicate adequately even if they experience angina symptoms  we have found that poststroke  most patients could not undergo exercise treadmill testing secondary to a variety of factors  inability to coordinate limbs  poor endurance  inability to follow directions  and or lack of attention  we now propose that 24 hour monitoring for st t wave changes poststroke should be considered as part of a vigorous investigation for myocardial ischemia during the rehabilitation of these patients because they have an increased risk of cardiac morbidity  
class10	neuromuscular function in polio survivors at one year follow up  published erratum appears in arch phys med rehabil 1991 mar 72 3  213  many polio survivors complain of progressive loss of strength  work capacity  endurance  and ability to recover from fatiguing activity  these variables were measured initially and one year later in the quadriceps muscles of 28 symptomatic and 16 asymptomatic persons who had polio and 38 control individuals  peak knee extension torque was measured isokinetically and isometrically  endurance  or the amount of time the subject could maintain isometric torque at 40  of maximal torque  was measured  work capacity was determined as the product of isometric torque and endurance time  recovery of strength was measured at regular intervals for ten minutes after the endurance test  statistical analysis was done by repeated measures anova  although the initial measures showed significant deficits in mean peak torque  work capacity  and recovery of strength in symptomatic postpolio subjects  no significant changes were found one year later in any of the variables  we conclude that symptomatic postpolio subjects do not lose significant neuromuscular function in one year  
class10	open depressed skull fracture missed on computed tomography  a case report  a case of an open depressed skull fracture that was missed on standard computed tomographic  ct  scan is presented  the fracture was seen on a ct generated lateral scout film  and after repositioning the gantry  further ct images clearly showed the fracture and underlying brain injury  the authors recommend that all patients with head trauma undergoing head ct have either a ct generated lateral scout film or a lateral skull radiograph to assess the vertex of the skull  an area poorly visualized on standard axial images  
class10	vertebrobasilar occlusion following minor trauma in an 8 year old boy  an 8 year old boy developed seizures and coma 2 days after a trivial bicycle accident  computed tomography failed to show pathology  magnetic resonance imaging of the head showed infarction of the pons and right cerebellum  angiography showed occlusion of the right vertebral and basilar arteries  minor traumatic injuries to the cervical spine may result in vertebrobasilar occlusion  the neurologic manifestations of this disorder and emergency department diagnosis and management are discussed  
class10	cat scratch disease  an unusual cause of combative behavior  acute encephalitis is an unusual manifestation of cat scratch disease  the authors present the case of a 27 year old man who exhibited the acute onset of encephalitis manifested by violent behavior and confusion  the diagnosis of drug abuse was presumed initially  but a careful examination revealed the true cause to be cat scratch disease  emergency physicians are frequently faced with the challenging task of evaluating confused and combative patients  this case demonstrates the importance of a complete physical examination and a thorough laboratory evaluation  
class10	sudden cervical pain  spontaneous cervical epidural hematoma  three cases of cervical epidural hematoma are reported  acute neck pain usually associated with a mild effort  closely followed by radicular pain and a neurologic deficit below the lesion is the typical presentation of this extremely rare and difficult diagnosis  as prognosis depends on preoperative neurologic state  the authors emphasize the importance of prompt identification of this lesion  the diagnosis is confirmed by computed tomography  and emergency neurosurgical laminectomy is mandatory  
class10	differential reading recovery in patients with severe to moderate closed head injury  a differential recovery was seen when alternate forms of a nationally standardized test of reading vocabulary  literal reading comprehension and inferential reading comprehension was administered serially to 10 consecutive closed head injury admissions to a university rehabilitation hospital  inferential reading comprehension was the most impaired and had the fastest recovery rate  subtle cognitive deficits in inferential reading comprehension were detected when reading vocabulary was at or better than a twelfth grade level  maximal recovery of all three reading functions occurred within 4 months after trauma  with most occurring in the first 3 months  the reading recovery pattern parallels the recovery of intelligence scores in the literature  
class10	motor evoked potentials reflect spinal cord function in post traumatic syringomyelia  the purpose of this study was to examine electrophysiologic abnormalities  including motor evoked potentials  in a patient with post traumatic syringomyelia before and after syringopleural shunting  a patient with c5 quadriplegia presented with pain  ascending sensory loss  and new weakness in the left upper extremity two yr after spinal cord injury  mri revealed a syrinx extending from c2 to t12  we measured central motor conduction times  cmcts  to the biceps  median f wave latencies  needle electromyography and motor nerve conduction studies  six days before surgery  cmcts were 9 0 ms on the left and 7 8 ms on the right  normal less than 8 0   median f waves were absent on the left and needle emg revealed evidence of denervation in the left biceps  fifteen days after syringopleural shunting at the t7 level  cmcts had dropped to 6 9 ms on the left and 4 6 ms on the right  the left median f wave reappeared with a normal latency  repeat mri revealed the syrinx to be smaller in diameter  these results suggest that cmcts measured from magnetic stimulation of the motor cortex may be useful in the diagnosis of post traumatic syringomyelia  as well as for following such patients postoperatively  
class10	spasticity in spinal cord injured persons  quantitative effects of baclofen and placebo treatments  spasticity commonly occurs after a spinal cord injury and is characterized by increased resistance to passive movement of peripheral joints  this study examined the effect of an antispasticity medication on stiffness from the myotatic reflex response generated by passive sinusoidal ankle motion  a repeated measures  multiple base line  single subject  double blind design was employed  the independent variable was spasticity medication treatment  where the levels were 40 mg day and 80 mg day of baclofen v placebo treatment  viscous and elastic stiffness measurements were taken at the ankle joint during a placebo base line phase and during treatment with baclofen for five adult males with traumatic spinal cord injuries  ankle sinusoidal oscillation frequencies were from 3 to 12 hz during test sessions  mean viscous and elastic stiffness scores for all frequencies were calculated for each phase of the study  randomization tests of mean changes in stiffness measurements between each treatment phase of the study failed to provide any convincing evidence of a significant treatment effect for reduction of spasticity in the traumatic spinal cord injured subjects studied  further testing is needed to exclude potential confounding factors before this conclusion can be confirmed  the results suggest that baclofen is not a universal treatment of choice for all individuals with spasticity resulting from traumatic spinal cord injury  
class10	spinal nerve stimulation in the diagnosis of lumbosacral radiculopathy  direct spinal nerve stimulation was compared with needle electromyography  emg  in 40 patients who were suspected of having an l5 or s1 radiculopathy  for spinal nerve stimulation  we adapted a monopolar needle electrode inserted deep into the paraspinal muscle  the minimal latency  amplitude  and negative phase area of compound muscle action potential from myotomal muscles were recorded with computer assistance  abnormality was considered to be significant when the value fell outside of 2 sd of control mean values  among 17 patients with clinical evidence of radiculopathy  needle emg was abnormal in 10 patients  58 8    whereas in the nerve stimulation test the abnormalities were shown in 16 patients  94 1    in amplitude difference and the abnormal area  differences were shown in 12 patients  70 6    among 23 patients with only subjective symptoms of radiculopathy  needle emg was abnormal in nine patients  39 1    whereas the abnormal amplitude differences were shown in 18 patients  78 3   and 15 patients  65 2   with abnormal area difference by spinal nerve stimulation  respectively  direct spinal nerve stimulation is recognized as an objective and sensitive test in the diagnosis of lumbosacral radiculopathy  
class10	spinal anaesthesia in day care surgery with a 26 gauge needle  we studied 106 day care surgical patients  52 male  aged 18 70 yr  mean 49 6 yr  who received spinal anaesthesia with a 26 gauge spinal needle  the incidence of headache  back pain and patient acceptability were investigated after operation using a questionnaire  the incidence of postspinal headache was 7 5   and 11 3  of patients developed back pain  one patient remained in hospital because of hypotension and dizziness  there were no major complications and patient acceptability was almost 100   we conclude that spinal anaesthesia for day care surgery is easy to perform and cost effective  
class10	unconsciousness associated with midazolam and erythromycin  an 8 yr old boy suffering from an asymptomatic ventricular septal defect was given erythromycin for antibiotic prophylaxis before adenoidectomy  sixty minutes after premedication with oral midazolam 0 5 mg kg 1 and oral atropine 0 03 mg kg 1  an infusion of erythromycin 400 mg was started  when 200 mg of erythromycin had been infused  the patient lost consciousness  but other vital functions remained normal  after 45 min  he awakened spontaneously  at the time the plasma concentration of midazolam was 134 ng ml 1  in order to investigate possible interactions between midazolam and erythromycin  we studied the pharmacokinetics of midazolam in six children of the same age undergoing minor otolaryngological surgery  the plasma concentration of midazolam in the patient who lost consciousness was significantly greater than in six other children without concomitant administration of erythromycin  the altered pharmacokinetics of midazolam may result from reduced hepatic clearance of midazolam caused by an enzyme inhibiting drug  erythromycin  
class10	a study of cyproheptadine in the treatment of metastatic carcinoid tumor and the malignant carcinoid syndrome  sixteen patients with metastatic neuroendocrine tumors and the malignant carcinoid syndrome were treated with cyproheptadine  periactin  merck  sharp   dohme  west point  pa  at maximum tolerable doses that ranged from 12 to 48 mg daily  usual side effects were mild sedation and dry mouth  but three patients found it impossible to sustain treatment due to nausea and vomiting  most patients had significant relief of diarrhea  frequently associated with weight gain  relief of flushing was uncommon  the therapeutic benefit produced by cyproheptadine would appear to be a peripheral effect because 5 hydroxyindoleacetic acid  5 hiaa  excretion in these patients was not reduced  although there have been case reports of objective tumor regression with cyproheptadine therapy  this was not observed in any of these 16 patients  cyproheptadine would appear to be a useful therapeutic tool for the management of diarrhea associated with the malignant carcinoid syndrome  an appropriate initial total daily dose is 0 4 mg kg divided in three fractions with prompt modification to produce minimal and tolerable side effects  
class10	radiosurgery of acoustic neurinomas  eighty five patients with acoustic neurinomas underwent stereotactic radiosurgery with the gamma unit at the university of pittsburgh  pittsburgh  pa  during its first 30 months of operation  neuroimaging studies performed in 40 patients with more than 1 year follow up showed that tumors were smaller in 22  55    unchanged in 17  43    and larger in one  2    the 2 year actuarial rates for preservation of useful hearing and any hearing were 46  and 62   respectively  previously undetected neuropathies of the trigeminal  n   12  and facial nerves  n   14  occurred 1 week to 1 year after radiosurgery  median  7 and 6 months  respectively   and improved at median intervals of 13 and 8 months  respectively  after onset  hearing loss was significantly associated with increasing average tumor diameter  p   0 04   no deterioration of any cranial nerve function has yet developed in seven patients with average tumor diameters less than 10 mm  radiosurgery is an important treatment alternative for selected acoustic neurinoma patients  
class10	ontogenetic features of audiogenic seizure susceptibility induced in immature rats by noise  although numerous models are currently used for systematic study of the mechanisms of epileptogenesis in mature brain  few animal models have been developed that allow similar explorations in the developing nervous system  one experimental model of epilepsy supports a premise that perinatal experience can lead to eventual seizure susceptibility  however  audiogenic seizure  ags  susceptibility can be induced during a critical developmental period in normal mice by auditory deprivation and therefore by cochlear trauma  we studied the developmental parameters that affect success of both induction and testing of ags susceptibility in the rat  intense high frequency noise exposure was used as the traumatizing agent  the wistar rat strain used is inherently seizure resistant because in greater than 400 trials  untreated rats have never exhibited susceptibility at any age  although single prolonged exposures to high intensity noise were administered to groups of rats at ages between postnatal days  pnds  12 and 36  pnd 14 was the age when exposure was most likely to result in eventual seizure susceptibility  furthermore  duration of initial exposure on pnd 14 determined the rate of susceptibility when measured 2 weeks later  accordingly  we noted that single noise exposures at an intensity of 125 db and ranging between 6 and 10 min in duration induced susceptibility in 100  of rats tested on pnd 28  nonetheless  seizures among the rats exposed for 8 min were the most severe  typically  these seizures began as wild running attacks and were followed by tonic clonic convulsions  
class10	effects of discontinuation of phenytoin  carbamazepine  and valproate on concomitant antiepileptic medication  we report a prospective  controlled study of the effects of the reduction and discontinuation of phenytoin  pht   22 patients   carbamazepine  cbz   23 patients   and valproate  vpa   25 patients  with concomitant antiepileptic drugs  aeds   the principal changes in the serum concentrations of concomitant aeds were  a  phenobarbital  pb  concentrations decreased by a mean of 30  on discontinuation of pht   b  total cbz concentrations increased by a mean of 48  and free cbz concentrations increased by a mean of 30  on discontinuation of pht  with no change in cbz 10  11 epoxide  cbz e  concentrations   c  vpa concentrations increased by a mean of 19  on discontinuation of pht   d  vpa concentrations increased by a mean of 42  on discontinuation of cbz   e  ethosuximide  esm  concentrations increased by a mean of 48  on discontinuation of cbz   f  pht concentrations decreased by a mean of 26  on discontinuation of cbz   g  pht free fraction decreased from a mean of 0 11 to 0 07 on discontinuation of vpa  and  h  the mean concentrations of total and free cbz increased by a mean of 10 and 16   respectively  on vpa discontinuation  with a concomitant mean 24  decrease in total cbz e and a 22  decrease in free cbz e  apart from the decrease in pb concentrations on pht discontinuation  all significant changes had occurred by 1 week after the end of aed discontinuation  the implication for clinical practice is that a serum aed concentration at this time reflects the new steady state  free concentrations did not add any clinically useful information to that gained from analysis of total serum concentrations  
class10	cognitive function and time of day variation in serum carbamazepine concentration in epileptic patients treated with monotherapy  different parameters of antiepileptic drug  aed  treatment have been shown to affect cognitive function  the drug  dose  and duration of treatment have been studied  the present study assessed cognitive function in relation to time of day variation in serum carbamazepine  cbz  concentration in epileptic patients treated with monotherapy  we studied 10 males and 12 females with a mean age of 36 years and a mean duration of cbz therapy of 4 4 years  patients had been seizure free for at least 1 month and took two daily cbz doses  the test battery included tests of motor speed  reaction time  attention  and memory  in the experimental design  the subjects were tested twice at times close to expected daily maximum and minimum serum cbz concentration  they were studied in two balanced blocks  block 1 tested at 8 a m  and noon  block 2 tested at noon and 8 p m    blood samples were collected every 2 hr from 8 a m  to 8 p m  the subjects showed significant differences in serum cbz concentration between testing times  with suggested maximum concentration between 10 a m  and noon  the test battery showed no consistent differences between performance at times of high versus low serum concentration  a supplementary analysis of correlations between mean performance level on cognitive tests and variables related to cbz treatment did not show consistent trends  
class10	immunologic aspects of carbamazepine treatment in epileptic patients  immune abnormalities have been found in epileptic patients receiving antiepileptic drugs  aeds   phenytoin  pht  produces a decrease in serum iga and igm levels and a decrease in blastic transformation of circulating lymphocytes stimulated with phytohemoagglutinin  pha   the effects of carbamazepine  cbz  on the immune response are still conflicting  to elucidate the effects of cbz on some immunologic parameters  serum concentrations of iga  igg  igm  the phagocytosis and killing properties of polymorphonuclear leukocytes  pmns   the cytotoxic activity of natural killer cells and the response of lymphocytes to mitogenic agents were studied  forty healthy individuals and 39 epileptic patients treated with carbamazepine  cbz  monotherapy  age range 18 40 years  entered the study  student s t test was used to evaluate the data  cbz had no effect on the serum immunoglobulin concentrations or on lymphocytic reactivity to phytohemoagglutinin  pha  mitogen  cbz produced a significant enhancement of phagocytosis and killing properties of pmns and an increase in natural killer  nk  cell activity  therefore  a negative effect of cbz therapy on the immune system was not observed in this study  
class10	carbamazepine induced antinuclear antibodies and systemic lupus erythematosus like syndrome  a 20 year old woman developed a systemic lupus erythematosus  sle  like syndrome and a positive antinuclear antibody  ana  soon after initiation of carbamazepine  cbz  therapy  symptoms and serology became normal after cbz was discontinued  cbz induced sle is an important but underecognized phenomenon  
class10	effect of felbamate on plasma levels of carbamazepine and its metabolites  felbamate  fbm  is a novel antiepileptic drug  aed  currently undergoing clinical evaluation in the united states  during a controlled clinical trial conducted at the national institutes of health clinical center  fbm was added to constant carbamazepine  cbz  monotherapy  cbz total concentrations were reduced during active fbm treatment  mean reduction 25   range 10 42   p less than 0 001   the effect was evident after the first week of treatment and reached a plateau in 2 4 weeks  to clarify the interaction mechanism  free and total concentrations of cbz and its plasma metabolites were determined by high performance liquid chromatography  hplc  and ultrafiltration in four patients  in these patients  fbm treatment reduced cbz concentrations and increased cbz epoxide  cbz e  concentrations  p less than 0 01   free fractions of all compounds were unmodified  fbm appears to be capable of inducing cbz metabolism  cbz fbm interaction may be clinically relevant  
class10	double blind  placebo controlled  cross over trial of progabide as add on therapy in epileptic patients  in a double blind  cross over trial  progabide  pgb  and placebo were compared as add on therapy in 59 patients with moderate to severe epilepsy  eight patients did not complete the study  4 because of adverse drug reactions  elevation of liver transaminases  2  gastritis  1  and acute psychosis  1  and 4 because of administrative reasons  among the remaining 51 patients  seizure frequency was reduced greater than 50  in 18 patients with pgb treatment and in 8 patients with placebo  p less than 0 05   the number of days with seizures was significantly  p   0 034  reduced during pgb treatment  both patients  and physicians  preferences at the end of the trial were in favor  p less than 0 01  of pgb  mild clinical side effects were present in 54 7  of the patients treated with pgb and in 37 7  with placebo  increase in liver transaminases was observed in 2 patients during the double blind study and in 1 during the follow up period  our data show that pgb  as previously reported  is useful in 30 40  of patients who are not responding completely to other antiepileptic drugs  aeds   the compound is well tolerated  but liver function must be monitored  
class10	development and reversal of contingent inefficacy and tolerance to the anticonvulsant effects of carbamazepine  the relationship of the timing of drug administration to anticonvulsant efficacy against amygdala kindled seizures was studied  during kindling development  rats received carbamazepine  cbz  15mg kg  before  cbz before  or after each amygdala stimulation  cbz after   after kindling to full seizures  when all animals were given cbz before the stimulation  only the cbz after group showed a good anticonvulsant response  the rats that had received cbz before  during development of kindled seizures  remained unresponsive to cbz treatment  contingent inefficacy   when drug naive or cbz after animals repeatedly received cbz before electrical stimulation  they developed tolerance to its anticonvulsant effects  contingent tolerance   the tolerance could be reversed by a period of treatment with cbz after or by kindling the animal drug free  but not by cbz administration alone or by time off from both drug and seizures  these findings suggest that inefficacy and tolerance to cbz may be affected by the temporal contingencies of drug administration and that responsiveness can be reinstated by altering these contingencies  
class10	kindling susceptibility and genetic seizure predisposition in inbred mice  olfactory bulb kindling rates were studied in two inbred strains of genetically seizure prone mice  dba 2 and el  and in three non epileptic inbred strains  c57bl 6  b6   ddy  and c3h he  c3h    none of the dba 2 mice had been stimulated to seizure before or during the kindling and all mice were studied at 4 6 weeks of age  before development of spontaneous or movement induced seizure activity in the el strain  the audiogenically seizure susceptible dba 2 mice required the fewest number of stimulations to reach stage 5 seizure  mean     se   4 0     0 6   the nonepileptic c3h mice required the most stimulations to reach stage 5 seizures  22 6     1 4   kindling rates for b6  9 6     0 6   el  14 8     1 1   and ddy  18 5     1 0  strains were intermediate  and the kindling rate for each strain was significantly different from that of the other strains  these findings show that the seizure susceptible el mouse kindles more rapidly than the genetically similar but nonepileptic ddy control and suggest that an inherited seizure susceptibility accelerates the kindling rate  nonepileptic b6 mice kindled more rapidly than el mice  however  suggesting that genetic factors other than those that influence seizure susceptibility are of primary importance in the determination of the kindling rate  
class10	changes of hippocampal glucose utilization subsequent to amygdaloid kindled generalized seizures  local changes in cerebral glucose utilization during the postictal phase of amygdaloid kindled generalized seizures were studied with the quantitative autoradiographic 2  14c deoxyglucose method in conscious rats  measurement was initiated either just after termination of a behavioral seizure  gs i  or 30 s after seizure termination  gs ii  to determine dynamic metabolic changes in the postictal phase  although glucose utilization of the neocortex was remarkably depressed in both gs i and gs ii  that of the hippocampus significantly increased in gs i and then decreased in gs ii as compared with control  these changes of hippocampal glucose utilization were observed in all sectors of the pyramidal cell layer  ca 1 4  and in the molecular layer  because metabolic changes associated with development of amygdaloid kindled seizures begin in the limbic structures including the hippocampus  the transient increase in hippocampal glucose utilization observed in the early postictal phase indicates that the hippocampus is one of the key structures not only for initiating and maintaining but also for terminating kindled seizures  
class10	panic disorder in seizure patients  a diagnostic pitfall  panic disorder is a psychiatric diagnosis whose main feature is paroxysmal attacks of anxiety that strike suddenly without apparent provocation  physicians explain the attacks as an ictal phenomenon in patients with known seizures because of their similarities to complex partial seizures  we report eight patients with seizures and panic disorder  recognition of a second diagnostic entity resulted in a beneficial change in treatment in six of the eight  we did not find an increased incidence of panic disorder in our seizure clinic population as compared with the general population  
class10	effect of epilepsy and sleep deprivation on the rate of benign epileptiform transients of sleep  seventy eight individuals with eeg records containing benign epileptiform transients of sleep  bets  were identified among 7 400 records reviewed in our laboratory in a 6 year period  the records contained no other abnormality in 51 patients  65    genuine epileptiform discharges were found in the records of 19 patients  14 had a history of epilepsy  thirty five patients  45   had a proven history of epilepsy with antiepileptic drug  aed  therapy  in the records of these patients  the mean number of bets per unit of time was significantly higher  11 88     2  than in the record of the rest of the laboratory population with bets  6 89     0 9   p less than 0 02   among five conventional surface montages  ipsilateral ear referential montage  ierm  showed a significantly higher number of bets per unit of time than did any other surface montage used in the study  thirty nine records  50   were performed after sleep deprivation  sd   when only ierm was considered  sd records showed a significantly higher number of bets per unit of time  7 36     1 1  than did non sd records  3 89     0 69   p less than 0 01   our findings support the general consensus that individual bets may be normal variants  but a high occurrence of bets in the record should raise suspicion of underlying epilepsy  
class10	dreams and epilepsy  the relationship between dreams and epilepsy is illustrated by two patients whose awake epileptic seizures and recurrent dreams during night sleep had similar content  in both of our cases the eeg showed right anterior temporal spike discharge  suggesting a role for the temporal lobe in the association between dreams and seizures  
class10	epilepsy with continuous spike waves during slow sleep and its treatment  five children with epilepsy with  continuous spike waves during slow sleep   csws  are reported  the main clinical features of csws include  a  onset between 5 and 7 years of age   b  the occurrence of several types of seizure  i e   partial motor  generalized motor  and atypical absence   and  c  the presence of language disturbances and abnormal behavior based on emotional impairment  the eeg findings were characterized by sleep tracings showing almost continuous  greater than 95    diffuse slow spike and wave activity  after treatment with valproate  vpa   or ethosuximide  esm  and clonazepam  czp   the spike and wave complex status disappeared  symptoms and signs of the csws also decreased  we suggest that combined treatment is an appropriate treatment for csws  
class10	postnatal epilepsy after eeg confirmed neonatal seizures  we examined infants whose neonatal seizures were confirmed by randomly recorded ictal eeg tracings to determine the types and frequency of postnatal epilepsy  pne   unprovoked  recurring postnatal seizures  perinatal and postnatal clinical and eeg variables were also examined for their relevance to pne  forty infants with eeg documented neonatal seizures of diverse etiologies were studied  the 27 survivors were followed for a mean of 31 months  pne developed in 56   15 of 27  of the cohort  the first seizure appeared at a mean corrected age of 12 7 months and occurred despite ongoing antiepileptic medication in 60   9 of 15  of the group  seizures were classified as infantile spasms or minor motor  7 patients   complex partial  4 patients   or generalized tonic clonic  4 patients   perinatal variables that significantly correlated with pne included the presence of coma but not the age at seizure onset  the estimated gestational age  or apgar scores  pne occurred in 68   13 of 19  of patients with moderately or markedly abnormal eeg backgrounds but in only 25   2 of 8  without  p   0 035   there was a strong trend for pne to develop in patients with greater than 10 electrographic seizures per hour but in only 45   9 of 20  of infants with fewer seizures  p   0 058   several postnatal variables were significantly related to pne  the presence of cerebral palsy  cp   mental retardation  mr   cp with mr  and follow up eegs  pne occurred in only 27   3 of 11  of patients without spikes or sharp waves on postnatal eegs performed at age 3 months but in 100   3 of 3  of patients with spikes or sharp waves  p   0 022   
class10	photosensitive epilepsies and photoconvulsive responses in arabs  the occurrence of photosensitivity  ps  was examined in 327 arabs greater than or equal to 15 years of age with epilepsy by intermittent photic stimulation  ips   a control group of 192 nonepileptic arabs greater than or equal to 15 years of age were also examined by ips  of the epileptic patients  24  7 3   were photosensitive  an incidence comparable to that in whites in contradistinction to the reported rarity among african blacks  this finding indicates that environmental factors  particularly excessive sunshine  does not appear to influence the occurrence of ps among epileptic patients  the occurrence of ps among epileptic patients may depend more strongly on the presence of an epileptic syndrome known to have association with ps  
class10	sexual behavior of a sample of females with epilepsy  a sample of 700 female epileptic outpatients was examined between 1985 and 1987  the incidence of psychosexual disorders was 18   epileptic females with psychosexual disorders were compared with epileptic females without sexual disorders and with normal female controls on selected clinical and eeg parameters  epileptic females with sexual disorders showed  lower marriage rates  a longer duration of illness  sexually colored prodromata  predominance of partial complex seizures  83   and a higher incidence of menstrual abnormalities  hyposexuality and exhibitionism were the psychosexual disorders most frequently noted  temporal lobe eeg abnormalities were significantly higher  
class10	attitudes of major employers toward the employment of people with epilepsy  a 30 year study  beginning in 1956  major san francisco bay area employers were sampled at 10 year intervals for a 30 year period to assess attitudes toward the employment of epileptic workers  in this time  we documented a trend of sustained positive change that appears to validate the efforts of organizations that have focused on raising public awareness of this disorder  
class10	antiepileptic drug monitoring at the epilepsy clinic  a prospective evaluation  to assess the value of on site therapeutic drug monitoring at the epilepsy clinic  management decisions were recorded before and immediately after antiepileptic drug  aed  concentrations became available  in the first year of this prospective study  632  277 carbamazepine  cbz   170 phenytoin  pht   113 valproate  vpa   and 72 phenobarbital  pb   assays were performed during 488 clinic attendances in 182 actively managed epileptic patients  the results of drug analysis led to alterations in management at 114 patients visits  i e   23  of those monitored  dosage was increased in response to the circulating aed concentration in 12  of consultations and decreased in another 7 5   unsuspected poor compliance was uncovered in eight patients  and in three others an aed was added or discontinued on the basis of the assay result  the time of the next appointment was rearranged in 58 attendances  only 50  of results were in the  therapeutic  ranges for the four major aeds  dosage was adjusted  50 up  16 down  after 54  of low results   therapeutic  levels were followed by a change in aed dose  52 up  31 down  in 26   only 29  of concentrations above the  therapeutic  range persuaded the doctor to alter the dosage regimen  and in 20  of these an increase in dose was recommended  on site aed monitoring had an immediate impact on clinical decision making in greater than 23  of consultations but in a form more subtle than the simple quest for a therapeutic result  
class10	effects of lactulose and lactitol on protein digestion and metabolism in conventional and germ free animal models  relevance of the results to their use in the treatment of portosystemic encephalopathy  protein digestion and metabolism have been studied in laboratory rats and miniature pigs to investigate the mechanisms of action of lactulose and lactitol when used in the treatment of patients with portosystemic encephalopathy  lactulose  beta d galactopyranosyl  1    4  beta d fructofuranose  and lactitol  beta d galactopyranosyl  1    4  d glucitol  increased the excretion of nitrogenous material in the faeces and decreased nitrogen excretion in the urine in a similar degree to that reported for human patients  in studies with germ free rats given lactulose no such effect was observed  suggesting that  for lactulose at least  these effects are mediated by the gut flora  measurement of the alpha   epsilon diaminopimelic acid content of the faeces confirmed that the enhancement of faecal nitrogen was due to an increased contribution from bacteria  the similarity in the results for lactulose and lactitol suggests that  from the perspective of protein metabolism  lactitol acts in a similar way to lactulose in the treatment of portosystemic encephalopathy  
class10	posterior transfer of the adductors in children who have cerebral palsy  a long term study  seventy eight posterior transfers of the adductors of the hip in forty two children who has spastic cerebral palsy were reviewed an average of 5 7 years after the operation  range  two to 14 6 years   the results were assessed on the basis of the patient s ability to walk  the range of motion of the affected hip or hips  and the radiographic measurements  in 88 per cent of the patients  the transfer was successful in improving or maintaining abduction  extension  functional walking  and stability of the hip  the failures were all in patients who were unable to walk and who had spastic quadriplegia  tenotomy of the iliopsoas tendon at the time of the transfer procedure resulted in an improved range of motion of the hip  
class10	deformities of the hip in adults who have sickle cell disease and had avascular necrosis in childhood  a natural history of fifty two patients  we report the natural course of the hip in fifty two patients  ninety five hips  who had sickle cell disease and had had avascular necrosis in childhood  there were twenty one african  twenty one west indian  and ten mediterranean patients  at the most recent follow up examination  at an average duration of nineteen years after the onset of the disease   80 per cent of the hips that had been affected by avascular necrosis during childhood were painful and had permanent damage with regard to decreased mobility  limb length discrepancy  and an abnormal gait  when the patients were evaluated  at an average age of thirty one years  fifteen hips  16 per cent  had had an operation for progressive disability and sixty  63 per cent  had major problems because of pain  of the twenty hips  21 per cent  that were not painful  five were in patients who had an abnormal gait  with decreased agility  the mean iowa hip rating score at the most recent follow up examination was 73 points  range  30 to 100 points   correlations were found between the hip score and the patient s age at the onset of the disease and at the latest follow up  between the hip score and degenerative changes in the hip  and between degenerative changes and radiographic evidence of deformity of the hip  
class10	the relation of pain to depression among institutionalized aged  nursing home and congregate apartment residents  n   598  were classified on the basis of a dsm iiir symptom checklist as suffering possible major  minor  or no depression  they also completed the geriatric depression scale  gds  and the profile of mood states  poms   possible major depressives reported more intense pain and a greater number of localized pain complaints than did minor depressives  nondepressed individuals reported the least intense pain and fewest localized complaints  the effect remained strong even when functional disability and health status were controlled statistically  both pain intensity and number of localized complaints were correlated with gds and poms factor scores  but strength and direction of associations varied with level of depression  item by item examination of localized complaints again indicated that more depressed individuals were more likely to report pain  particularly where physicians had identified a physical problem that might account for the pain  results are compared with previous research on pain among younger individuals  implications for treatment of depressed elderly are discussed  
class10	is gastric acid responsible for the pain in patients with essential dyspepsia  the pathogenesis of symptoms in patients with essential dyspepsia is not known  since treatment with h2 receptor antagonists has provided symptomatic relief in some reports  we carried out the present study to investigate whether gastric acid is responsible for symptoms in these patients  fifty patients with essential dyspepsia and 25 healthy control subjects were studied  after an overnight fast  a nasogastric tube was passed and its tip positioned in the antrum under fluoroscopic control  normal saline or 0 1 m hydrochloric acid was infused in a randomized  double blind fashion  eleven  22   patients developed pain with acid infusion  but none with normal saline  p less than 0 005   in 10 of these 11 patients  pain recurred on rechallenge with acid infusion but was promptly relieved with infusion of 1 m sodium bicarbonate  none of the healthy controls developed pain on infusion of acid or saline  these observations suggest that acid has a definite role in the pathogenesis of symptoms in some patients with essential dyspepsia  although other factors may also be important  
class10	oestrogen and progesterone receptors in acoustic neuroma  tissue samples from fourteen consecutive  8 male  6 female  acoustic neuromas were assayed for hormone receptors using either a monoclonal antibody  ma   dextran coated charcoal  dcc  or isoelectric focusing  ief  technique  in this series there were no unequivocally positive results  a finding at variance with previously published results  
class10	uses and complications of uvulopalatopharyngoplasty  uvulopalatopharygoplasty has become widely performed for chronic snoring and for cases of obstructive sleep apnoea  unfortunately this operation is not without morbidity and complications  we report our results of a prospective series of 50 patients undergoing uvulopalatopharyngoplasty with a minimum follow up of one year  snoring was abolished in 18  36 per cent  and substantially reduced in the remainder  obstructive sleep apnoea syndrome  identified in 11 patients pre operatively  was reduced in severity in all but three  troublesome complications were seen in 18  36 per cent  patients  namely intermittent velopharyngeal incompetence in five  10 per cent   pharyngeal dryness in 11  22 per cent  and loss of taste in five  10 per cent   one patient had nasopharyngeal stenosis requiring correction  a cautious approach to this operation is required with rigorous case selection  the importance of full assessment and careful follow up should not be underestimated  
class10	use of emla cream as an analgesic in the management of painful otitis externa  a new application of emla cream is described  relief of pain in otitis externa is difficult and systemic analgesics for this localized condition are often ineffective  meticulous cleaning of the external auditory meatus is an essential step in the treatment  emla cream is an effective analgesic which can be used to relieve pain and anaesthetize the external auditory meatus to allow cleaning in patients with intact tympanic membranes  
class10	ulcerative colitis and giant cell arteritis associated with sensorineural deafness sensorineural deafness is rarely associated with both ulcerative colitis and giant cell arteritis  a patient is described in whom acute sensorineural deafness occurred in association with episcleritis  ulcerative colitis and clinical features suggesting giant cell arteritis  
class10	the frequency  causes and timing of death within 30 days of a first stroke  the oxfordshire community stroke project  in a prospective  community based study of 675 consecutive patients with a first ever stroke  of whom over 90  had computed tomography  ct  and or necropsy examinations  129 deaths occurred within 30 days of the onset of symptoms  a case fatality rate  cfr  of 19   the 30 day cfr for patients with cerebral infarction was 10   57 of 545  for primary intracerebral haemorrhage 52   34 of 66   for subarachnoid haemorrhage 45   15 of 33  and for those of uncertain pathological type 74   23 of 31   the cfr for patients who had been functionally dependent pre stroke was 33  compared with 17  for those who had been independent pre stroke  the age adjusted relative risk of death for patients who had been functionally dependent pre stroke was not significantly greater  1 8  95  confidence interval 0 to 4 3   there was a significant trend for cfr to increase with age  chi square for trend   4 0  p less than 0 05   this relationship was found in those patients who had been functionally independent prestroke  chi square for trend   7 9  p less than 0 005  but not in those who had been dependent pre stroke  chi square for trend   0 5  ns   the pattern of increasing cfr with increasing age amongst those who had been independent prestroke was seen particularly in patients with cerebral infarction  chi square for trend   8 6  p less than 0 005   the age adjusted relative risk of death for patients with cerebral infarction who had been functionally dependent pre stroke was 2 2  95  confidence interval 1 2 to 4 1   fifty three percent of all deaths within 30 days of stroke were due to the direct neurological sequelae of the stroke  
class10	the natural history of non arteritic anterior ischaemic optic neuropathy  seventy one patients with non arteritic anterior ischaemic optic neuropathy were studied retrospectively  sixty three  89   were followed to the end of the study or death  mean follow up time was 5 3 years  whilst twenty  28   had diabetes or hypertension  in thirty nine  55   no predisposing condition was identified  in those who had monocular disease at presentation  68   subsequent involvement of the second eye occurred in seventeen  25    seven within the first year  nineteen patients died within the study period  of these  nine died from myocardial infarction and four from cerebrovascular disease  this is a significant increase above figures calculated from the office of population census and surveys  p less than 0 001 for all causes  p less than 0 002 for myocardial infarction and cerebrovascular disease   such an increase in mortality has not been previously reported  and implies that this condition carries a more sinister systemic prognosis than is frequently supposed  
class10	syndromes of transient amnesia  towards a classification  a study of 153 cases  of 153 patients presenting with acute transient amnesia  114 fulfilled the proposed strict diagnostic criteria for transient global amnesia  tga   the prognosis of this group was excellent with the exception of a small subgroup  7    largely identifiable because of atypically brief or recurrent attacks  who developed epilepsy of temporal lobe type on follow up  computerised tomography  ct  scans performed on 95 patients were normal  evidence for covert alcoholism was lacking and there was a familial incidence of approximately 2   by contrast  the group of 39 patients who did not meet the criteria for tga had a significantly worse prognosis with a high incidence of major vascular events  the groups could not be distinguished on the basis of behavioural characteristics during the attack  the following classification was proposed  1  pure tga  attacks fulfilling the strict criteria  and of more than one hour in duration which do not require detailed investigation  2  probable epileptic amnesia  attacks of less than an hour or rapidly recurrent  3  probable transient ischaemic amnesia  a minority of cases with additional focal neurological deficits during the attack  
class10	effect of nicardipine on somatosensory evoked potentials in patients with acute cerebral infarction  we evaluated the effect of nicardipine  a calcium channel blocker  on somatosensory evoked potentials  sep  in 26 patients with acute cerebral infarction  post treatment  58   15 26  of the n20 and p25 latencies were prolonged in the affected hemispheres  8   2 26  were shortened  and 35   9 26  did not change  the mean n20 and p25 latencies were significantly prolonged two hours post treatment in the affected hemisphere  n20  p less than 0 01  p25 p less than 0 01   nicardipine  ni  had no effect on sep components in the intact hemispheres  seventy five per cent of the 12 patients with hypertension had a decrease in blood pressure  bp  after taking nicardipine  but there were no undesirable side effects or worsening of neurological signs  our study demonstrates that nicardipine prolongs the latencies of short latency components of sep in the affected hemisphere after acute ischaemic stroke and also decreases bp  these observations suggest that nicardipine therapy might impair neuronal function in the ischaemic zone  
class10	platelet monoamine oxidase b activity in parkinsonian patients  monoamine oxidase b  mao b  plays a pivotal role in n methyl 4 phenyl 1 2 3 6 tetrahydropyridine  mptp  induced parkinsonism  an increased mao b activity in platelets of patients with idiopathic parkinson s disease  pd  is reported in this study  the possibility that high mao b activity may represent a trait of vulnerability for pd by enhancing the neurotoxic effects of environmental compounds is discussed  
class10	changes in the basal dendrites of cortical pyramidal cells from alcoholic patients  a quantitative golgi study  although a variety of pathological changes have been described in the brains of chronic alcoholic patients  there have been no studies which have addressed the question of alterations in cortical neuronal dendritic arborisation  loss of neurons from the superior frontal gyrus and shrinkage of neurons from both the superior frontal gyrus and motor cortex has been documented in chronic alcoholic patients  these areas were chosen for this study  using a modified rapid golgi technique the basal dendritic arborisation of layer iii pyramidal neurons was compared in 15 male alcoholic patients and 15 age matched male controls  all parameters measuring basal dendritic arborisation were significantly less in the alcoholic cases for both the superior frontal and motor cortices  changes in the arbor are in the terminal branches  which is consistent with other models of dendritic plasticity  such changes may explain both permanent and reversible functional deficits in chronic alcoholic patients  
class10	temporal movement control in patients with parkinson s disease  patients with parkinson s disease  pd  have been reported to be unable to modify their movement velocity to adapt to changing environmental demands  for example  when movement amplitude is varied  pd patients usually exhibit a nearly constant peak velocity  whereas elderly subjects show an increase of their peak velocity with increased amplitude  the experiment examined the ability of pd patients to vary the duration of their movement  four different percentages of their maximum  under conditions where temporal  but not spatial  control was emphasised  pd patients had longer movement times than control subjects  but were able to vary the duration of their movement with comparable temporal accuracy to that of elderly subjects  for both groups  the agonist emg activity increased with decreased movement duration  for the pd patients  the number of agonist bursts increased with increased movement duration  
class10	specificity of affective and autonomic symptoms of depression in parkinson s disease  previous investigators have suggested that numerous symptoms used to diagnose depression  such as sleep or appetite disturbance  are non specific in medically ill patients  and alternative diagnostic criteria should be developed  in the study this hypothesis was tested in parkinson s disease  pd  by comparing patients with pd who reported a depressive mood with patients having pd but without a depressive mood  depressed patients showed a significantly higher frequency of both autonomic and affective symptoms of depression  depressed patients with pd reported a significantly higher frequency of worrying  brooding  loss of interest  hopelessness  suicidal tendencies  social withdrawal  self depreciation  ideas of reference  anxiety symptoms  loss of appetite  initial and middle insomnia  and loss of libido when compared with non depressed patients  no significant between group differences  however  were observed in the frequency of anergia  motor retardation  and early morning awakening  
class10	neurophysiological observations on corticospinal projections to the upper limb in subjects with rett syndrome  the aim of the present study was to investigate the excitability of corticospinal neurons and the integrity of their projections to the alpha motor neurons through the corticospinal tract in subjects of different ages with rett syndrome  electromagnetic stimulation of the motor cortex and cervical motor roots was used to evoke motor action potentials in the biceps brachii and hypothenar muscles  the phasic stretch reflex in the biceps brachii was also recorded to study the excitability of spinal alpha motor neurons  motor cortex stimulation evoked motor action potentials at low threshold and with abnormally short latencies and prolonged durations  in contrast cervical motor root stimulation resulted in responses of normal latency and duration  the phasic stretch reflex had a low threshold  short latency and prolonged duration  it is concluded that in rett syndrome the corticospinal pathway is intact  the results suggest disordered synaptic control of the betz cell of the motor cortex and or the spinal alpha motor neuron  although the involvement of the latter might be a consequence of dysfunction in supraspinal descending motor pathways  
class10	motor units in incomplete spinal cord injury  electrical activity  contractile properties and the effects of biofeedback  the electrical and contractile properties of hand muscles in a selected population of quadriplegic subjects were studied intensively before and after emg biofeedback  spontaneously active motor units and units that could only be slowly and weakly activated were observed in these subjects  in addition to units that were voluntarily activated normally  this suggests a considerable overlap of surviving motor neurons to a single muscle that are below  near or above the level of a lesion  despite the common occurrence of polyphasic potentials and other signs of neuromuscular reinnervation  the average twitch tension of single motor units in hand muscles of quadriplegic subjects was not significantly different from that in control subjects  nor did it increase after biofeedback training that typically increased the peak surface emg by a factor of 2 5 times  the percentage of spontaneously active units was also constant  the surface emg may be increased during biofeedback by using higher firing rates in motor units that can already be activated  rather than by recruiting previously unavailable motor units  
class10	visual evoked potential monitoring of optic nerve function during surgery  a study was made with intra operative flash  visual evoked potentials  vep  monitored using a fibre optic contact lens photo stimulator in 57 patients undergoing intra orbital surgical procedures with potential risk to the optic nerve  the veps recorded under enflurane and nitrous oxide anaesthesia did not differ significantly in latency or amplitude from the pre operative recordings  transient abolition of the vep was seen under many circumstances and did not correlate with the outcome of surgery  but absence of a previously normal vep for more than four minutes during surgical manipulation within the orbit did show a correlation with post operative impairment of vision  the technique provides early warning to the surgeon of threats to the integrity of the optic nerve  
class10	determination of ventricular fluid outflow resistance in patients with ventriculomegaly  resorption of the ventricular fluid was studied by measuring ventricular fluid outflow resistance during steady state 1 5 and 5 0 ml min infusions in 26 patients with substantial enlargement of the supratentorial ventricular system  this test may avoid unnecessary use of shunts  but a shunt could be introduced during the same procedure  
class10	neuropsychological profile linked to low dopamine  in alzheimer s disease  major depression  and parkinson s disease  a distinct pattern of neuropsychological deficits was associated with low homovanillic acid  hva  in the cerebrospinal fluid of 21 patients with  alzheimer s disease  9   parkinson s disease  8  and major depressive disorders  4   regardless of clinical diagnosis  patients with low hva were slower on a test of efficiency of processing timed information  and showed greater benefit from semantic structure on a verbal fluency task than patients with high hva  however  low hva subjects were not significantly impaired on confrontation naming  boston naming test   across three diagnostic groups  patients with lower hva also tended to have more extrapyramidal motor signs and were significantly more depressed  these results demonstrate a significant relationship between specific neuro behavioural deficits and dopaminergic activity which cuts across traditional diagnostic categories  
class10	a case of amnesia after excision of the septum pellucidum  tumours of the septum pellucidum  sp  are rare and seldom associated with memory impairment either before or after operation  a patient is described who developed amnesia after transcallosal excision of a tumour of the sp  radiology did not show any major lesion of the brain areas traditionally associated with amnesia  because septal nuclei could have been damaged during surgery their possible role in memory functions is discussed  
class10	stroke rehabilitation  australian patient profile and functional outcome  a prospective  multi institutional  population based study identified 1274 non surgical stroke admissions to all hospitals in a major australian city during 1984  the demographic and diagnostic profile and the nature of functional recovery of all 258 first stroke survivors who were referred for inpatient rehabilitation are presented  the median duration of rehabilitation stay was 49 days  the mean functional independence score  as measured on a modified barthel index at admission was 44  compared with 78 on discharge  a mean improvement of 34  stair climbing had the lowest mean value on admission  12   while bowel control had the lowest residual deficit on discharge  95   the stroke study group was representative of the unimpaired aged population in all respects except ethnicity  where differences are attributed to age  the variables identified as significant are  side and severity of paralysis  age and sex  marital status and ethnicity  stroke rehabilitation outcome was not influenced by etiology  site of lesion  arterial distribution  occupation or education  
class10	status of cochlear implantation in children  american academy of otolaryngology head and neck surgery subcommittee on cochlear implants  the cochlear implant is a medical device  part of which is placed surgically  that uses electrical stimulation to provide hearing  for almost a decade  investigational studies have been ongoing to define its safety and efficacy in profoundly deaf children  during this period  more than 500 children aged 2 through 17 years have been implanted with either a single electrode or multielectrode device  extensive auditory  speech  educational  and psychologic testing has been performed before and after implantation  results show that the cochlear implant provides auditory detection over much of the speech signal  compared with the preimplant period  there is significant improvement in auditory discrimination and speech production skills  limited open set word and sentence recognition is possible for at least some children  complications with the device have been minimal  the cochlear implant can provide sound to deaf children unable to benefit from hearing aids  the complex assessment  rehabilitation  and parent counseling should be performed by centers with the multidisciplinary staffs necessary to provide effective care for patients with this specialized auditory prosthesis  
class10	asymmetric growth of the lateral cerebral ventricle in infants with posthemorrhagic ventricular dilation  lateral cerebral ventricular volume in 36 preterm infants with or without an intraventricular hemorrhage  and with or without posthemorrhagic hydrocephalus  was measured longitudinally and compared with the ventricular index measurements of the same ventricles  a poor correlation was found  r2   0 67   to determine a reason for this poor relationship  we analyzed the volumes of the regions of the ventricles by a segmental volume analysis  the occipital region of the lateral cerebral ventricle enlarged at a much faster rate  1 904     0 477 ml day  than either the anterior region  0 546     0 253 ml day  p less than 0 01  or the middle region   0 209     0 334 ml day  p less than 0 01  in infants with posthemorrhagic hydrocephalus  the rate of growth of the middle region of the lateral cerebral ventricles was the same for all infants  linear indexes  such as the ventricular index and the lateral ventricular ratio  do not allow for accurate serial estimates of ventricular size in posthemorrhagic hydrocephalus because of asymmetric growth of the lateral cerebral ventricle  we conclude that sequential volume measurements are more useful than ventricular index measurements to follow ventricular size sequentially in infants with posthemorrhagic hydrocephalus  
class10	phenotypic variability in glutaric aciduria type i  report of fourteen cases in five canadian indian kindreds  we describe 14 patients with glutaric aciduria type 1 in five canadian indian kindreds living in manitoba and northwest ontario  the patients had marked clinical variability of the disease  even within families  eight followed the typical clinical course of normal early growth and development until the onset of neurologic abnormalities  often precipitated by infection  between 6 weeks and 7 1 2 months of age  five patients had early developmental delay  one was thought to be normal until 8 years of age  three patients died  seven are severely mentally and physically handicapped  and four have only mild mental retardation or incoordination  six patients had macrocephaly in the neonatal period  computed tomography was done for 12 patients  and findings were abnormal in 11  glutaric acid and 3 hydroxyglutaric acid were detected in increased amounts in the urine of all patients  but the concentrations were much lower than those in most other reported patients  glutaryl coenzyme a dehydrogenase activity in skin fibroblasts  interleukin 2 dependent lymphocytes  or both  ranged from 0  to 13  of control values  there was no correlation between clinical severity and urine glutaric acid concentration or level of residual enzyme activity  we recommend that organic acid analysis of the urine be done in patients with unexplained cerebral palsy like disorders  especially if the computed tomographic scan is abnormal  if there is suspicion of glutaric aciduria  glutaryl coenzyme a dehydrogenase should be measured in fibroblasts or lymphocytes even if glutaric acid is not increased in the urine  
class10	the management of mid face fractures with intracranial injury  recent advances have radically changed the management of facial fractures  ct scanning  extensive exposure  and rigid plate fixation in the setting of the trauma center have permitted early operation with improved results  a subset of patients with facial fractures will also have intracranial injuries  ici   we sought to identify parameters associated with an increased risk for ici  we also sought to examine the safety and limits of early craniofacial repair in patients with intracranial injuries  of 114 mid face fractures treated over a 1 year period  43  38   had a concomitant ici  the majority  36  84    were from motor vehicle accidents  mva   frontal sinus and orbitoethmoid fractures were at the highest risk for ici  although orbitozygomatic fractures caused by mvas also had a surprisingly high incidence of ici  our results show that early craniofacial repair can be performed safely with appropriate general surgical and neurosurgical support  
class10	multipiece tire rim injuries  multipiece tire rims can explode during tire change  causing severe injury  although more than 450 such accidents  with at least 80 deaths  have been recorded by the national highway traffic safety administration  nhtsa   we found no reports in the surgical literature on such injuries in the united states  this report describes experience with seven patients who sustained injuries in explosions of multipiece tire rims  all victims suffered massive maxillofacial trauma with associated ocular  cranial  intracranial  and extremity injuries  two patients died  both because of intracerebral hemorrhage  one patient suffered serious long term disability  all survivors required extensive reconstructive surgery  the design of the multipiece tire rim is inherently hazardous  since many accidents of this type are not reported to the nhtsa  the incidence of such injuries may be significantly higher  an alternative  nonhazardous tire rim is available  design modifications or a law restricting use of multipiece tire rims would prevent many accidents  
class10	multicenter trial of l carnitine in maintenance hemodialysis patients  ii  clinical and biochemical effects  since carnitine deficiency has been reported in some patients undergoing maintenance hemodialysis  we studied the effects of intravenous infusion of l carnitine or placebo at the end of each dialysis treatment  the trial  which lasted seven months  one month baseline  6 months treatment  was multicenter  double blind  placebo controlled  and randomized  eighty two long term hemodialysis patients  who were given either carnitine  n   38  or placebo  n   44   completed this study  in each group  clinical and biochemical parameters during treatment were compared with baseline values  intra dialytic hypotension and muscle cramps were reduced only in the carnitine treated group  while improvement in post dialysis asthenia was noticed in both carnitine and placebo groups  maximal oxygen consumption  measured during a progressive work exercise test  improved significantly in the carnitine group  111     50 ml min  p less than 0 03  and was unchanged in the placebo group  l carnitine treatment was associated with a significant drop in pre dialysis concentrations of serum urea nitrogen  creatinine and phosphorus  means     sem  101     4 5 to 84     3 9  16 7     0 67 to 14 7     0 64  and 6 4     0 3 to 5 5     0 4 mg dl  respectively  p less than 0 004   no significant changes in any of these variables were noticed in the placebo group  mid arm circumference and triceps skinfold thickness were measured in 11 carnitine and 13 placebo treated patients  calculated mid arm muscle area increased in the carnitine patients  41 37     2 68 to 45 6     2 82 cm2  p   0 05  and remained unchanged in the placebo patients  
class10	leukocyte alkaline phosphatase score in patients with cerebrovascular disease and in patients with primary and metastatic brain tumors  leukocyte alkaline phosphatase  lap  activity in peripheral blood was determined in 54 patients with cerebrovascular disease  cvd   11 patients with primary brain tumor  and 23 patients with metastatic brain tumor  the lap score of the primary brain tumor patients  155     40  was significantly higher  p less than 0 03  than the lap score for cerebrovascular disease patients  96     87   the lap score levels of the metastatic brain tumor patients  251     55  was significantly higher as compared with both the cerebrovascular disease  p less than 0 001  and primary brain tumor groups  p less than 0 001   the lap score could serve as an additional  although non specific  marker to assist in the differentiation between cerebrovascular disease and brain tumors  
class10	coronary bypass surgery  is the operation different today  patients undergoing coronary bypass grafting have undergone an evolution in recent years  to document this change  we analyzed two groups of patients in 1981  n   1586  and 1987  n   1513  to document preoperative and postoperative variables important in determining immediate morbidity and mortality after isolated coronary bypass  between 1981 and 1987  patients were found to be older  greater than or equal to 70 years  8 7  versus 21 8   p less than 0 0001   more often diabetic  15  versus 24   p less than 0 0001   have a greater prevalence of triple vessel disease  14 5  versus 46 1   p less than 0 0001   and have more left ventricular dysfunction  ejection fraction 0 60     14 versus 0 54     13  p less than 0 0001   to facilitate analysis and because of overlap between subgroups  we subdivided patients into three subgroups for statistical comparison of the years 1981 and 1987  subgroup i  no prior procedure  n   1546 in 1981 and 1396 in 1987   subgroup ii  optimal group  n   503 in 1981 and 292 in 1987  and defined as no prior procedure  ejection fraction greater than or equal to 0 50 and age less than 65 years   subgroup iii  patients having reoperations  n   40 in 1981 and 117 in 1987   internal mammary artery grafting was infrequently used in 1981 but was used in 72 1  in 1987  major postoperative morbidity between the 2 years for the total population increased significantly  need for intraaortic balloon pumping  1 4  versus 4 7   p less than 0 0001  myocardial infarction 3 5  versus 5 5   p less than 0 008  stroke  1 4  versus 2 8   p less than 0 008  and wound infection  1 0  versus 3 0   p less than 0 001  wound infection  all types  in 1987 was increased sevenfold in patients having a perioperative myocardial infarction  0 7  versus 5   p less than 0 0001   for young patients with good left ventricular function  subgroup ii   there was no increase in these morbid events between 1981 and 1987  hospital mortality in the total population increased significantly between 1981 and 1987 from 1 2  to 3 1   p less than 0 0002   respectively  it was lowest for the patients in optimal condition  subgroup ii  in both years  0 8  versus 1 1   and highest for reoperative patients  5 3  versus 4 3   in 1981  58  of patients  503 870  were in the optimal group compared with 35   292 828  in 1987  p less than 0 0001   the last six years have seen a progressive trend in surgically treating older  sicker patients who have more complex disease  with a significant reduction in the best candidate group  abstract truncated at 400 words   
class10	feasibility of reversing benzodiazepine tolerance with flumazenil to examine whether the benzodiazepine antagonist flumazenil can reverse tolerance to benzodiazepines but without precipitating withdrawal seizures  the antiepileptic effect of flumazenil itself and its ability to reverse tolerance at a dose that would leave sufficient receptors free for the binding of benzodiazepines were investigated  electroencephalographic studies in 6 patients with partial and 6 with generalised seizures showed that flumazenil had a short  20 min  non dose dependent suppressant effect on epileptic discharges in those with partial seizures  receptor occupancy studies in 12 patients showed that 1 5 mg flumazenil given intravenously occupied 55  receptors  whereas 15 mg occupied nearly all receptors  when 3 patients with partial seizures who had become tolerant to clonazepam were given 1 5 mg flumazenil  they were seizure free for 6 21 days after the injection  the value of intermittent therapy with a benzodiazepine antagonist for preventing or reversing tolerance to benzodiazepine agonists ought to be investigated further  
class10	haemorrhagic shock encephalopathy and sudden infant death in 2 pairs of non identical twins  haemorrhagic shock encephalopathy syndrome developed in 1 co twin while the other died of sudden infant death syndrome  the twin pairs were aged 3 and 4 months  respectively  and no cause was identified  we suggest that stress protein deficiency may underlie both syndromes  
class10	the electrodiagnostic findings in polyneuropathies associated with igm monoclonal gammopathies  electrodiagnostic studies were analyzed in patients with neuropathy associated with igm monoclonal proteins  7 with anti myelin associated glycoprotein reactivity  mag  and 7 nonreactive to mag  the findings were distinctly different in the two groups  the electrodiagnostic studies of all the mag reactive patients had demyelinating features with slowing of conduction and prolonged distal latencies while only one of the mag nonreactive patients had a demyelinating pattern  in fact  the mag nonreactive patients were a heterogeneous group  both electrodiagnostically and clinically  this study supports the concept that mag reactive polyneuropathy is demyelinating in type  and is caused by the activity of the igm m protein directed at an antigen in the myelin sheath  
class10	carpal tunnel syndrome  correlations between pressure measurement and intraoperative electrophysiological nerve study  in 19 carpal tunnel syndrome  cts  patients and 4 control subjects a catheter was introduced into the carpal tunnel and slowly retracted in 5 mm steps  pressure was measured with the continuous infusion technique  in the same group of patients and controls  median nerve antidromic sensory action potential  asap  was detected intraoperatively stimulating proximally  s1   in the center  s2   and distally  s3  to the carpal tunnel and recording from the third finger  r   sensory conduction velocity  scv  and asap amplitude were considered in s1 s2  s2 s3 and s3 r segments  the intracarpal tunnel pressure was significantly higher in cts patients than in controls  with the highest values located between 25 and 35 mm distal to the proximal border of the flexor retinaculum  scv and asap amplitude were also decreased most often in the distal part  s2 s3  of the carpal tunnel  
class10	vector short latency somatosensory evoked potentials after median nerve stimulation  a new method has been developed for recording short latency somatosensory evoked potentials after median nerve stimulation  negative electrical forces recorded with three orthodiagonal bipolar electrodes in the neck had a direction opposite to that of impulse conduction in the proximal peripheral and cervical somatosensory pathway  sequential tracings of vectors opposite the electrical forces were made in three dimensional display  thus reproducing the actual time sequence of electrical events in those structures  fixed generators such as the subcortical nuclei were also analyzed with this technique  and multiple generators of n13 potential  n13a and n13b  were visualized  this technique may be useful in the functional evaluation of the somatosensory pathway in the cervical cord  
class10	sick building syndrome   sick building syndrome   sbs  is one of the more colorful terms describing an increasingly common pattern of symptoms found among workers in modern office buildings  core symptoms include lethargy  mucous membrane irritation  headache  eye irritation  and dry skin  to prompt a diagnosis of sbs  these otherwise common symptoms must be  excessively  reported and primarily  work related   the world health organization now estimates that 30  of new or remodeled office buildings show signs of sbs  and that between 10  and 30  of the occupants of these buildings are affected by sbs  despite such figures  sbs remains poorly researched and even more poorly understood  the following review provides the clinician an overview of sbs that will allow a more accurate differential diagnosis and will help to prevent the widespread suffering that can accrue when sbs is not quickly recognized  
class10	complications of lateral c1 2 puncture myelography  this study reviewed the technical complication of 112 cases of lateral c1 2 puncture myelography for cervical spinal cord disorders  spinal cord puncture and contrast injection  puncture between the occiput and c1  and blood vessel puncture were the main complications  these principally depended on the positioning of the patient s neck  hyperextension  and misdirection of the x ray beam  for preventing major arterial puncture  the authors also reviewed 164 vertebral angiograms and determined the pathway of the vertebral arteries and the incidence of anomaly  
class10	clinical value of magnetic resonance imaging for cervical myelopathy  the magnetic resonance imaging  mri  findings in 115 cases of cervical myelopathy  121 cases of cervical radiculopathy  and 64 cases of neck pain with no neurologic deficit were prospectively studied to investigate the clinical value of mri for cervical myelopathy  the mri findings in the t1 weighted sagittal projection were classified into four groups according to the degree of the compressed deformities of the cervical cord  the degree of compression of the cervical cord on mri findings showed a significant correlation with the severity of myelopathy  the anteroposterior diameter of the spinal column  and the degree of compression of the dural tube in the myelograms  p less than 0 01   fifty one patients of cervical myelopathy had undergone both preoperative and postoperative mri  of these  the spinal canal of 47 patients that was well decompressed was recognized according to plain computed tomography  ct   however  24  51   of these 47 patients showed on mri a deformity in the spinal cord amounting to cord atrophy  the correlation between the clinical function of the spinal cord and the recovery of the cord deformity on mri at the operative levels was accurately investigated in 34 patients who had no cord deformities in the adjacent intervertebral levels  twenty patients with cord atrophy had slightly poor clinical results  although no significant difference was found between these 20 and 14 patients with recovery in the cord deformities  from these results  it was evident that t1 weighted mri is useful in the accurate diagnosis of compression myelopathy  in accurately deciding the level of the disease focus  and in the accurate assessment of the surgical results  
class10	motion analysis of the cervical spine in athetoid cerebral palsy  extension flexion motion  frequently instability and premature onset of spondylosis of the cervical spine are found in athetoid cerebral palsy  cp  patients  these structural abnormalities appear to be related to athetoid motion of the neck in cp  through motion analysis  the authors aimed to clarify the abnormalities of cervical motion that could precipitate structural abnormalities  the gross characteristic feature of cervical motion in athetoid cp is  whip movement   both velocity and acceleration during extension flexion motion were greater than in normal subjects  especially at the upper cervical levels  also  a sudden increase in velocity and acceleration occurred during rapid motions at certain levels  followed by a larger range of motion of the cervical spine  such kinematic abnormalities were thought to generate a greater shearing force and bending moment exerted on the corresponding cervical articulations discs and facets  olisthetic instability often accompanied disc degeneration at the upper cervical levels  a large range of extension  flexion motion of the cervical spine  analogous to a cantilever  caused a repeated bending moment of extraordinary magnitude and was regarded as a precipitative factor for disc degeneration and osteophytosis common at the middle and lower levels of the disc  
class10	pathomechanism  pathogenesis  and results of treatment in cervical spondylotic myelopathy caused by dynamic canal stenosis  in this study  the pathomechanism and pathogenesis of dynamic canal stenosis caused by cervical instability in patients with cervical spondylotic myelopathy and the validity of the concept of instability are clarified by analyzing the results of treatment in 53 cases  in cases of cervical spondylotic myelopathy caused by dynamic canal stenosis  the authors found that the posterior slide of the vertebral body occurs as a result of degeneration in the cervical spine due to aging changes  and that the dynamic sagittal diameter of the spinal canal decreases with an increase of the degree of posterior slide  this is followed by gradual aggravation of the clinical symptoms  continuous cervical traction was found to be the first choice of treatment  surgical treatment is indicated in cases in which the traction was ineffective  or even when it was effective  in cases in which the japanese orthopaedic association  joa  score remained low or when there was a tendency toward rapid aggravation of symptoms  it was demonstrated that the shorter the duration of the myelopathy  the better the results of treatment obtained  a limit of the dynamic sagittal diameter of the spinal canal of 12 mm was considered as valid  
class10	problems and solutions of pedicle screw plate fixation of lumbar spine  fifty seven patients with low back pain and sciatica of various causes were reviewed with reference to problems associated with pedicle plate fixation of the lumbar spine  eleven percent of patients had neurologic problems postoperatively and 3 5   two patients  had severe sensory impairments  all patients had this complication in the early phases of the study  of 297 screws  17 broke  ie  5 7   these breakages occurred in 12 of 57 patients  21    in patients with spondylolisthesis  the degree of slip correction averaged 53  postoperatively  which decreased to 35  at the 1 year follow up  slip angle was maintained after correction  pedicle screw plate fixation is an effective form of immobilization of the lumbar spine used in achieving arthrodesis  the surgeon must be fully trained in methodology  it is recommended that screw and plate materials be improved to prevent screw breakage  
class10	postoperative lumbar spinal instability occurring or progressing secondary to laminectomy  the manifestations and pathomechanism of postoperative lumbar spinal instability  occurring or progressing secondary to laminectomy  was clarified by means of functional radiographic analysis in a series of 46 patients over 40 years of age  the relation between instability and the clinical symptoms also is discussed  in patients under 60 years of age  instability at the operated level tended to appear in cases of wide laminectomy more often than in cases of partial laminectomy  occurrence or progress of instability seems to be promoted by resection of the posterior spinal elements rather than the disc  it is further considered that the postoperative aggravation of clinical symptoms may be influenced not only by instability  but also by the other factors  
class10	germ cell tumor of testis in a patient with von hippel lindau disease  germ cell testicular tumor is a previously undescribed entity in association with von hippel lindau disease  this case exemplifies the variety of pathologic entities encountered in von hippel lindau disease and stresses the importance of thorough evaluation of the patient  as well as careful follow up  to ensure early detection of potentially malignant lesions  
class10	the painful shoulder  part i  extrinsic disorders  shoulder disorders are most commonly manifested by pain and limited function  careful history and examination help the physician localize the problem to the shoulder joint  the surrounding tissues or adjacent sites that can cause referred pain to the shoulder  common extrinsic causes of shoulder pain include postural problems and cervical spine disorders  
class10	utility of upright tilt table testing in the evaluation and management of syncope of unknown origin purpose  vasovagally mediated hypotension and bradycardia are believed to be common  but difficult to diagnose  causes of syncope  upright tilt table testing has been proposed as a possible way to test for vasovagal episodes  this study investigated the clinical utility of this technique in the evaluation and management of patients with syncope of unknown origin  patients and methods  twenty five patients with recurrent unexplained syncope and six control subjects were evaluated by use of an upright tilt table test for 30 minutes  with or without an infusion of isoproterenol  1 to 3 micrograms minute given intravenously   in an attempt to provoke bradycardia  hypotension  or both  of the 25 patients  there were 14 males and 11 females  with a mean age of 50     16 years  six control patients with no history of syncope were also studied  all tilt positive patients received therapy with either beta blockers  disopyramide  transdermal scopolamine  or hydroflurocortisone  the efficacy of which was evaluated by another tilt table test  results  syncope occurred in six patients  24   during the baseline tilt and in nine patients  36   during isoproterenol infusion  total positives  60    none of the controls had syncope during the test  all patients who had positive test results eventually became tilt table negative by therapy  and over a mean follow up period of 16     2 months no further episodes have occurred  conclusion  from this study we conclude that upright tilt table testing combined with isoproterenol infusion is clinically useful in the diagnosis of vasovagal syncope and the evaluation of pharmacologic therapy  
class10	diagnostic evaluation of syncope syncope is a common medical problem and is caused by a wide variety of diseases ranging from physiologic derangements with few consequences to conditions that may be immediately life threatening  because of the large differential diagnosis  many diagnostic tests are available for its evaluation  however  a cause of syncope is not established in 38  to 47  of patients despite these tests  in those patients in whom a diagnosis can be assigned  the history and physical examination identify a potential cause in 49  to 85   furthermore  in 8  of additional patients  history and physical examination are suggestive of causes that need confirmation by specific tests  routine blood tests rarely yield diagnostically helpful information  in those patients in whom a potential cause for syncope is identified  arrhythmias are diagnosed by electrocardiogram in 2  to 11  of patients  cardiac monitoring in 3  to 27   telemetry or holter   stress test in less than 1   carotid massage in less than 1   and electrophysiologic studies in less than 3   diagnosis of arrhythmias as a cause of syncope is problematic because symptomatic correlation during electrocardiographic monitoring is rarely found  approximately 4    and as a result  there is no uniform agreement on diagnostic criteria for abnormalities  similar problems exist in the use of electrophysiologic studies  upright tilt testing and psychiatric examination may be useful in evaluation of recurrent syncope of unknown cause in patients without organic heart disease  based on the results of recent studies  strategies for evaluation of patients with syncope are possible that utilize selective and goal directed diagnostic testing  
class10	antiepileptic medication in pregnancy  late effects on the children s central nervous system development  in a follow up study long term effects of antenatal exposure to two anticonvulsant drugs  phenobarbital and carbamazepine on central nervous system development were evaluated  children aged 6 to 13 years of epileptic mothers who used phenobarbital  n   13   carbamazepine  n   12   phenobarbital plus carbamazepine  n   12   or no medication  n   24  during pregnancy were studied  none of the mothers had seizures during pregnancy  a control group carefully matched for confounding variables was selected of children of nonepileptic mothers  n   61   minor and major congenital anomalies appeared to be more related to mother s epilepsy than to maternal medication  there were no neurologic differences between the groups  exposure to phenobarbital was associated with smaller head circumference  an accompanying negative effect of phenobarbital on cognitive development was suggested  further research on this intriguing phenomenon seems warranted  
class10	tables for estimation of individual risks of fetal neural tube and ventral wall defects  incorporating prior probability  maternal serum alpha fetoprotein levels  and ultrasonographic examination results  tables are provided for estimation of the risk of open spina bifida in patients who have elevated maternal serum alpha fetoprotein levels but normal results on detailed anatomy ultrasonographic scan  risks are provided for various prior population risks  for various levels of elevated maternal serum alpha fetoprotein  and for various assumptions about the sensitivity of ultrasonographic examination  the formula used is based on sequential multiplication of odds with the use of bayes  theorem  but an arbitrary reduction  to the power of 0 5  in the degree to which ultrasonographic information modifies the odds has been made to allow for the nonindependence of ultrasonography and maternal serum alpha fetoprotein tests  the wide range of resulting risks shows that the decision to offer amniocentesis after a negative scan should be individualized  
class10	relationship of laparoscopic findings to self report of pelvic pain  an assessment battery including standardized measures of behavioral and psychosocial factors associated with other chronic pain conditions was administered to 102 women scheduled for laparoscopic surgery  surgeons who were blinded to the patient s self reported pain data completed the american fertility society classification for endometriosis and adhesions on the basis of observed physical disease  although american fertility society classification scores were significantly related to self assignment into pain or no pain groups  the extent of physical disease evaluated by this procedure was not significantly correlated with ratings of pain levels or a number of indexes of impairment  the group of patients with laparoscopically diagnosed pathologic conditions reported higher pain levels and greater interference than the group who reported pain and had negative laparoscopic results  however  some women with observable pathologic conditions reported no pain symptoms  
class10	acute tolerance in morphine analgesia  continuous infusion and single injection in rats  this study aimed to determine whether the decline of the analgesic effect of morphine with a continuous infusion or that after a single injection correlates with the changes in brain concentration of morphine  the analgesic effect of morphine and its brain and serum concentrations were determined with a continuous 8 h infusion at a constant rate and after a single subcutaneous injection of the agent  the analgesic effect was determined by measuring the threshold of motor response to noxious stimulation  brain and serum concentrations of morphine were detected by radioimmunoassay with the use of 125i labeled morphine  with the constant rate  4 mg kg 1 h 1  intravenous  morphine infusion  the peak of analgesia could not be maintained  the increase in the pain threshold at 2 h was 1 003 g and at 8h was 286 g  a decrease in analgesia by 72   p less than 0 0002   at the same time  the brain morphine concentration tended to increase  to 278 ng g at 2 h and 329 ng g at 8 h  after the single morphine injection  6 mg kg  subcutaneous   recovery from analgesia occurred at a much faster rate than did the decrease in morphine brain concentration  the decrease in pain threshold was 79  at 90 vs  30 min after the injection  p less than 0 0001   and the corresponding decrease in brain concentration was 28   ns   the absence of correlation between analgesia and morphine brain concentration both with the constant rate morphine infusion and after the single injection suggests the development of acute tolerance  which is pharmacodynamic in nature  
class10	effect of systemic medetomidine  an alpha 2 adrenoceptor agonist  on experimental pain in humans  the effect of systemic  intravenous  medetomidine  an alpha 2 adrenoceptor agonist  on pain thresholds was studied in healthy human subjects  n   6   medetomidine produced a dose dependent  cumulative doses  25 and 50 micrograms  sedative effect evaluated by visual analog scale  also  a dose dependent decrease of blood pressure but not of heart rate was seen after administration of medetomidine  pain threshold to electric stimulation of the tooth pulp and cutaneous heat pain threshold were uninfluenced by medetomidine  an index of cutaneous thermal sensitivity to innocuous stimuli  the width of the thermoneutral zone  also was uninfluenced by medetomidine  medetomidine produced a significant attenuation of the affective motivational component  unpleasantness  of tourniquet induced ischemic pain  whereas the sensory discriminative component  pain magnitude estimate  of the ischemic pain was not attenuated  the results suggest that systemic medetomidine alone at subanesthetic but sedative and hypotensive doses does not significantly influence the intensity and thresholds of experimental pain  whereas the affective motivational component of pain can be attenuated  
class10	snoring and sleep architecture  the purpose of this study was to examine whether snoring adversely affects sleep architecture and sleep efficiency  and thus may account for the frequent complaints of daytime tiredness and fatigue expressed by heavy snorers  we recruited eight self confessed heavy snorers and six self confessed nonsnorers  all subjects had full nocturnal polysomnography  including continuous monitoring of snoring  which was quantified by counting the number of snores per hour of sleep  snoring index   the number of snores per minute of snoring time  snoring frequency   maximal and mean nocturnal sound intensity  dbmax and dbmean  respectively   we found that even the self confessed nonsnorers snored lightly  with significantly smaller frequency and index than the heavy snorers  sleep architecture was similar in both groups  distribution of snoring among the sleep stages differed for light and heavy snorers  light snorers snored uniformly throughout all sleep stages  whereas heavy snorers tended to snore more during slow wave and rem sleep  snoring frequency and snoring index were similar during all sleep stages in light snorers  but they were higher during slow wave sleep in heavy snorers  wakefulness time after sleep onset and sleep efficiency correlated significantly with the snoring index  we conclude that although snoring does not affect sleep architecture in general  it influences sleep efficiency and wakefulness time after sleep onset  this may have an adverse effect on daytime function of heavy snorers  
class10	anton s syndrome in a patient with posttraumatic optic neuropathy and bifrontal contusions  we describe a patient who manifested anton s syndrome after sustaining head trauma that resulted in optic nerve damage and bifrontal contusions  denial of monocular blindness  generalized anosognosia  and confabulation were prominent neurobehavioral features  anton s syndrome is most commonly encountered in patients with bilateral occipital cortex lesions  patients previously described who demonstrated anton s syndrome secondary to a peripheral lesion have had an associated delirium or profound dementia  our case demonstrates that anton s syndrome may occur in association with blindness from a peripheral lesion  even in the absence of a delirium or significant dementia  we suggest that the bifrontal dysfunction may have been a critical factor in the production of anton s syndrome  implications for the role of frontal lobe dysfunction in the genesis of anosognosia and confabulation are discussed  
class10	pupil sparing oculomotor nerve palsy due to midbrain infarction  vasculopathic oculomotor nerve palsies with pupillary sparing are thought to be due to ischemic damage to the nerve in the subarachnoid space or the cavernous sinus  we present two cases of patients with isolated pupil sparing oculomotor nerve palsies due to midbrain infarcts  focal ischemic midbrain lesions should be considered in cases of pupil sparing oculomotor nerve palsies  
class10	initial therapy of patients with wilson s disease with tetrathiomolybdate  patients with wilson s disease who present with acute neurological symptoms often become clinically worse when initially treated with penicillamine  other available anticopper drug therapies do not appear to offer a solution to this treatment problem  we are developing and evaluating a new drug  ammonium tetrathiomolybdate for this purpose  theoretically  tetrathiomolybdate has optimal properties  including an immediate blockade of copper absorption and the property of forming complexes with copper in the blood  rendering the copper nontoxic  in this article  we present results from six patients treated with tetrathiomolybdate for up to 8 weeks as initial therapy  none of the five patients who had presented with acute neurological symptoms worsened  also presented are methods of assay  preliminary stability studies  and methods of evaluating therapeutic end points with respect to copper metabolism  
class10	the influence of dialysate sodium and variable ultrafiltration on fluid balance during hemodialysis  an important factor in the development of hypotension during hemodialysis  hd  is a decrease in blood volume  due to ultrafiltration  uf  and an insufficient refill of the intravascular compartment  this insufficient refill might be caused by a transcellular fluid shift from the extracellular to the intracellular compartment  we studied the influence of dialysate sodium concentration and uf rate on the refill rate  blood volume  intracellular  icv  and extracellular fluid volume  ecv   three different hd strategies were studied in 15 patients   a  conventional hd  dialysate sodium 140 mmol l    b  hd with a sodium profile  140 148 mmol l   and  c  hd with a sodium profile and a variable uf rate  high low uf rate   icv and ecv were measured by non invasive conductivity measurements  blood volume was calculated from erythrocyte counts before and after treatment  blood volume decrease was most pronounced during conventional hd  due to insufficient refilling without a detectable transcellular fluid shift  the sum of the decrease in icv and evc was less than during  b  and  c   the insufficient refill led to a higher prevalence of hypotension and cramps  the strategies  b  and  c  led to an significant and comparable transcellular fluid shift to the extracellular compartment  thus  the use of a sodium profile led to a better intravascular refill and clinical tolerance of hd  addition of a uf profile did not improve this any further  
class10	cognitive and behavioural impairment among elderly people in institutions providing different levels of care  objective  to compare the prevalence and degree of cognitive and behavioural impairment in elderly patients in institutions providing different levels of care  design  prevalence study  setting  a nursing home  a home for the aged and psychogeriatric wards in a provincial psychiatric hospital  patients  only subjects 65 years of age or older were eligible for inclusion  a random sample was selected comprising 25  of the residents in the nursing home and the home for the aged  of the 119 asked to participate 95 agreed  44 in the nursing home and 51 in the home for the aged   all 50 on the psychogeriatric wards agreed to participate  main outcome measures  the mini mental state examination  mmse  and the kingston dementia rating scale  kdrs   results  an mmse score of less than 24  cognitive impairment  was given to 37  84   of the residents in the nursing home  43  84   of those in the home for the aged and 48  96   of the patients in the psychiatric hospital  the corresponding numbers for a kdrs score of more than 0  cognitive impairment  were 41  93    48  94   and 50  100    the seven patients receiving the highest level of care at the home for the aged  special care  had more behavioural problems than those in the psychiatric hospital did  p less than 0 001   conclusions  cognitive and behavioural impairment was widespread in the three institutions regardless of the level of care  when planning services and allocating resources government funding agencies should consider the degree and prevalence of such impairment among elderly people in institutions  
class10	physiologic and psychobehavioral research in oncology  a major thrust in research in psychosocial oncology is the study of the interaction of psychologic and physiologic variables  this discussion reviews the current status and future directions of such research  areas addressed include pain  nausea and vomiting with chemotherapy  sexuality  effects of cancer on psychologic and neuropsychologic function  impact of psychologic factors on cancer and its treatment  and psychoneuroimmunology  in addition  specific recommendations for strategies to facilitate research in these areas of psychosocial oncology are proposed  
class10	evolution of energy expenditure and nitrogen excretion in severe head injured patients  objective  the aim of the study was to estimate the influence of therapeutic changes on the level of energy expenditure  ee  and n excretion in a homogeneous group of patients usually considered hypermetabolic  design  ee and n excretion of head injured patients were measured simultaneously at phases 1 and 2  patients treated 4     3 and 18     8 days after injury  respectively   setting  acute care hospital  patients  eight severe head injured patients  mean weight 63 1     6 1  sd  kg  mean age 21     3 8  sd  yr  interventions  at phase 1  all patients were sedated with fentanyl  6 7     1 9 micrograms kg hr  plus flunitrazepam  9 1     4 8 micrograms kg hr  and were mechanically ventilated  all patients received continuous total parenteral nutrition  the nonprotein caloric intake averaged 1092     200 kcal day  including 77  glucose and 23  fat  intralipid 20    the total n intake averaged 7     5 g day  consisting of crystalline amino acids  at phase 2  no patient received any sedative and all were breathing spontaneously via tracheostomy  all patients received parenteral and or enteral nutrition  the nonprotein caloric intake averaged 1929     200 kcal day consisting of 65  carbohydrates and 35  fat  the total n intake averaged 13     2 g day  measurements and main results  the ee was significantly higher at phase 2 than at phase 1  2121 vs  1737 kcal   but the interindividual variability was low at both phases  n excretion was high at the two periods of the study and not correlated to the level of ee  the rq was 0 75 at both periods  indicating predominant fat oxidation  conclusions  we could not demonstrate any parallelism in the evolution of ee and protein catabolism in head injured patients  the therapeutics  mechanical ventilation  sedation  and nutrition  have a major effect on ee but little on n excretion  
class10	noninvasive cerebral optical spectroscopy for monitoring cerebral oxygen delivery and hemodynamics  objective  to present an algorithm for noninvasive measurement of cerebral oxygen saturation  cerebral oximetry  and cerebral hemodynamics with near infrared spectroscopy  design  in vitro correlation of oximetry measurements with reference measurements  illustrative cases of hemodynamic and oximetric recordings  setting  tertiary care neuroscience icu  patients  brain injured patients with a prolonged  decreased level of consciousness chosen as illustrative examples  interventions  two channel multiple wavelength diffuse infrared transmission spectroscopy was interfaced with the scalp using adhesive  transmission data were collected with gross superficial to deep spatial resolution  saturation calculation based on the deep signal was observed longitudinally in the patient  with the same technology  arterial input and cerebral response functions  generated by iv tracer bolus  were deconvoluted to measure mean cerebral transit time  measurements and main results  a positive linear regression fit between diffuse transmission oximetry and measured blood oxygen saturation over the range 23  to 99   r2    98  p less than  001  was noted  conclusions  the approach used overcomes previously identified difficulties with cerebral oximetry  and demonstrates excellent in vitro correlation  the technique can be performed clinically without difficulty  a simultaneous measure of mean cortical transit time is possible  
class10	methodology of head up tilt testing in patients with unexplained syncope prolonged 60 degree head up tilt has been shown to be valuable in the investigation of unexplained syncope  diagnosing neurally mediated bradycardia hypotension or malignant vasovagal syndrome  to evaluate the methodology of tilt testing  the following were examined  reproducibility of results  tilt duration  angle of tilt  method of tilt support and effect of age in patients and control subjects  seventy one patients with recurrent unexplained syncope underwent 60 min of 60 degree tilt  53  75   had an abnormal test with vasovagal syncope at 24     10 min  mean     sd   tilting to 60 degrees resulted in an abnormal test in only 2  7   of 27 control subjects without cardiovascular symptoms  p less than 0 001   and 5  15   of 34 patients with syncope and documented conduction tissue disease  p less than 0 001   of 15 youthful fainters  3  20   had vasovagal reactions as did 1  8   of 12 asymptomatic youthful control subjects  these 12 control subjects also underwent tilting with a saddle support and 7  67   had vasovagal reactions  it is concluded that the duration of tilting at 60 degrees should be 45 min  mean time to syncope  2 x sd in the 53 patients with abnormal results   twenty percent of patients with an abnormal tilt test may not demonstrate syncope with repeat tilting  saddle tilt testing in unexplained syncope may result in a loss of specificity  tilting at less than 60 degrees results in a loss of sensitivity  head up tilt may be less useful in youthful subjects with vasovagal syncope than in other subjects  
class10	lack of prognostic value of syncope in patients with wolff parkinson white syndrome syncope in patients with wolff parkinson white syndrome may be considered a premonitory event heralding the future development of sudden death  therefore  the clinical and electrophysiologic data of 101 patients with wolff parkinson white syndrome referred for invasive evaluation of known arrhythmias were reviewed to assess the incidence and clinical relevance of syncope  thirty six patients reported the occurrence of one or more syncopal episodes  group 1  and 65 patients had no syncope  group 2   these two groups did not differ significantly with regard to age  gender  incidence and characteristics of arrhythmia  clinical history  frequency of arrhythmic events and presence of associated cardiac disease  there were 10 patients in group 1 and 12 in group 2 who had ventricular fibrillation  there were no statistical differences between the two groups with respect to the effective refractory period of the right atrium  atrioventricular node  accessory pathway and right ventricle  furthermore  no differences between the two groups were noted with respect to cycle length of circus movement tachycardia  mean heart rate during atrial fibrillation  and minimum rr interval during atrial fibrillation  in addition  the accessory pathway location was not significantly different between group 1 and group 2  the occurrence of syncope could not be predicted from any electrophysiologic finding and this symptom had a low sensitivity and specificity for recognition of dangerous rapid heart rates  furthermore  the prognostic value of syncope was less accurate and predictive than the shortest rr interval during atrial fibrillation and the anterograde effective refractory period of the accessory pathway for aborted sudden death occurrence  
class10	superiority of transesophageal echocardiography in detecting cardiac source of embolism in patients with cerebral ischemia of uncertain etiology  the diagnostic yield of transesophageal and transthoracic echocardiography for identifying a cardiac source of embolism was compared in 79 patients presenting with unexplained stroke or transient ischemic attack  there were 35 men and 44 women with a mean age of 59 years  range 17 to 84   52  had clinical cardiac disease  both transthoracic and transesophageal echocardiograms were performed using doppler color flow and contrast imaging  transesophageal echocardiography identified a potential cardiac source of embolism in 57  of the overall study group compared with only 15  by transthoracic echocardiography  p less than 0 0005   compared with transthoracic echocardiography  transesophageal echocardiography more frequently identified atrial septal aneurysm associated with a patent foramen ovale  9 versus 1 of 79 patients  p less than 0 005   left atrial thrombus or tumor  6 versus 0 of 79 patients  p less than 0 05  and left atrial spontaneous contrast  13 versus 0 of 79 patients  p less than 0 0005   all cases of left atrial thrombus or spontaneous contrast were identified in patients with clinically identified cardiac disease  in the 38 patients with no cardiac disease  transesophageal echocardiography identified isolated atrial septal aneurysm and atrial septal aneurysm with a patent foramen ovale more frequently than transthoracic echocardiography  8 versus 2 of 38 patients  p less than 0 05   the two techniques had a similar rate of identifying apical thrombus and mitral valve prolapse  overall  transesophageal echocardiography identified abnormalities in 39  of patients with no cardiac disease versus 19  for transthoracic echocardiography  p less than 0 005   thus  transesophageal echocardiography identifies potential cardiac sources of embolism in the majority of patients presenting with unexplained stroke  
class10	clonotypic analysis of anti acetylcholine receptor antibodies from experimental autoimmune myasthenia gravis sensitive lewis rats and experimental autoimmune myasthenia gravis resistant wistar furth rats  a single immunization of lewis rats with purified acetylcholine receptor  achr  emulsified in adjuvant typically stimulates the production of oligoclonal achr reactive antibodies  as demonstrated by ief  dominated by the igg2a subclass  of moderate but clonotypically heterogeneous relative ag binding avidity  and capable of inducing symptoms of experimental autoimmune myasthenia gravis  although similar immunization of wistar furth rats produces achr reactive antibodies with similar characteristics of clonotypic heterogeneity  avidity  and isotype expression  no detectable signs of achr dependent muscle impairment is observed  this contrasts the ability to induce impaired achr function upon the passive transfer of pre formed lewis anti achr antibodies into naive wistar furth rats  suggesting that disease resistance in this model is not conferred at the level of the achr itself  moreover  if more aggressive immunization protocols are used  i e   multiple injections of achr   a transient breakthrough of achr dependent muscle dysfunction can be induced directly in the wistar furth strain indicating that the potential for the production of disease causing antibodies does exist in the wistar furth repertoire  ief analysis of wistar furth anti achr antibodies has revealed that hyperimmunization results in modified antibody clonotype expression that might explain changing expression of disease symptoms  however  explanations for the apparent  resistance  of wistar furth rats to disease induction are likely to be complex  
class10	elevated expression of the genes for transforming growth factor beta 1 and type vi collagen in diffuse fasciitis associated with the eosinophilia myalgia syndrome  full thickness skin biopsies obtained from four patients with rapidly progressive diffuse fasciitis associated with the eosinophilia myalgia syndrome  ems  were examined for the expression of transforming growth factor beta 1  tgf beta 1   type vi collagen  and fibronectin genes employing immunohistochemistry and in situ hybridizations  the immunohistochemical studies demonstrated increased deposition of tgf beta  type vi collagen  and fibronectin epitopes in the extracellular matrix of the fascia in comparison to the adjacent dermis in the same specimens  increased levels of type vi collagen mrna  as evidenced by positive in situ hybridization signals with an alpha 2 vi  collagen cdna  were also found in the fascia in comparison with the dermis  in situ hybridizations of affected fascia with a human sequence specific tgf beta 1 cdna demonstrated numerous fibroblasts displaying positive hybridization signals indicative of high levels of transcripts for this cytokine  in contrast  no hybridization signal for tgf beta 1 was detected in fibroblasts in the adjacent dermis  these findings suggest that tgf beta 1 may play an important role in the development of the connective tissue alterations present in ems associated diffuse fasciitis  
class10	carbamazepine overdose  a prospective study of serum levels and toxicity  a cooperative prospective study of consecutive cases of carbamazepine overdose was conducted to determine if serum levels were predictive of toxicity and if risk factors such as age  chronic exposure  or previous disorder or cardiovascular disease could be used as prognostic indicators  seventy three consecutive cases were collected from two regional certified poison control centers from january 1989 to august 1989  there were 25 exposures in children less than 6 yrs   11 exposures in adolescents  and 37 exposures in adults  ten adult cases and one adolescent case were excluded from the study due to the presence of coingestants or inadequate information  peak measured serum levels ranged from 0 3 to 56 mcg ml  using the presence of coma  seizure activity or respiratory depression requiring mechanical ventilation as measures of toxicity  we found poor correlation between rising serum levels of carbamazepine and toxicity  increased serum levels of carbamazepine did appear to correlate with increased hospital stay  but not with icu stay  history of a seizure disorder appears to pose increased risk of a seizure in carbamazepine overdose  in this series chronic exposure to carbamazepine did not appear to increase the risk of coma or respiratory depression for a given toxic serum level and may add some protective effect  serum levels below 40 mcg ml do not appear to accurately predict the severity of toxicity  cardiac conduction defects were rare  one child   anticholinergic findings  as evidence by decreased bowel motility and sinus tachycardia were common  previous cardiovascular disease and age did not appear to be important prognostic indicators  
class10	long term follow up of patients operated on for recurrent carotid stenosis  we reviewed our experience with 29 operations for recurrent carotid stenosis in 27 patients who underwent both their primary carotid endarterectomy and their reoperations at our institution  these 27 patients represent 4  of the 667 patients who underwent primary carotid endarterectomies at our institution and who are included in our carotid follow up registry  reoperation was prompted by recurrent symptoms in 19 29  65 5   cases  comparison of long term stroke prevention in those patients who did  84  at 5 years  78 6  at 10 years  and did not  90 3  at 5 years  83 6  at 10 years  develop recurrent stenosis requiring reoperation revealed no statistically significant difference  p   0 48  when measured from the time of primary operation  the perioperative stroke and death rates for reoperation  3 4  and 0   were acceptable  we conclude that with our acceptably low perioperative stroke morbidity  3 4    surgery for recurrent carotid stenosis in symptomatic patients or in asymptomatic patients with high grade  greater than or equal to 75   stenosis maintains the durable stroke prevention offered by primary carotid endarterectomy  
class10	angiographic localization of spinal cord blood supply and its relationship to postoperative paraplegia  forty seven patients underwent selective catheterization of middle and lower thoracic intercostal and upper lumbar arteries to define the origin of the artery of adamkiewicz  one patient had significant atheroembolism  and a second had transient lower extremity paresthesias  no other complications occurred  the origin was found in 26  55    and 21 patients underwent thoracoabdominal aneurysm repair with this knowledge  when the critical lumbar or intercostal artery could be included as part of a long proximal or distal anastomosis  all 12 patients could be included as part of a long proximal or distal anastomosis  all 12 patients survived  and one was paralyzed  however  if the aneurysm repair mandated a midgraft anastomosis to intercostal arteries critical to spinal cord perfusion  seven of nine patients either died or were paralyzed  p less than 0 05   in the group of 19 patients operated on in whom spinal cord blood supply was not identified three patients had a technically unsuccessful operation  two died  and one was paralyzed  twelve of 16 patients who had an adequate  but unsuccessful attempt at localization were treated by intercostal  neglect  and survived  late paresis developed in two patients  but they are walking now  one of the patients who died had multiple systems failure and awakened paraplegic  she had a patent  enlarged  thoracic radicular artery at t 5 which probably supplied to spinal cord and which was missed angiographically  paralysis was associated with aneurysm extent  group 2 and iii b  dissections vs group 1   3  p less than 0 05   selective intercostal angiography requires further refinement  but it is safe and offers the promise of understanding the mechanisms and risks of spinal cord complications after repair of extensive thoracoabdominal aneurysms  
class10	a prospective randomized study of cerebrospinal fluid drainage to prevent paraplegia after high risk surgery on the thoracoabdominal aorta  this article is concerned with the study of the effect of several variables  principally that of cerebrospinal fluid drainage  on the incidence of neurologic deficit in a prospective randomized series of patients with extensive aneurysms of the descending thoracic and abdominal aorta  thoracoabdominal type i and ii   forty six patients had cerebrospinal fluid drainage  and 52 were controls  with a total of 98 available for study  cerebrospinal fluid pressure was continuously monitored in the former group and pressure maintained less than or equal to 10 mm hg in 20  less than or equal to 15 mm hg in 20  and greater than 15 mm hg in 6 patients during period of aortic clamping  the method of treatment including reattachment of intercostal and lumbar arteries  p   0 2   temporary atriofemoral bypass during aortic occlusion  p   0 3   and spinal fluid drainage  p   0 8  were not statistically significant in reducing the incidence of neurologic deficits  thus cerebrospinal fluid drainage as we used it  was not beneficial in preventing paraplegia  on appropriate statistical analysis we found that the only significant predictor of delayed deficits was postoperative hypotension  p   0 006   
class10	mesenteric blood flow in patients with diabetic neuropathy  we examined flow velocities in the superior mesenteric artery and celiac artery in normal controls  group c  n   11   diabetic patients  group d  n   8   and diabetic patients with clinically evident autonomic neuropathy  group dn  n   6  to further define the usefulness of duplex examination in the evaluation of the mesenteric circulation in normal and disease states  by use of a 3 mhz duplex scanner  peak systolic velocity  peak diastolic forward velocity  end diastolic forward velocity  and peak diastolic reverse velocity were measured in centimeters per second before and after a standardized meal  the vessels  diameters in centimeters were also measured  after the meal peak diastolic reverse velocity disappeared in all patients  the average vessel diameter in the superior mesenteric artery  0 7 cm  and celiac artery  0 8 cm  did not change  flow velocities in the celiac artery were not significantly altered by the meal  in the control group  peak systolic velocity in the superior mesenteric artery increased 38   peak diastolic forward velocity rose 66   and end diastolic forward velocity increased by 70   in the diabetic nonneuropathic group the changes were 15   98   and 100   respectively  these changes were statistically significant  p less than 0 01   on the other hand  the patients with diabetic autonomic neuropathy presenting a picture of gastroparesis did not exhibit the expected increases in postprandial velocities  moreover  this alteration in blood flow velocity  although similar to that encountered in patients with intestinal angina  did not appear to be due to occlusive arterial disease on the basis of clinical examination and b mode scanning  
class10	driving and epilepsy  a review and reappraisal driving and epilepsy is a problem that involves physicians as both care providers to patients and consultants to regulatory authorities  driving restrictions for people with seizure disorders are intended to ensure the public s safety  but such restrictions may unduly harm the welfare of many people with seizures  in the united states  all states now permit some people with epilepsy to drive  in general  only people whose seizures are adequately controlled are licensed to drive  adequate control has been judged principally by the seizure free interval  but individual state standards widely vary  there is a trend toward greater liberalization of driving standards for people with seizure disorders  but the appropriateness and application of these standards continue to raise questions  as does the role physicians should have in the licensing process  our responsibilities to persons with disabilities and advances in our understanding of seizures and the nature of driving risks warrant a reappraisal of the current medical  legal  and social implications of driving and epilepsy  
class10	elderly men with histories of heavy drinking  correlates and consequences  recognition that the physical  psychological and social consequences of substance abuse may persist throughout the life span has led to increased study of the impact of lifetime drinking habits on the elderly  we examined the characteristics of elderly men with self reported histories of having ever been heavy drinker  h   in a population based  n   1 155  mean age   73 7 years  longitudinal survey of community dwelling elders  10 4  of the men reported that they had been heavy drinkers at some time during their lives  h  men were younger and less educated than non heavy drinkers  h   or never drinkers  n   mortality was higher among h  men who were current drinkers than among h  or n men  h  men reported more major illnesses  poorer self perceived health status  more physician visits  more depressive symptoms  lower levels of life satisfaction and smaller social networks than did h  or n men  self reported ability to perform activities of daily living and instrumental activities of daily living was poorest among h  men  who also scored the lowest on a mental status examination  thus  a history of having ever been a heavy drinker is predictive of widespread impairments in physical  psychological and social health and functioning among elderly men  
class10	diagnostic utility of lower extremity radiographs of young children with gait disturbance  the diagnostic utility of lower extremity radiographs was evaluated using 84 outpatients 1 to 5 years of age with gait disturbance whose lower extremities appeared physically normal  chief complaints included limp  65 children  77     refusal to walk or stand  37 children  44     and frequent falling  6 children  7     a total of 43 children  51   had more than one complaint  the mean age of patients was 26 months and the median duration of symptoms was 1 day  trauma was reported in 43  51   cases and fever in 14  17    results of radiographical studies appeared normal in 81 children  96    demonstrated soft tissue swelling in 2 children  and revealed a bony island in 1 child  in 1 patient admitted to the hospital for failure to thrive and irritability  and whose radiographic results appeared normal  findings consistent with osteomyelitis later developed  of the remaining children  68  81   were available for follow up observation 4 to 28 months after the initial visit and all reported spontaneous resolution of the initial complaint  it was concluded that in a well appearing child with an otherwise normal physical examination results  an acute gait disturbance is likely to be a self limiting condition and radiographs are unlikely to contribute to the diagnosis  
class10	individual differences in children s response to pain  role of temperament and parental characteristics  sixty five families were enlisted in a study exploring factors associated with distress behavior in 5 year old children receiving diphtheria tetanus pertussis immunizations  at a home visit 1 month before the immunization  the following measures were obtained   1  the behavioral style questionnaire  a measure of temperament   2  parental self reports of medically related attributes  eg   good patient     3  parental attitudes toward pain in children and responsiveness to their child s pain  and  4  parental prediction of distress at upcoming immunization  the child s distress behavior during the immunization was evaluated using a modification of the procedure rating scale revised and  after the procedure  the child s assessment of his or her pain was elicited using the oucher  children s mean procedure rating scale revised score was 2 57 of a possible 11  thirty one  48   had low  less than or equal to 1  and 7  11   had high distress scores  greater than or equal to 2 sd above the mean   factors positively correlated with distressed behavior included more  difficult child  cluster characteristics  the individual temperamental dimension of adaptability  but few parental attitudes and attributes  parent s predictions of distress were the strongest correlates  these findings document the variation that children demonstrate in response to pain and offer some insight into associated innate and environmental factors  these results imply that treatment strategies derived from parental knowledge and tailored to individual characteristics of the child may be most effective in alleviating pain related distress in medical settings  
class10	methsuximide for intractable childhood seizures  methsuximide was added to the therapeutic regimens of 25 children with intractable epilepsy  in 15 patients the drug was well tolerated and resulted in a 50  or greater reduction in seizure frequency  no serious or irreversible adverse effects were seen  methsuximide is frequently overlooked and may be an effective adjunctive antiepileptic for children with intractable seizures  
class10	ehrlichiosis in children  tick borne rickettsiae of the genus ehrlichia have recently been recognized as a cause of human illness in the united states  in the years 1986 1988  10 cases of ehrlichiosis were diagnosed in children in oklahoma  fever and headache were universal  myalgias  nausea  vomiting  and anorexia were also common  rash was observed in six patients but was a prominent finding in only one  leukopenia  lymphopenia  and thrombocytopenia were common laboratory abnormalities  six patients were treated with tetracycline  three with chloramphenicol  and one was not treated with antibiotics  all recovered  the onset of illness in spring and early summer for most cases paralleled the time when amblyomma americanum and dermacentor variabilis are most active  suggesting that one or both ticks may be vectors of human ehrlichiosis in oklahoma  
class10	sucrose as an analgesic for newborn infants  the effectiveness of sucrose as an analgesic agent for newborn infants was assessed during two standard painful hospital procedures  blood collection via heel lance and circumcision  infants who drank 2 ml of a 12  sucrose solution prior to blood collection cried 50  less during the blood collection procedure than did control infants who had received 2 ml of sterile water  crying of infants who ingested sucrose returned to baseline levels within 30 to 60 seconds after blood collection whereas control infants required 2 5 to 3 0 minutes to return to baseline  like findings were obtained for infants who received sucrose on a pacifier prior to and during circumcision  specifically  control infants who underwent a standard circumcision procedure without intervention cried 67  of the time  a water moistened pacifier reduced crying to 49   p less than  01   crying was reduced further to 31   p less than  05  by providing infants with a sucrose flavored pacifier to suck  these findings  which parallel results obtained in studies of pain in infant rats  provide a potent yet simple  benign intervention to help alleviate stress and pain routinely experienced by human infants  
class10	infantile systemic hyalinosis  newly recognized disorder of collagen  four infants with stiff skin and painful joint contractures in the first few months of life are described  other features included small papules  particularly on the face and trunk  perianal nodules  hyperpigmentation over the metacarpophalangeal joints and over the malleoli  gingival hyperplasia  persistent diarrhea  and failure to thrive  two of these infants died before the age of 18 months  in each case hyaline material was found in the papillary dermis  ultrastructurally  there was a distinctive fibrillogranular appearance in which a banding pattern could be observed  this material was also found within membrane bound vacuoles in macrophages and fibroblasts  it had an appearance and localization identical with that of collagen type vi  these features are similar to those reported in juvenile hyaline fibromatosis  it is believed that these infants have a closely related  but nonetheless distinctive  inherited disorder of collagen  
class10	neuroleptic malignant syndrome  life threatening complication of neuroleptic treatment in adolescents with affective disorder  neuroleptic malignant syndrome  nms  is an uncommon  potentially fatal side effect of neuroleptic treatment characterized by hyperthermia  rigidity  rhabdomyolysis  and delirium  in recent clinical studies of adults it was suggested that affective disorder is a risk factor for the development of neuroleptic malignant syndrome  the cases of two adolescents with neuroleptic malignant syndrome who were treated with neuroleptic therapy because of psychotic symptoms in association with primary affective disorders are reported  the occurrence of these cases  as well as the observations in adults  suggests that attention to the primary psychiatric diagnosis is important in neuroleptic usage and that physicians should be vigilant to the occurrence of neuroleptic malignant syndrome in the pediatric population  
class10	cerebral infarction  early detection by means of contrast enhanced cerebral arteries at mr imaging  the authors describe a new magnetic resonance  mr  imaging sign of acute cerebral ischemia infarction  abnormally contrast material enhanced curvilinear structures were demonstrated in eight patients in the evolving area of cerebral ischemia infarction within 26 hours after the ictus on contrast enhanced  high field strength  1 5 t   t1 weighted spin echo images  the abnormal enhancement is considered to represent cortical arterial vessels of markedly slowed circulation in areas of underlying brain injury  which will eventually progress to frank brain infarction  this was demonstrated at computed tomographic  ct  and follow up mr examinations  characteristically  the degree of the contrast enhancement of vessels appeared most intense in the proximal portions  and the intensity of enhancement gradually diminished in the more distal portions of these vessels as they pass over the convexities and finally disappear  
class10	cerebral venography with mr  the authors describe a two dimensional time of flight magnetic resonance  mr  angiography technique to create projection venograms of the head  the technique was applied to 27 healthy volunteers and 39 patients  the superior sagittal and straight sinuses  the internal cerebral veins  and the galen vein were visualized in all the volunteers  other veins were seen in a high percentage of subjects  systematic comparison of digital subtraction angiography  dsa  after intraarterial contrast medium injection and mr venography in patients showed good correlation between the two techniques  mr venography proved helpful in identifying thrombosis or patency of cerebral veins and sinuses and showed collateral venous drainage and venous drainage from arteriovenous malformations  there was good correlation between conventional contrast angiography and mr venography  in conclusion  mr venography is considered reliable for showing the cerebral venous system and provides information additional to that of conventional spin echo imaging  
class10	marked cerebrospinal fluid void  indicator of successful shunt in patients with suspected normal pressure hydrocephalus  the authors blindly reviewed the charts of 20 patients with normal pressure hydrocephalus  a disease of unknown cause characterized radiologically as chronic communicating hydrocephalus and clinically by gait apraxia  dementia  and incontinence  who had undergone creation of a ventriculoperitoneal shunt  the initial clinical response to surgery was graded excellent  good  fair  or poor  5 year follow up was available in 55  of cases  the magnetic resonance  mr  images obtained in these patients were also blindly reviewed for the magnitude of cerebrospinal fluid  csf  flow void  graded on the basis of extent rather than degree of signal loss  in the cerebral aqueduct  a significant  p less than  003  correlation existed between good or excellent response to surgery and an increased csf flow void  the presence of associated deep white matter infarction on mr images did not correlate with a poor response to surgery  on the basis of these findings  it is suggested that patients who fulfill the clinical criteria of nph and have an increased csf flow void undergo creation of a shunt  
class10	characterization of  peak e   a novel amino acid associated with eosinophilia myalgia syndrome  epidemiologic studies strongly associate eosinophilia myalgia syndrome  ems  with ingestion of tryptophan containing a contaminant   peak e    prior reports have suggested that peak e is the di tryptophan n alpha animal of acetaldehyde  spectral and chemical studies now demonstrate that peak e is 1 1  ethylidenebis tryptophan   this novel amino acid may be the etiological agent responsible for ems  or it may be a marker of a still unidentified causal agent  
class10	functional outcome measures in stroke rehabilitation  i examine statistical considerations in the analysis of functional outcome following stroke and discuss the mathematical relation between improvement in function and discharge functional score  i demonstrate mathematically that the predictor variables of improvement and discharge functional score are the same and that the regression coefficients for improvement and discharge functional score will be equal  except for the admission functional score  for which a mathematically defined relation exists  i argue that the relation between admission functional score and discharge functional score must be positive and strong and that the relation between admission functional score and improvement must be negative for the stroke population  i believe that an ignorance of statistical concepts  especially confounding  and of the differences between raw correlations  partial correlations  and predictors have led to much confusion in functional outcome research  
class10	activation of coagulation in acute cardioembolic stroke  the hematologic disorders in patients with acute cardioembolic stroke are not fully understood  and no reliable measures are available to identify patients at high risk for recurrent embolism  we analyzed coagulation and fibrinolytic functions in 22 patients with cardiogenic cerebral embolism less than or equal to 24 hours after onset and in 25 age matched controls  the levels of antithrombin iii  protein c  and alpha 2 plasmin inhibitor were significantly lower in the patients than in the controls  p less than 0 001  0 02  and 0 05  respectively   in contrast  the plasma concentrations of thrombin antithrombin iii complex and crosslinked d dimer were markedly higher in the patients than in the controls  p less than 0 01 and 0 001  respectively   at the time of admission  the plasma concentrations of thrombin antithrombin iii complex and crosslinked d dimer in the eight patients at high risk for recurrent embolization  one with prodromal embolism  three with intracardiac thrombi  and four with recurrent embolization  were 2 8 and 3 5 times  respectively  higher than those in the 14 patients without recurrence or thrombus formation  the lowest concentration of crosslinked d dimer in the eight patients at high risk for recurrent embolization was 600 ng ml on admission  our results suggest that patients with acute cardioembolic stroke have various degrees of consumption coagulopathy and that the plasma concentrations of thrombin antithrombin iii complex and crosslinked d dimer can be useful indicators of those who are prone to recurrent embolization during this stage  
class10	platelet volume  aggregation  and adenosine triphosphate release in cerebral thrombosis  we compared whole blood platelet aggregation  adenosine triphosphate release  platelet count  platelet crit  percentage volume of platelets   and mean platelet volume during the acute  subacute  and chronic periods of cerebral thrombosis in 22 patients with value in 29 controls  during the acute and subacute periods  platelet aggregation  platelet count  platelet crit  and mean platelet volume were significantly less in the patients than in the controls  p less than 0 05 0 01  while the adenosine triphosphate release rate per volume of platelets was significantly greater  p less than 0 05   during the acute period  infarct size showed a significant positive correlation with platelet aggregation  r   0 59  p less than 0 01  and adenosine triphosphate release rate  r   0 70  p less than 0 001  but a negative correlation with platelet count  r    0 44  p less than 0 05   our results suggest that platelet aggregation is reduced during the acute period due to the consumption of platelets during thrombogenesis but that the remaining individual platelets are hyperactive  platelet consumption during the acute period increases with infarct size  during the chronic period  platelet crit and mean platelet volume were significantly less in the patients than in the controls  p less than 0 01  while the adenosine triphosphate release rate was significantly greater  p less than 0 01   suggesting sustained platelet consumption and chronically enhanced secretion of individual platelets  
class10	the role of neutrophils and platelets in a rabbit model of thromboembolic stroke  cerebral ischemia is accompanied by many of the cardinal features of acute inflammation such as neutrophil and platelet activation and accumulation  we sought to determine whether circulating neutrophils or platelets contribute to brain injury in a rabbit model of thromboembolic stroke that includes a fixed duration of superimposed systemic hypotension  we randomized 18 rabbits to receive either antineutrophil antiserum  n   6   antiplatelet antiserum  n   5   or nonimmune serum  n   7   we assessed brain ischemia by measuring cerebral blood flow  intracranial pressure  and infarct size  following the intracarotid administration of an autologous clot  cerebral blood flow in all groups fell to less than 5 ml 100 g min during induced hypotension  after restoration of baseline blood pressure  mean cerebral blood flow in neutropenic animals recovered to 20 30 ml 100 g min while that in control and thrombocytopenic rabbits remained at less than 10 ml 100 g min  intracranial pressure in control animals rose steadily to a final value of 241  of baseline  while a much smaller increase  148  of baseline  was noted in the thrombocytopenic group  no change from baseline was evident in the neutropenic group  infarct size was significantly  p less than 0 05  reduced in the neutropenic group but not in the thrombocytopenic group  these results suggest that neutrophils may be important contributors to ischemia induced brain injury whereas the role of platelets is more subtle  
class10	attenuated neuropathology by nilvadipine after middle cerebral artery occlusion in rats  we investigated the effects of nilvadipine  a calcium antagonist  on cerebral ischemia in rats  under halothane anesthesia  30 rats had a 3 0 nylon suture introduced through the extracranial internal carotid artery to occlude the left middle cerebral artery  nilvadipine was dissolved in polyethylene glycol 400  immediately following occlusion  group 1 rats  n   10  were treated subcutaneously with vehicle and group 2 and 3 rats were treated with 1 0  n   10  and 3 2  n   10  mg kg nilvadipine  respectively  perfusion fixation was performed 24 hours later  and the histopathologic outcomes were quantified  in group 1 infarct volume was 28 2     11 4  of the total cerebral volume  in groups 2 and 3 infarct volumes were 25 5     11 6   ns  and 13 9     9 2   p less than 0 05 different from group 1   respectively  nilvadipine decreased ischemic neuronal injury in a dose dependent manner and may be of use in the treatment of cerebral ischemia  
class10	hypertension  cigarette smoking  and the decline in stroke incidence in eastern finland  finland has high rates of both cardiovascular disease and cardiovascular disease risk factors  we studied random samples of the population 30 59 years of age for risk factors in two provinces of eastern finland in 1972 and 1977  we then followed both cohorts until 1985 through linkage with national hospital discharge and death certificate registers  the prevalence of hypertension and smoking in both provinces declined between 1972 and 1977  as did the stroke incidence in the 8 year period of follow up of each cohort  we observed no differences in stroke incidence between the two provinces  the relative risk of stroke in the later period  1977 1985  was 0 71 and 0 58 for men and women  respectively  when compared with the earlier period  1972 1980   overall  28  of all stroke events could be attributed to hypertension  17  to smoking  and 43  to these two factors jointly  the decrease in the prevalence of hypertension and smoking accounted for about 29  of the decline  
class10	a novel treatment for ischemic intracranial hypertension in cats  there is no accepted efficacious treatment for ischemic cerebral edema  we show in a cat model of focal cerebral ischemia that infarct volume can be reduced  p less than 0 05  by ventriculocisternal perfusion with an oxygenated fluorochemical emulsion  bis perfluorobutylethylene   an accompanying effect of such ventriculocisternal perfusion is a reduction in intracranial pressure  at 18 hours following the start of the perfusion  there was a significant  p less than 0 05  difference in intracranial pressure between nonperfused controls  mean 11 4  range 2 3 23 0  torr  n   6  and cats perfused with an oxygenated nutrient solution not containing fluorochemical  mean 11 3  range 3 0 29 0  torr  n   8  or animals perfused with the oxygenated fluorochemical emulsion  mean 2 21  range 0 3 5  torr  n   7   perfusion with this oxygenated fluorochemical emulsion warrants further study as a treatment for elevated intracranial pressure  
class10	cerebral infarction in patients with nephrotic syndrome  we describe two adult patients who presented with acute cerebral infarction and were found to have a hypercoagulable state due to nephrotic syndrome  one patient had a deficiency of free protein s  the other patient had a pulmonary embolus 4 months after the stroke  our cases demonstrate that the hypercoagulable state associated with nephrotic syndrome can be associated with cerebral arterial thrombosis and infarction in adults  examination of the urine remains an important part of the evaluation of patients with recent stroke  the presence of severe proteinuria and a low serum albumin content should prompt consideration of a hypercoagulable state  our experience suggests that anticoagulant drugs may be required to reduce the risk of new thrombotic events  
class10	recurrent transient ischemic attacks and stroke in association with an internal carotid artery web fibromuscular dysplasia is a nonatherosclerotic vascular disease that most commonly affects cervical carotid arteries at the c1 c2 level when cephalic arteries are involved  several histopathologic and angiographic subtypes of fibromuscular dysplasia exist  most have a benign natural history  we describe the third reported case of a pathologically proven  symptomatic proximal internal carotid artery web and suggest that patients with this lesion are at a higher risk for stroke  
class10	neuroendocrine carcinoma of the ampulla of vater  a case of absence of somatostatin in a vasoactive intestinal polypeptide   bombesin   and cholecystokinin producing tumor  a 31 year old patient with a clinical picture of obstructive jaundice had surgical treatment  and a primary carcinoid of the ampulla of vater  va  was found  the tumor was studied with light microscopy  immunohistochemistry  and electron microscopy  the neoplasm had histopathologic and cytopathologic features similar to those encountered in typical neuroendocrine neoplasms  it is interesting that immunohistochemical techniques disclosed the presence of vasointestinal polypeptide  cholecystokinin  and bombesin  however  unlike most neuroendocrine neoplasms arising in va  no somatostatin immunoreactive cells were found  
class10	the bone marrow in human immunodeficiency virus  hiv  related disease  morphology and clinical correlation  to determine the true incidence of abnormalities in bone marrow specimens from patients infected with human immunodeficiency virus  hiv  and the clinical significance of these abnormalities regarding their cause and their role in the production of hematologic complications  216 bone marrow biopsies  aspirates  and or imprint preparations from 178 patients who either were seropositive for hiv infection or met the centers for disease control  cdc  criteria for acquired immunodeficiency syndrome  aids  were studied  detailed morphologic review was performed in a blind fashion as to clinical status  extensive clinical  therapeutic  and laboratory data were collected for each patient  statistical analysis was performed to detect significant correlations between morphologic findings and clinical therapeutic laboratory features  among the most common bone marrow findings were hypercellularity  53  of specimens   myelodysplasia  69    evidence of reticuloendothelial  re  iron blockade  65    megaloblastic hematopoiesis  38    fibrosis  20    plasmacytosis  25    lymphocytic aggregates  36    and granulomas  13    a number of statistically significant correlations between morphologic findings and clinical features were noted  no significant association was detected between any morphologic finding and therapy with a variety of drugs  in 7 of 14  50   patients found to have marrow involvement by malignant neoplasm  the bone marrow represented the initial site of diagnosis of the neoplasm  most of the bone marrow abnormalities associated with hiv infection appear to be related directly to the infection or its complications and not to therapeutic intervention  in certain clinical situations  bone marrow examination continues to be useful in the management of patients infected with hiv  
class10	persistence and remission of depressive symptoms in late life  objective  the relation of poor health to the onset of depression symptoms in late life is well recognized  but little attention has been given to characteristics that might predict persistence or remission of depressive symptoms  in previous analyses the authors found that increasing disability and declining health preceded the emergence of depressive symptoms in older community residents and accounted for 70  of the variance explained by discriminant analyses  the aim of the present analysis was to examine the relevance of changes in health and disability to the persistence of depressive symptoms  method  a representative sample of 1 855 adults aged 65 or older were assessed with the center for epidemiologic studies depression scale at baseline  twenty four months later  1 577 individuals were available for a second assessment of depressive symptoms  the characteristics of the 97 community residents whose depressive symptoms persisted over 24 months were compared to those of the 114 whose symptoms remitted  results  changes in health  differences in age  sleep disturbance  and added formal support services accounted for more than 30  of the variance between the persistently depressed and remission groups  advanced age and worsening health were associated with persistent symptoms  improved health with remission  conclusions  previous studies have indicated that untoward changes in health and disability play a major role in the onset of depressive symptoms  these findings show a substantial contribution to chronicity as well  
class10	olfactory identification deficits in hiv infection  objective  impaired odor identification is described in a number of cns disorders  and human immunodeficiency virus  hiv  infects the cns in a large percentage of patients  to evaluate whether impaired olfaction may indicate cns disease  the authors measured odor identification in patient groups defined along a continuum of progressive immunodeficiency and in a comparison group  method  most of the 42 hiv infected patients in the study were outpatients in a clinic specializing in treatment of hiv infected individuals  the comparison subjects were 37 healthy age  and sex matched individuals who were recruited from hospital and medical school personnel  ten of the patients were hiv seropositive but had no symptoms  24 had clinical evidence of immunocompromise  and eight had hiv dementia  all subjects were given the university of pennsylvania smell identification test  which presents common odorants and requires the subject to identify the odor from a four item word list  the data were analyzed by using analysis of variance after arc sine transformation and scheffe post hoc analysis  results  all patients scored significantly lower on the smell identification test than did the comparison subjects  the patients with hiv dementia had significantly lower scores than did the other two groups of patients  conclusions  clinically  impaired olfaction might serve as a marker of early cns hiv involvement  future studies should attempt to match comparison and experimental populations for socioeconomic status and hiv risk behavior  
class10	cerebral palsy  why we must plan for survival  the survival of children in the south east thames region  born between 1970 and 1979 and diagnosed as having some form of cerebral palsy was investigated  of the 732 children studied  651  90   are still alive  and hence cerebral palsy must be regarded as a condition with which people live rather than a condition of which they die  survival varies considerably among the different diagnostic groups  those suffering from spasic quadriplegia  dyskinetic and  mixed  cerebral palsy are most severely affected  our evidence suggests that  though immobility and severe mental subnormality are the strongest predictors of mortality in children with cerebral palsy  the majority of even the most severely affected patients survive to adulthood  it is therefore appropriate to plan for their survival by funding and evaluating programmes to maximise health  independence  and quality of life  
class10	low level lead exposure in the prenatal and early preschool periods  language development  inconsistent results continue to be reported from studies linking low level lead exposure and child development  this inconsistency is seen for both prenatal exposure and exposure in the preschool years  the primary outcome measures in most reports are indices of cognitive development  including iq  verbal skills may be particularly vulnerable to toxic insult  the fact that 2 y of age is both a time of peak exposure and also a time of rapid language development suggests that this may be a critical period for such an effect  the later prenatal and early infancy period  at which time the nervous system is developing rapidly  may also be critical exposure period  we examined the relationship of maternal and cord blood lead  pbb  at birth and venous pbb at 6 mo  2 y  and 3 y with language measures at 1  2  and 3 y of age  the sample consisted of disadvantaged urban children  multivariate analyses revealed no statistically significant relationship of either prenatal pbb or early preschool pbb with language measures after control of cofactors  supplementary partial correlations revealed a marginal relationship of cord pbb and mean length of utterance  mlu   which describes a child s ability to form meaningful word combinations  because this analysis was one of a large number of analyses with both positive and negative regression coefficients  the possibility that this was a chance effect was considered  if there is an effect of low level lead exposure on language development  that effect is not robust  
class10	amebic meningoencephalitis in a patient with aids caused by a newly recognized opportunistic pathogen  leptomyxid ameba  a fatal case of meningoencephalitis due to a leptomyxid ameba in a patient with the acquired immunodeficiency syndrome is presented  this opportunistic organism has not been previously recognized as a human pathogen  a 36 year old male intravenous drug abuser died after an 18 day hospital course heralded by fever and headache and followed by nuchal rigidity and hemiparesis  computed tomography of the head showed multiple hypodense lesions  neuropathologic examination showed that in addition to human immunodeficiency virus encephalomyelitis  there was multifocal meningoencephalitis with trophozoites and cysts morphologically indistinguishable from those of acanthamoeba  these organisms were also found in the kidneys and adrenal glands  by immunofluorescence  the parasites showed antigenic identity with a free living leptomyxid ameba and failed to react with any of a spectrum of antiacanthamoeba antisera  this emphasizes the importance of immunofluorescence identification of morphologically indistinguishable ameba species  
class10	glossopharyngeal neuralgia associated with cardiac syncope  long term treatment with permanent pacing and carbamazepine  glossopharyngeal neuralgia associated with cardiac syncope developed in a 53 year old man  symptoms were controlled with temporary and permanent transvenous pacing and carbamazepine  
class10	salmeterol in nocturnal asthma  a double blind  placebo controlled trial of a long acting inhaled beta 2 agonist objective  to determine whether inhaled salmeterol  a new long acting inhaled beta adrenergic agonist  reduces nocturnal bronchoconstriction and improves sleep quality in patients with nocturnal asthma  design  randomised  double blind  placebo controlled crossover study  setting  hospital outpatient clinics in edinburgh  subjects  twenty clinically stable patients  13 women  seven men  with nocturnal asthma  median age 39  range 18 60  years  interventions  salmeterol 50 micrograms and 100 micrograms and placebo taken each morning and evening by metered dose inhaler  rescue salbutamol inhalers were provided throughout the run in and study periods  main outcome measures  improvement in nocturnal asthma as measured by peak expiratory flow rates and change in sleep quality as measured by electroencephalography  results  salmeterol improved the lowest overnight peak flow rate at both 50 micrograms  difference in median values  95  confidence interval for difference in medians  69  18 to 88  l min  and 100 micrograms  72  23 to 61  l min  doses twice daily  while taking salmeterol 50 micrograms twice daily patients had an objective improvement in sleep quality  spending less time awake or in light sleep   9   4 to  44  min  and more time in stage 4 sleep  26  6 34  min   conclusions  salmeterol is an effective long acting inhaled bronchodilator for patients with nocturnal asthma and at a dose of 50 micrograms twice daily improves objective sleep quality  
class10	health care screening for people with mental handicap living in the community objective  to determine what contact people with mental handicap had had with their general practitioner in the previous year  what prescribed drugs they were taking and whether these had been reviewed  when hearing and vision had last been screened  and what medical problems were found on examination  design  case series  setting day centre for adults with mental handicap  subjects  a balanced sample of 75 of the 150 people attending the day centre  10 were excluded because consent was not given  results  the subjects did not consult their general practitioners more frequently than the general population but were more likely to be taking prescribed drugs  and 57  of these prescriptions had not been reviewed by a doctor  thirty three people failed vision screening  including 13 who wore glasses  twenty seven of the 62 who were testable had a hearing impairment  conclusions  as only eight out of 65 people examined in the study did not have an appreciable problem brought to light  screening seems to be worth while  whether such screening needs to be done by a medically qualified person needs further research  
class10	levels of the human hepatocyte growth factor in serum of patients with various liver diseases determined by an enzyme linked immunosorbent assay  we have found a hepatotrophic factor in plasma or sera of patients with fulminant hepatic failure and have purified human hepatocyte growth factor from plasma of these patients  in this study we developed an enzyme linked immunosorbent assay with high specificity and sensitivity for human hepatocyte growth factor in human serum  this assay for serum human hepatocyte growth factor is a sandwich method consisting of three steps  the standard curve for human hepatocyte growth factor appeared to be linear in the range of 0 20 to 12 50 ng purified human hepatocyte growth factor ml  2 35 to 147 pmol l   the assay took about 4 hr  serum human hepatocyte growth factor values in patients with fulminant hepatic failure measured by enzyme linked immunosorbent assay showed a strong positive correlation with that by bioassay using rat hepatocytes in primary culture  the mean value of serum human hepatocyte growth factor for 30 normal subjects was 0 24     0 12  s d   ng ml  that for 23 patients with fulminant hepatic failure was 8 06     1 76  s e m   ng ml  greater than 30 times greater than the mean value for normal subjects  serum human hepatocyte growth factor levels in patients with acute hepatitis  chronic hepatitis and cirrhosis were found to be slightly higher than those in normal subjects  but only the increase in serum human hepatocyte growth factor of acute hepatitis patients was statistically significant  the enzyme linked immunosorbent assay for serum human hepatocyte growth factor should prove useful for serum human hepatocyte growth factor level measurement in patients with various liver diseases  
class10	drug induced refractory headache  clinical features and management  two hundred patients who were taking daily symptomatic or immediate relief medications  often in excessive quantities  yet suffering from daily or near daily severe headaches were studied  one hundred and sixteen  58   of them were also taking concomitant prophylactic medications and they were ineffective  low tyramine  low caffeine dietary instructions and biofeedback training were given to all patients  the effect of continuing symptomatic medications  discontinuing symptomatic medications  and adding or changing prophylactic medications were studied in the various treatment groups  it is concluded that  1   daily use of symptomatic or immediate relief medications result in chronic daily headache  2   discontinuing daily symptomatic medications itself result in improvement of headache  3   concomitant use of symptomatic medications nullifies the effect of prophylactic medications  4   discontinuing daily symptomatic medications enhances the beneficial effect of prophylactic medications  
class10	acetylsalicylic acid vs  metoprolol in migraine prophylaxis  a double blind cross over study  in a double blind cross over study  28 patients  5 male and 23 female  aged 31     14 years  after a run in period of 8 weeks  were treated for 3 months with acetylsalicylic acid and for another 3 months with metoprolol  both in a prophylactic mode  attack frequency was reduced significantly with both therapeutic regimens  asa p less than 0 001  metoprolol p less than 0 00005   reduction of attacks below 50  was seen with metoprolol in 14 cases  and with asa in three cases  even though asa was of statistically significant efficacy in migraine prophylaxis  it clearly is not the drug of first choice in migraine prophylaxis  
class10	the ver as a diagnostic marker for childhood abdominal migraine  abdominal migraine is a common childhood migraine equivalent  for which diagnostic criteria have not been defined  as in other children with migraine equivalents this leads to difficulties in diagnosis and determination of prevalence  by recording the fast wave activity  beta rhythmn  in the visual evoked response  ver  to red and white flash  the pattern stimulation  27 out of 28 children with clinically diagnosed abdominal migraine revealed significant differences compared with normal controls  outside the attack phase  comparisons with children diagnosed as migraine with or without aura revealed  from the ver findings of higher amplitude fast wave activity and the presence of paroxysmal sharp wave activity  that abdominal migraine appears to be a specific form of childhood migraine  we found that both clinically and electrophysiologically  abdominal migraine changes with age  older children exhibiting a shorter duration of abdominal pain during attacks  and less evidence of sharp wave activity in the ver  
class10	99mtc hm pao spect in pediatric migraine  99mtc hm pao spect brain imaging was performed during the headache free period in 19 young migraineurs  affected by common migraine  cm  10 cases   classic migraine  clm  6 cases  and hemiplegic migraine  hm  3 cases   spect findings were negative in all 10 patients with cm  in 3 cases of clm and in 2 cases of hm  positive findings in the remaining 4 patients  3 cases of clm and 1 of hm  showed a decreased tracer distribution in the temporo occipital regions  2 cases  and parietal regions  2 cases   the two with decreased temporo occipital perfusion reported prodromal symptoms exclusively contralateral to the areas of hypoperfusion  an impaired regional cerebral vascular autoregulation may exist even during headache free intervals in patients suffering from classic and hemiplegic migraine  
class10	cerebral vein thrombosis shown by mri  a 46 year old man with a short history of left facial pain and numbness  and subsequently headaches  had a normal physical examination and a normal ct scan of head  lumbar puncture yielded normal csf under increased pressure  mri showed thrombosis of the superior sagittal sinus  subsequently confirmed by angiography  mri is a sensitive test for detecting intracranial venous thrombosis  and may be the investigation of choice when this disorder is suspected  
class10	the cluster diathesis  we present further evidence for a sympathetic defect of vasomotor control of the anterior cerebral artery  aca  on the side of the headache during cluster periods  in 119 cluster headache patients  utilizing transcranial doppler  we measured co2 reactivity of the major intracranial vessels  in and out of cluster  reactivity was significantly lower during the cluster period  but only in the aca on the side of the headache  nineteen patients followed sequentially for a full cycle  ie both in and out of a cluster period  showed the same changes  in 3 out of 6 patients in an active cluster period  we describe a lesion on gallium single photon emission computerized tomography  spect  in the region of the cavernous sinus which fades as the patient moves out of cluster  it is felt that this lesion may represent the cavernous sinus plexus lesion postulated as the central lesion in cluster  changes in the sympathetic outflow at this point could explain the changes we have described in aca co2 reactivity during cluster  
class10	cluster headache  the effect of low oxygen saturation the present study concerns the possible relationship between hypoxia and the generation of cluster headache attacks  fifteen controls and 25 cluster headache patients were studied  the patients were allocated into two groups according to cluster headache stage  i e  cluster or remission period  during the tests  all the subjects were asked to inhale 12  oxygen  88  n2  for 30 min  and the decreasing oxygen saturation  sao2   was monitored  patients in the remission period showed nearly the same decrement of sao2  as controls  at the end of the test  patients in the bout showed significantly less reduction of sao2  than the controls  in 5 patients  the test was carried out both in and outside the cluster periods  the tendency to less decrement in oxygen saturation in the cluster phase was as marked with this comparison  but the difference between the groups was not significant  probably partly due to the low number of tests carried out  only one patient got a typical attack  it seems that hypoxia of this magnitude per se is not the cause of attacks  the different pattern with respect to sao2  following 12  o2 inhalation in cluster headache may be due to an abnormality in central regulation and or chemoreceptor sensitivity  
class10	relaxation training in school classes does not reduce headache complaints  the effect of teacher presented progressive relaxation training  prt  on headaches  fear of failure and school problems was studied in school students  during ten physical education lessons  students received either prt  n   110  or placebo training  n   92   the effect of the training was investigated in students who indicated the presence of headaches in a pre training diary  no significant differences were found between both training groups regarding headache frequency  duration and intensity and the psychological variables  on the basis of these and previous findings  it is recommended to present prt to fairly small groups of self selected subjects instead of complete classes  
class10	recurrent tension headache in adolescents treated with self help relaxation training and a muscle relaxant drug  forty eight adolescents suffering from recurrent tension headache participated in a controlled trial conducted in a high school setting  during the first treatment phase self help relaxation training was compared with a waiting list group  following this phase a pharmacological regimen consisting of a muscle relaxant  chlormezanone  and placebo was superimposed on relaxation therapy in a double blind crossover design  each treatment phase encompassed a 5 week period  in addition to the evaluation of headache complaints  psychological distress among students was measured with respect to their experience of somatic complaints  depressive  anxiety and stress symptoms  although self help relaxation training significantly decreased the severity and annoyance of adolescents  headache besides their somatic complaints  the clinical improvement of headache was modest  the addition of chlormezanone did not help those who were nonresponders to self help relaxation training  finally  a set of pretreatment variables consisting of baseline headache severity and annoyance  experience of anxiety and daily life stress among adolescents could predict outcome of self help relaxation therapy  
class10	pharmacokinetics of tiaprofenic acid after oral administration in fasting patients during and between migraine attacks  this study examined the pharmacokinetics of 300 mg of tiaprofenic acid  a nsaid belonging to the 2 arylpropionic class  as a single oral dose  in 10 migraine patients during and out of migraine attacks  plasma concentration of tiaprofenic acid was determined by hplc analysis  drug absorption appeared to be the same during and out of migraine attacks  absorption half life  during attack  0 249     0 122 hr  out of attack  0 249     0 105 hr  maximum plasma concentration  during attack  37 8     9 8 ug ml  out of attack  40 1     13 2 ug ml   the other pharmacokinetic parameters evaluated were not affected by headache attacks as well  we conclude that tiaprofenic acid absorption and metabolism are not affected by migraine attacks  also  our data suggest that tiaprofenic acid might be useful in the treatment of migraine  
class10	treatment of status migrainosus  the american experience  dependence upon a variety of drugs  ergotamine  analgesics  benzodiazepines  corticosteroids  is a major reason for patients to enter an intractable phase of their migrainous disorders  repeated dosing of dihydroergotamine has proven to be remarkably effective in stabilizing the mechanism of migraine  allowing these patients to make the transition to a more reasonable as well as more specific form of therapy  
class10	sumatriptan in acute migraine  pharmacology and review of world experience  the introduction of sumatriptan  a novel abortive antimigraine agent  has generated a significant amount of preclinical and clinical interest during the past few years  at the scientific level  sumatriptan is unique in terms of its selective pharmacological properties  the effects of sumatriptan in various experimental paradigms have led to new insights into the pathophysiology of migraine  at the clinical level  sumatriptan appears to be an effective abortive anti migraine agent with minimal side effects  its ability to decrease  rather than exacerbate  the nausea and vomiting of migraine appears to be an important advance in the treatment of migraine  
class10	atelectasis affects the rate of arterial desaturation during obstructive apnea  chronic hemodynamic disturbances are more profound in patients with obstructive sleep apnea when underlying lung disease with abnormal gas exchange  low arterial po2  is present  previous studies suggest that pulmonary gas exchange could influence the rate of fall of arterial oxygen saturation  dsao2 dt  in obstructive sleep apnea  we postulated that abnormal gas exchange in the form of atelectasis would steepen dsao2 dt and thereby lower nadir arterial oxyhemoglobin saturation  sao2  for the same duration of apnea  apneas were created by clamping an indwelling cuffed endotracheal tube at end expiration in eight spontaneously breathing adult baboons  apneas of the same duration were then repeated during temporary endobronchial occlusion of one lobe of the lung  sao2 and mixed venous o2 saturation were continuously monitored  and cardiac output was calculated  worsening of pulmonary gas exchange during atelectasis was documented by an increase in calculated venous admixture from 10 5     0 8 to 25 0     0 7   p less than 0 001   the dsao2 dt was independent of apnea duration at 30  45  and 60 s  during endobronchial occlusion  apnea dsao2 dt increased 20   and nadir sao2 was significantly lower  possible mechanisms for steepening of dsao2 dt during atelectasis are discussed  
class10	paratope  and framework related cross reactive idiotopes on anti acetylcholine receptor antibodies  cross reactive idiotopes are a possible target for therapeutical interventions in autoimmune diseases  to investigate their role in the pathogenesis of experimental autoimmune myasthenia gravis  eamg  we analyzed the id of rat anti achr mab 6  35  61  65 and a control myeloma protein ir27  anti id 6  35  61  65 bound in a direct binding assay with various affinity to all rat anti achr mab that were tested  anti id ir27 recognized none of the anti achr mab  the specificity of these crossreactions was confirmed by inhibition studies with anti achr mab and two control rat myeloma proteins  ir27 and ir241   in addition  the id expression on mab d6  a mouse anti human achr mab was recognized by anti id 6  35  and 65  anti id  except anti id ir27  bound to affinity purified igg from the sera of rats with eamg  but not to preimmune lewis igg  these results suggest extensive sharing of idiotopes among anti achr mab  which are also present in eamg serum  anti achr mab against the main immunogenic region  6  35  65  from different rat strains  shared at least one paratope related cross reactive idiotopes  in the view of the fact that anti main immunogenic region antibodies might form a predominant fraction of the polyclonal response against achr  it is conceivable that an anti id recognizing these antibodies could have therapeutical applications as for example a selective immune absorbent or in immunotoxin therapy  
class10	randomized comparison of ceftriaxone and cefotaxime in lyme neuroborreliosis  in this prospective  randomized  open trial  33 patients with lyme neuroborreliosis were assigned to a 10 day treatment with either ceftriaxone  2 g intravenously  iv  every 24 h  n   17   or cefotaxime  2 g iv every 8 h  n   16   of the 33 patients  30 were eligible for analysis of therapeutic efficacy  neurologic symptoms improved or even subsided in 14 patients of the cefotaxime group and in 12 patients of the ceftriaxone group during the treatment period  at follow up examinations after a mean of 8 1 months  17 of 27 patients examined were clinically asymptomatic  in one patient borrelia burgdorferi was isolated from the cerebrospinal fluid  csf  7 5 months after ceftriaxone therapy  csf antibiotic concentrations were above the mic 90 level for b  burgdorferi in nearly all patients examined  patients with lyme neuroborreliosis may benefit from a 10 day treatment with ceftriaxone or cefotaxime  however  as 10 patients were symptomatic at follow up and borreliae persisted in the csf of one patient  a prolongation of therapy may be necessary  
class10	ataxia in myxoedema  a neurophysiological reassessment  in a long standing case of myxoedema with ataxia and dysarthria  neurophysiological investigations were carried out to assess how much of the ataxic dysbasic syndrome depended on the slowness of mechanical contraction and how much resulted from primary cerebellar involvement  it was observed that the achilles reflexogram showed a marked prolongation of contraction and relaxation time and that in both quadriceps and triceps surae mechanical percussion induced a marked myxoedema and prolonged relaxation time  the emg of these muscles during voluntary contraction and stopping reaction detected an excessive recruitment of the antagonistic muscles  starting without any abnormal delay  a finding at variance with a typical cerebellar pattern  post urographic analysis gave a pattern of oscillations still within the normal range  these findings suggest that the gait alterations of our patient depended on the increase in muscle contraction time and the consequent excessive recruitment of the antagonists  
class10	skin and epidural recording of spinal somatosensory evoked potentials following median nerve stimulation  correlation between the absence of spinal n13 and impaired pain sense  a clinical lesion study and intraoperative epidural recordings were made to test the origin and clinical significance of the spinal n13 and p13 of somatosensory evoked potentials  sep  that follow median nerve stimulation  intraoperatively  the respective peak latencies of spinal p13 and n13 coincided with those of the n1 component of the dorsal cord potential and its phase reversed positivity  on both the ventral and dorsal sides of the cervical epidural space  maximal amplitude was at the c5 vertebral level to which nerve input from the c6 dermatome is the main contributor  the modality of sensory impairment in the hand dermatome was examined in selected patients with cervical lesions  who showed such normal conventional sep components as erb n9  far field p9  p11  p14  n18 and cortical n20  with or without loss of spinal n13  statistically  the loss of spinal n13 was associated with decrease of pain sensation in the c6 dermatome  this was interpreted as being due to damage to the central grey matter of the cord  including the dorsal horn  our results suggest the spinal n13 and p13 originate from the same source in the c6 spinal cord segment and that they are good indicators for the detection of centromedullary cervical cord damage  
class10	the development of infratentorial atrophy in patients with idiopathic cerebellar ataxia of late onset  a ct study  the development of infratentorial atrophy in six patients suffering from idiopathic cerebellar ataxia of late onset was studied by a retrospective evaluation of consecutive computed tomography  ct  scans  four patients had evidence of olivopontocerebellar atrophy  opca  both on clinical testing and magnetic resonance imaging  mri   in these four patients  atrophy of the cerebellum and brain stem became visible at the same time and progressed in a roughly parallel manner  whereas in the remaining two the brain stem was left intact  in all patients with opca  definite brain stem atrophy was visible earlier than the appearance of non cerebellar clinical symptoms  the present data suggest that ct investigations at regular intervals may be of prognostic value in cerebellar ataxias  
class10	impairment of vertical motion detection and downgaze palsy due to rostral midbrain infarction  we present two cases with acute onset of vertical gaze palsy  mainly consisting of impaired downgaze and apraxia of downward head movements  together with neuropsychological deficits  hypersomnia  impaired attention and disorders of memory and affective control   ct and mri revealed bilateral post ischaemic lesions in the dorsomedial thalamus and the mesodiencephalic junction  dorsomedial to the red nucleus  thus being restricted to the territory of the posterior thalamosubthalamic paramedian artery  which includes the region of the rostral interstitial nucleus of the medial longitudinal fascicle as the main premotor nucleus for the generation of vertical saccades  in our patients  oculographic examination with electro oculography and magnetic search coil recording showed severe impairment of downward more than upward saccades and only minor deficits of vertical pursuit and the vestibulo ocular reflex  visual functions were normal  with one exception  a psychophysical test of motion perception revealed a significant deficit in the detection of vertical movements  this could be due to a central adaptive mechanism which  in order to minimize oscillopsia  might elevate thresholds for vertical motion perception in cases of vertical gaze palsy  as an alternative explanation  lesions within the midbrain tegmentum could have damaged subcortical visual pathways involved in motion perception  
class10	fasciculations due to verapamil in a patient with neuropathy  a patient with pre existing peripheral neuropathy developed generalized fasciculations under verapamil which ceased after discontinuation of the drug  it is suggested that the increase in acetylcholine  ach  release at the neuromuscular junction by verapamil may trigger fasciculation in the state of regeneration at ach sensitive sites of axon terminals and immature axon sprouts  
class10	epirubicin at two dose levels with prednisolone as treatment for advanced breast cancer  the results of a randomized trial  two hundred eleven patients with advanced breast cancer were randomized to receive either epirubicin  e  50 mg m2 and prednisolone  lep  or e 100 mg m2 and prednisolone  hep   the intended treatment consisted of 16 courses of lep or eight courses of hep given at 3 weekly intervals  reasons for stopping treatment early included progressive disease  stable disease without symptomatic improvement  or severe toxicity deemed intolerable by either the patient or physician  toxicity was recorded at 3 weekly and response at 9 weekly intervals using the world health organization  who  criteria of response and toxicity  two hundred nine patients were eligible for analysis  98  of whom have been followed for more than a year  one hundred four patients received lep and 105 hep  significantly worse myelosuppression  alopecia  nausea and vomiting  and mucositis were seen in the high dose arm  p less than or equal to  001   more patients in the lep arm stopped treatment before the fourth course than in the hep arm  and the commonest reason for stopping was progressive disease  a similar median number of courses was given in each arm  there was a significantly higher response in the hep arm  hep   complete response  cr    partial response  pr    41   lep   cr   pr   23    despite this  no statistically significant differences was seen in overall survival or progression free interval  the median survival for hep and lep was 44 and 46 weeks  respectively  
class10	cerebral palsy and rhizotomy  a 3 year follow up evaluation with gait analysis  a recent increase in the popularity of selective rhizotomy for reduction of spasticity in cerebral palsy has led to a demand for more objective studies of outcome and long term follow up results  the authors present the results of gait analysis on 14 children with spastic cerebral palsy  who underwent selective posterior rhizotomy in 1985  sagittal plane gait patterns were studied before surgery and at 1 and 3 years after surgery using a digital camera system  the parameters measured included the range of motion at the knee and thigh  stride length  speed of walking  and cadence  the range of motion at the knee was significantly increased at 1 year after surgery and further improved to a nearly normal range at 3 years after surgery  in contrast  postoperative measurements of thigh range exceeded normal values at 1 year  but decreased toward normal range at 3 years  while improvements in range of motion continued between years 1 and 3  the children developed a more extended thigh and knee position  which indicated a more upright walking posture  stride length and speed of walking also improved  while cadence remained essentially unchanged  this 3 year follow up study  the first to examine rhizotomy using an objective approach  has provided some encouraging results regarding early functional outcome  
class10	acute subdural hematoma  morbidity  mortality  and operative timing  traumatic acute subdural hematoma remains one of the most lethal of all head injuries  since 1981  it has been strongly held that the critical factor in overall outcome from acute subdural hematoma is timing of operative intervention for clot removal  those operated on within 4 hours of injury may have mortality rates as low as 30  with functional survival rates as high as 65   data were reviewed for 1150 severely head injured patients  glasgow coma scale  gcs  scores 3 to 7  treated at a level 1 trauma center between 1982 and 1987  101 of these patients had acute subdural hematoma  standard treatment protocol included aggressive prehospital resuscitation measures  rapid operative intervention  and aggressive postoperative control of intracranial pressure  icp   the overall mortality rate was 66   and 19  had functional recovery  the following variables statistically correlated  p less than 0 05  with outcome  motorcycle accident as a mechanism of injury  age over 65 years  admission gcs score of 3 or 4  and postoperative icp greater than 45 mm hg  the time from injury to operative evacuation of the acute subdural hematoma in regard to outcome morbidity and mortality was not statistically significant even when examined at hourly intervals although there were trends indicating that earlier surgery improved outcome  the findings of this study support the pathophysiological evidence that  in acute subdural hematoma  the extent of primary underlying brain injury is more important than the subdural clot itself in dictating outcome  therefore  the ability to control icp is more critical to outcome than the absolute timing of subdural blood removal  
class10	endoscopic ventricular fenestration using a  saline torch   the fiberoptic endoscope has never gained popularity among neurosurgeons although it is ideally suited for navigating within the cerebral ventricles  recent advances in optics and miniaturization make the application of endoscopy in neurosurgery more practical  the authors report eight children who underwent ventriculoscopic fenestration of symptomatic loculated cerebrospinal fluid  csf  collections  these csf collections were either isolated ventricular cysts or trapped lateral ventricles secondary to obstruction at the foramen of monro  cyst wall dissection was carried out with a  saline torch  dissector which was introduced through a working channel in the ventriculoscope  the torch was used to coagulate vessels and to sculpt large windows in cyst walls or in the septum pellucidum  ventriculoscope guided cyst fenestration can be performed safely and easily under direct vision  the technique may permit simplification of shunt systems in some patients and elimination of shunts in others  
class10	intracranial arachnoid cysts in children  a comparison of the effects of fenestration and shunting  the best operative intervention for children with arachnoid cysts remains the subject of controversy  recent reports stress that craniotomy for cyst fenestration is associated with a low incidence of morbidity and mortality and may leave the child shunt independent  the cases of 40 pediatric patients with arachnoid cysts treated between 1978 and 1989 are reported  five children with mild symptoms and small cysts that remained stable on follow up studies have not required surgical intervention  of 15 patients with cysts initially treated by fenestration  10  67   showed no clinical or radiographic improvement postoperatively and have undergone cyst peritoneal  eight patients  or ventriculoperitoneal  vp  shunting  one patient   or revision of a vp shunt placed for hydrocephalus before cyst fenestration  one patient   two other patients with existing vp shunts required no further procedures  thus  only three  20   of 15 patients initially treated by fenestration remain shunt independent after a median follow up period of 8 years  the 20 other patients were initially treated by cysts shunting and all improved postoperatively  shunt revision has been necessary in six  30   of these 20 patients because of cysts recurrence  cyst location influenced the success of shunt treatment  none of the seven middle cranial fossa cysts treated by shunting have required revision  but results with cysts in other locations were less favorable  in all locations  though  shunting was more successful than fenestration  it is concluded that cyst peritoneal or cyst vp shunting is the procedure of choice for arachnoid cysts in most locations  including those in the middle cranial fossa  
class10	an epithelial cyst in the cerebellopontine angle  case report  a case of a benign epithelial cyst in the posterior cranial fossa is described  it had the unique histological feature of a double layered cuboidal epithelial lining  detailed immunohistochemical and electron microscopic studies supported an endodermal origin  the differential diagnosis and the histogenesis of epithelial cysts in the central nervous system are discussed  
class10	spontaneous decompression of syringomyelia  magnetic resonance imaging findings  case report  the case of a 30 year old woman with chiari i malformation and a cervicothoracic syrinx is presented  the patient was followed clinically over a 2 1 2 year period  spontaneous and complete resolution of the syrinx  as documented by serial magnetic resonance studies  was accompanied by only a minimal change in objective symptomatology  
class10	familial hemifacial spasm associated with arterial compression of the facial nerve  case report  this report of an 88 year old woman with familial hemifacial spasm includes the first published postmortem description of hemifacial spasm with cross compression of the seventh cranial nerve root exit zone by a redundant loop of the anterior inferior cerebellar artery and associated vascular plexus  histological examination of the seventh and eighth cranial nerve complex suggested nerve degeneration because increased numbers of corpora amylacea were present just distal to the compression concavity  there was no evidence of demyelination or gliosis of the nerve  this case suggests that vascular compression of the nerve root exit zone is an important condition in the etiology of most of these cases  this is the third reported case of familial hemifacial spasm  to date  all such patients have had left facial involvement  the family pedigree in this case suggests a pattern of autosomal dominant inheritance with partial penetrance  the genetic basis for familial hemifacial spasm may involve anatomical variants or anomalies of the posterior circulation  since both posterior inferior cerebellar arteries were congenitally absent in this case  
class10	accessory arm  dysraphism or disparity  case report  the case of a 3 month old infant with an accessory third arm is reported  the extra appendage was attached at the midcervical region and was associated with posterior cervical dysraphism and a cervical cord lipoma  possible theories of origin are examined  
class10	treatment of intractable arterial hemorrhage during stereotactic brain biopsy with thrombin  report of three patients  of 165 consecutive patients undergoing computerized tomography  or magnetic resonance imaging guided stereotactic brain biopsies at the cleveland clinic between june  1987  and november  1989  four patients  2 4   developed arterial hemorrhage refractory to conventional efforts to secure hemostasis  craniotomy was performed in one of these patients to control the hemorrhage  in the other three  0 5 to 2 cc of thrombin  5000 u cc  was slowly injected via the biopsy cannula  resulting in immediate control of bleeding in all three cases  postoperatively  the first two patients treated with 1 to 2 cc of thrombin were slow to awaken  one had evidence of vasospasm by transcranial doppler ultrasound studies and multiple infarcts on cranial computerized tomography  while the other had a moderate sized frontal hematoma with intracranial hypertension  after prolonged recovery periods  only mild neurological deficits persisted in both patients  the third patient  treated with 0 5 cc of thrombin  had an uneventful postoperative course  thrombin is highly effective for stopping intractable arterial hemorrhage during stereotactic brain biopsy  however  it is a vasospastic agent and may have been responsible for the cerebral infarctions in one patient  therefore  thrombin should be used only as a last resort  short of craniotomy  to control intractable arterial hemorrhage during stereotactic brain biopsy  
class10	carbon monoxide induced delayed amnesia  delayed neuronal death and change in acetylcholine concentration in mice  we investigated the interrelationship of delayed amnesia  delayed neuronal death and changes in acetylcholine concentration induced by carbon monoxide  co  exposure in mice  in the test for retention of the passive avoidance task  amnesia was observed 5 and 7 days after co exposure when the mice were exposed to co 1 day after training  in the case when the mice were exposed to co 5 and 7 days before training  amnesia was also observed in a retention test given 1 day after training  the number of pyramidal cells in the hippocampal ca1 subfield was lower than that of the control 3  5 and 7 days after co exposure  but the neurodegeneration in the parietal cortex  area 1  was not observed until 7 days after co exposure  the findings indicated that the amnesia and the neuronal death were produced after a delay when the mice were exposed to co  in addition  the delayed amnesia was closely related to the delayed neuronal death in the hippocampal ca1 subfield  moreover   3h glutamate and  3h glycine binding sites did not change after co exposure but  7 days after co exposure  the concentration of acetylcholine and the binding of  3h quinuclidinyl benzilate in the frontal cortex and the striatum were found to have significantly changed  but those in the hippocampus did not show significant change  therefore  we suggest that delayed amnesia induced by co exposure may result from delayed neuronal death in the hippocampal ca1 subfield and dysfunction in the acetylcholinergic neurons  in the frontal cortex  the striatum and or the hippocampus  
class10	meta analysis of sulfasalazine in ankylosing spondylitis  at present there is no widely accepted therapy for ankylosing spondylitis  as   a progressive debilitating disease  the effectiveness of sulfasalazine in as still lacks strong evidence  as well  the magnitude of its benefit is unknown  a meta analysis was carried out to assess the effectiveness of sulfasalazine in as  a search of the literature was done using medline  index medicus  the reference lists of articles located and contacting content experts to reveal unpublished studies  five randomized controlled trials  rct  comparing sulfasalazine to placebo were located and assessed methodologically  the methodologic quality of all 5 rct was considered satisfactory and consequently these studies were included in the meta analysis  the pooled estimate of clinical benefit  and its 95  confidence interval  favoring sulfasalazine  over and above that observed in the placebo group was as follows  duration of morning stiffness  28 2    54 6 to  1 8    severity of morning stiffness  30 6    52 5 to  8 7    severity of pain  26 7    44 3 to  9 1    general well being  7 1    24 3 to 10 0    erythrocyte sedimentation rate  9 2    24 8 to 6 4    and iga  11 7    18 8 to  4 7    adverse effects  mostly mild  were more frequently observed in the sulfasalazine group  odds ratio  or    1 5746  p   0 1082   the occurrence of dropouts  or   1 1554  p   0 6119  was similar in both groups  sulfasalazine is a safe and effective drug in the short term treatment of as  
class10	a self administered hand symptom diagram for the diagnosis and epidemiologic study of carpal tunnel syndrome  noninvasive tests for carpal tunnel syndrome  cts  are of limited diagnostic value  a self administered hand symptom diagram has been developed for use in the diagnosis and epidemiologic study of cts  diagrams are rated classic cts  probable  possible or unlikely  diagram ratings were compared with nerve conduction diagnoses in 110 patients with upper extremity complaints  a hand diagram rating of classic or probable cts had sensitivity of 0 64  specificity of 0 73 and positive predictive value of 0 58  the negative predictive value of an unlikely diagram was 0 91  we conclude that the diagram is a useful diagnostic tool and may be valuable for occupational and population screening  
class10	l tryptophan induced eosinophilia myalgia syndrome  we describe the spectrum of clinical and histologic abnormalities of 11 women with l tryptophan induced eosinophilia myalgia syndrome  the illness is characterized by musculoskeletal symptoms including myalgias  arthralgias and paresthesias  the physical findings consist of muscle tenderness  neuropathies  rash  peripheral and periorbital edema  electroneurography performed in 10 patients demonstrated a neuropathy in 5 and myopathic changes in 3  skin and muscle biopsies showed fascial edema  inflammation and perivascular infiltrates in the skin  whereas perineural infiltrates and venulitis were identified in muscle  seven patients were treated with prednisone  eosinophilia disappeared promptly although myalgias and neuropathy persisted  
class10	eosinophilia myalgia syndrome associated with l tryptophan use  the eosinophilia myalgia syndrome associated with the use of oral preparations of the amino acid l tryptophan was recognized in late 1989  we describe the clinical and laboratory manifestations  pathological findings and early clinical course of 20 patients with the eosinophilia myalgia syndrome  prominent clinical findings included severe myalgias limiting function  fatigue  rashes  edema and weight gain  weight loss  muscle weakness and shortness of breath  laboratory findings included eosinophilia  often marked   normal erythrocyte sedimentation rate  and elevated aldolase with normal or low creatine kinase values  on biopsy fascial inflammation was always seen consisting of lymphocytes  histiocytes and eosinophils in a perivascular distribution  invasion of the vascular wall by lymphocytes was seen in 20   capillary and arteriolar endothelial cell thickening was found in most cases on electron microscopy and endothelial cell necrosis or mural invasion by lymphocytes was seen in 25  of cases  two patients improved with no therapy  ten patients responded to therapy with prednisone alone  three patients have had progressive disease and one of these died  the relationship of this syndrome to previously described disease entities associated with eosinophilia is discussed  
class10	microangiopathy in the eosinophilia myalgia syndrome  the eosinophilia myalgia syndrome associated with the ingestion of l tryptophan was recognized in late 1989  we describe our pathologic study of skin  fascial  and muscle biopsies from 21 patients evaluated by light microscopy  histochemistry  and electron microscopy  a perivascular  lymphocytic infiltrate with eosinophils was present in the dermis  fascia  and skeletal muscle  lymphocytic infiltration of arteries and arterioles was seen  ultrastructurally  capillary and arteriolar endothelial cell thickening and necrosis was present  this microangiopathy suggests that ischemia may be a contributing factor to the findings in this syndrome  
class10	an eosinophilia myalgia syndrome associated with an l tryptophan containing product  a syndrome of eosinophilia and myalgias associated with the usage of l tryptophan containing products has been recently described by the centers for disease control  we report a case of this new clinical entity  highlighted by severe myositis  and compare this illness with similar reported syndromes  
class10	eosinophilia myalgia syndrome in association with l tryptophan ingestion  the association between the recently described eosinophilia myalgia syndrome and l tryptophan is now well established  we describe a patient with eosinophilia myalgia syndrome who developed incapacitating myalgias and peripheral eosinophilia responsive only to high dose corticosteroids  when massive upper gastrointestinal hemorrhage developed while receiving corticosteroid therapy  surgery was complicated by striking abdominal wall rigidness  a discussion of this case and of eosinophilia myalgia syndrome is presented  
class10	l tryptophan associated eosinophilia myalgia syndrome  environmental chemicals are increasingly incriminated in the pathogenesis of several disease states  the eosinophilia myalgia syndrome is a recently described entity attributed to the ingestion of the normal dietary amino acid l tryptophan  we describe a patient who fulfills criteria for the eosinophilia myalgia syndrome and who was ingesting supplemental l tryptophan  exhaustive investigations failed to reveal other causes for her eosinophilia or her myalgic neuropathic complaints  and she improved dramatically when she discontinued the l tryptophan supplements  the mechanisms whereby this chemical may induce this syndrome are discussed  
class10	acute urinary retention secondary to herpes simplex meningitis  we report a case of acute urinary retention in a 24 year old man with herpes simplex meningitis without genital lesions  since the differential diagnosis in young patients who present with acute urinary retention also includes multiple sclerosis  lumbosacral disk herniation  rheumatological disorders and drug intoxication  a thorough history and careful neurological examination are of paramount importance in distinguishing these syndromes  as part of a directed neurological evaluation prompt performance of lumbar puncture is indicated  a lymphocytic pleocytosis is suggestive of herpetic meningitis  culture of herpes simplex virus from the cerebrospinal fluid should be attempted  we recommend conservative management only  typically with intermittent catheterization  since bladder function usually normalizes within 10 to 14 days  
class10	motor neuron disease  amyotrophic lateral sclerosis   amyotrophic lateral sclerosis is an insidiously developing  adult onset  progressive anterior horn cell degeneration with associated degeneration of descending motor pathways  it has been recognized as an important clinical syndrome since the middle of the 19th century  despite increasing clinical and research interest in this condition  its cause remains obscure  even in the broadest terms  epidemiologic characteristics of the disease have been interpreted as evidence of both genetic and environmental causes  a major change in the view of this disease is the widely developing perception that it is a disease of elderly persons more than of middle aged adults as was previously taught  etiologic hypotheses encompass a broad range of postulated pathophysiologic mechanisms  and we review these in detail  the clinical limits of the disease can now be better defined by using modern diagnostic techniques  although interest in supportive symptomatic therapy is growing  no intervention has yet been shown to modify the biologically determined motor system degeneration  
class10	tourette syndrome and other tic disorders  diagnosis  pathophysiology  and treatment  in this report  we discuss the definition  characteristics  pathophysiology  and treatment of tic disorders with a major emphasis on tourette syndrome  although the diagnosis of a tic disorder depends on the presence of motor and or phonic tic s   patients with these problems also have a variety of co morbid features including obsessive compulsive symptoms  attention deficit hyperactivity disorder  behavioral difficulties  and learning disabilities  conservative estimates for tourette syndrome suggest a prevalence rate of 0 1 1 0 per 1000  this syndrome is inherited in a sex influenced autosomal dominant pattern with either chronic multiple tic disorder or obsessive compulsive disorder as alternative phenotypes of the putative gene  current evidence continues to support a pathophysiologic mechanism involving synaptic neurotransmission  with the dopaminergic system as a primary candidate  therapeutically  it is essential to clarify whether a patient s problems are related to tics or associated behavioral difficulties  pharmacotherapy for motor and phonic tics is strictly symptomatic and should be reserved for those with functionally disabling symptoms  a comprehensive individualized treatment program is often required in the care of individuals with tic disorders  
class10	predictors of morbidity and mortality in neonates with herpes simplex virus infections  the national institute of allergy and infectious diseases collaborative antiviral study group  background  in a controlled trial comparing acyclovir with vidarabine in the treatment of neonatal herpes simplex virus  hsv  infection  we found no significant difference between the treatments in adjusted mortality and morbidity  hence  we sought to define for the entire cohort  n   202  the clinical characteristics that best predicted the eventual outcome in these neonates  methods  data were gathered prospectively at 27 centers between 1981 and 1988 in infants less than one month of age who had virologically confirmed hsv infection  we examined the outcomes by multivariate analyses of 24 variables  disease was classified in one of three categories based on the extent of the involvement at entry into the trial  infection confined to skin  eyes  or mouth  encephalitis  or disseminated infection  results and conclusions  there were no deaths among the 85 infants with localized hsv infection  the mortality rate was significantly higher in the 46 neonates with disseminated infection  57 percent  than in the 71 with encephalitis  15 percent   in addition  the risk of death was increased in neonates who were in or near coma at entry  relative risk  5 2   had disseminated intravascular coagulopathy  relative risk  3 8   or were premature  relative risk  3 7   in babies with disseminated disease  hsv pneumonitis was also associated with greater mortality  relative risk  3 6   in the survivors  morbidity was most frequent in infants with encephalitis  relative risk  4 4   disseminated infection  relative risk  2 1   seizures  relative risk  3 0   or infection with hsv type 2  relative risk  4 9   with hsv infection limited to the skin  eyes  or mouth  the presence of three or more recurrences of vesicles was associated with an increased risk of neurologic impairment as compared with two or fewer recurrences  
class10	pretreatment neuropsychological status and associated factors in children with primary brain tumors  we report on the neuropsychological status of 31 children with primary brain tumors who underwent assessment before receiving therapy  overall  the children performed within normal limits in all test areas  the exception was the group with anterior hemispheric tumors who demonstrated deficits in executive cognitive functions  also  when compared according to tumor type  children with midline tumors and hydrocephalus performed more poorly than others on measures of intelligence  executive abilities  visual motor skills  and fine motor functions  although one half to two thirds of the children with supratentorial midline and infratentorial tumors had cranial nerve  oculomotor  or cerebellar deficits  only the latter were associated with specific neuropsychological deficits  poorer performance on fine motor and visual motor tests   age did not appear to be a factor in these children s neuropsychological test performances  
class10	brain retractor edema during induced hypotension  the effect of the rate of return of blood pressure  this study evaluated the hypothesis that the postoperative formation of cerebral edema may be influenced by the rate of blood pressure return after induced hypotension in a graded brain retractor injury  nineteen cats underwent unilateral craniotomy  isoflurane induced hypotension to a mean of 50 mm hg  and application of a brain retractor at 20 mm hg of pressure for 1 hour  blood pressure was returned to normal either within 3 minutes or over 20 minutes  the degree of cerebral edema formation was determined by evans blue dye and coronal magnetic resonance imaging  all animals showed extravasation of evans blue dye in the retracted hemisphere that was most marked at the periphery of the retractor  t1 relaxation times were significantly prolonged in the retracted hemispheres of both the fast return and slow return groups  18 8  and 17 8   respectively  and more so at the evans blue sites  42 8  and 40 8    although not so strikingly beneath the retractor itself  6 3  and 7 8    t2 relaxation times were similarly prolonged but to approximately half the degree of the t1 times  in the nonretracted hemisphere  drug induced hypotension alone did not result in significant acute cerebral edema or blood brain barrier alteration  there was no significant difference between the fast and slow groups in evans blue extravasation or magnetic resonance changes  thus  in a retractor induced brain injury  restoration of arterial pressure to normal either gradually or rapidly did not influence the degree or extent of edema formation  
class10	effects of repeated temporary clipping of the middle cerebral artery on pial arterial diameter  regional cerebral blood flow  and brain structure in cats  temporary clipping of the major arterial trunk is an important maneuver to control excessive unexpected bleeding in neurosurgical operations  however  repeated temporary clipping can give rise to severe neurological deficits after surgery  the present study was performed to confirm and explain these clinical findings  initially  a single 20 minute or 1 hour occlusion of the middle cerebral artery was performed in each of 5 cats  pial arterial diameter was determined by video imaging  regional cerebral blood flow was measured by autoradiography  and cerebral edema and infarction were observed  in the 20 minute occlusion group  no abnormal changes were found 5 hours after recirculation  in the 1 hour occlusion group  pial arteries were dilated by 45   and regional cerebral blood flow increased to more than twice the resting cortical values  the extent of cerebral edema was 41 2     7 5   se  and infarction was 34 5     9 5   se  of the hemisphere  in the second experiment  three 20 minute occlusions of the middle cerebral artery in a 1 hour interval were performed in 20 cats  in 10 of them  thiopental  40 mg kg  was used to protect the brain  in the group without barbiturate treatment  pial arteries were dilated by 40  at the end of experiment  regional cerebral blood flow decreased to about 70  compared with single 20 minute occlusion  cerebral edema was 19 5     8 1   se   and infarction was 8 1     3 7   se  of the hemisphere  in the treated group  these were only trivial changes  the effect of repeated clipping may cumulatively cause brain damage  and barbiturates should be used whenever repeated clipping is necessary  
class10	cerebral infarction and release of platelet thromboxane after subarachnoid hemorrhage  platelet aggregation induced by adenosine diphosphate and the release of thromboxane b2 were studied in 68 patients with subarachnoid hemorrhage during the second week after the hemorrhage  when delayed ischemic deterioration most often occurs  follow up computed tomographic scans were performed later than 1 month after subarachnoid hemorrhage to reveal permanent hypodense areas consistent with cerebral infarction  occurrence of hypodense lesions on the follow up computed tomographic scan was significantly associated with the presence of delayed ischemic deterioration  did   p less than 0 01   patients with subcortical or cortical cerebral infarctions due to did released more platelet thromboxane b2 than those with no evidence of a hypodense lesion on the computed tomographic scan  p less than 0 05   hypodense areas caused by an intracerebral hematoma or small  deep seated infarcts due to did were not associated with significantly elevated release of thromboxane b2  but the lacunar type infarcts were associated with increased aggregation of platelets  the results suggest that augmented platelet function may be involved in the pathogenesis of cerebral infarction due to did  
class10	effect of hydrocephalus on prostaglandins and thromboxane b2 in ventricular cerebrospinal fluid  the concentrations of prostaglandin f2 alpha  prostaglandin e2  6 ketoprostaglandin f1 alpha  prostacyclin metabolite   and thromboxane b2 were assayed in ventricular cerebrospinal fluid obtained from 28 patients with hydrocephalus  17 obstructive  11 communicating   seven patients received dexamethasone or hydrocortisone on the day of sampling  no patient received nonsteroidal anti inflammatory compounds for 48 hours before sampling  the median values did not differ significantly between the two types of hydrocephalus or from the concentrations in lumbar cerebrospinal fluid obtained from patients without intracranial pathology during lumbar myelography for possible lumbar disc disease  hence  there is no evidence that eicosanoids accumulate in the ventricles in hydrocephalus  and it is unlikely that they have a significant role in its symptomatology  
class10	observations on the pathophysiology of nelson s syndrome  a report of three cases  nelson s syndrome is generally regarded as an unusual sequela of primary bilateral adrenalectomy when performed for cushing s disease  it is classically defined by cutaneous hyperpigmentation  considerably elevated adrenocorticotropic hormone  acth  levels  and an enlarged sella turcica  in this report  we present three cases initially treated by transsphenoidal sellar exploration for cushing s disease  in two of these cases  remission of hypercortisolism did not occur after the initial pituitary exploration  a microadenomectomy was performed in one case and  in the other  no microadenoma was found  in both  nelson s syndrome occurred after adrenalectomy  a second transsphenoidal operation and radiotherapy were required to control tumor growth  in another case  transsphenoidal adenomectomy of an acth secreting tumor initially led to a remission of hypercortisolism for 4 years  but recurrent cushing s disease necessitated adrenalectomy  and again nelson s syndrome occurred  the documentation of a pre existing acth secreting basophilic pituitary microadenoma before adrenalectomy  as seen in two of our cases  has not been previously reported  and these observations of  non classical  courses have major implications for the pathophysiology of nelson s syndrome  
class10	occult  bilateral anterior sacral and intrasacral meningeal and perineurial cysts  case report and review of the literature  none of the more than 180 cases of anterior sacral meningocele reported in the past 150 years has been bilateral  and only two have been associated with occult intrasacral meningocele  we report a unique case of bilateral anterior sacral cysts  communicating with the subarachnoid space  associated with occult intrasacral meningeal and perineurial  tarlov s  cysts  in an asymptomatic woman  the pertinent clinical and diagnostic imaging literature is reviewed  
class10	neurinoma in the cavernous sinus  report of two cases  two cases of trigeminal neurinoma located solely in the cavernous sinus are reported  preoperatively  magnetic resonance imaging provided the accurate localization of the lesions  allowing precise planning of the surgical approach  that is  a subtemporal lateral approach and a pterional superior approach  respectively  the neurinomas inside the cavernous sinus were removed successfully  and the patients developed no new neurological deficits except for anesthesia in the 1st division of the trigeminal nerve  the characteristic magnetic resonance imaging findings of trigeminal neurinoma in the cavernous sinus are presented  and the different surgical approaches are discussed  
class10	 moustache  appearance in craniopharyngiomas  unique magnetic resonance imaging and computed tomographic findings of perifocal edema  this report describes two cases of craniopharyngioma with perifocal edema  in both patients  computed tomography and magnetic resonance imaging  mri  revealed that the tumors occupied the suprasellar cistern  invaginated the floor of the 3rd ventricle and were tightly adherent to the ventricular walls  the intraventricular portions of the tumors were cystic  containing protein rich fluid as suggested by mri and confirmed by operative findings  there was perifocal edema in the hypothalamus adjacent to the intraventricular tumor  the optic tracts  and the posterior limbs of the internal capsules  resembling the shape of a moustache on axial computed tomographic and mri scans  the perifocal edema subsided after treatment of the intraventricular tumor by surgical resection or radiation therapy  the  moustache  appearance seems a unique  characteristic feature of perifocal edema  which is observed infrequently with certain craniopharyngiomas  
class10	delayed hearing loss after neurovascular decompression  we report two unusual cases of delayed hearing loss after neurovascular decompression of structures within the cerebellopontine angle  in the first case  the patient noted a unilateral hearing loss 3 weeks after undergoing vascular decompression of the trigeminal nerve for tic douloureux  this gradually improved over an 18 month period  in the second case  the patient awoke on the 4th day after vascular decompression of the facial nerve for hemifacial spasm with a bilateral hearing loss that has remained unchanged after the onset  these are examples of delayed acoustic dysfunction occurring with a shift in surgically freed vessels and may have been induced by newly directed neurovascular compression or distortion  
class10	immunoglobulins from animal models of motor neuron disease and from human amyotrophic lateral sclerosis patients passively transfer physiological abnormalities to the neuromuscular junction  amyotrophic lateral sclerosis  als  is a devastating human disease of upper and lower motoneurons of unknown etiology  in support of the potential role of autoimmunity in als  two immune mediated animal models of motoneuron disease have been developed that resemble als with respect to the loss of motoneurons  the presence of igg within motoneurons and at the neuromuscular junction  and with respect to altered physiology of the motor nerve terminal  to provide direct evidence for the primary role of humoral immunity  passive transfer with immunoglobulins from the two animal models and human als was carried out  mice injected with serum or immunoglobulins from the animal disease models and human als but not controls demonstrated igg in motoneurons and at the neuromuscular junction  the mice also demonstrated an increase in miniature end plate potential  mepp  frequency  with normal amplitude and time course and normal resting membrane potential  indicating an increased resting quantal release of acetylcholine from the nerve terminal  the ability to transfer motoneuron dysfunction with serum immunoglobulins provides evidence for autoimmune mechanisms in the pathogenesis of both the animal models and human als  
class10	vascularized full thickness parietal bone grafts in maxillofacial reconstruction  the role of the galea and superficial temporal vessels  reconstruction of bony structures of the face is always a problem as big as the defect and the function that must be replaced  everything from simple grafts to sophisticated distant bone flaps has been used  based on the studies of cutting et al   psillakis et al   and casanova et al   we have developed the full thickness galeoparietal bone flap  initially for mandibular reconstruction  but of great use for all maxillofacial reconstructions  from july of 1987 to december of 1988  14 patients have been operated on  the experience with this flap is shown in four patients as follows  primary reconstruction of a mandible as a result of ameloblastoma  secondary reconstruction of a mandible with associated old fractures and malalignment of segments  bilateral malar reconstruction in a patient with treacher collins syndrome  and severe sequelae of an already treated romberg case  small variations could be made to best accommodate the technique used to the defect we were treating  some technical details  the experience  the results  and possible sequelae or complications are also discussed  
class10	botulinum a toxin for the treatment of adult onset spasmodic torticollis  thirty five patients with adult onset idiopathic torticollis were treated by local injections of botulinum a toxin into dystonic cervical muscles  substantial improvement with respect to reduction and elimination of pain was found in 81 percent  improvement in posture deformity and involuntary spasms in 70 percent  increased range of motion of the neck in 78 percent  reduction in visible sternocleidomastoid hypertrophy in 86 percent  and improvement in tremor in 65 percent  the syndrome was divided into four subtypes based on pattern of dystonic muscle groups involved in the dystonia  head and shoulder posture  and sternocleidomastoid muscle hypertrophy  injection strategy based on this subdivision is described  
class10	reflex sympathetic dystrophy syndrome  consensus report of an ad hoc committee of the american association for hand surgery on the definition of reflex sympathetic dystrophy syndrome  this report proposes that reflex sympathetic dystrophy be defined as a pain syndrome in which the pain is accompanied by loss of function and evidence of autonomic dysfunction  in the clinical setting  this diagnosis is usually associated with other anatomic and psychological diagnoses and may be associated with a variety of systemic illnesses and medicolegal factors  all components should be assessed before a treatment plan is established  priorities should go to emergency care  acute injuries  and systemic illness  psychiatric problems  and chronic anatomic problems  in that order  early  accurate diagnosis improves prognosis  
class10	clinical features and natural history of von hippel lindau disease the clinical features  age at onset and survival of 152 patients with von hippel lindau disease were studied  mean age at onset was 26 3 years and 97 per cent of patients had presented by aged 60 years  retinal angioma was the first manifestation in 65 patients  43 per cent   followed by cerebellar haemangioblastoma  n   60  39 per cent  and renal cell carcinoma  n   15  10 per cent   overall  89 patients  59 per cent  developed a cerebellar haemangioblastoma  89  59 per cent  a retinal angioma  43  28 per cent  renal cell carcinoma  20  13 per cent  spinal haemangioblastoma and 11  7 per cent  a phaeochromocytoma  renal  pancreatic and epididymal cysts were frequent findings but their exact incidence was not accurately assessed  mean age at diagnosis of renal cell carcinoma  44 0     10 9 years  was significantly older than that for cerebellar haemangioblastoma  29 0     10 0 years  and retinal angioma  25 4     12 7 years   the probability of a patient with von hippel lindan disease developing a cerebellar haemangioblastoma  retinal angioma or renal cell carcinoma by age 60 years was 0 84  0 7 and 0 69  respectively  a comprehensive screening protocol for affected patients and at risk relatives is presented  based on detailed analysis of age at onset data for each of the major complications  median actuarial survival was 49 years  with renal cell carcinoma the leading cause of death  
class10	spontaneous neurodegeneration in transgenic mice with mutant prion protein transgenic mice were created to assess genetic linkage between gerstmann straussler scheinker syndrome and a leucine substitution at codon 102 of the human prion protein gene  spontaneous neurologic disease with spongiform degeneration and gliosis similar to that in mouse scrapie developed at a mean age of 166 days in 35 mice expressing mouse prion protein with the leucine substitution  thus  many of the clinical and pathological features of gerstmann straussler scheinker syndrome are reproduced in transgenic mice containing a prion protein with a single amino acid substitution  illustrating that a neurodegenerative process similar to a human disease can be genetically modeled in animals  
class10	t cell receptor peptide therapy triggers autoregulation of experimental encephalomyelitis  encephalitogenic t cells specific for myelin basic protein share common v beta 8 peptide sequences in their t cell receptor  tcr  that can induce autoregulatory t cells and antibodies that prevent clinical signs of experimental autoimmune encephalomyelitis  eae   it is not known  however  if tcr peptides can treat established disease  to test its therapeutic value  tcr v beta 8 39 59 peptide was injected into rats with clinical signs of eae  this treatment reduced disease severity and speeded recovery  apparently by boosting anti v beta 8 t cells and antibodies raised naturally in response to encephalitogenic v beta 8  t cells  these results demonstrate that synthetic tcr peptides can be used therapeutically  and implicate the tcr v beta 8 39 59 sequence as a natural idiotope involved in eae recovery  similarly  human tcr peptides may be effective in enhancing natural regulation of autoreactive t cells that share common v genes  
class10	lyme disease  neurologic and ophthalmic manifestations  lyme disease is tick borne infection which produces early and late manifestations in many organ systems  prominent symptoms and signs occur in skin  heart  joints and nervous system  many ocular and neuro ophthalmic abnormalities recently have been attributed to lyme disease  but some cases have not been well established as direct sequelae  this review of the contemporary state of knowledge about lyme disease was undertaken so that more rigorous criteria can be applied in future diagnosis  
class10	automatic rifle injuries  suicide by eight bullets  report of an unusual case and a literature review  a 25 year old man committed suicide by shooting himself with eight bullets fired from a military rifle set on automatic  this rifle has two firing modes  an automatic mode and a self loading  single shot mode  using this case as an example  some important aspects of firearm injuries are discussed with special emphasis on those points that are relevant to automatic military rifles and most applicable to forensic pathology practice  some of the pathologic features of firearm wounds are reviewed and the role of the pathologist is discussed  lastly  the most important points that help the pathologist to determine the type or nature of a firearm death  that is  whether it is an accident  homicide  or a suicide  are discussed  classically  the number of the firearm wounds is used to differentiate suicide from homicide  as in the case reported here  however  when an automatic rifle or a military rifle set on automatic is used  the number of wounds is not a reliable indicator of the type of death  
class10	multidisciplinary baseline assessment of homosexual men with and without human immunodeficiency virus infection  iii  neurologic and neuropsychological findings  we explored the possibility that neurologic and neuropsychological changes constitute the earliest detectable manifestations of human immunodeficiency virus  hiv  infection  without knowledge of hiv status  we assessed neurologic signs and symptoms and administered a battery of neuropsychological tests to 208 homosexual men  of whom 84 were hiv negative  49 were hiv positive and asymptomatic  29 were mildly symptomatic  and 46 had significant medical symptoms but not the acquired immunodeficiency syndrome  there was no difference between the hiv negative and hiv positive men in the frequency of neurologic signs or of defective or borderline performance on any neuropsychological test  however  hiv positive men performed slightly but significantly worse than hiv negative men on tests of verbal memory  executive function  and language  similar results were obtained when comparisons were limited to hiv positive medically asymptomatic and hiv negative men  there was no degradation of neurologic status or neuropsychological performance across stages of hiv severity  but neurologic and neuropsychological summary scores correlated with cd4 cd8 ratios in the hiv positive group  ratings of neurologic signs and symptoms correlated with neuropsychological summary scores in the hiv positive group only  cognitive complaints were more frequent in the hiv positive men  they correlated with actual test performance in the hiv positive but not hiv negative men  the constellation of subjective and objective neuropsychological and neurologic findings suggests the possibility of a definable syndrome associated with hiv infection in asymptomatic individuals  
class10	effect of vaginal delivery on the pelvic floor  a 5 year follow up  we have studied the pelvic floor musculature and its innervation in 14 of 24  58 per cent  multiparous women who had been recruited into a study of the effect of childbirth on the pelvic floor as part of a prospective investigation that began in 1983  these 24 women had all delivered by the vaginal route without forceps assistance  five of the 14 had developed clinical symptoms of stress incontinence 5 years later  two of them had had a further uncomplicated vaginal delivery during this time  there was manometric and neurophysiological evidence of weakness because of partial denervation of the pelvic floor striated sphincter musculature  with pudendal neuropathy  which was more marked in those women with incontinence  these findings provide direct evidence for the hypothesis that pudendal neuropathy due to vaginal delivery persists and may worsen with time  
class10	extradural haematoma in the irish republic  an analysis of 82 cases with emphasis on  delay   eighty two cases of extradural haematoma were analysed to elucidate the factors contributing to delay in treatment and poor outcome  the majority of cases occurred in the first three decades of life with falls being the commonest aetiological factor  five distinct modes of presentation are described  excessive delay occurred in recognizing the condition and in subsequent transfer of patients  this resulted in many patients being operated on while in coma  associated intracranial and extracranial injury occurred in a significant number of cases  recommendations for the management of these patients are outlined  
class10	congenital demyelinating motor and sensory neuropathy with focally folded myelin sheaths  six patients  5 index cases and 1 sib  with a congenital motor and sensory neuropathy are described  the clinical  genetic and electrophysiological features resembled dejerine sottas disease or hereditary motor and sensory neuropathy  hmsn  type iii  sural nerve biopsy of 5 patients revealed segmental demyelination and remyelination with hypertrophic changes  although onion bulbs were not as ubiquitous as in classical hmsn type iii  a striking discriminating feature from hmsn type iii was an abundance of focal myelin thickenings  tomacula  present in nearly all teased fibres  possible pathogenic implications are discussed  these cases corroborate the heterogeneity of congenital motor and sensory neuropathies  
class10	symptomatic and essential rhythmic palatal myoclonus  rhythmic palatal myoclonus  rpm  is a rare movement disorder consisting of continuous synchronous jerks of the soft palate  muscles innervated by other cranial nerves and  rarely  trunk and limb muscles  it usually develops secondary to brainstem or cerebellar disease  symptomatic rpm   some patients  however  fail to show evidence of a structural lesion  essential rpm   a total of 287 cases with rpm from the literature including 210 cases with symptomatic and 77 cases with essential rpm have been reviewed and analysed statistically to look for criteria separating the two conditions  patients with essential rpm usually have objective earclicks as their typical complaint which is rare in the symptomatic form  eye and extremity muscles are never involved  the jerk frequency is lower in essential than in symptomatic rpm  patients with essential rpm are younger and have a balanced sex distribution as compared with a male preponderance in the symptomatic form  the rhythmicity of rpm seems to be more profoundly influenced by sleep  coma and general anaesthesia in essential than in symptomatic rpm  we conclude from these results that essential rpm should be separated as a distinct clinical entity  symptomatic rpm is a rhythmic movement disorder whose pathogenesis is quite well established  the cells of the hypertrophied inferior olives are believed to represent the oscillator  among other possibilities  essential rpm may represent its functional analogue  based on transmitter changes only  such a relationship could be of theoretical interest for the understanding of rhythmic hyperkinesias in general  
class10	experiential phenomena of temporal lobe epilepsy  facts and hypotheses  experiential phenomena that occur in temporal lobe seizures and can be reproduced by electrical stimulation of temporal lobe structures typically encompass perceptual  mnemonic and affective features  either in combination or in isolation  which commonly relate to the patient s individual past experience  these phenomena raise interesting questions concerning brain mechanisms involved in human psychophysiology  the anatomical substrates for the evocation of these phenomena are widely distributed within the temporal lobe and include temporal isocortex and limbic structures  amygdala  hippocampus and parahippocampal gyrus   arguments are presented which indicate that experiential phenomena are positive expressions of temporal lobe and limbic function and do not result from its ictal paralysis  recent concepts of parallel distributed processing  rumelhart and mcclelland  1986  and the importance of parallel distributed cortical networks for higher cognitive functions  goldman rakic  1988a  b  provide a theoretical framework on which a hypothesis explaining experiential phenomena can be based  in conformity with these concepts the hypothesis assumes that temporal lobe epileptic discharge or electrical stimulation of temporal lobe structures can induce the elaboration of patterns of excitation and inhibition in widely distributed neuronal networks  some of which are capable of forming a specific matrix representing the substrate of a given experience  neuronal networks engaged in parallel distributed processing  1  have the capacity to recreate the totality of a given experience when only a fragment of the network is activated  and  2  they tolerate a great deal of degradation by random inactivation of its components or by interference through random noise without serious loss of information content  these features are compatible with the assumption that localized epileptic neuronal discharge or electrical stimulation involving some temporal lobe structures could create a matrix representing features of individual experience of the kind activated in the course of temporal lobe seizures  such an experience could  up to a certain limit  resist the degrading influence of mounting noise which inevitably must attend seizure discharge  
class10	the role of diencephalic pathology in human memory disorder  evidence from a penetrating paranasal brain injury  a patient  b j   is reported who developed severe memory impairment following a penetrating brain injury caused by a snooker cue which entered through his left nostril into the basal regions of the brain  initially  his memory disorder had the clinical features of a dense amnesic syndrome  with both anterograde and retrograde amnesia  but b j  subsequently showed significant recovery of memory function  formal memory testing was carried out 21 months after injury  this demonstrated marked verbal memory impairment  as severe as that seen in patients with the amnesic syndrome  on nonverbal memory tests  his impairment was relatively mild and patchy  his retrograde amnesia had regressed mainly to affect a 6 month period before the injury  on other cognitive tasks  he performed at an average or above average level  and there was no neuropsychological evidence of frontal lobe dysfunction  neuroradiological investigations at various stages after his injury failed to demonstrate a lesion in any of the thalamic nuclei  magnetic resonance imaging showed a lesion in the hypothalamus in the region of the mamillary bodies  our study demonstrates that marked  relatively focal  memory disorder after diencephalic injury can occur without direct pathology to the body of the thalamus  it also indicates that structures in or adjacent to the hypothalamus  such as the mamillary bodies  may play a more important role in human memory functioning than has hitherto been considered  
class10	single unit analysis of the human ventral thalamic nuclear group  activity correlated with movement  during neurosurgical operations for the relief of movement disorders  single thalamic neurons  n   107  were identified with activity which was related to verbally cued active movements  movement related cells   the activity of each neuron was examined during different contralateral movements in order to determine the movement which was associated with the most consistent and pronounced change in firing rate  the optimal response   the optimal response was determined by analysis of histograms of neuronal activity which were constructed by using the onset of emg activity to synchronize successive repetitions of the active movement  movement related cells exhibited optimal responses associated with such movements as making a fist  extension or flexion of the wrist  flexing or extending the elbow  pointing with the entire upper extremity  extending the tongue and lifting the leg  most movement related cells recorded in a single parasagittal plane in an individual patient had optimal responses related to movements involving the same part of the body  movement related cells were classified into those that were activated in response to somatosensory stimulation  combined cells  n   20  and those which were not  voluntary cells  n   87   combined cells were activated in advance of emg activity during active movement and so could be distinguished from cells responding only to sensory stimulation  sensory cells   movement related cells  combined and voluntary cell types  were located anterior to sensory cells and tended to show a mediolateral somatotopic organization parallel to that of sensory cells with cutaneous receptive fields  combined cells responded to somatosensory stimulation of the same part of the body as that involved in the active movement related to the optimal response of the cell  combined cells responding to passive movements of a joint always had their optimal response during active movement about the same joint  the activity of combined cells during parkinsonian tremor may clarify the role of sensory feedback in tremor  
class10	striatonigral degeneration  a clinicopathological study  the clinical and pathological features of 10 cases of striatonigral degeneration are described  5 were misdiagnosed in life as parkinson s disease  retrospectively  helpful early pointers to the diagnosis in these cases included unexplained falls  autonomic dysfunction  absence of rest tremor and failure to respond to l dopa  but these were not always present  the pathological diagnosis could not be excluded on macroscopic examination of the striatum  relative preservation of the putamen occurred in the 4 patients who benefited from l dopa  the caudate nucleus was involved in all cases and there was no sparing of the large striatal neurons  in mild cases  involvement of the putamen was confined to its posterior two thirds  dorsolaterally  with increasing severity this extended in a dorsal to ventral and posterior to anterior direction  seven of the cases had evidence of olivopontocerebellar damage  but only 2 of these had clinical evidence of cerebellar disease  correlation was found between the neuronal counts in caudate putamen  striatum nigra compacta  globus pallidus nigra compacta  nigra compacta locus coeruleus  the most severely involved part of the substantia nigra pars compacta was the ventrolateral zone  which projects to the dorsal putamen  the earliest site of striatal disease  
class10	spongiform encephalopathy transmitted experimentally from creutzfeldt jakob and familial gerstmann straussler scheinker diseases  a comparison was made of the effects of experimental intracerebral inoculation into marmosets of brain homogenates from a case of creutzfeldt jakob disease  cjd  and from a member of the wo  family with cerebral amyloid and spongiform encephalopathy  the gerstmann straussler scheinker  gss  syndrome  all the inoculated marmosets developed spongiform encephalopathy  se  after incubation times of 20 23 months in the cjd group and 25 32 months in the gss group  subsequent passage from 1 affected animal in each group resulted in se developing after 17 months incubation  in every animal inoculated with cjd or gss material and in the 2 passage experiments the most severely affected region of the brain was the thalamus which in all cases was almost totally occupied by vacuoles  other grey matter masses were less severely and less consistently affected  vacuolation was observed in the cerebellar granule cell layer as well as in the molecular layer and the brain stem was finely vacuolated in all cases  there were only minor and inconsistent differences between the disease transmitted from cjd compared with gss and some differences between the original transmissions and the se caused by passaged inocula  severe astrocytic gliosis accompanied the spongiform changes but no amyloid was identified in any of the marmosets with experimentally transmitted disease  the pathogenesis of the spongiform change in the thalamus was studied in a series of marmosets by light and electron microscopy 3 22 months after the intracerebral inoculation of cjd or gss homogenates and was compared with controls  dilated irregularly shaped cisternae and the large complex vacuoles typical of se  present in abundance after 18 and 22 months incubation  were considered most probably to be derived from cisternae of neuronal smooth endoplasmic reticulum  
class10	percutaneous balloon pulmonary valvuloplasty in sickle cell anemia  a case report  percutaneous balloon pulmonary valvuloplasty was performed on a 19 year old female who had moderate pulmonary valve stenosis with sickle cell anemia  the patient developed sickle cell crisis resulting in occipital infarction  but she made a good recovery  we describe this case and the methods of reducing the risk of sickle cell crisis  
class10	the turp syndrome  this article discusses the presentation  aetiology  treatment and prevention of central nervous system disturbances after transurethral resection of the prostate  nausea and vomiting  visual symptoms  and altered states of consciousness have been reported as complications due to intravascular absorption of irrigating fluid  hypotonicity after absorption of the irrigating fluid causes cerebral oedema  hyperglycinaemia may cause visual disturbances and hyperammonaemia may cause delayed coma  
class10	high incidence of cardiopulmonary complications associated with implantation of adrenal medullary tissue into the caudate nucleus in patients with advanced neurologic disease  objective  the purpose of our study was to examine the cardiopulmonary complications of a group of patients who had undergone implantation of adrenal medullary tissue into the caudate nucleus for treatment of neurologic disease  design  prospective study with partially matched historical controls  setting  tertiary care community medical center  patients and methods  seven patients with advanced parkinson s disease and three patients with progressive supranuclear palsy underwent implantation of adrenal medullary tissue into the caudate nucleus  these patients were compared with respect to their cardiopulmonary complications with a control group who had undergone craniotomy and then compared with a control group who had undergone only abdominal surgery  results  in the study group  six patients developed major postoperative complications including development of large pleural effusions  lobar atelectasis  pneumonia  upper airway obstruction  and cardiac arrest  three patients had minor complications including development of small pleural effusions  subsegmental atelectasis  purulent bronchitis  mild congestive heart failure  and atrial flutter fibrillation  one patient had an unremarkable postoperative course  the first control group  whose only surgery was a craniotomy  had only one major complication  the second control group  the abdominal surgery control group  had one major and five minor complications  conclusion  the particular neurologic disease  its severity  and the type of surgery performed appear to be causative factors in the high incidence of complications in the study group  
class10	hemodynamic effects of nasal cpap examined by doppler echocardiography  the effects of incremental application of nasal continuous positive airway pressure  0 to 15 cm h2o  on heart rate  pulmonary artery pressure  and cardiac index were studied noninvasively by doppler echocardiography  by two way analysis of variance within two groups  19 normal volunteers and six sleep apnea patients   no significant effects on heart rate  pulmonary artery pressure  ventricular size  or cardiac index could be found with increasing positive intrathoracic pressures and consequent lung hyperinflation  in subjects with normal cardiac function  nasal cpap is safe from a hemodynamic viewpoint  this simple  repeatable and noninvasive technique may be used to assess the clinical safety and efficacy of prescribed nasal cpap on cardiac hemodynamics in individual patients  
class10	respiratory muscle strength and control of ventilation in patients with neuromuscular disease  to assess the relationship between respiratory mechanics and muscle strength and control of ventilation in patients with neuromuscular disease  nmd   we compared pimax and pemax at rv  frc and tlc  total respiratory elastance  ers  with vt  ti  tt  ve  vt ti  ti tt  p 01  and p 01  vt ti  effective impedance in 21 patients with nmd and 21 healthy control  c  subjects  in seated position breathing room air  ers in nmd patients was 79 percent higher than in the c subjects  while ti  tt  and vt in nmd were approximately half the corresponding c values  p 01 was 66 percent greater than in the c subjects  both p less than 0 001   nmd pimax and pemax ranged from 37 to 52 percent of corresponding c values  respectively  despite significant respiratory muscle weakness  only 7 of 16 patients demonstrated a paco2 greater than 45 mm hg  ventilatory output in nmd was modulated by respiratory mechanics as indicated by the increased p 01  in spite of muscle weakness  central drive in patients with nmd is not decreased  and in fact  is often increased  ve is not an accurate measure of central drive because of abnormal intrinsic respiratory mechanics and the effects of conscious responses or reflexes  
class10	effect of ethanol on the efficacy of nasal continuous positive airway pressure as a treatment for obstructive sleep apnea  the effect of ethanol ingestion on the efficacy of nasal continuous positive airway pressure  nasal cpap  as a treatment for the obstructive sleep apnea  osa  syndrome was studied in ten obese male subjects undergoing this therapy  on the first night of polysomnography  the lowest level of cpap that maintained airway patency was determined  critical level   on the second  control  night  c   subjects slept the entire night on this level of cpap  on the third night  e   subjects ingested either 1 5 ml kg  part a  n   6  or 2 0 ml kg  part b  n   4  of 50 percent ethanol  100 proof vodka  over one half hour starting 1 h before bedtime  a serum ethanol level was obtained at bedtime  part a  63 7     17 3 mg dl  part b  108 6     20 6 mg dl   and subjects were monitored on the critical level of cpap  comparison of nights c and e for parts a   b showed no difference in total sleep time  tst  or the amount of different sleep stages as an absolute time or a percentage of tst except that there was more stage 2  as a percent of tst  on e nights  the apnea   hypopnea index and c and e nights did not differ and was quite low  3 6     3 7 h vs 1 9     2 7 h   similarly  ethanol ingestion did not increase the number of desaturations to at or below 90 and 85 percent  or lower the mean arterial oxygen saturation in nrem or rem sleep  analysis of parts a and b separately also showed no differences with respect to the apnea   hypopnea index or the number of desaturations on control and ethanol nights  we conclude that acute moderate ethanol ingestion does not decrease the efficacy of an optimum level of nasal cpap  
class10	acute pulmonary embolism triggered by the act of defecation  pulmonary embolism associated with the act of defecation has not been previously well described  recently  we reported our experience with four patients who presented to us over a 12 month period with syncope  near syncope  or sudden death following the act of defecation  in all four cases  acute pulmonary embolism was shown to be the etiology of the defecation associated events  a retrospective chart review of all patients with the diagnosis of pulmonary embolism at our institution over a three year period yielded five additional patients with the diagnosis of defecation associated pulmonary embolism  these nine patients accounted for 6 8 percent of all patients with a discharge diagnosis of pulmonary embolism seen at our institution during the three year study period  six of the nine patients died from their defecation associated pulmonary embolism  these six deaths accounted for 25 percent of all deaths from pulmonary embolism seen at our institution during the study period  based on our experience  we suggest that the act of defecation may trigger the development of acute pulmonary embolism in some patients with deep vein thrombosis  
class10	effect of cardiac output reduction on rate of desaturation in obstructive apnea  the nadir of sao2 during an obstructive apnea is dependent upon the apnea s duration and the rate of fall of saturation  dsao2 dt   we postulated that a low q  such as in patients with congestive heart failure with sleep apnea  or a reduction in q  as seen in some humans during obstructive sleep apnea  might steepen dsao2 dt  the mechanism postulated was lowering of svo2 with increased pulmonary capillary blood oxygen uptake and faster depletion of alveolar oxygen  this study examines dsao2 dt following the onset of apnea in eight spontaneously breathing adult baboons  nonrepetitive obstructive apneas  30  45  and 60 seconds  were created by clamping an indwelling cuffed endotracheal tube at the end of expiration  following baseline measurements  the animals were given a bolus of a rapid acting beta adrenergic blocker followed by continuous infusion to reduce cardiac output and to limit the cardiovascular response to obstructive asphyxia  fiberoptic catheters were used for continuous monitoring of sao2  svo2  and cardiac output  esophageal pressure and relative thoracic gas volume  respitrace  were monitored to insure equivalence of lung volume at the onset of apnea  beta adrenergic blockade reduced resting q by a mean of 25 percent  the blocked vs unblocked dsao2 dt was 0 73 vs 0 72 percent s  0 76 vs 0 73 percent s  and 0 70 vs 0 71 percent s for 30 second  45 second  and 60 second apneas  respectively  thus  mean dsao2 dt for all durations of apneas was unaffected by beta adrenergic blockade  we concluded that dsao2 dt is not influenced by limited q preceding or induced by obstructive asphyxia  
class10	hyperprolactinemia increases and hypoprolactinemia decreases tyrosine hydroxylase messenger ribonucleic acid levels in the arcuate nuclei  but not the substantia nigra or zona incerta  the effects of experimentally produced hypoprolactinemia and hyperprolactinemia on tyrosine hydroxylase  th  mrna signal levels were examined in dopaminergic neurons ovariectomized rats  th mrna signal levels and relative th quantity in the arcuate nuclei  zona incerta  and substantia nigra were evaluated by in situ hybridization and immunocytochemistry  respectively  the catalytic activity of th in the stalk median eminence  sme  was determined from the in vitro rate of 3 4 dihydroxyphenylalanine  dopa  accumulation after inhibiting dopa decarboxylase with brocresine  chronic administration of bromocriptine  bromo   a dopamine  da  agonist  for 3 days reduced circulating rat prl  rprl  levels compared to those in the vehicle treated controls  bromo treatment decreased th mrna signal levels in the arcuate nuclei  the intensity of th immunostaining in the arcuate median eminence area  and the rate of dopa accumulation in the sme  concomitant administration of ovine prl  oprl  reversed the effects of bromo on th  resulting in markedly increased th mrna signal levels  intensity of th immunostaining  and rate of dopa accumulation  treatment with oprl by itself for 3 days increased th mrna signal levels in the arcuate nuclei and th activity in the sme  compared to vehicle  chronic treatment with haloperidol  a da antagonist  increased circulating levels of endogenous rprl and increased th activity in the sme to values similar to those after oprl treatment  however  in contrast to oprl  mrna levels in the arcuate nuclei of haloperidol treated rats were similar to levels in vehicle treated animals  to evaluate whether the effect of prl on th was species specific  oprl or rprl was continuously infused into the jugular vein using an osmotic minipump  th mrna levels in the arcuate nuclei were elevated above control levels by either oprl or rprl administration  th mrna levels in the da perikarya located in the zona incerta and substantia nigra were not altered by treatment with a da agonist  a da antagonist  or prl  these results indicate that hypoprolactinemia or hyperprolactinemia can selectively reduce or augment  respectively  th mrna levels in the tuberoinfundibular dopaminergic neurons  the alterations in th mrna content probably contribute to the decrease or increase in th activity associated with hypoprolactinemia or hyperprolactinemia  respectively  
class10	humor  aggression  and aging  humor response to aggressive cartoons was investigated by using ratings of pain and funniness of cartoons by 154 young and elderly men and women  no significant age differences were found  however  sex differences were found  for both young and elderly females  an inverted u described the relationship between pain and funniness ratings  for young and elderly males  there was no relationship between pain and funniness  this is a preliminary step in exploring age differences in humor but may be relevant for those working with elderly persons  
class10	pathogenesis and pathophysiology of meningitis  advances in the understanding of the pathogenesis and pathophysiology of meningitis have occurred primarily through the use of experimental animal models  these models have proven to be particularly valuable in experimental bacterial meningitis  focusing on the bacterial virulence factors responsible for the initiation of infections  cns invasion  and induction of sas inflammation  recent studies have examined the formation of host inflammatory cytokines in response to these virulence factors  these cytokines may be responsible for many of the pathophysiologic consequences of bacterial meningitis  eg  increased bbb permeability  cerebral edema  and increased intracranial pressure   meningitis due to c  neoformans occurs most commonly in patients with defects in cell mediated immunity  eg  aids   and the depletion of t helper cells in aids patients may allow unrestricted cryptococcal growth  viral meningitis is an illness of low prevalence when compared with the overall occurrence of viral infections at other sites  cns infection usually occurs by means of traversal across barriers that normally exclude viral invasion of the cns  primarily through hematogenous dissemination from initial sites of infection  these advances in the pathogenesis and pathophysiology of bacterial  fungal  and viral meningitis may lead to the development of innovative treatment strategies for these disorders  
class10	approach to diagnosis of meningitis  cerebrospinal fluid evaluation  csf evaluation is the single most important aspect of the laboratory diagnosis of meningitis  analysis of the csf abnormalities produced by bacterial  mycobacterial  and fungal infections may greatly facilitate diagnosis and direct initial therapy  basic studies of csf that should be performed in all patients with meningitis include measurement of pressure  cell count and white cell differential  determination of glucose and protein levels  gram s stain  and culture  in bacterial meningitis  limulus lysate assay and tests to identify bacterial antigens may allow rapid diagnosis  where there is strong suspicion of tuberculous or fungal meningitis  csf should also be submitted for acid fast stain  india ink preparation  and cryptococcal antigen  unless contraindicated by increased intracranial pressure  large volumes  up to 40 50 ml  should be obtained for culture  if a history of residence in the southwest is elicited  complement fixing antibodies to coccidioides immitis should also be ordered  newer tests based on immunologic methods or gene amplification techniques hold great promise for diagnosis of infections caused by organisms that are difficult to culture or present in small numbers  despite the great value of lumbar puncture in the diagnosis of meningitis  injudicious use of the procedure may result in death from brain herniation  lumbar puncture should be avoided if focal neurologic findings suggest concomitant mass lesion  as in brain abscess  and lumbar puncture should be approached with great caution if meningitis is accompanied by evidence of significant intracranial hypertension  institution of antibiotic therapy for suspected meningitis should not be delayed while neuroradiologic studies are obtained to exclude abscess or while measures are instituted to reduce intracranial pressure  
class10	the acute aseptic meningitis syndrome  the acute aseptic meningitis syndrome is an entity that presents a diagnostic challenge to the clinician  although many infectious and noninfectious etiologies exist for this syndrome  viruses  especially nonpolio enteroviruses  are the classic and most important agents encountered  the incidence of polio and mumps meningitis has declined dramatically in the vaccine era  but recently described pathogens  such as human immunodeficiency virus and borrelia burgdorferi  lyme disease agent  are now important considerations in the differential diagnosis  specifically treatable entities  eg  mycobacterial or fungal meningitis  herpes simplex encephalitis  parameningeal infection  that may mimic aseptic meningitis in their initial presentations must not be overlooked  a careful approach to the patient and a rational use of laboratory studies are the basis for establishing a specific diagnosis and assuring a favorable outcome  
class10	bacterial meningitis in neonates and children  a high index of suspicion of meningitis is needed when evaluating neonates and young infants because clinical findings can be minimal and are often subtle and nonspecific  analysis of the csf constitutes the most effective method to document meningeal bacterial infection  although overlap with normal csf values can occur  especially in newborns and very young infants  the introduction of highly active third generation cephalosporins  ceftriaxone  cefotaxime  and their safety and efficacy in treating a broad array of bacterial pathogens that cause meningitis in all age groups has simplified selection of initial antibiotic therapy  in neonates  however  conventional antibiotic therapy with ampicillin and an aminoglycoside is appropriate because of its proven record of safety and efficacy  and because routine use of cephalosporins in the hospital nursery could lead to selection of resistant strains among gram negative enteric bacilli  despite the availability of modern intensive care management of infants and children with bacterial meningitis and the advent of potent antibiotics  case fatality rates and morbidity remain high  because of this  recent research has focused on the complex interaction between bacteria and the host and on means to attenuate the meningeal inflammatory response  the clinical benefits demonstrated recently with the use of dexamethasone therapy in infants and children with bacterial meningitis underscore the importance of anti inflammatory therapy to reduce audiologic and neurologic sequelae  future studies of new methods to modulate meningeal inflammation such as the use of monoclonal antibodies directed against cytokines or of agents that interfere with leukocyte endothelial interactions are indicated  the implication of routine h  influenzae type b immunization in young infants with the conjugated vaccines and optimal intrapartum prophylaxis against group b streptococcal disease in newborns will have an important impact on the incidence of meningitis in infants and children  
class10	bacterial meningitis in adults  bacterial meningitis continues to be an important cause of morbidity and mortality despite the availability of effective bactericidal antibiotics  penicillin or ampicillin remains the drug of choice for meningitis caused by streptococcus pneumoniae and neisseria meningitidis  the third generation cephalosporins have revolutionized the treatment of gram negative meningitis  future therapy for bacterial meningitis will use recent developments in the understanding of pathogenic and pathophysiologic mechanisms underlying this disease  
class10	general principles of therapy of pyogenic meningitis  in bacterial meningitis  several pharmacodynamic factors determine therapeutic success when defined as sterilization of the csf   1  local host defense deficits in the cns require the use of bactericidal antibiotics to sterilize the csf   2  csf antibiotic concentrations that are at least 10 fold above the mbc are necessary for maximal bactericidal activity  protein binding  low ph  and slow bacterial growth rates are among the factors that may explain the high antibiotic concentrations necessary in vivo   3  high csf peak concentrations that lead to rapid bacterial killing appear more important than prolonged suprainhibitory concentrations  probably because very low residual levels in the csf prevent bacterial regrowth  even during relatively long dosing intervals   4  penetration of antibiotics into the csf is significantly impaired by the blood brain barrier and thus  very high serum levels are necessary to achieve the csf concentrations required for optimal bactericidal activity  beyond these principles  recent data suggests that rapid lytic killing of bacteria in the csf may have harmful effects on the brain because of the release of biologically active products from the lysed bacteria  since rapid csf sterilization remains a key therapeutic goal  the harmful consequences of bacterial lysis present a major challenge in the therapy of bacterial meningitis  currently  dexamethasone represents that only clinically beneficial approach to reduce the harmful effects of bacterial lysis  and novel approaches are required to improve the outcome of this serious infection  
class10	meningitis in the neurosurgical patient  in the patient with a basilar skull fracture and csf leak  the risk of meningitis is greatly increased  the diagnosis of both leak and infection can be obscured by the patient s other injuries  and requires aggressive investigation of symptoms that suggest infection  although the diagnosis is made with csf cultures  when clinically suspected  treatment should begin after appropriate cultures have been obtained  treatment should be directed against the most likely organisms  streptococcus pneumoniae  haemophilus influenzae  and the other organisms common to the upper respiratory tract  there are no good indications for prophylactic antibiotic usage in patients with known csf leaks  the patient with a shunt or other cns prosthetic device may have various manifestations of infection  depending on the type of device and its termination  frank meningitis or ventriculitis is not always present  diagnosis requires direct culturing of the shunt milieu  with the most frequent isolates being staphylococcal species and gram negative enteric bacilli  the most effective therapy  for both eradication of the infection and minimization of the duration and morbidity of therapy  involves removal of the infected shunt  external drainage during parenteral antibiotic therapy  and complete replacement of hardware at the time of internalization  the postsurgical patient will not develop meningitis very frequently  but like the posttrauma patient  concurrent factors can make the diagnosis difficult  differentiating infectious from chemical meningitis must often be initially based on csf cell counts and chemistries alone  treatment to cover the most likely organism  staphylococcal species and respiratory flora  should be started before the culture results are finalized  
class10	spirochetal infection of the central nervous system  four spirochetal diseases frequently involve the central nervous system  syphilis  leptospirosis  relapsing fever  and lyme borreliosis  in particular  syphilis and lyme borreliosis are increasing problems  during the spirochetemic phase there is seeding of the nervous system  after a quiescent latent period  there may be late disease flareups producing a variety of neurologic syndromes  cerebrospinal fluid examination is very helpful in these infections  
class10	persistent neutrophilic meningitis  persistent neutrophilic meningitis is an unusual but distinct clinical variant of chronic meningitis characterized by csf neutrophilia with hypoglycorrhachia which persists for more than 1 week on serial csf studies  documented etiologies include selected bacteria and higher bacteria such as brucella  nocardia and actinomyces as well as  opportunistic  fungi such as candida  aspergillus  the zygomycetes  and pseudallescheria  recognition of the syndrome is important  as empiric therapy  e g   cotrimoxazole and amphotericin b  may differ significantly from that used for classic chronic meningitis  
class10	tuberculous meningitis  tuberculous meningitis is an uncommon but potentially devastating form of tuberculosis  current antituberculous drugs are highly effective when treatment is initiated early  before the onset of altered mentation or focal neurologic deficits  because the clinical outcome depends greatly on the stage at which therapy is initiated  early recognition is of paramount importance  patients with the meningoencephalitis syndrome and csf findings of low glucose levels  elevated protein levels  and pleocytosis should be treated immediately if there is evidence of tb elsewhere in the body  or if prompt evaluation fails to establish an alternative diagnosis  examination of csf is the best diagnostic approach  with sufficient diligence  serial afb smears and cultures will usually yield positive results  even days after therapy has been started  the ct scan is an important and highly effective tool for the diagnosis and management of patients with tbm  in a patient with compatible clinical features  the combination of basilar meningeal enhancement and any degree of hydrocephalus is strongly suggestive of the diagnosis of tbm  serial evaluation by ct scanning is useful for following the course of hydrocephalus and tuberculoma  particularly in reference to the need for  or response to  adjunctive therapy with corticosteroids and surgery  the decision to administer corticosteroids should be based on careful correlation of the clinical and radiographic features of the case  surgical shunting should be considered early in the patient with hydrocephalus and symptoms of raised intracranial pressure  tuberculomas are best treated medically  often in conjunction with corticosteroids where cerebral edema is believed to contribute to neurologic decline  the recommended chemotherapy regimen is isoniazid and rifampin in all patients  together with pyrazinamide for the first 2 months  
class10	fungal meningitis  fungal meningitis tends to be a subacute or chronic process  however  it may be just as lethal as bacterial meningitis if untreated  there are many similarities between the pathogenic fungi  most of the fungi are aerosolized and inhaled  and initiate a primary pulmonary infection which is usually self limited  hematogenous dissemination may follow the initial infection  with subsequent involvement of the cns  rarely  trauma or local extension provides the route to cns infection  the host is frequently  although not always  immunosuppressed  the hyphae of molds generally cause focal disease with hemorrhagic necrosis secondary to vascular thrombosis  the yeasts tend to cause a more diffuse process with the base of the brain being primarily affected  such that hydrocephalus is seen as a frequent complication of chronic disease  diagnosis may be difficult  as the csf may be normal  with negative smears and sterile cultures  although more often there is at least one abnormality indicating disease  serologies  if available  depending on the fungus  may point towards the proper diagnosis  as may a careful travel history  currently  amphotericin b is still the drug of choice in most situations  however  the newer azole antifungal agents offer great promise  especially in the treatment of cryptococcal meningitis  the precise role of such agents will remain unclear until appropriate large scale studies of their effectiveness have been completed  the treatment of the unusual cns mycoses will continue to be based on clinical experience  and reports of the use of new azoles in these diseases need to be critically evaluated  
class10	meningitis due to protozoa and helminths  this article reviews the microbiology  pathogenesis  epidemiology  clinical manifestations  diagnostic tests  and recent advances in the therapy of protozoan and helminthic infections of the central nervous system  with more emphasis given to protozoan than to helminthic infections  
class10	chronic pain in primary care  identification and management of psychosocial factors  chronic pain is a problem of great public health importance that is frequently seen in the primary care setting  pain chronicity shows a strong association with psychosocial factors  assessment of these factors should be composed of two parts   1  psychological factors and  2  psychiatric illness  psychological factors include all those pain associated alterations in the patient s environment that reinforce illness behavior  psychiatric illness includes those syndromes that retard recovery from illness or injury  such as depression  anxiety  substance abuse  and dementia  psychiatric and psychological interventions can be successfully introduced in the context of a comprehensive rehabilitation effort  usually these interventions can be accomplished by the family physician in concert with a consultant psychiatrist or psychologist  in severely disabled or resistant patients  referral to a multidisciplinary pain clinic will be necessary  
class10	a multicentre follow up study of 1152 patients with myasthenia gravis in italy  a multicentre retrospective study was carried out on the characteristics and course of myasthenia gravis  mg  in italy  data from 1152 patients  fairly representative of the myasthenic population seeking medical advice  were analysed for diagnostic criteria  clinical aspects and therapeutic approaches  mean follow up was 4 9 years  the disease was correctly diagnosed within 2 years of the onset in 80  of cases  onset of symptoms peaked in the second and third decade in females and fell between 20 and 59 years in males  at first observation 87  of the patients had generalized mg  maximal worsening was observed within 3 years in 77  of patients  at the last follow up  35  of cases were symptom free  pharmacological remission 24   remission without treatment 11    the more severe the disease at the first observation and at the maximal worsening of symptoms  the lower was the proportion of remissions  steroids were given in 54  and immunosuppressants in 18   thymectomy was performed in 72   mostly in women  younger than age 40  and with generalized mg  thymectomy seemed to improve the course of the disease  mostly in patients operated on shortly after diagnosis and those with generalized mild to moderate disease and with a normally involuted thymus  mg was lethal in 4  of patients  principally men  older than 40  in grade 3 or worse at first observation  with a short history of disease  and with thymona  
class10	motor dysfunction in hiv infected patients without clinically detectable central nervous deficit  motor tests were performed in 50 hiv infected patients in all stages according to the current cdc classification  but without any clinically evident central nervous system deficit  and the results compared with an age matched control group  patients were excluded from the study if there was alcohol or drug abuse  fever and or opportunistic cerebral infection  the parameters tested were postural tremor of the outstretched hands  most rapid voluntary alternating index finger movements  mram  and rise time of most rapid index finger extensions  mrc   whereas tremor peak frequencies did not differ significantly in the patients and controls  mram and rise times of mrcs showed significant slowing in the patient group  morphologically  the motor test performance of the hiv infected patients was similar to that of patients with manifest basal ganglia disease  parkinson s  huntington s and wilson s diseases   mri scans of all patients were normal  it is concluded that in hiv infected patients there is a very early subclinical central nervous system affection  especially of the basal ganglia  which is detectable with appropriate  quantitative motor function tests  these functional abnormalities precede the structural alterations in the mri scans  
class10	oculo bulbar myasthenic symptoms as the sole sign of tumour involving or compressing the brain stem  four patients with tumours involving or compressing the brain stem are described whose initial clinical symptoms of fluctuating paresis of the external ocular muscles and or the pharyngeal muscles without other neurological deficits led to the primary diagnosis of focal myasthenia  the combination of an unusual clinical pattern  involvement of muscles of only one ocular nerve or severe dysphagia dysarthria without extension of the myasthenic symptoms  should lead to further investigation to exclude other reasons of a focal myasthenic syndrome such as a brain stem tumour  
class10	fluctuations of interictal brain imaging in repeated 123i imp spect scans in an epileptic patient  single photon emission computed tomography  spect  brain scans with n isopropyl  iodine 123  p iodoamphetamine  123i imp  were performed three times in interictal periods in a 35 year old man with intractable frontal lobe epilepsy and normal x ray ct findings  the first scan showed decreased 123i imp uptake in the right frontal lobe  this abnormal image was regarded as the primary focus of his epilepsy on the basis of its regional agreement with focal epileptic discharges on eegs  in the second scan  he showed normal imaging  while the third scan showed the same abnormal image as before  in the right frontal lobe  the frequency of his clinical seizures was almost unchanged during the intervals between scans and further eegs recorded soon after each scan showed almost no changes in the basic activities and frequency of the epileptic discharges  such fluctuations in spect brain imaging suggest that the severity of functional inactivation underlying the focal hypoperfusion image as an epileptic focus may fluctuate considerably in the interictal state with no relation to the clinical features of epilepsy  
class10	primary intracerebral sarcoma in childhood  case report with electron microscope study  a case of a primary intracerebral sarcoma is described in a 5 year old girl  histology and immunohistochemistry excluded the diagnosis of a leiomyosarcoma  a malignant haemangiopericytoma or a fibrosarcoma  electron microscopical findings indicated that the origin of the sarcoma was in the pia mater  
class10	aberrant regeneration in a case of syringobulbia  selective co activation of abducens and facial nerves during saccades  a patient suffering from syringobulbia and syringomyelia exhibited a phasic contraction of the ipsilateral facial muscles  mainly the levator labii  whenever he looked to the left or right  facial muscle twitches occurred exclusively with saccades  the selective co activation of abducens and facial nerves is interpreted as the result of bilateral misrouting of regenerating neurons from the parapontine reticular formation to the facial nerve in the tegmentum pontis  
class10	familial eating epilepsy  eating related seizures affecting 20 individuals among 59 siblings belonging to nine families are presented  the type of epilepsy was partial in all the affected individuals  and the seizures complex in 15 and simple in 5  secondarily generalized in the majority  the onset of epilepsy  in most cases  was in the second decade of life  a remarkable degree of intra family consistency was observed with regard to age at onset  symptomatology of seizures and timing of eating seizures  the study demonstrates sibling clustering in a partial epilepsy  implicating for the first time genetic susceptibility in the aetiology of eating epilepsy  
class10	transient ischaemic attacks and small vessel disease  dutch tia study group histories and computed tomograms of 606 patients with transient cerebral ischaemia were studied  all symptoms and signs had completely resolved within 24 hours  and any episodes suggestive of posterior fossa ischaemia were excluded  computed tomography  done after the clinical features had resolved  showed 79 relevant infarcts  46 were small  deep  lacunar infarcts  58   95  confidence interval  ci  47 69    and 33 were larger cortical infarcts  the histories and the type of infarct in these 79 patients were compared to see whether lacunar infarcts were preceded by a history of unilateral motor or sensory symptoms without features usually attributed to the cerebral cortex  the positive predictive value of such lacunar symptoms was 0 74  with a negative predictive value of 0 61  11 patients had a cortical infarct despite a history of lacunar tias  but only one occurred in the left hemisphere and speech was not affected  of 527 patients with transient ischaemic attacks without a relevant infarct visible on computed tomography  335  64   had a history suggestive of lacunar ischaemia  whereas in several other studies 20 25  of patients with ischaemic stroke have evidence of lacunar infarcts  lacunar tias may therefore have a better prognosis than cortical tias or may often precede cortical infarcts  alternatively  many cortical infarcts may occur without warning  
class10	the role of conditioning and verbal expectancy in the placebo response  both conditioning and expectancy models have been offered in recent years as explanations for the placebo response  following our earlier work on conditioning placebo responses in human subjects the current study examined the relative contribution made by conditioning and verbal expectancy  group 1 received a combined expectancy and conditioning manipulation  group 2 received expectancy alone  group 3  conditioning alone  and group 4 was the control group  subjects  responses were compared with and without a placebo cream  using iontophoretic pain stimulation  the results suggest that conditioning was more powerful than verbal expectancy in creating a placebo response  
class10	the robustness of an empirically derived taxonomy of chronic pain patients  there is currently no classification system for chronic pain patients that has achieved consensus  the lack of a classification that is used consistently across settings has impaired advance of knowledge and treatment of chronic pain patients  recently  an empirically derived multivariate classification system  the multiaxial assessment of pain  map  patients  has been developed  in this paper  the generalizability of the map system was evaluated by contrasting the map classification of 3 common but diverse chronic pain syndromes  namely  low back pain  headache  and temporomandibular disorders  the results indicate that although the proportion of patients classified into the 3 subgroups of the map taxonomy differ  the profiles based on the pattern of interrelationship among the assessment scales were remarkably similar  these data suggest that the psychosocial and behavioral responses associated with chronic pain are common to diverse samples of pain patients despite differences in demographic characteristics and medical diagnosis  the implications of these results for research and clinical practice are discussed  the potential utility of a polydiagnostic approach using more traditional medically based classifications such as proposed by the iasp  merskey  h   pain  suppl  3  1986  s1 s225  complemented by classification based on the map psychosocial behaviorally based taxonomy are examined  
class10	litigation and employment status  effects on patients with chronic pain  in order to study the effects of compensation and litigation  201 chronic pain patients were selected from a sample of 444  99 were working  15 were working and litigating  53 were receiving worker s compensation  and 34 were receiving worker s compensation and litigating  employment  working vs  worker s compensation  and litigation status  litigating vs  not litigating  were analyzed in a 2 x 2 factorial design with measures of pain  disability  psychological distress  and selected demographics as dependent variables  compared to worker s compensation patients  working patients reported significantly less disability  down time  days spent in bed  interference of pain in daily activities  and pain of a longer duration  compared to litigating patients  non litigating patients reported less pain  on the mcgill pain questionnaire  and less disability  stopping activity  interference of pain in daily activities   on two measures of psychological distress  depression  anxiety   there were significant interactions  worker s compensation patients who were litigating reported less distress than non litigants  while working patients who were litigating reported more distress than non litigants  the results indicate clear differences in self reports of disability associated with both employment and litigation status  they also suggest that litigation may function as a coping response for patients who are distressed by the adversarial nature of the worker s compensation system  limitations of the study as well as suggestions for further research also are discussed  
class10	profiles of opioid analgesia in humans after intravenous bolus administration  alfentanil  fentanyl and morphine compared on experimental pain  this report examines the relationship of plasma drug concentration to analgesic effect following bolus doses of alfentanil  fentanyl and morphine and assesses individual differences in analgesic response among volunteers  we predicted that the 3 opioids would yield disparate analgesic profiles because their physicochemical and pharmacokinetic characteristics differ  ten healthy volunteers received intravenous bolus doses of either alfentanil  fentanyl  morphine or normal saline on different days  we stimulated their teeth electrically and measured brain evoked potential  ep  and pain report  pr  repeatedly over 2 h to assess analgesic effect  concurrently  we drew 18 blood samples to assess opioid plasma concentrations during the test period  the relationship between opioid plasma concentration and analgesic effect was well defined for alfentanil but ambiguous for morphine  fentanyl exhibited a marked hysteresis  we observed noteworthy individual differences in analgesic response with all 3 drugs but these differences were greatest for morphine and least for alfentanil  inter  and intrasubject variability in analgesic response across drugs is related to the physicochemical properties of the drugs tested  
class10	neglected factors in chronic pain treatment outcome studies  referral patterns  failure to enter treatment  and attrition  an increasing number of chronic pain treatment outcome studies have appeared in the literature  in general  these studies support the efficacy of multidisciplinary pain programs  as well as specific treatment modalities such as biofeedback and relaxation  reviews of this literature have tended to be cautiously optimistic  some concerns  however  have been raised about the methodological adequacy of these studies  particularly in terms of the lack of control groups  the brief duration of follow up periods  and the vague criteria used for establishing the success of the therapeutic interventions  other factors that mitigate conclusions regarding the generalizability of the favorable results reported need to be considered  in this paper 3 rarely discussed topics that are implicit within most treatment outcome studies and that need to be given greater attention are examined  these topics include   1  referral patterns to pain clinics  who are referred to pain clinics  when  and how representative is the referred sample     2  failure to enter treatment  e g   exclusion criteria  lack of available financial support to cover the cost of treatment  patient s refusal to accept recommendations   and consequently  the representativeness of the treated sample  and  3  patient s attrition  in this paper we discuss each of these factors as they underscore important qualifications that have to be made in evaluating treatment outcome studies  
class10	heart rate changes as an autonomic component of the pain response  autonomic variables have been recommended as measures of the affective motivational component of the pain response in objective algesimetry  in the present study components of heart rate responses to painful heat stimuli and their relation to stimulus and sensation variables were analyzed  twelve healthy subjects served  sixty phasic stimuli of varying temperatures above and below pain threshold were delivered through a marstock thermode in 1 session  heart rate  respiration  and subjective stimulus ratings were recorded simultaneously  phasic heat stimulation above and below pain threshold induced a tonic increase of the heart rate lasting up to more than 20 sec  high intensity stimulation generated steeper rises and greater mean increase than low intensity stimulation  in general  heart rate responses were more closely related to subjective sensation than to stimulus intensity  however  differential temporal analysis demonstrates that  until about 3 sec after stimulation  the autonomic response is determined solely by stimulus temperature  whereas  after approximately 6 sec  it is related only to subjective judgement  accordingly  the heart rate responses reflect both a brief nocifensive reflex induced by the sensory component and  subsequently  a longer lasting response which seems to be related to affective and or cognitive evaluation  this separation of different stages of pain processing by an autonomic indicator may be useful in clinical algesimetry  
class10	opiates suppress carrageenan induced edema and hyperthermia at doses that inhibit hyperalgesia  this study determined whether opiates alter vascular components of inflammation  hyperthermia  edema and plasma extravasation  in addition to the suppression of hyperalgesia  rats were administered carrageenan into one hind paw and saline into the other hind paw  followed by i p  injection of morphine  0 2 5 0 mg kg  or saline at 60 min  and testing at 90 min after hind paw injections  morphine produced a dose dependent reduction in carrageenan induced hyperalgesia  17 53    hyperthermia  39 53   and edema  24 36    morphine treatment did not alter the temperatures of the contralateral saline injected paws  indicating that opiate suppression of hyperthermia was not confounded by alterations in systemic body temperature or blood flow  the opiate effects on inflammation were stereospecific since levorphanol  1 mg kg   but not dextrorphan  1 mg kg   suppressed carrageenan evoked hyperalgesia  hyperthermia and edema  pre treatment with naltrexone  1 5 mg kg  blocked the effects of a 5 mg kg dose of morphine sulfate on hyperalgesia  hyperthermia and edema  in a separate study  i v  injection of morphine sulfate  2 mg kg  reduced plasma extravasation by 41   p less than 0 01   morphine administration resulted in significantly greater increases in paw withdrawal latencies in the inflamed  38 139   than the contralateral  saline treated paws  4 19    the results indicate that opiates exert a moderate  though significant  reduction in the vascular signs of inflammation in addition to their reduction of hyperalgesia  the mechanisms for this vascular effect involve inhibition of both vasodilation  as indicated by a decrease in hyperthermia  and inhibition of vascular permeability  in addition  opiates exhibit enhanced antinociceptive effects in inflamed paws  even when compared to uninjured paws in the same animal  
class10	effects of the calcium antagonist nilvadipine on focal cerebral ischemia in spontaneously hypertensive rats  we studied the efficacy of preischemic and postischemic systemic treatment with a new calcium antagonist nilvadipine in a permanent focal cerebral ischemia model of spontaneously hypertensive rats  rats that underwent microsurgical middle cerebral artery occlusion were blindly assigned to a single intraperitoneal injection of nilvadipine  0 32 mg kg  or the same amount of polyethylene glycol either 15 minutes before  immediately after  1 hour after  or 3 hours after occlusion of the left middle cerebral artery  neurologic conditions of rats were closely examined  and rats were killed 24 hours later  removed brains were sliced coronally  stained with triphenyltetrazolium chloride  and the size of infarct was determined  although no neurologic improvements were observed in the treated rats  the area of infarcts was significantly reduced in the groups treated before  immediately after  and 1 hour after occlusion of the middle cerebral artery  treatment started 3 hours after occlusion was ineffective  
class10	glossopharyngeal schwannoma  review of five cases and the literature  glossopharyngeal schwannomas are rare tumors in spite of the fact that acoustic schwannomas account for 8  10  of intracranial tumors  there have been 23 reported cases in the literature  this report of five cases is the largest series of these tumors  the presentation  radiological workup  operation  and long term postoperative results will be presented  along with a review of the literature  
class10	a single case of huntington s disease simultaneously occurring with obstructive hydrocephalus  a case of simultaneously occurring huntington s disease and obstructive hydrocephalus is presented  huntington s and other neurodegenerative diseases have been described with normal pressure hydrocephalus  however  no such description with obstructive hydrocephalus has been reported  the obstructive hydrocephalus displays a familial tendency in its presentation  
class10	embolism of cerebral tissue  a cause of coagulopathy and cerebral infarction  report of a case  we report a case of potentially survivable closed head injury  which was complicated by disseminated intravascular coagulation and bilateral cerebral infarction  autopsy disclosed pulmonary emboli composed of cerebral tissue  we suggest that the entry of brain tissue into the systemic blood circulation caused severe disseminated intravascular coagulation  with consequent thrombosis of cerebral veins and spreading infarction  
class10	the painful shoulder  part ii  intrinsic disorders and impingement syndrome  intrinsic disorders that can cause shoulder pain include arthritis  gout  pseudogout and osteonecrosis  in its mildest form  impingement syndrome may cause only minimal discomfort  at its worst  impingement syndrome may lead to rotator cuff tear  bicipital tendinitis and rupture of the biceps tendon may also be associated with impingement  early rehabilitative intervention is important  physical therapy is directed toward restoring range of motion and muscle strength  
class10	the effect of quinidine and mexiletine on the adaptation of ventricular refractoriness to an increase in rate  the purpose of this study was to determine the effects of quinidine and mexiletine on the adaptation of ventricular refractoriness to a change in heart rate  the ventricular effective refractory period was measured at a basic drive cycle length of 500 msec with basic drive train durations of two beats  eight beats  20 beats and 3 minutes  the ventricular refractory periods were measured in the baseline state and after oral treatment with quinidine or mexiletine in 20 subjects each  in the baseline state  there was progressive shortening of the ventricular refractory period as the drive train duration increased from two beats to 3 minutes  quinidine prolonged refractoriness by 5   p less than 0 001  at each drive train duration  mexiletine did not affect the ventricular effective refractory period at any of the drive train durations  in a control group of 20 subjects  there were no significant differences between two determinations of refractoriness at each basic drive train duration  in conclusion  neither quinidine nor mexiletine affect the adaptation of ventricular refractoriness to an increase in rate  although the ventricular effective refractory period measured with a conventional basic drive train duration of eight beats is often more than 20 msec longer than the actual ventricular effective refractory period measured with a drive train duration of 3 minutes  the effects of quinidine and mexiletine on the conventionally measured ventricular effective refractory period accurately reflect the effects of these drugs on the actual ventricular effective refractory period  
class10	why are autism and the fragile x syndrome associated  conceptual and methodological issues  investigations of the association between autism and the fragile x syndrome have yielded conflicting results with some studies indicating a strong correlation and others indicating no relation between the disorders  in this paper  we review the relevant research on this controversy and discuss the conceptual and methodological problems involved in such an inquiry  we conclude that autism and fragile x are associated and that this relation will prove fruitful in understanding the role of the x chromosome in a variety of behavior disorders and in unraveling various theoretical accounts on the etiology of autism  
class10	progress in the search for genetic linkage with tourette syndrome  an exclusion map covering more than 50  of the autosomal genome  gilles de la tourette syndrome is a neuropsychiatric disorder with an autosomal dominant mode of inheritance and reduced penetrance at a single genetic locus  several research groups have genetic linkage studies underway to detect the chromosomal location of the gene that predisposes for this disorder  strong and clear evidence of linkage has not yet been produced for tourette syndrome  this paper presents an overview of the methods and progress of the groups centered at yale university and erasmus university in excluding linkage from a large portion of the genome  our labs have screened 228 genetic marker loci for linkage with a gene for this disorder in a series of affected families in the united states  canada  the netherlands  and norway  more than 50   and perhaps as much as 66   of the autosomal genome has now been excluded on the assumption that genetic heterogeneity is not an important factor in the tourette syndrome pedigrees pooled for this summary  
class10	x linked sideroblastic anemia and ataxia  linkage to phosphoglycerate kinase at xq13  molecular linkage analysis was performed on a kindred with x linked sideroblastic anemia and ataxia  two point analysis with a dna probe for phosphoglycerate kinase  pgk1   which maps to xq13  suggested linkage to the disorder by a lod score of at least 2 60 at a recombination fraction of zero  the disease in this kindred appears to be clinically and genetically distinct from that in previously reported families with x linked hereditary ataxia or spastic paraparesis  no mapping data are available for inherited x linked sideroblastic anemia without neurologic abnormalities  however  structural alterations of band xq13 may be involved in the development of idiopathic acquired sideroblastic anemia  no alterations in the restriction patterns of two x linked genes involved in erythrocyte formation i e   a dna binding protein  gf 1  and 5 aminolevulinate synthase  alas  were detected in dna from affected males  arguing against a large deletion in either of these candidate genes  
class10	molecular genetic basis of maple syrup urine disease in a family with two defective alleles for branched chain acyltransferase and localization of the gene to human chromosome 1  maple syrup urine disease in humans results from inherited defects in branched chain alpha ketoacid dehydrogenase  a mitochondrial multienzyme complex  a variety of genetic changes may produce this phenotype by affecting the function of any of the three complex specific subunits  the varied clinical expression observed in patients may be partially explained by the defects in the involved subunit  here we report localization of the gene for the branched chain acyltransferase component of the complex to human chromosome 1 and describe a proband who is a compound heterozygote at this locus  one allele  inherited from the father  produces transcripts with 124 nucleotides deleted from the coding region  the deletion is not found in the branched chain acyltransferase gene  implying that the deleted transcripts arise by an error in transcript processing  cells from the patient s mother contain 50  of the normal amount of mrna for the subunit  and the proband has inherited this nonexpressing allele from her  as a result  the proband produces no acyltransferase protein and therefore has greatly impaired complex activity  a phenotypically normal sibling is shown to be genetically similar to the mother having inherited the mother s nonexpressing allele and the father s normal allele  
class10	tay sachs disease in moroccan jews  deletion of a phenylalanine in the alpha subunit of beta hexosaminidase  tay sachs disease is an inherited lysosomal storage disorder caused by defects in the beta hexosaminidase alpha subunit gene  the carrier frequency for tay sachs disease is significantly elevated in both the ashkenazi jewish and moroccan jewish populations but not in other jewish groups  we have found that the mutations underlying tay sachs disease in ashkenazi and moroccan jews are different  analysis of a moroccan jewish tay sachs patient had revealed an in frame deletion  delta f  of one of the two adjacent phenylalanine codons that are present at positions 304 and 305 in the alpha subunit sequence  the mutation impairs the subunit assembly of beta hexosaminidase a  resulting in an absence of enzyme activity  the moroccan patient was found also to carry  in the other alpha subunit allele  a different  and as yet unidentified  mutation which causes a deficit of mrna  analysis of obligate carriers from six unrelated moroccan jewish families showed that three harbor the delta f mutation  raising the possibility that this defect may be a prevalent mutation in this ethnic group  
class10	validation of a surveillance case definition of carpal tunnel syndrome the national institute for occupational safety and health  niosh  has proposed a surveillance case definition for work related carpal tunnel syndrome  cts   the case definition requires the presence of median nerve symptoms  one or more occupational risk factors  and objective evidence of cts including one of three physical examination findings or nerve conduction tests diagnostic of cts  we evaluated the performance of the niosh case definition  restricting our analysis to cases in which physical examination findings served as the objective criterion  nerve conduction studies were used as the gold standard  seventy eight workers were studied  38 percent had cts  the niosh case definition had sensitivity of 0 67  95  ci   0 57  0 77   specificity of 0 58  95  ci   0 47  0 69   and positive and negative predictive values of 0 50  95  ci   0 39  0 61  and 0 74  95  ci   0 64  0 84   respectively  overall 38 percent of subjects were classified incorrectly  in a sample with a prevalence of 15 percent  as might be encountered in high risk workplaces  the positive predictive value would be 0 22  in conclusion  when physical examination findings serve as the objective criterion the performance of the case definition is modest reflecting the limited diagnostic value of its component tests and indicating that effective screening for cts awaits improved diagnostic techniques  
class10	propofol infusion for control of status epilepticus  two patients with status epilepticus who were resistant to conventional treatment but responded to propofol infusions are reported  an electroencephalogram confirmed the seizures and their successful treatment  
class10	32 gauge spinal catheters through 26 gauge needles small diameter intrathecal catheters potentially combine the certainty of intrathecal injection and the advantage of repeatability  without the risk of a high incidence of headache after dural puncture  we report problems placing such catheters  
class10	paraesthesia with lumbar epidural catheters  a comparison of air and saline in a loss of resistance technique  the epidural space was located in 32 obstetric patients using loss of resistance to air  while in a further 35 saline was used  the incidence of paraesthesia was 56  in the air group and 57  in the saline group  there was no significant difference between the groups in terms of other complications or in the quality of analgesia provided  
class10	eosinophilic fasciitis associated with tryptophan ingestion  a manifestation of eosinophilia myalgia syndrome  recently  the ingestion of tryptophan has been associated with eosinophilia myalgia syndrome  which is characterized by eosinophilia  myalgias  and several less consistently reported findings  we treated 13 patients who exhibited clinical features of eosinophilic fasciitis who were taking high dose tryptophan before the onset of clinical symptoms  twelve patients exhibited eosinophilia  with eosinophil counts ranging from 0 13 to 0 88  the remaining patient was taking oral corticosteroids when her eosinophil count was determined  eight patients complained of myalgias  other symptoms included arthralgias  pruritus  cutaneous burning  weakness  fever  rashes  malaise  edema  muscle spasms  and alopecia  5 hydroxyindoleacetic acid levels were elevated in four of the eight urine specimens that were tested  our findings suggest that previously diagnosed cases of eosinophilic fasciitis may represent variants of tryptophan associated eosinophilia myalgia syndrome  derangements in the metabolism of tryptophan may play a role in sclerotic diseases  
class10	supported employment  an alternative model for vocational rehabilitation of persons with severe neurologic  psychiatric  or physical disability  participation in paid work in competitive industry through placement in supported employment is compared and analyzed for 278 severely disabled persons  differential outcomes are described for persons with chronic mental illness  cerebral palsy  traumatic brain injury  and dual diagnosis of chronic mental illness and mental retardation  results indicated that supported employment appears to be an effective means of assisting these historically unemployable individuals to acquire and retain work  cross disability group differences were found in areas such as hourly wages  type of employment  services provided by employment specialists  and job retention  the results represent a baseline from which to evaluate future efforts at competitive work placement for persons with severe disabilities  using the supported employment model  
class10	telephone use to elicit voice or speech in brain injured subjects  the initiation of speech is often delayed in the early stages of recovery from a serious brain injury  we have found a high percentage of patients with both speech and swallowing problems  this makes bedside assessment of swallowing safety difficult because one cannot listen for the sound of aspirated material on the vocal cords when a patient is at high risk for silent aspiration and is often unable to cooperate with a videofluoroscopic study  the use of the telephone has been described several times for aphasia treatment  but not to elicit speech or assess swallowing safety early after brain injury  this study  therefore  recruited subjects who had brain injuries and  1  were referred early for swallowing and other evaluations   2  were out of coma and able to follow some commands  and  3  did not initiate voice or speak when asked to  subjects were asked three questions under two different conditions  face to face and after ringing the telephone from another room  the results were recorded on videotape and analyzed by another investigator for quantifiable differences  six of the seven subjects responded better with the telephone stimulus than without  this technique may elicit voice or speech early after brain injury in some patients and may be useful in bedside assessment of swallowing safety  it may also serve as an example of appropriate stimulation of brain injured subjects coming out of coma  
class10	the disabled driver  an unmet challenge  a survey was undertaken to determine if driving impairment secondary to a disabling injury is addressed in state licensing laws and training programs  in 35 states drivers submit voluntarily to reevaluation after disabling injuries  but no provision is made for reporting such individuals  only 15 states authorize physicians to report impaired drivers  and only seven require such reporting  based on a survey of licensing bureaus in the capital or a major city of every state  clerks  who are likely to be the source of information to injured persons  are generally not aware of reporting requirements and supervisors are only slightly better informed  of the 100 rehabilitation centers surveyed  only 36 provided on site training for disabled drivers  voluntary submission for reevaluation after head injury does not often occur  despite being asked to do so  none of the 35 head injured patients  followed up to two years post onset  sought reevaluation  although 21 had resumed regular driving  two of the 21 were involved in subsequent traffic accidents  common guidelines need to be established across states to ensure reevaluation of individuals with disabling conditions  delivery of accurate information concerning licensing  and availability of training programs  
class10	psychosocial  functional  and quality of life assessment of patients with posttraumatic fracture nonunion  chronic refractory osteomyelitis  and lower extremity amputation  one hundred nine patients with long bone fracture nonunion  chronic refractory osteomyelitis  or posttraumatic amputation were evaluated for the impact of chronic disability on quality of life  as measured by the arthritis impact measurement scale  aims  and the psychosocial adjustment to illness scale  pais   a self administered pais for spouses assessed psychosocial adjustment of spouses or significant others  a final questionnaire ranked the reasons for either continuing medical therapy or accepting amputation  the pais scores differed significantly between osteomyelitis patients and both nonunion and amputation patients  p less than  05   the presence or absence of pain produced significant differences in aims and pais scores of nonunion and osteomyelitis patients  p less than  05   subscale analysis of aims scores revealed significant differences among the three groups in health perception and scale of orthopedic problem  osteomyelitis patients were more severely affected than nonunion or amputation patients  the pais detected no statistically significant difference in psychosocial adjustment of spouses of patients in the three population groups  the most common reason for continuing medical and surgical management of nonunion and osteomyelitis was expectation for cure  the amputee group chose ablation to avoid further treatment  differences in psychosocial and functional ability were related to disease diagnosis  pain  status of fracture healing  and timing of amputation  
class10	costs of operating a supported work program for traumatically brain injured individuals  this paper presents a preliminary analysis of costs associated with a return to work program emphasizing a supported employment approach for persons who had sustained severe traumatic brain injuries  this analysis spans almost three years  results indicated that a mean of 237 8 hours of staff intervention time was required to achieve job stabilization  at a cost of  6896  ongoing follow along and support services averaged 1 64 hours per week at a cost of  47 56  over 68  of total staff time and costs were expended in job site training and advocacy efforts  application of these findings to state level and agency level policies should be weighed against individual characteristics and needs of clients  program design  and outcomes which clients achieve as a result of services  
class10	reversible nerve conduction block in patients with polyneuropathy after ultrasound thermotherapy at therapeutic dosage  this study investigated the effect of ultrasound on nerve conduction in patients with polyneuropathy  eight able bodied controls  group c  and 16 patients with clinical and physiologic evidence of polyneuropathy were tested  eight patients  group np  had no aching pain symptoms  eight patients  group p  had severe aching pain  burning sensation  unpleasant tingling  and or hyperesthesia in the lower extremities  for two minutes  therapeutic ultrasound in doses of 0 5  1 0  and 1 5w cm2 were applied over the anterior surface of the leg along the pathway of the deep peroneal nerve  peroneal nerve conduction studies were performed before  during  and after ultrasound treatment  the compound muscle action potential  cmap  was recorded from the extensor digitorum brevis muscle  nerve conduction studies on all eight patients in group p revealed a significant decrease  41 4  and 44  reduced for doses of 1 0w cm2 and 1 5w cm2  respectively  p less than  05  in amplitude of cmap  from baseline to the first negative peak   and an increase  6 4  and 6 7  increased for doses of 1 0w cm2 and 1 5w cm2  respectively  p less than  05  in proximal latency one minute after ultrasound application with a dose of 1 0 or 1 5w cm2  but not with a dose of 0 5w cm2  p greater than 0 1   changes returned to pretreatment values within five minutes of cessation of ultrasound therapy  in groups c and np  there were no significant changes in amplitudes of cmap or proximal latency before  during  or after ultrasound therapy at a dose of 0 5  1 0  or 1 5w cm2  it was concluded that ultrasonic therapy with therapeutic dosage may cause a reversible conduction block on patients with painful polyneuropathy  
class10	goal attainment scaling and outcome measurement in postacute brain injury rehabilitation  relationships among two month and final goal attainment scaling  gas  scores  preadmission and final portland adaptability inventory  pai  scores  and work outcome for 16 graduates of a comprehensive  postacute brain injury rehabilitation program were examined  final gas scores were higher for program graduates who obtained the most desirable work outcomes  and preadmission and final pai scores were lower for the successful program graduates  final gas scores were significantly correlated with other outcome measures  preadmission pai scores predicted work outcome  and two month gas scores predicted final gas scores  initial pai scores distinguished between program successes and failures  but not between program successes and dropouts  a brief look at one case illustrates the modified application of gas in postacute brain injury rehabilitation  results of this study and case analyses support gas as a quantifiable  individualized measure that is useful for  1  monitoring patient progress   2  structuring team conferences   3  ongoing rehabilitation planning and decision making   4  concise  relevant communication to family  referral sources  and funding sources  and  5  overall program evaluation when used in the context of other objective outcome measures  although our results support the clinical utility of gas  further study is recommended to assess the psychometric characteristics of gas in this application  
class10	factors predicting satisfactory home care after stroke  this study prospectively investigated factors predicting optimal poststroke home care  one hundred and thirty five first occurrence stroke patients and their primary support persons were evaluated during the initial hospitalization after stroke and again one year poststroke  discriminant function analysis was used to identify two groups from the baseline data  home care situations which were rated optimal and those which were not  group membership was predicted and validated with 72 6  accuracy  patients at risk for less than optimal home care had caregivers who were  1  more likely to be depressed   2  less likely to be married to the patient   3  below average in knowledge about stroke care  and  4  reporting more family dysfunction  our findings suggest that caregiver related problems can have a collective effect on rehabilitation outcome and that treatment should reduce caregiver depression  minimize family dysfunction  and increase the family s knowledge about stroke care  
class10	visual illusions in a patient with lateral medullary syndrome  the disturbance of visual perception associated with nystagmus is a rare phenomenon  this is a case of a 61 year old woman who developed progressive right hemisensory deficit  left facial sensory deficit  vertigo  staggering to the left  left ptosis  vertical diplopia  and ataxia of the left upper extremity  she had rotatory nystagmus in primary position  which increased in amplitude with left gaze  the above signs and symptoms were consistent with lateral medullary syndrome  during her rehabilitation  the patient complained of visual disturbances typical of oscillopsia  these disturbances  or illusions  are compensatory mechanisms for nystagmus and its resultant retinal error  the purpose of this case presentation was to study the pathophysiology underlying oscillopsia in patients with nystagmus and to stimulate awareness of such visual disturbances in stroke patients  
class10	a videofluoroscopy chair for the evaluation of dysphagia in patients with severe neuromotor disease  due to the difficulties encountered in positioning severely neurologically impaired individuals for videofluoroscopic studies  the rehab tech video fluorochair was developed  the purpose of the chair is to provide the severely disabled patient with safe  stable postural support in an upright position for videofluoroscopic studies  with anterior posterior  lateral  and rotational views easily performed  the chair features a removable headrest  a full back support  armrests  lateral truncal supports  and a patented base which is clamped to the footboard of the radiology table and allows for 200 degrees rotation of the patient  two case studies illustrate the practical use and versatility of the rehab tech video fluorochair  
class10	cotton wool spots and retinal light sensitivity in diabetic retinopathy  in 14 eyes of 14 patients with diabetic retinopathy the light sensitivity of retinal cotton wool spots was studied by computerised perimetry  and the visual field data were accurately correlated with the corresponding morphology as seen on fundus photographs and fluorescein angiograms  in 12 of the eyes the examinations were repeated within one year in order to follow changes in retinal light sensitivity during the evolution of the lesions  retinal cotton wool spots were in all eyes associated with localised non arcuate scotomata in the visual field  in four eyes the cotton wool spots disappeared within three months of the first examination  and in two of these cases the corresponding scotomata disappeared together with the morphological lesions  in eight eyes the cotton wool spots  and the corresponding scotomata  had not resolved one year after the first examination  the mean blood pressure showed no significant difference between the patients in whom the lesions resolved within three months and the patients in whom the lesions persisted longer  
class10	traumatic retinal detachment  seventy seven patients developed retinal breaks following an episode of ocular contusion  and 65  84 4   of these developed rhegmatogenous retinal detachment  surgical treatment successfully restored or maintained retinal apposition in 74  96 1   of the eyes  thirty six  46 8   eyes recovered visual acuity of 6 9 or better  of the retinal breaks recognised dialysis at the ora serrata was observed in 49 eyes  of which 28 were situated at the lower temporal quadrant  seventeen eyes had irregular breaks arising within necrotic retina at the site of scleral impact  twenty four  31 2   patients had retinal break or retinal detachment diagnosed within 24 hours of injury and 49  63 6   within six weeks  immediate retinal detachment was a feature of necrotic retinal breaks  while inferior oral dialyses led to a slow accumulation of subretinal fluid  delayed diagnosis of retinal detachment was due either to opaque media or to failure to examine the retina after injury  visual prognosis was good when retinal break or detachment were diagnosed within six weeks of injury  however  those patients who escaped initial retinal examination and were lost to follow up had a less favourable visual outcome  
class10	anisocoria in unilateral ophthalmic disease  pupillary diameters in the affected and unaffected eyes of 327 patients with uniocular red eye were assessed during fixation of a distant target  the mean pupillary diameters were similar in the unaffected eyes in each of eight diagnostic groups  but were significantly different  f   3 84  p less than 0 001  in the diseased eyes  with corneal abrasions  p less than 0 001   marginal keratitis  p less than 0 05   and acute anterior uveitis  p less than 0 001  the mean pupillary diameter for the affected eye was significantly smaller than that of the unaffected eye  the observed differences of pupillary diameter probably reflect the role of neuronal and autocoid mechanisms in the unilateral control of pupillary size  
class10	long term efficacy of primary laser trabeculoplasty  sixty glaucomatous eyes of 60 patients treated with laser trabeculoplasty as primary therapy were reviewed retrospectively  there were 42 eyes with capsular glaucoma and 18 with simple glaucoma  the mean prelaser intraocular pressure  iop  was 35 2  sd   6 5  mmhg  success was defined as iop less than or equal to 22 mmhg without medication  the probability of success was 0 73 at 1 year  0 66 at 2 years  0 57 at 3 years  and 0 50 at 4 years  three eyes experienced progressive visual field loss or disc damage in spite of an intraocular pressure below 22 mmhg without medication  high prelaser pressure and the severity of the visual field defects were significant predictors of treatment failure  
class10	electrophysiology and colour perimetry in dominant infantile optic atrophy  a typical finding in dominant infantile optic atrophy  dioa  is the variation of the phenotypic expression of the dioa gene even within one family  it is of special interest for genetic consultation to evaluate an examination method for detecting subclinically involved patients  seven patients of two families were examined  three of them had the typical symptoms of dioa  reduced visual acuity  tritan defect  temporal pallor of both optic discs  and a relative central scotoma for white test spots  in visual evoked cortical potentials  vecp  the amplitudes were reduced  and in one patient the latencies were slightly delayed and two patients considerably so  the amplitude of the negative component of the perg was markedly reduced  while the positive component was normal  in the remaining four family members normal retinal and cortical responses were recorded under standard conditions and visual fields and colour vision  fm 100 hue  were also normal  however  static perimetry with blue test spots showed in two family members enlarged central scotomas  thus proving that they had subclinical dioa  
class10	local injection treatment of tennis elbow  hydrocortisone  triamcinolone and lignocaine compared  corticosteroid injections are the mainstay of treating tennis elbow even though their effectiveness has not been well established by controlled studies  a survey of consultant rheumatologists confirmed a widespread preference for this treatment but they varied in their choice of steroid dose and preparation  we examined the value of some practices by comparing local injections of 2 ml 1  lignocaine with either 10 mg triamcinolone or 25 mg hydrocortisone made up to 2 ml with 1  lignocaine  study 1   the investigation was conducted double blind  within the first 8 weeks  pain relief was greater for triamcinolone than hydrocortisone although the differences were not statistically significant  the response to both steroid preparations was significantly better than for lignocaine up to this point but at 24 weeks  the degrees of improvement were similar for all three groups and many patients still had pain  relapse was common  in a separate but similarly designed study  triamcinolone 10 mg was compared with 20 mg of the same agent  improvements of pain were similar and followed the same time scale  post injection worsening of pain occurred in approximately half of all steroid treated patients in both studies and this was sometimes severe and persistent  it was less frequent amongst those given lignocaine alone  skin atrophy was reported in all groups but was more frequent amongst those given triamcinolone in study 1  in conclusion  more rapid relief of symptoms was achieved with 10 mg triamcinolone than with 25 mg hydrocortisone or lignocaine alone and there was less needed to repeat injections  results obtained with 20 mg triamcinolone were similar to those of the smaller dose  
class10	higher incidence of carpal tunnel syndrome in oophorectomized women  to determine whether the hormonal changes of the menopause are related to the onset of carpal tunnel syndrome  cts   53 healthy women  younger than 44 years  and subjected to bilateral oophorectomy between 1 and 4 years before the study  were evaluated  seventy healthy menstruating women matched for age were used as controls  in those complaining of symptoms and presenting signs suggestive of cts  sensory and motor nerve conduction studies were done  in the oophorectomized group  17 of 53  32   had clinical cts  while only seven of 70 of the control group  10   did so  relative risk for the oophorectomized group   4 25  95  confidence intervals 1 47 and 12 61   the nerve conduction studies were abnormal in 14 of 16 oophorectomized women  87 5    and in only one of seven of the control group  14 2   p less than 0 002   symptoms tended to be milder in the controls  symptoms developed in the first year after oophorectomy in 14 of the 17 women with cts  this suggests that women develop cts after oophorectomy more frequently than controls  
class10	malignant glandular triton tumor  a case of left brachial plexus related malignant peripheral nerve sheath tumor showing neoplastic  glandular  and rhabdomyoblastic elements in a 39 year old chinese man is reported  the authors suggested that this tumor be termed a malignant glandular triton tumor in view of the presence of the adenocarcinomatous component  the patient had extensive local recurrence comprising mainly the schwann spindle cells within a year after complete piecemeal removal and died 15 months later after the initial presentation  the natural behavior of this tumor  as in other reported cases of malignant triton tumor  is extremely aggressive  unlike malignant schwannoma or glandular malignant schwannoma  the histogenesis of this tumor is likely to be from primitive neural crest cells  schwann s cell precursors  or metaplastic malignant schwann s cells  
class10	differentiation in embryonal neuroepithelial tumors of the central nervous system  ninety six embryonal neuroectodermal tumors were studied histologically and immunohistologically with a panel of antibodies including glial  neuronal  epithelial  mesodermal  and myelin markers  in 71 tumors there was glial and neuronal differentiation and expression both of an s  photoreceptor  antigen and vimentin  in five tumors there was only glial differentiation and in 20 tumors only neuronal differentiation  no reactivity for myelin and epithelial markers was found  histologic and immunohistologic findings identified various degrees of differentiation in different tumors  which was bipolar  glial and neuronal  in most tumors and unipolar in the remainder  the authors suggest that their findings may be the result of normal or aberrant oncogenic differentiation  agreeing with the nomenclature of the world health organization classification for these tumors with and the inclusion of a category for ependymoblastoma  
class10	effects of local reduction in pressure on distensibility and composition of cerebral arterioles  this study examined effects of local reductions in mean and pulse pressures on cerebral arterioles in normotensive wistar kyoto rats  wky  and stroke prone spontaneously hypertensive rats  shrsp   wky and shrsp underwent clipping of one carotid artery at 1 month of age  at 10 12 months of age  mechanics of pial arterioles were examined in vivo in anesthetized rats  bilateral craniotomies were performed to expose pial arterioles in the sham and clipped cerebral hemispheres  stress strain relations were calculated from measurements of pial arteriolar pressure  servo null   diameter  and cross sectional area of the arteriolar wall  point counting stereology was used to quantitate individual components in the arteriolar wall  before deactivation of smooth muscle with edta  mean  pm  and pulse  pp  pressures were significantly less  p less than 0 05  in clipped than in sham arterioles in wky  pm  63     2 versus 73     2 mm hg  pp  23     3 versus 30     3 mm hg  and shrsp  pm  94     4 versus 110     4 mm hg  pp  27     2 versus 38     3 mm hg   cross sectional area of the arteriolar wall was less  p less than 0 05  in clipped than in sham arterioles in both groups of rats  1 403     125 versus 1 683     125 microns2 in wky  1 436     72 versus 1 926     134 microns2 in shrsp   there was a correlation between cross sectional area of the vessel wall and pulse pressure  r2   0 66   but not mean pressure  r2   0 09   during maximal dilatation with edta  the stress strain curve was shifted to the left in clipped arterioles of shrsp  but not of wky  which indicates that carotid clipping in shrsp reduces passive distensibility of cerebral arterioles  the proportion of distensible components in the vessel wall  smooth muscle  elastin  and endothelium  was reduced in clipped arterioles in shrsp  but not in wky  these findings suggest that 1  vascular hypertrophy of cerebral arterioles is related more closely to pulse pressure than to mean pressure  and 2  reduction of pial arteriolar pressure completely prevents cerebral vascular hypertrophy and attenuates increases in passive distensibility of cerebral arterioles in shrsp  
class10	optimum results of the surgical treatment of carotid territory ischemia  continuing controversy over the role of carotid endarterectomy in stroke prevention is based largely on reports in which high perioperative morbidity and mortality rates obviate possible long term benefit from the procedure  the purpose of this review is to examine optimal results of carotid surgery in order to describe the potential for the procedure in stroke prevention  optimal surgical results are compared with optimal medical results in the therapy of symptomatic patients and with optimal nonsurgical results in the therapy of asymptomatic patients  factors common to series with excellent results  such as patient selection and operative technique  are examined  and problems such as recurrent carotid stenosis and coexisting coronary disease  which continue to plague even the best surgical series  are discussed  
class10	advances in the treatment of complex cerebrovascular disorders by interventional neurovascular techniques  treatment of complex cerebrovascular disorders  including intracranial aneurysms  carotid cavernous sinus fistulas  vertebral fistulas  arteriovenous malformations  atherosclerosis of brachiocephalic vessels  and arterial vasospasm  is being performed in selected cases by interventional neurovascular techniques  recent advances in microballoon technology  permanent solidifying polymers  newer embolic agents  high resolution digital subtraction angiography with road mapping technique  and steerable micro guide wires and catheters have greatly improved access in the distal intracranial circulation and markedly reduced the morbidity associated with these procedures  interventional neuroradiology is emerging as an important adjunct to neurosurgery for selected cerebrovascular disorders  
class10	limits of brain tolerance to daily increments in serum sodium in chronically hyponatraemic rats treated with hypertonic saline or urea  advantages of urea  1  at present there is no consensus about the optimal management of hyponatraemia to prevent demyelinating brain lesions  we have evaluated in a large series of rats  n   136  the protective role of urea for the brain in the treatment of severe chronic hyponatraemia  urea  group i  n   51  was compared with hypertonic saline in boluses  group ii  n   46  and with hypertonic saline in divided doses  group iii  n   39   treatment was administered intraperitoneally over 48 h  the severity of brain lesions was assessed by histological scoring  2  for 95  of the injured animals treated with hypertonic saline  brain lesions appeared for an absolute increment in serum na  concentration  delta sna   of 20 mmol day 1 l 1  above this limit neurological injuries gradually worsened  and beyond a transition zone  delta sna  greater than or equal to 20 less than or equal to 23 mmol day 1 l 1  89   group iii  to 100   group ii  of the animals were injured  this limit can be reached rapidly  as attested by the comparable severity of brain lesions observed in group ii  mean delta sna  1 h after a bolus injection  19 mmol l  and in group iii  mean delta sna  1 h after an injection  2 mmol l   both groups achieving similar daily delta sna   3  a correction above the threshold of 20 mmol day 1 l 1 is as toxic during the first 24 h as during the second day of the treatment  
class10	role of diabetologist in evaluating diabetic retinopathy  objective  to evaluate the ability of diabetologists to screen diabetic patients for diabetic retinopathy  research design and methods  comparison of eye examination performed by diabetologists with direct ophthalmoscopy through an undilated pupil and by ophthalmologists through a dilated pupil with seven field stereoscopic fundus photography  gold standard   the study consisted of 67 insulin dependent and non insulin dependent diabetic outpatients attending a diabetes clinic  results  on the basis of fundus photography  patients were classified as having no or insignificant  30    minimal  31    moderate  24    or severe  15   retinopathy  the diabetologists and ophthalmologists performed similarly in their ability to classify severity of diabetic retinopathy accurately  when no or insignificant retinopathy  isolated microaneurysms only  was detected by examination  clinically significant retinopathy detected by fundus photography was highly unlikely  less than 5    on the other hand  if more than isolated microaneurysms were seen on examination  all examiners missed more severe lesions detected by fundus photography  patients with corrected visual acuity worse than 20 30 had a high likelihood  100   of moderate or severe retinopathy  conclusions  motivated well trained diabetologists can screen for diabetic retinopathy  the absence of detectable lesions by direct ophthalmoscopy indicates that automatic referral to an ophthalmologist is not necessary  however  if any level of retinopathy is detected or corrected acuity is worse than 20 30  referral to an ophthalmologist is required  in this setting  fundus photography is advised because it is the most sensitive means of detecting clinically significant retinopathy  if other nonophthalmologists can be trained to achieve similar results  current recommendations for ophthalmologic referral that require annual ophthalmologic examinations for most diabetic patients may need to be reconsidered  
class10	learning disabilities in epilepsy  neurophysiological aspects  subclinical generalized spike wave discharges are often accompanied by transitory cognitive impairment  demonstrable by psychological testing during eeg recording  transitory cognitive impairment is demonstrated most readily by difficult tasks and during generalized regular spike wave bursts lasting for more than 3 s  but can also be found during briefer and even focal discharges  that this is not simply a consequence of global inattention is shown by the fact that focal discharges exhibit some specificity  left sided focal spiking is more likely to produce errors on verbal tasks  for instance  whereas right sided discharges are more often accompanied by impairment in handling nonverbal material  both learning difficulties in general and specific abnormal patterns of cognitive functioning are well documented in children with epilepsy and are most pronounced in those with frequent interictal discharges  however  there is now evidence that intermittent cognitive impairment due to the discharges themselves contributes significantly to such neurophysiological abnormalities  the significance of transitory cognitive impairment accompanying subclinical eeg discharges for everyday functioning is uncertain  but there is experimental evidence that subclinical discharges may be accompanied by disruption of educational skills in children or by impairment of driving performance in motorists  in some individuals  suppression of discharges by antiepileptic drugs has demonstrably improved psychological function  but further work is required to determine the indications for such treatment  
class10	education and epilepsy  assessment and remediation  learning difficulties in children with epilepsy may be caused by brain damage and should be investigated  in many cases  however  seizures and or electroencephalographic  eeg  findings are the only signs of pathology  frequency and type of seizures may be determining factors that should  if necessary  be evaluated by long term eeg monitoring  preferably during school performance or in conjunction with neuropsychological assessment  this may prove that subclinical epileptiform discharges in the eeg can adversely affect the child s performance  secondary psychological problems in epilepsy patients  combined with side effects of antiepileptic drugs  may cause or heighten learning problems  prophylactic control of seizures with one appropriate drug may alleviate learning problems  computerized neuropsychological testing with simultaneous eeg recording may reveal the influence of epileptiform discharges on cognitive function and also help to evaluate the effects of antiepileptic drugs  objective assessment of subclinical epileptiform activity makes it easier to treat the pathology identified by the eeg with optimal dosage of the most appropriate drug  a balance is required because epileptiform discharges and even occasional seizures may be less disabling than side effects from large doses of several drugs  information to the school and the parents concerning the patient s abilities and limitations may be as important as seizure control  specialized teaching should be started early  when necessary  with the patient integrated into a normal school if possible  however  good functioning in a special school is preferable to marginal functioning in a normal school  
class10	antiepileptic drugs  cognitive function  and behavior in children  evidence from recent studies  the effects of antiepileptic drugs  aeds  on cognitive function and behavior in children are reviewed on the basis of published studies  individual aeds have been shown to differ  the deleterious effects of phenytoin generally contrasting with the relatively minimal effects of valproate and carbamazepine  some of the differences between results may be attributed to the psychological tests used and to age differences  however  there appears to be a dissociation between aeds that affect higher cognitive function  e g   phenytoin  and those mainly affecting motor function  e g   carbamazepine  which appears to increase speed of performance  aeds should be prescribed with care in children with epilepsy  taking account of their differing effects on cognitive function and behavior  
class10	computerized neuropsychological assessment of cognitive functioning in children with epilepsy  the value of a range of computer aided tests in the neuropsychological assessment was investigated in 94 177 children with epilepsy  aged 8 18 years  compared with 68 161 controls in the same age group  children from the age of 8 years could cope with rather complex tests in a wide range of functions  reaction time measurements  motor speed  information processing  and memory  the speed of performance tended to increase with age in both groups  with differences in information processing becoming apparent from the age of 12 years  the precise control of stimulus and response required to define the mainly minor differences between the epilepsy and control groups can only be fulfilled by computerized testing  which should undergo further refinement including voice and language recognition  followed by artificial intelligence  
class10	neuropsychological assessment of cognitive functioning in children with epilepsy  the variety of cognitive dysfunctions related to learning disabilities in children with epilepsy have been studied by linking electroencephalogram  eeg  and computerized neuropsychological testing  this showed that  subclinical  discharges impaired performance in 61  of the patients on a simple and a choice reaction time test  although some discharges lasted 1 s only  neuropsychological investigation of subclinical eeg discharges may help to determine their adverse effect on learning  
class10	electroencephalographic parameters in assessing the cognitive function of children with epilepsy  many biological and psychological possibilities have to be considered when attempting to explain cognitive dysfunction in the individual child with epilepsy  electroencephalographic  eeg  information  which may be particularly relevant in some children  has mainly been studied in relation to the possible direct effects of seizure discharges on learning and behavior  such discharges can be divided into transient  brief or prolonged  prolonged seizure discharges includes nonconvulsive status epilepticus during wakefulness and status epilepticus during slow wave sleep  in addition to the influence of seizure discharges  preliminary findings suggest that some children with epilepsy might have a subtle disorder of arousal mechanisms in sleep  possibly associated with impaired daytime performance  
class10	discontinuation of antiepileptic drugs in children who have outgrown epilepsy  effects on cognitive function  cognitive function is frequently impaired in children with epilepsy  compared with age matched controls  it can be hard to evaluate the significance of various contributory factors  the effects of antiepileptic drugs may be studied in children who have outgrown their epilepsy but are still being treated  a multicenter study to assess various aspects of cognitive function in children with different forms of epilepsy  both during and after treatment with antiepileptic drugs  is currently under way  definitive results are not yet available  interim analysis of the findings suggests that short term memory is decreased in all subgroups of children being treated for epilepsy  compared to controls  
class10	cognitive deficits in children  adaptive behavior and treatment techniques  impaired cognitive functioning impedes the development of age appropriate adaptive behavior  thus adding to the burdens of many children with epilepsy  detailed neuropsychological assessment can identify the underlying ability related impairments that contribute to the adaptive behavior deficiencies evidenced  particularly in the home and school settings  this information can serve as the basis for a multidisciplinary treatment plan tailored to individual needs  ideally  the need for such a treatment plan should be perceived early in childhood  so that it can be developed and applied preventively  the same remedial principles also apply in older children and are here set out in detail  
class10	educational policies  it is vital that teachers  parents  and health professionals recognize the major educational problems that affect students with epilepsy  children with epilepsy should be placed in the least restrictive schooling environment so that social  emotional  and educational requirements can be met in a setting best suited to the individual s present needs and future development  personal assessment and monitoring of progress form an equally important part of a child s educational program in integrated schools  but there is a need to develop suitable instruments to assist teachers in their assessments and decision making  in australia  the national epilepsy association has developed an  alert kit  based on the epilepsy foundation of americas  school alert kit  to provide basic medical information on epilepsy to teachers and pupils  
class10	neuropsychological aspects of learning disabilities in epilepsy  cognitive impairment is regarded as the link between epileptic conditions and the inability to learn in school  the neuropsychological approach to learning disabilities in epilepsy  therefore  first concentrates on analyzing the differential effects of epileptic factors on cognitive function  the impact of seizure activity  localization of epileptogenic foci  and antiepileptic treatment on cognitive functioning can be evaluated based upon the results of continuous assessment with a computerized neuropsychological test system  second  learning disabilities may be evaluated on observations made during classroom performance  three issues seem to predominate in learning studies among disabled children with epilepsy  test retest variability  deterioration  and the supposed specificity of the learning disabilities  
class10	mri  ct  spect  pet  their use in diagnosing dementia  the differential diagnosis of the dementia syndrome may pose a difficult clinical problem  since the most common dementia  alzheimer s disease  ad   is marked by normal laboratory tests  neuroimaging has played an important role in evaluating the demented patient  and its uses are growing  computed tomography  ct  is useful for excluding reversible and treatable causes of dementia  such as subdural hematoma and tumor  more recently  magnetic resonance imaging  mri  has improved our ability to diagnose vascular disease and may show the presence of cerebral infarcts and white matter disease not visible on ct  single photon emission computed tomography  spect  and positron emission tomography  pet   techniques that visualize such cerebral functions as glucose metabolism and blood flow  may provide positive evidence supportive of the diagnosis of ad  
class10	spinal instability secondary to metastatic cancer  fifty five patients with severe pain from spinal instability secondary to metastatic cancer were referred to hope hospital  none being judged to be in a terminal condition  one patient had too extensive disease for surgery so 54 were treated by 55 spinal stabilisations  49 obtained complete relief of pain and two had partial relief  there were three failures  twenty eight of the patients had clinical evidence of spinal cord or cauda equina compression and were decompressed at the time of stabilisation  of these  20 had major recovery of neurological function  patients with pre operative evidence of extradural tumour had  prophylactic  decompression at the time of stabilisation  none of these patients later developed signs of cord or cauda equina compression  the results suggest that alleviation of pain and restoration of mobility are best achieved by segmental spinal stabilisation  a few patients require a combined anterior and posterior stabilisation  postoperative radiotherapy should be given whenever possible  and the causative tumour should be treated by endocrine or chemotherapy  as indicated  
class10	surgical treatment of double major scoliosis  improvement of the lumbar curve after fusion of the thoracic curve  we have evaluated two methods of surgical treatment of adolescent idiopathic double major scoliosis in 59 patients  in group 1  31 patients were treated by fusion of the upper curve only  in group 2  28 patients had lumbar fusions also including most of the lower curve  the magnitude of the lower curve and the correction obtained in traction were good indicators of the correction achieved postoperatively  forty four patients were reviewed at a minimum of 10 years after operation  those in group 1 showed sustained improvement of the lower curve with minimal stiffness and pain  group 2 patients had lumbar curves of similar severity at review  but had significantly more low back pain and stiffness  the number of lumbar segments which remained mobile appeared to be a critical factor in determining the outcome  selective fusion of the upper curve in double major scoliosis produces satisfactory results if the lumbar curve is less than 50 degrees  it may also be appropriate for flexible lumbar curves of larger angle  
class10	tarsal tunnel syndrome  causes and results of operative treatment  from 1975 to 1988  operative treatment was performed on 50 feet in 45 patients with tarsal tunnel syndrome  the causes of this syndrome were correlated with operative findings and included ganglia in 18  and a bony prominence from talocalcaneal coalition in 15  five feet had sustained an injury  tumours were found in three and there was no obvious cause in nine  in most cases in need of operative treatment  there was a space occupying lesion  classifying the results according to causes  those with coalition or a tumour fared better  and idiopathic and traumatic cases had a worse outcome  in cases with a definite lesion  an excellent result can be expected from surgical treatment carried out soon after onset of the condition  
class10	scaphoid malunion  we reviewed 10 patients with symptomatic malunion of a carpal scaphoid fracture  all had displacement with dorsiflexed intercalated segment instability  and suffered from pain  restricted range of movement at the wrist and decreased grip strength  the restriction of flexion extension and the decreased grip strength correlated with the severity of the disi deformity  seven patients had a corrective osteotomy  using an anterior wedge shape bone graft with internal fixation by herbert screw  and all had satisfactory results  we believe that symptoms associated with scaphoid malunion are related to consequent carpal deformity  
class10	internal fixation of femoral neck fractures  two methods compared  in a prospective randomised study  the hansson pin technique for internal fixation of fractures of the femoral neck was compared with the uppsala screw technique  the series consisted of 115 consecutive patients  97 women and 18 men  with a mean age of 80 years  there were 56 patients treated with hansson pins and 59 with uppsala screws  after one year 22 patients had died  eight in the hansson pin group and 14 in the uppsala screw group  p   0 28   twenty four complications had occurred  18 in the hansson pin group and six in the uppsala screw group  p   0 008   after exclusion of those with complications  the patients in the hansson pin group had significantly more pain  less mobility  and a smaller proportion were living in their own homes  
class10	intravenous administration of phosphorylated acid alpha glucosidase leads to uptake of enzyme in heart and skeletal muscle of mice  the lysosomal storage disorder glycogenosis type ii is caused by acid alpha glucosidase deficiency  in this study we have investigated the possible applicability of mannose 6 phosphate receptor mediated enzyme replacement therapy to correct the enzyme deficiency in the most affected tissues  bovine testes acid alpha glucosidase containing phosphorylated mannose residues was intravenously administered to mice and found to be taken up by heart  70  increase of activity  and skeletal muscle  43  increase   the major target organs  the uptake of nonphosphorylated human placenta acid alpha glucosidase by heart and skeletal muscle appeared to be significantly less efficient  whereas uptake of dephosphorylated bovine testes enzyme was not detectable  the phosphorylated bovine testes acid alpha glucosidase remained present in mouse skeletal muscle up to 9 15 d after administration  with a half life of 2 4 d  besides being measured in skeletal muscle and heart  uptake of phosphorylated bovine testes and nonphosphorylated human placenta acid alpha glucosidase was measured in several other organs  but not in brain  the increase of acid alpha glucosidase activity was highest in liver and spleen  we concluded that application of mannose 6 phosphate receptor mediated enzyme replacement therapy may offer new perspectives for treatment of glycogenesis type ii  
class10	the timed  up   go   a test of basic functional mobility for frail elderly persons  this study evaluated a modified  timed version of the  get up and go  test  mathias et al  1986  in 60 patients referred to a geriatric day hospital  mean age 79 5 years   the patient is observed and timed while he rises from an arm chair  walks 3 meters  turns  walks back  and sits down again  the results indicate that the time score is  1  reliable  inter rater and intra rater    2  correlates well with log transformed scores on the berg balance scale  r    0 81   gait speed  r    0 61  and barthel index of adl  r    0 78   and  3  appears to predict the patient s ability to go outside alone safely  these data suggest that the timed  up   go  test is a reliable and valid test for quantifying functional mobility that may also be useful in following clinical change over time  the test is quick  requires no special equipment or training  and is easily included as part of the routine medical examination  
class10	mini mental state exam scores vary with education in blacks and whites  previous studies have suggested that education and race may affect performance on standardized mental status tests  in order to more clearly define these relationships  a prospective longitudinal study was devised to answer two questions   1  whether race or level of education affects scores on the mini mental state  mms  exam in non demented people and  2  what numerical cutpoints maximize the sensitivity and specificity of utilizing the mms to help diagnose dementia in blacks of varying educational attainment  a total of 100 white and 258 black individuals  recruited from two city hospital primary care geriatric clinics  were evaluated and subsequently followed longitudinally over a 2 1 2 year period in order to assess accurately the presence or absence of dementia  in the non demented  total mms scores and performance on each item of the mms were analyzed  revealing that people with an 8th grade or less education consistently had significantly  p less than  01  worse results than the better educated  9th grade or better  on borough  attention items  recall of table and dog  copying  sentence writing  phrase repeating  and total score  furthermore  a total of 25  of the lower education group had an mms score in the 18 23 range  traditionally thought to suggest dementia  there were no consistently significant differences between blacks and whites of equal education  in the better educated groups  using a score of 23 or less to define dementia maximizes the sensitivity and specificity of using the mms in this diagnosis at 93  and 100   respectively  in the lower education group  using 17 or less to define dementia maximizes sensitivity and specificity at 81  and 100   respectively  
class10	physician practices in the diagnosis of dementing disorders  because there are both treatable and untreatable causes of dementia  the physician s ability to conduct  or refer a patient for  a differential diagnosis could have a profound effect on health outcomes for patients and on health care costs  this study was undertaken to assess physician practices with regard to the diagnosis of dementing disorders  data from 53 physicians  a response rate of 48   in several specialties were obtained from a self administered mail questionnaire  results indicate that the majority of physicians provided history taking  physical examination  and neurological examination  physicians were more likely to refer patients for psychiatric and neuropsychological examinations than to provide these services themselves  the results also point to deficiencies in two key areas  the use of formal  published diagnostic criteria  and the use of mental status and cognitive function tests  over 75  of physicians surveyed did not use either dsm iii or nincds adrda diagnostic criteria  and 42  of physicians did not provide any mental status tests themselves  the need for continuing education to close knowledge gaps is emphasized  
class10	postauricular cerebellar encephalocoele secondary to chronic suppurative otitis media and mastoid surgery  cerebellar herniation into the mastoid through the posterior aspect of the temporal bone as a result of chronic suppurative otitis media and mastoid surgery is a rare event  a case is reported in which such a hernia presented subcutaneously behind the pinna  its repair is discussed  
class10	temporal bone findings in two cases of head injury  temporal bone findings in two cases of head injury are reported  in one patient  longitudinal fractures occurred in both temporal bones  and extended to the middle ear bilaterally  bleeding was seen in the tympanic cavity  mastoid air cells  internal auditory meatus and facial nerve canal  bleeding was observed in the scala tympani  cochlear aqueduct and endolymphatic sac  but there were no fractures  in the other patient  bleeding was seen in the internal auditory meatus and facial nerve canal  in the right ear  endolymphatic hydrops was observed in all turns of the cochlea  
class10	very high blood pressure in acute stroke  in a study sample consisting of 388 unselected  consecutive acute stroke patients  27 with systolic blood pressure greater than or equal to 200 mmhg and diastolic blood pressure greater than or equal to 115 mmhg were compared with the other 361 patients  the patients with high blood pressure were younger  65 vs  73 years  and much more often had a history of hypertension  78 vs  42    cardiac and vascular hypertensive manifestations were more frequent  particularly when only those patients with a history of hypertension were compared in the two groups  alcohol abuse was mentioned in a higher proportion of hypertensives in the summaries of their medical records  no definite conclusions could be drawn with regard to the size and location of the brain lesions  clinical symptoms did not differ between the groups  neither did the proportion of patients who could be discharged from hospital immediately  mortality was higher in the high blood pressure group  30 vs  14   p less than 0 05   thus the characteristics of patients with very high blood pressure were  younger age  much more frequent and severe previous hypertension  alcohol abuse might be an important factor  the type  size and location of the brain lesion itself could not be statistically related to the high blood pressure  but very large lesions  particularly haemorrhages  might be associated with a reactive blood pressure response  
class10	increased arterial adrenaline is related to pain in uncomplicated myocardial infarction  plasma levels of catecholamines  beta thromboglobulin  btg  and arginine vasopressin  avp   and degree of pain were examined in 22 patients with suspected uncomplicated myocardial infarction within 24 h following onset of chest pain  sixteen patients developed infarction with peak creatine phosphokinase at 1280 ul 1  range 293 3770 ul 1   fifteen healthy men served as controls  c   arterial adrenaline levels were significantly higher in patients with pain  1 15     0 23 nmol l 1  n   8  mean value     sem  than in those without pain  0 60     0 10 nmol l 1  n   14  p less than 0 05   plasma catecholamines were moderately but significantly elevated in myocardial infarction  the concentration of arterial adrenaline was 0 83     0 14 nmol l 1 and that of arterial noradrenaline was 2 70     0 28 nmol l 1 compared with 0 44     0 04 nmol l 1  p less than 0 025  and 1 47     0 05 nmol l 1  p less than 0 0005   respectively  in c  one week later  plasma catecholamines had returned to baseline levels  plasma btg showed borderline elevation  1 0     0 1 pmol l 1  compared with c  0 6     0 1 pmol l 1  p   0 04   and remained unchanged 1 week later  plasma avp was at baseline level  uncomplicated myocardial infarction  regardless of size  was associated with only moderately increased sympathetic tone  plasma adrenaline was related more to the degree of pain than to the presence of acute myocardial infarction  arterial adrenaline may be a sensitive marker of sympatho adrenal activity related to pain  
class10	localization of technetium 99m glucarate in zones of acute cerebral injury  the potential structural similarity of technetium 99m labeled glucaric acid  99mtc glucarate  to that of fructose suggests that this agent may enter cells by a sugar transport system  studies with llc pk1 cells demonstrated inhibition of 99mtc glucarate uptake by fructose  confirming this potential relationship  since anaerobic metabolism can use either glucose or fructose  we hypothesized that 99mtc glucarate may concentrate in areas of acute ischemic injury  to test this hypothesis  63 adult rats with middle cerebral artery  mca  occlusion followed by reperfusion were injected with 99mtc glucarate and in vivo and ex vivo images were acquired  seven animals were also studied with 18fdg and high resolution pet imaging  the radionuclide images were compared to the results of triphenyl tetrazolium chloride  ttc  staining and conventional histopathology  thirty five rats had significant accumulation of 99mtc glucarate and no ttc staining  indicating infarction  in the involved hemisphere  of the remaining 28 rats with ttc staining  suggesting viability  of the involved hemisphere  16  57   had 99mtc glucarate accumulation  in the seven rats that were studied with both 99mtc glucarate and 18fdg  99mtc glucarate accumulated at the center of the occluded mca territory while 18fdg activity was decreased in this region  these results suggest that 99mtc glucarate is a sensitive marker of acute severe cerebral injury  but its mechanism of localization is probably different from that of 18fdg  
class10	creutzfeldt jakob disease in pituitary growth hormone recipients in the united states  to assess the magnitude of creutzfeldt jakob disease  cjd  occurrence among recipients of pituitary derived human growth hormone  hgh   we conducted an epidemiologic follow up of 6284 recipients of hgh distributed through the national hormone and pituitary program  seven neuropathologically confirmed cases of cjd have occurred in this population to date  six patients with clinical cjd presented with ataxia and imbalance  rather than with altered mentation  which is the most common initial manifestation in sporadic cjd  and one patient died in the preclinical incubation state of the disease  all seven cases occurred among the nearly 700 hgh recipients who started therapy before 1970  since only 10  of the cohort has been followed up for the 15 year average incubation interval from midpoint of hgh treatment to onset of symptoms  the great majority of potentially exposed patients have not yet attained the requisite incubation period for expression of cjd  the median duration of hgh therapy of 100 months in the cjd cases was significantly longer than 41 months for all patients starting treatment before 1970  thus  the duration of pituitary hgh therapy is a major risk factor for cjd  
class10	meralgia paresthetica after coronary bypass surgery  meralgia paresthetica is a neurologic disorder characterized by localized paresthesia and numbness on the anterolateral aspect of the thigh and involving the lateral femoral cutaneous nerve  it involves no motor deficits  meralgia paresthetica  which may result from a variety of causes  has been observed as a rare complication in heart operations  its cause when associated with such operations is uncertain but may be prolonged relaxed positioning on the operating table and recovery room stretcher  another possible cause of meralgia paresthetica after heart operations is the  frog leg  position of the legs during vein harvesting  patients with this condition should be advised of its untreatable  but benign and self limiting  nature  
class10	pulse oximetry during apparent tonic clonic seizures  a pulse oximeter was used to monitor arterial oxygen saturations in 11 patients during apparent tonic clonic seizures  8 had a clinical diagnosis of genuine fits  6 of whom showed striking falls in oxygen saturation during the seizures  3 had a clinical diagnosis of pseudoseizures  none of whom had hypoxia during these episodes  pulse oximetry during apparent tonic clonic seizures may help to identify patients with low arterial oxygen tension who need immediate intervention  
class10	comparison of continuous subcutaneous and intravenous hydromorphone infusions for management of cancer pain  to compare the safety and efficacy of subcutaneous and intravenous infusion of opioid analgesics  a randomised  double blind  crossover trial was carried out in inpatients  15 patients with severe cancer pain received two 48 h infusions of hydromorphone  one subcutaneously and one intravenously in randomly allocated order  the study was made double blind by the use of two infusion pumps throughout  during the active subcutaneous infusion the intravenous pump delivered saline and vice versa  serial measurements of pain intensity  pain relief  mood  and sedation by means of visual analogue scales showed no clinically or statistically significant difference between the two infusion routes  side effects were slight  and the mean number of morphine injections for breakthrough pain did not differ significantly between the routes  4 8  sd 4 5  for intravenous vs 5 3  5 6  for subcutaneous   plasma hydromorphone concentrations measured at 24 h and 48 h of infusion showed stable steady state pharmacokinetics  the mean bioavailability from subcutaneous infusion was 78  of that with intravenous infusion  because of the simplicity  technical advantages  and cost effectiveness of continuous subcutaneous opioid infusion into the chest wall or trunk  intravenous opioid infusion for the management of severe cancer pain should be abandoned  
class10	neurofibromatosis type 2  report of a family and review of current evaluation and treatment  significant advances during the past decade have greatly improved our understanding of neurofibromatosis type 2  a genetic disease which results in bilateral acoustic neuromas  the emergence of gadolinium enhanced magnetic resonance imaging has allowed early detection of minute intracanalicular eighth nerve tumors  less than 1 cm in diameter  recombinant dna studies have clarified the genetics that underlie neurofibromatosis type 2 and separate it from a variety of related conditions  such as von recklinghausen s neurofibromatosis  early diagnosis and surgical removal of these tumors may offer the only hope of preserving hearing and facial nerve function  a report of the evaluation and treatment of a family with multiple affected individuals will exemplify these conclusions  
class10	reversible myeloneuropathy of nitrous oxide abuse  serial electrophysiological studies  detailed electrophysiological studies were performed in 4 patients with myeloneuropathy induced by abuse of nitrous oxide for 1 to 4 years  all presented with paresthesias  weakness  and lhermitte s phenomena  and exhibited signs of sensorimotor polyneuropathy  ataxia  and arreflexia  two had subnormal serum vitamin b12 levels  baseline electrophysiologic testing revealed reduced motor unit potentials  prolonged f wave latencies  absent h reflexes  denervation potentials  and delays in motor and sensory conduction  three had peripheral and nuchal delay after median nerve stimulation  all were reevaluated after 3 to 12 months  abstinence and treatment with vitamin b12  and all showed substantial clinical improvement  parallel improvement in electrophysiologic findings occurred  but residual minor conduction delays  loss of h reflexes  electromyographic evidence of denervation  or abnormalities of posterior tibial sep were noted  these findings confirm the reversibility of myeloneuropathy of nitrous oxide abuse and describe the profile of electrophysiologic recovery in subjects who abstain from further neurotoxic exposure  
class10	nerve muscle involvement in a large family with mitochondrial cytopathy  electrophysiological studies  thirteen patients with mitochondrial cytopathy were investigated  they represent different generations  ages  stages  and severities of the disease  all were assumed to have the same metabolic defect  the disease is a multisystem disorder with a metabolic defect located at complex 1 in the respiratory chain  clinically  the disorder gives symptoms such as hearing loss  retinal pigmental degeneration  ataxia  cardiomyopathy  muscular fatiguability and neuropathy  the patients were investigated with nerve conduction studies  concentric needle emg  sfemg  and macro emg examinations  neurophysiologic studies revealed signs of myopathy in both the younger members and in those with slight muscular symptoms  in the more advanced stages  neuropathic changes of the axonal type were seen as well  macro emg was interpreted as indicating muscle fiber membrane abnormalities in the early stages  single fiber emg studies indicate that this metabolic defect does not disturb neuromuscular transmission  
class10	diagnostic and prognostic value of electrophysiologic tests in meralgia paresthetica  electrophysiologic diagnosis of unilateral meralgia paresthetica is usually assessed by side to side comparison of snap amplitudes  sncvs  and sep latencies following stimulation of lateral femoral cutaneous nerves  to determine the relevance for diagnosis of these tests and side to side comparison  the results were compared in patients with unilateral meralgia paresthetica and normal subjects  the long term outcome was also considered  in order to determine whether electrophysiologic findings contribute to the prognosis  in our study  snap amplitude comparison was found to be more useful for diagnosis than sncv and sep latency comparisons  however the value of the snap amplitude on the affected side  just as the results of the other tests  was not found to be predictive of the outcome  also the results of the tests depend on the methods used and on the nerve s route  
class10	abnormal single motor unit behavior in the upper motor neuron syndrome  we studied the discharge pattern of single motor units  smus  in the left and right biceps muscles from a patient with nonspastic weakness of the left arm  detailed statistical analysis of the behavior of discharge patterns of 4 of 4 single motor units on the affected side showed abnormalities with characteristic features of an upper motor neuron lesion  five out of 5 single motor units recorded from the right biceps were normal  an upper motor neuron lesion affecting the left arm  predicted by our results  was confirmed by magnetic resonance imaging  mri   which showed a lesion in the right precentral gyrus  it appears that changes in single motor unit firing characteristics  caused by an upper motor neuron lesion  can be detected at a time when there is no evidence of increased  tone  and or hyperreflexia  spasticity  in the affected extremity  
class10	effects of short spaceflights on mechanical characteristics of rat muscles  the aim of this study was to investigate the contractile protein characteristics after 5 day  cosmos 1514  and 7 day  cosmos 1667  spaceflights  the experiments were performed on skinned fibers from the soleus  gastrocnemius lateralis  and plantaris muscles isolated from wistar rats  a reduction in fiber diameter might explain the decrease in the maximal tension in the soleus  whereas this tension was unaltered in the gastrocnemius and the plantaris  moreover the calcium sensitivity of the myofilament appeared modified in the soleus and in the gastrocnemius  the tension pca relationships were shifted toward higher calcium concentrations  indicating a decrease in the apparent calcium binding constant of the troponin c  the tension pca relationship appeared unaltered in the plantaris after spaceflight  finally  the studies of the time to reach a steady tension indicated an increase in the rate of force development in the soleus and  on the contrary  a slowing down in the plantaris  no change in the gastrocnemius was found  the results were analyzed with references to the different muscle functions in disuse atrophy  
class10	a placebo controlled trial of maintenance therapy with fluconazole after treatment of cryptococcal meningitis in the acquired immunodeficiency syndrome  california collaborative treatment group  background and methods  in patients with the acquired immunodeficiency syndrome  aids   the rate of relapse after primary treatment for cryptococcal meningitis remains high  we conducted a controlled  double blind trial to evaluate the efficacy of maintenance therapy with fluconazole  at entry into the study  all participants had sterile cultures of cerebrospinal fluid  blood  and urine after following a standardized course of therapy for culture proved cryptococcal meningitis  the patients were randomly assigned to take either fluconazole or placebo as maintenance therapy  the dose of fluconazole was 100 mg daily in the first phase of study and 200 mg daily in the second phase  results  of 84 patients initially enrolled  16  19 percent  were found to have silent  persistent infection on the basis of cultures that became positive after entry into the study  7 other patients were lost to follow up shortly after entry  of the remaining 61 patients  10 of 27 assigned to placebo  37 percent  and 1 of 34 assigned to fluconazole  3 percent  had a recurrence of cryptococcal infection at any site  difference in risk  34 percent  95 percent confidence interval  15 to 53   of the 11 recurrent infections  7 were detected in urine obtained after prostatic massage  there were four recurrent meningeal infections in the patients taking placebo  but none in those taking fluconazole  mean duration of follow up  164 days   p   0 03   in multivariate analyses  the best predictors of recurrence free survival were fluconazole treatment  p   0 02  relative hazard  13 2   a lower serum cryptococcal antigen titer  p   0 05  relative hazard  1 2   and more prolonged primary therapy with flucytosine  p   0 09  relative hazard  1 1   survival and toxicity were similar in the two maintenance treatment groups  conclusions  in patients with aids  silent persistent infection is common after clinically successful treatment for cryptococcal meningitis  maintenance therapy with fluconazole is highly effective in preventing recurrent cryptococcal infection  
class10	young onset parkinson s disease  a clinical review  young onset parkinson s disease  yopd  is arbitrarily defined as that which produces initial symptoms between the ages of 21 and 39  inclusive  the special problems and concerns of the patient with yopd present as much of a challenge and opportunity for the clinician as the disease itself does for the researcher  in contrast to juvenile parkinsonism  which is a heterogeneous group of clinicopathologic entities presenting  also arbitrarily  before age 21  yopd appears to be the same nosologic entity as older onset pd  it comprises approximately 5  of referral populations in western countries and about 10  in japan  its annual incidence relative to the population at risk is about 1 10 that of pd at age sixty  yopd tends to have more gradual progression of parkinsonian signs and symptoms  earlier appearance of levodopa related dyskinesias and levodopa dose related motor fluctuations  and frequent presence of dystonia as an early or presenting sign  studies conflict with regard to the suspected greater familial frequency and lesser frequency of dementia than in older onset pd  
class10	the role of htlv in hiv 1 neurologic disease  we performed a serologic survey for antibodies to htlv i ii in the course of a longitudinal study of the neurologic complications of hiv 1 infection  nine  3 7   of 242 hiv 1 seropositive subjects and none of 60 hiv 1 seronegative control subjects had antibodies to htlv i ii by elisa  western blot and polymerase chain reaction confirmed the presence of htlv i in 2 subjects and htlv ii infection in 2 others  both hiv 1 htlv i coinfected subjects and 1 hiv 1 htlv ii coinfected subject had a slowly progressive myelopathy clinically identical tropical spastic paraparesis htlv i associated myelopathy  tsp ham   the presence of a myelopathy resembling tsp ham in the coinfected subjects suggests that hiv 1 may enhance the expression of neurologic disease caused by htlv  patients with a progressive myelopathy occurring in association with hiv 1 infection should be serologically tested for the presence of htlv  establishing dual infection has therapeutic and prognostic import as 1 of the hiv 1 htlv i subjects substantially improved with corticosteroids and the hiv 1 htlv ii subject with myelopathy had a marked improvement in the absence of therapeutic intervention  
class10	early development of levodopa induced dyskinesias and response fluctuations in young onset parkinson s disease  we evaluated whether patients with young onset parkinson s disease  pd   onset between 21 and 40 years  develop levodopa induced dyskinesias and motor response fluctuations more frequently and earlier than patients with older onset pd  onset after 40 years  by determining the period from levodopa introduction to development of dyskinesias or fluctuations in 25 young onset  mean age at onset  33 54 years  and in 25 matched older onset pd patients  mean age at onset  55 76 years   young onset pd patients had significantly higher frequency for both dyskinesias and fluctuations after both 3 and 5 years of levodopa  young onset pd patients also developed both levodopa induced dyskinesias and fluctuations earlier than older onset pd patients  we suggest that the introduction of levodopa therapy in patients with young onset pd should be postponed as long as possible  
class10	patient perception of tics and other movement disorders  to determine the subjective perception patients have of abnormal movements  170 patients with various hyperkinesias were interviewed with questions directed at the  voluntary  or intentional versus  involuntary  aspects of their symptoms  one hundred and two of 110 patients with non tic disorders thought that the abnormal movements were entirely involuntary  forty one of 60 tic disorder patients stated that all their motor and phonic tics were intentionally produced  fifteen others had both voluntary and involuntary components  usually with the former predominating  a  voluntary  response could be used to predict the correct diagnostic category  tic versus non tic  in 8 of 9 patients for whom the referral category was incorrect  these results suggest that a large proportion of the motor and phonic symptoms experienced by tic patients are irresistibly but purposefully executed  more akin to compulsions than to the other  involuntary  hyperkinesias with which they are commonly discussed  
class10	hashimoto s encephalopathy  a steroid responsive disorder associated with high anti thyroid antibody titers  report of 5 cases  we describe 5 patients with a relapsing encephalopathy in association with hashimoto s disease and high titers of anti thyroid antibodies  the presentation is usually with a subacute onset of confusion  alteration in conscious level  and focal or generalized seizures  the relapsing course  association with myoclonus or tremulousness  and episodes of stroke like deterioration are characteristic features  the long term prognosis is favorable with steroid therapy  though additional immunosuppressive therapy may be required  neurologic investigation typically shows a diffusely abnormal eeg  high csf protein level without pleocytosis  and normal brain ct and cerebral angiogram  isotope brain scan may show patchy abnormal uptake  hashimoto s encephalopathy should be recognized as a definite neurologic entity and added to the list of cns complications of thyroid disease  
class10	essential tremor  clinical correlates in 350 patients  to study the demographic and clinical correlates of essential tremor  et   we analyzed a comprehensive database of 350 patients evaluated at the movement disorders clinic at baylor college of medicine from 1982 to 1989  the age at onset of tremor showed bimodal distribution for both male and female patients  with peaks in 2nd and 6th decades  et appeared most frequently in hands  followed by head  voice  tongue  leg  and trunk  half of the patients  47   had associated dystonia  including cervical dystonia  writer s cramp  spasmodic dysphonia  and cranial dystonia  and 20  of the patients had associated parkinsonism  at least one 1st degree relative of 62 5  of et patients reported tremor  alcohol relieved tremor in 2 3 of et patients  sixty eight percent of patients who had adequate follow up improved with propranolol  and 72  with primidone  there was no significant difference in various clinical variables between the 219 patients with familial et and 131 with sporadic et  patients with early onset et were more likely to have hand involvement and associated dystonia than patients with late onset et  dystonia was more frequently associated with mild et than with severe et  patients with low frequency tremor were older and had more head but less hand involvement than patients with high frequency tremor  the lack of relevant differences between et subgroups suggests that  despite variable expression  et represents a single disease entity  
class10	symptoms and disease associations in idiopathic intracranial hypertension  pseudotumor cerebri   a case control study  to identify the symptoms and coexisting medical conditions associated with idiopathic intracranial hypertension  iih   we administered an 83 item questionnaire at the time of diagnosis to 50 iih patients and 100 aged matched controls  ninety percent of the iih patients were women  the mean age was 33  obesity and recent weight gain were much more common among patients than controls  symptoms most commonly reported by iih patients were headache  94    transient visual obscurations  tvo   68    and intracranial noises  icn   58    daily occurrence of these symptoms was much more common among patients than controls  controls also reported these and other iih symptoms  but at lower frequencies  several conditions previously associated with iih were no more common in patients than controls including iron deficiency anemia  thyroid disease  pregnancy  antibiotic intake  and use of oral contraceptives  we conclude that previous studies of iih  mostly uncontrolled and retrospective  have underestimated the frequency of symptoms in iih patients and reported chance and spurious associations with common medical conditions and medications  the profile of a young obese woman with headaches and either tvo or icn should alert the clinician to the diagnosis of iih  especially when the symptoms occur daily  
class10	lateral medullary infarction  prognosis in an unselected series  we describe the acute and long term prognosis in 43 patients with lateral medullary infarction  lmi  collected from a population based stroke registry from 1982 to july 1988  mean age was 63 9 years and median time of follow up was 33 months  in the acute phase  5 patients  11 6   died from respiratory and cardiovascular complications and 2 new strokes occurred  both in the posterior circulation  during follow up  recurrent vertebrobasilar territory strokes occurred in only 2 patients  a rate of 1 9  per year   the mechanisms of stroke were vertebral artery  va  branch occlusion  causing a medial medullary syndrome  and basilar artery thrombosis propagating from a contralateral  distal va stenosis  in the acute phase of lmi  respiratory and cardiovascular events  presumably caused by autonomic dysfunction related to the lateral medullary lesion  are the major hazards  recurrent posterior circulation strokes were uncommon during follow up  
class10	infarction in the anterior rostral cerebellum  the territory of the lateral branch of the superior cerebellar artery   we report 9 patients with an isolated infarct of the anterior part of the rostral cerebellum  ie  the territory of the lateral branch of the superior cerebellar artery  clinicoanatomic correlations are based on ct  mri  or both in 8 patients and on pathologic data in the ninth  the main clinical features were ipsilateral dysmetria and axial lateropulsion  dysarthria  and unsteadiness  in 1 patient  the clinical presentation mimicked a lacunar stroke  dysarthria and clumsy hand syndrome   there were no edematous cerebellar infarcts with signs of brainstem compression  and all patients spontaneously improved without significant sequellae  angiography in 2 patients and pathologic examination of arteries in 1 patient disclosed no occlusion in the vertebrobasilar system  six patients had a cardiac source of emboli  in conclusion  infarcts of the anterior part of the rostral cerebellum can be regarded as a benign condition in which there is  frequently  a cardiac source of emboli  
class10	myotonic heart disease  a clinical follow up  we followed 37 patients with myotonic dystrophy for a mean of 6 years  two developed atrial flutter or fibrillation  6 developed a new bundle branch block  1 developed complete heart block requiring a pacemaker  and another with progressive 1st degree heart block and a widening qrs interval had a sudden death  most patients had predictable  gradually progressive disease of their cardiac conduction system  we recommend that patients with progressive atrioventricular block or widening qrs interval due to myotonic heart disease have yearly ecgs and be questioned about syncope or presyncope to determine the need for a cardiac pacemaker  
class10	epidermal nevus syndrome  a neurologic variant with hemimegalencephaly  gyral malformation  mental retardation  seizures  and facial hemihypertrophy  the epidermal nevus syndrome  ens  is a sporadic neurocutaneous disorder that consists of epidermal nevi and congenital anomalies involving the brain and other systems  from among over 60 patients with ens presenting with neurologic manifestations  we identified 17 who had hemimegalencephaly based on pathologic or radiologic studies  associated brain and neurologic abnormalities included gyral malformations in 12 of 12  mental retardation in 13 of 14  seizures in 16 of 17  including 9 with infantile spasms   and contralateral hemiparesis in 7 of 12  all had ipsilateral epidermal nevi of the head  and several had ipsilateral facial hemihypertrophy  we concluded that these abnormalities comprise a recognizable neurologic variant of ens that we believe represents the full expression of primary brain involvement  several patients also had evidence of acquired brain lesions such as infarcts  atrophy  porencephaly  and calcifications  which are best explained by prior ischemia or hemorrhage  given repeated observations of blood vessel anomalies in ens patients  we hypothesize that underlying vascular dysplasia predisposes to these acquired lesions  the same cause may be invoked to explain the wide variety of neurologic symptoms reported in ens patients without hemimegalencephaly  while the cause of ens remains unknown  several observations suggest a somatic mutation  
class10	comparison of functional and structural brain disturbances in wilson s disease  we assessed the functional and structural brain disturbances in wilson s disease  wd  by evoked potentials  eps  and magnetic resonance imaging  mri   all the 25 neurologically symptomatic and 44  of the 16 asymptomatic patients  assessed by both eps  n   48  and imaging  n   41   had at least 1 abnormality of either prolonged ep conduction times  imaging outlined presence of cerebral lesions  or brain atrophy  our findings indicate that eps and mri are sensitive techniques for the evaluation of brain involvement in wd  
class10	vascular abnormalities in epidermal nevus syndrome  we report a patient with epidermal nevus syndrome and right hemispheric infarct and review 3 others with neurologic manifestations best explained by ischemia or hemorrhage  each had a significant vascular abnormality such as occlusion or blood vessel dysplasia  none had hemimegalencephaly  we hypothesize that underlying vascular dysplasia is the cause of the neurologic lesions in these patients  
class10	percutaneous aspiration of brain tumor cysts via the ommaya reservoir system  we performed percutaneous aspiration of 21 brain tumor cysts in 20 patients using the ommaya reservoir system  ages ranged from 3 to 70 years  median 48  sixteen were primary tumors  12 anaplastic glioma  2 craniopharyngioma  1 oligodendroglioma  1 brainstem glioma  and 4 were metastatic  fourteen had the ct appearance of a true cyst and 7 a pseudocyst  we placed 18 catheters through twist drill holes via ct stereotactic guidance and 3 through burr holes via ct guidance and effectively aspirated 3 to 50 ml cyst fluid from 1 to 18 times in each patient  postaspiration ct showed complete or significant reduction in cyst size in all patients in whom it was performed  18 after initial aspiration and 9 after subsequent aspirations   asymptomatic intracyst hemorrhage occurred in 2 patients after cyst wall biopsy and catheter placement  there have been no other complications at follow up of 4 to 114 weeks  in our experience  tumor cyst aspiration by the ommaya reservoir system is as effective as percutaneous needle aspiration  but after catheter placement aspiration can be performed with minimal technical skill  avoiding repeated ct guidance required for needle aspiration of recurrent deep seated cysts  
class10	reciprocal inhibition between forearm muscles in spastic hemiplegia  we studied reciprocal inhibition of h reflexes in the forearm flexor and extensor muscles in 14 patients with spastic hemiplegia secondary to a focal cerebral lesion and 14 normal volunteers  in the spastic limb  the hmax mmax ratio was increased in both flexor and particularly extensor wrist muscles  the 3 normal inhibitory phases of reciprocal inhibition between extensor and flexor forearm muscles were markedly reduced on the spastic side of patients  the early disynaptic phase showed the greatest alteration  reduced or absent inhibition between forearm muscles associated with increased spinal motoneuron excitability may be typical to spastic hemiplegia  
class10	interictal spiking during wakefulness and sleep and the localization of foci in temporal lobe epilepsy  we examined variations in interictal spiking during sleep and wakefulness to assess differences in reliability for localizing epileptic foci  forty patients were studied prospectively  spikes were assessed for rates  field  and appearance of new foci  final localization was determined by surgery  electrocorticography  and seizure onset  comparison of interictal eeg foci with final localization was made  in 39 patients  slow wave sleep activated spiking compared with wakefulness  most patients showed maximal spiking in sleep stages 3 or 4  restriction of field in rapid eye movement  rem  sleep and wakefulness  and extension of field in slow wave sleep occurred  new foci appeared in non rapid eye movement sleep in 53  of patients  similar but not identical spiking rates  foci  and field distributions were seen in wakefulness and rem sleep  all rem foci were unilateral  our findings suggest that localization of the primary epileptogenic area is more reliable in rem sleep than in wakefulness  and in wakefulness more than in slow wave sleep  
class10	phenytoin toxicity due to interaction with clobazam  the benzodiazepine antiepileptic drug clobazam can be added to existing aed treatment  usually without clinical toxicity  we report 3 patients in whom the addition of clobazam led within several weeks to clinically obvious phenytoin  pht  intoxication in patients who had been taking maximum tolerable pht doses  symptoms and high pht levels resolved with lowering the pht dose  clobazam and norclobazam levels were not elevated  this interaction is probably related to interference with hepatic degradation of pht  clinicians should be aware of possible pht intoxication in patients starting clobazam  
class10	eosinophilia myalgia syndrome associated with ingestion of l tryptophan  muscle biopsy findings in 4 patients  muscle biopsies of 4 patients with the eosinophilia myalgia syndrome associated with ingestion of l tryptophan showed lymphocytic infiltrates with occasional eosinophils largely restricted to interstitial fibrous tissue and perivascular areas  there was inflammation and fibrosis of muscle spindle capsules in 3 patients  in the 2 sickest patients  there was profound muscle atrophy  affecting both muscle fiber types  
class10	cerebrospinal fluid eicosanoid levels  endogenous pgd2 and ltc4 synthesis by antigen presenting cells that migrate to the central nervous system  we analyzed csf from patients with multiple sclerosis  patients with other neurologic diseases  and healthy controls for the presence of prostaglandin  pg  e2  f2 alpha  d2  i  a  and leukotriene  lt  c4  control csf had little measurable pgs or lts  csf eicosanoids from patients with progressive ms were increased  we found pgd2 only in ms csf  csf monocytes from patients in active disease produced significantly increased pgd  pge  and ltc4 than paired peripheral blood monocytes and monocytes from healthy controls  we saw no significant difference in ltc4 production between ms and control peripheral blood monocytes  
class10	syphilitic meningomyelitis  a 28 year old nonimmunocompromised man developed secondary syphilis confirmed by serum and csf findings  his course was complicated by chorioretinitis  extensive skin lesions  and spastic paraparesis secondary to syphilitic meningomyelitis  mri of the spinal cord was strikingly abnormal  
class10	the  numb cheek limp lower lid  syndrome  a patient developed isolated numbness  1st confined to the lateral nose and upper lip  but later involving the cheek  lower lip  upper gingiva  and the palate  this numbness was later associated with paresis of the muscles of the upper lip and angle of the mouth and with ipsilateral lower lid droop  the  numb cheek limp lower lid  syndrome   squamous cell carcinoma was discovered infiltrating the infraorbital nerve and distal branches of the facial nerve  cheek numbness associated with lower eyelid or upper lip weakness may herald a neoplasm affecting the infraorbital nerve and distal facial nerve branches  
class10	repetitive conservative surgery for recurrence of endometriosis  we evaluated the recovery of fertility and the relief of pain symptoms in a long term follow up of 42 women undergoing repetitive conservative surgery for recurrent endometriosis  the mean age of the patients was 31 1     4 3 years  at the time of their second operation the disease was stage iv in 14 women  stage iii in 25  and stage i in three  after reoperation  the patients were followed for a mean period of 41 8     30 3 months  pain symptoms returned in eight women  dysmenorrhea and deep dyspareunia in eight  and pelvic pain in seven  eight of the 28 women  28 6   who attempted to conceive achieved a total of 13 pregnancies  the corrected pregnancy rate was 35   and the cumulative rate at 27 months was 30 7   a third operation was necessary in six women after a mean period of 35 months  conservative surgery is an effective therapeutic option for infertile patients with recurrent endometriosis  
class10	pyogenic spinal sepsis in adults  twenty adult patients presented with bacteriologically and histologically proven nontuberculous spinal sepsis  thirteen patients presented with varying degrees of neurologic impairment  all patients underwent spinal decompression  in 11 this was combined with an anterior fusion using autogenous tricortical iliac grafts  all patients have recovered and are ambulatory  and no patient s disorder was made worse by surgery  twenty three separate organisms were cultured  only five of which were staphylococcus  the antibiotic courses were shorter and pain relief more rapid with anterior fusion  all anterior bone grafts incorporated rapidly  and there was no progression of kyphosis or sequestration of grafts  regardless of organisms or level  the rational treatment of adult spinal sepsis necessitates the securing of tissue from the spine for histologic and bacteriologic examination  pain relief  stabilization  and neural decompression can best be achieved with anterior decompression and fusion  autogenous iliac crest grafts incorporate in the presence of sepsis  
class10	osteoblastoma of the spine  a review of 75 cases  clinical and radiologic features of 75 cases of osteoblastoma of the spine were reviewed  in addition to pain  which was the most frequent complaint  18 patients demonstrated objective neurologic deficit  while scoliosis was observed in 17 patients  aspirin yielded pain relief in 13 patients  pathologic fracture was not encountered  the radiologic and histologic characteristics of osteoblastoma of the spine are indistinguishable from those arising in other sites  the typical lesion exhibited a well defined  geographic margin with a sclerotic  frequently lobulated border  approximately one half of the cases were predominantly lucent  the remainder displaying varying degrees of matrix mineralization  distribution of the osteoblastomas through the spinal axis was as follows  cervical 29  thoracic 16  lumbar 17  sacral 13  other significant findings included posterior element involvement in 73 of 75 cases  and a striking male to female ratio of 2 5 to 1  
class10	hemibody irradiation in advanced prostatic carcinoma  in summary  hemibody irradiation has developed as a safe  efficient technique for palliating multiple sites of symptomatic osseous metastases  which occur so often in advanced prostatic carcinoma  the rapidity  frequency  and duration of pain relief  as well as the convenience to the patient of a solitary treatment to multiple symptomatic areas simultaneously  make this type of treatment especially appealing  by following premedication and radiation dose guidelines  both acute and delayed side effects can be kept tolerable or at a minimal incidence  although sequential hemibody radiation has also been explored as  systemic  therapy  the results in prostatic carcinoma have not proved dramatic  and complications have been considerable  hormonal therapy would certainly seem to be less life threatening and equally beneficial according to present data  as a palliative treatment  however  hemibody irradiation is a pragmatic option for relieving prostatic cancer pain  
class10	use of intravenous stilbestrol diphosphate in patients with prostatic carcinoma refractory to conventional hormonal manipulation  the patient presenting with severe bone pain after primary hormonal therapy  with vertebral collapse  or with uremia resulting from ureteric obstruction should be considered for intravenous stilbestrol diphosphate therapy  the urologist can expect early marked improvement in the patients  mobility and pain  with a reduction in analgesic requirements  from a single 7 day course of treatment  in addition  the drug is inexpensive and free of the side effects commonly associated with cytotoxic therapy  accurate monitoring of the response is possible with serum prostate specific antigen measurements  which also enable further therapy to be planned efficiently  
class10	combination of anandron with orchiectomy in treatment of metastatic prostate cancer  results of a double blind study  a multicenter  randomized double blind study was carried out in 203 patients with metastatic prostate cancer  in order to compare the efficacy of complete suppression of androgens achieved with surgical castration and nilutamide  anandron   100 mg t i d  the combined therapy was well tolerated by patients  and they noted a better relief of bone pain after six months than those in the control group  there was a greater number of favorable responses in the combined treatment group  in addition  despite a similar median progression free actuarial rate  the combined treatment  nilutamide plus orchiectomy  offered an improved survival time over orchiectomy alone  
class10	granulocytic sarcoma presenting as an epidural mass with acute paraparesis in an aleukemic patient  granulocytic sarcomas are rare tumors composed of granulocytic precursor cells  they are most commonly encountered in patients with acute myelogenous leukemias and myeloproliferative disorders in blast crisis  rarely  patients presenting with granulocytic sarcoma show no evidence of acute leukemia  the authors report an aleukemic patient with acute paraparesis from an epidural granulocytic sarcoma  only five such cases have been reported previously  immunoperoxidase stain for lysozyme and chloroacetate esterase stain were used to prove the myeloid origin of the tumor cells  
class10	prediction of free phenytoin levels based on  total phenytoin   albumin  ratios  potential errors with hypoalbuminemia  therapeutic monitoring of the pharmacologically active  free drug  fraction of protein bound medications  e g   phenytoin  represents a major diagnostic challenge in clinical and laboratory medicine  while free drug levels may be beneficial in many clinical situations  current methods for predicting free phenytoin concentrations are unreliable and not recommended for general use  the authors have demonstrated a linear relationship  r2   0 98  between serum levels of total and bound phenytoin in 56 patients with seizure disorders  no significant correlations were observed when total phenytoin and albumin levels were compared independently to measured concentrations of free phenytoin or percent free phenytoin  a good correlation  r2   0 89  existed between free phenytoin levels and  total phenytoin   albumin  ratios in patients with normal or elevated albumin levels  but significantly weaker correlations were found in patients with hypoalbuminemia  thus   total phenytoin   albumin  ratios may have clinical value in predicting free phenytoin levels in uncomplicated patients without hypoalbuminemia  
class10	endosalpingosis as a cause of chronic pelvic pain  endosalpingosis  a condition characterized by ectopic oviduct epithelium  is diagnosed histologically by the appearance of benign ciliated and nonciliated columnar cells in an abnormal location  endosalpingosis is typically without symptoms  our unusual case report shows symptomatic endosalpingosis first seen with chronic pelvic pain  various aspects of this disease will also be discussed  
class10	effects of acute hypermagnesemia on the threshold for lidocaine induced seizures in the rat  the effects of acute changes in plasma magnesium concentration on the threshold for lidocaine induced seizures were evaluated in mechanically ventilated rats receiving 70  nitrous oxide and 30  oxygen  in experiment 1  male rats were intravenously administered either 0 9  sodium chloride  group i  or 5 0  magnesium sulfate to elevate plasma magnesium levels to 5 8     0 1  group ii  or 10 5     1 0 mg dl  group iii   in experiment 2  pregnant rats were intravenously administered either 0 9  sodium chloride  normomagnesemia  or magnesium sulfate  resulting in a plasma magnesium concentration of 7 8     1 4 mg dl  thirty minutes later  a continuous intravenous infusion of lidocaine  2 3 mg kg per minute  was begun in both experiments  biparietal electroencephalographic activity was monitored continuously  at the onset of electroencephalographic seizure activity  arterial plasma magnesium and lidocaine concentrations were measured  in groups i and iii  experiment 1   brain parenchymal magnesium was also assayed  there were no differences in plasma lidocaine concentrations  in experiments 1 or 2  between saline solution and hypermagnesemic groups at onset of seizures  brain magnesium level was unaltered by magnesium sulfate infusion  we conclude that acute administration of magnesium sulfate alters neither brain magnesium level nor the plasma lidocaine concentration associated with onset of electroencephalographic seizures  
class10	visual recovery in patients with optic neuritis and visual loss to no light perception  we reviewed the records of 151 patients with optic neuritis examined over an eight year period  of these patients  12 developed visual acuity of no light perception during the first episode of optic neuritis in the affected eye  eight of the 12 patients recovered visual acuity of 20 40 or better  of these  five patients had visual acuity of 20 20 or better  one had visual acuity of 20 25  one had visual acuity of 20 30  and one had visual acuity of 20 40  four of the 12 patients recovered peripheral visual fields but had dense central scotomas and visual acuity of less than 20 400  dyschromatopsia persisted after visual recovery in 11 of 12 patients  
class10	systemic amyloidosis in transgenic mice carrying the human mutant transthyretin  met30  gene  pathologic similarity to human familial amyloidotic polyneuropathy  type i  to analyze the pathologic processes of amyloid deposition in type i familial amyloidotic polyneuropathy  fap   mice were made transgenic by introducing the human mutant transthyretin  ttr  gene  in these transgenic mice  amyloid deposition started in the gastrointestinal tract  cardiovascular system  and kidneys 6 months after birth and extended to various other organs and tissues with advancing age  at age 24 months  the pattern of amyloid deposition was similar to that observed in human autopsy cases of fap  except for its absence in the choroid plexus and in the peripheral and autonomic nervous systems  amyloid deposition was shown to be composed of human mutant ttr and  in addition  mouse serum amyloid p component  these results clearly indicate that human variant ttr produced in transgenic mice deposits is a major component of amyloid fibrils in various organs and tissues  thus this animal model is useful for analyzing how amyloid deposition initiates and proceeds in fap  
class10	keratin subsets in spindle cell sarcomas  keratins are widespread but synovial sarcoma contains a distinctive keratin polypeptide pattern and desmoplakins  the presence of individual keratin polypeptides and desmoplakins was immunohistochemically studied in 25 spindle cell sarcomas of different types using acetone fixed frozen sections  results revealed that keratins 8 and 18 were present in a high number of tumors  9 of 9 synovial sarcomas  5 of 7 leiomyosarcomas  5 of 5 malignant schwannomas  and 1 of 4 undifferentiated spindle cell sarcomas  in addition to keratins 8 and 18  the glandular component of synovial sarcoma showed prominent reactivity with antibodies to keratins 7 and 19  also the glandular epithelial cells in synovial sarcoma showed desmoplakin immunoreactivity preferentially in a luminal distribution  but desmoplakin was absent in other spindle cell sarcomas  furthermore keratin 13 was seen focally in 4 of 9 synovial sarcomas  in contrast  keratins 7  13  and 19 were practically absent in leiomyosarcomas  malignant schwannomas  and undifferentiated spindle cell sarcomas  the widespread presence of keratins 8 and 18 in various spindle cell sarcomas may reflect aberrant keratin expression in mesenchymal cells  previously described in cultured transformed fibroblasts  the presence of keratins 7 and 19 and desmoplakin is highly associated with morphologically observable epithelial differentiation restricted to synovial sarcoma among spindle cell sarcomas  
class10	substance abuse and cerebral blood flow  objective and method  this paper reviews acute and chronic effects of drugs of abuse on cerebral blood flow  cbf  and metabolism and their clinical significance  the most important source of information for the review is human research reports published in refereed journals  a few animal studies  book chapters  and abstracts that are especially relevant are also included  results  in humans  ethanol in small doses produces cerebral vasodilation  higher doses induce cerebral vasoconstriction  chronic alcoholism is associated with reduced cbf and cerebral metabolism  sedatives and antianxiety drugs lead to global reduction in cbf and cerebral metabolism  caffeine  even in small doses  is a potent cerebral vasoconstrictor  cerebral vasodilation is seen immediately after cigarette smoking  but chronic smokers show global reduction in cbf  changes in cbf after marijuana smoking are variable  both increases and decreases are seen  chronic marijuana smoking  however  seems to reduce cbf  most inhalants and solvents are vasodilators  chronic abuse is accompanied by a decrease in cbf  a number of drugs of abuse  including ethanol  amphetamines  cocaine  nicotine  and caffeine phenylpropanolamine combinations  increase the risk for stroke  reduction in cbf associated with chronic use of ethanol  nicotine  inhalants  and solvents is at least partially reversible upon abstinence  conclusions  topics for future research include regional brain function  which mediates drug induced mood changes  euphoria   cbf concomitants of psychological and physiological characteristics that increase addiction potential  changes in cbf that accompany withdrawal syndromes  mechanisms responsible for drug induced stroke  and effects of functional and organic complications on cbf  
class10	self injurious behavior  a review of the behavior and biology of self mutilation  objective  the authors describe the clinical characteristics of self injurious behavior  giving special emphasis to self injurious behavior occurring among individuals with character disorders  data collection  they review data suggesting the involvement of serotonergic  dopaminergic  and opiate neurotransmitter systems in the expression of self injurious behavior  findings  self injurious behavior occurs among mentally retarded individuals  psychotic patients  prison populations  and individuals with severe character disorders  although theoretical psychological models of self injurious behavior are helpful in understanding the patient s experience of self injury  no generally useful therapeutic approach has yet evolved from these models  data derived from animal models and treatment studies suggest the involvement of opiatergic and dopaminergic mechanisms in self injury among the mentally retarded  serotonergic influences on self injurious behavior may be present in varying forms of this behavior  the scientific literature on the benefits of pharmacological agents for mentally retarded individuals is beset with a number of problems  support is emerging  however  for the use of lithium and carbamazepine with self injuring mentally retarded patients  and some behavioral interventions appear to be successful for mentally retarded individuals  self injuring patients with borderline personality disorder may benefit from milieu treatment  conclusions  although no form of treatment has yet been demonstrated to be of general benefit  the literature suggests that therapeutic trials with dopamine antagonists  serotonin reuptake inhibitors  and opiate antagonists may be of value  
class10	a critical appraisal of mitogen induced lymphocyte proliferation in depressed patients  objective  the authors  goal was to evaluate the utility of mitogen induced lymphocyte proliferation assays in clinical research in psychoimmunology  method  they examined 23 depressed patients and 23 matched comparison subjects with this assay  there were no significant differences between these groups  they then combined the results of this study with the results of their previous study of 20 depressed patients and 20 comparison subjects to examine possible determinants of lymphocyte proliferation in depression  results  depressed patients with lower proliferative responses than their matched comparison subjects had lower depression subscale  anergia subscale  and total scores on the brief psychiatric rating scale than did patients with higher proliferative responses than their matched comparison subjects  this finding was unexpected and unexplained  depressed patients with lower proliferative responses than their matched comparison subjects also had fewer obsessions and compulsions and less psychomotor agitation according to the schedule for affective disorders and schizophrenia interview than did patients with higher proliferative responses than their matched comparison subjects  stepwise discriminant analysis and cluster analysis contributed little further understanding of the determinants of in vitro lymphocyte proliferation of cells from depressed patients  conclusions  longitudinal studies using multiple serial determinations of mitogen induced lymphocyte proliferation are the minimal design needed to make this assay useful in further evaluating any immune system changes in depression  
class10	depressive symptoms following stroke  objective  the primary purpose of this study was to assess the relation of lesion location to mood and vegetative disturbance following stroke  method  fifty two inpatients and outpatients who had had single  unilateral strokes were included  patients with past cns or psychiatric disorders were excluded  a modified visual analogue dysphoria scale was used to allow the inclusion of all but the most impaired aphasic patients  sleep and eating disturbances were measured by using both self report and nursing assessments  location of lesions was determined by ct scan and classified according to three dimensions  right left  dorsal ventral  and frontal nonfrontal  results  on measures of dysphoric mood and sleep disturbance  results indicated significant three way interactions among the three lesion dimensions  no differences were found with regard to eating disturbance  greater dysphoria and sleep disturbance were found in subjects with left parietal occipital  left inferior frontal  right superior frontal  and right temporal lesions than in subjects with lesions in other locations  depressive symptoms were not associated with functional impairment as measured by activities of daily living  motor strength  or severity of aphasia  conclusions  these results support the hypothesis that lesion location is a valid and significant factor in the mixture of influences which may result in a dysphoric mood state following stroke  the relation between the site of the lesion and subsequent depressive symptoms  however  may be more complex than has been reported previously  
class10	the nature and course of olfactory deficits in alzheimer s disease  objective  the aim of this study was to determine the specific nature and course of olfactory deficits in alzheimer s disease  previous studies had noted impaired odor identification  but there was no unanimity about the presence of odor detection deficits  method  odor identification was tested in 55 patients with alzheimer s disease and 57 elderly control subjects by using the university of pennsylvania smell identification test  odor detection was assessed in 46 subjects with alzheimer s disease and 40 control subjects by using a forced choice threshold test with geraniol as the odorant  results  significant deficits in olfactory identification were present in subjects who were in the earliest stages of cognitive impairment  and these deficits increased as alzheimer s disease progressed  there was some overlap in individual smell identification test scores between cognitively impaired patients and normal elderly subjects  on the other hand  odor detection deficits did not appear until alzheimer s disease was relatively advanced  smell identification test scores were correlated with mini mental state scores  but geraniol detection was not  conclusions  odor identification is impaired early in alzheimer s disease and may be more influenced by cognitive status than is acuity of odor detection  which is not altered until later in the disorder  the pattern of hyposmia in alzheimer s disease suggests that the disorder may not  begin in the nose   as has been theorized previously  further refinement of olfactory testing may be useful in the diagnostic evaluation of early dementia  
class10	nonfearful panic disorder in neurology patients validated by lactate challenge  objective  nonfearful panic disorder meets the dsm iii r criteria for panic disorder but is not associated with subjective fear and anxiety  the authors determined its prevalence in a group of neurology patients and assessed its diagnostic validity as a panic disorder subtype by evaluating the response of the patients with nonfearful panic disorder to sodium lactate and antipanic pharmacotherapy  method  the subjects were all neurology patients referred over 1 year to a university hospital s psychiatric consultation service because of negative medical workups for their symptoms  n   48   patients who met the dsm iii r criteria for panic disorder but did not report subjective anxiety or fear during panic episodes were diagnosed as having nonfearful panic disorder  afterward  each of those patients received a sodium lactate infusion and  5 hours later  a sodium chloride infusion  they were then treated with antipanic medication and followed for at least 6 months  results  of the 48 neurology patients referred for psychiatric evaluation  11  23   met the criteria for panic disorder  and all 11 met the criteria for nonfearful panic disorder  all 11 responded positively to lactate but not to placebo  and they each experienced an at least 75  reduction in symptoms during the 6 month follow up period  detailed case reports of three of these patients are presented  conclusions  these findings support the construct and predictive diagnostic validity of nonfearful panic disorder as a subtype of panic disorder and suggest that a lack of attention to this group leads to both the underestimation of the prevalence of panic disorder and to the withholding of potentially successful treatments for this group  
class10	ultrastructural evidence of a merocrine secretion in the human endolymphatic sac  the results of a light and transmission electron microscopic analysis of an endolymphatic sac  es  from a patient suffering from episodic vertigo  tinnitus  and hearing loss are presented  a biopsy of the intraosseous portion of the es was obtained during a translabyrinthine approach to section the vestibular nerve in the internal acoustic meatus  the material consisted mainly of tubular epithelial structures filled with heavily stained material  pathologically dilated and degranulated rough endoplasmic reticuli and disaggregation of polyribosomes with accumulation of solitary ribosomes in the cytosol and endoplasmic reticulum suggested a disturbed epithelial cell protein synthesis  ultrastructural evidence of an increased merocrine secretion of glycoprotein conjugates into the es was noted  this made it possible to analyze the presumed intracellular secretory pathways  an increased number of intraepithelial lymphocytes and monocytes was observed  since the inner ear had been subjected to surgical intervention before the vestibular nerve section  no conclusions can be drawn as to whether the patient s symptoms were related to the disturbed protein metabolism and hypersecretion of glycoprotein conjugates into the es  the findings support earlier experimental results that indicate that the es has not only a resorptive function but also a secretory one  
class10	organ procurement in patients with fatal head injuries  the fate of the potential donor  a 46 month  retrospective review of all victims of fatal head injury at a level 1 trauma center was undertaken to estimate donor organ availability  determine causes of procurement failure  and analyze the functional results of organs transplanted from this group of donors  causes of procurement failure in 126 patients who died principally from their head injuries included failure of initial resuscitation  14    ineligibility  28    failure of physiologic support  14    and denial of consent  20    of 73 eligible donors  29  41   were able to donate one or more vascular organs  heart  liver  kidney   in only one instance was an eligible donor not appropriately identified as such  failure of physiologic support to prevent early death  25    and denial of consent  34   were found to be the two major  potentially remediable causes of procurement failure in this series  based on this data  an estimated 29 patients million population year will survive initially and meet all eligibility requirements for organ donation  data on 47 kidneys transplanted from the donor group demonstrated a 77  overall graft survival rate at a follow up period averaging 23 months  prolonged donor hypotension  but not the use of high dose vasopressors  adversely affected allograft survival  the current limitations of organ procurement in victims of fatal head injury stem from a limited ability to maintain cardiopulmonary function long enough for the procurement process to be completed and a high overall rate  46   of denial of consent for organ harvest by next of kin  
class10	lipids  vascular disease  and dementia with advancing age  epidemiologic considerations  elevated plasma lipid and lipoprotein levels are associated with an increased risk of cardiovascular disease in middle aged men and women  it is still not clear  however  whether lipid and lipoprotein abnormalities continue to be risk factors for cardiovascular disease in the elderly population  it is not even clear what normal lipid values are in the elderly  and whether diet or drug therapy should be advised on the basis of lipid values established in middle aged populations  ischemic heart disease does remain the leading cause of death in the elderly  and there is now preliminary evidence from epidemiologic studies that relative elevations of levels of lipid and lipoprotein fractions in an elderly population might be associated with an independent and increased risk of coronary heart disease  stroke  and possibly dementia  intervention studies are about to begin that will assess various lipid and lipoprotein modifying therapies and their ability to reduce vascular disease risk in the elderly  
class10	giant cell arteritis  a case with unusual neurologic manifestations and a normal sedimentation rate  giant cell  temporal  arteritis is a serious inflammatory condition that can lead to blindness  stroke  or other adverse sequelae if not properly treated  an elevated erythrocyte sedimentation rate has traditionally been emphasized as a criterion for making this diagnosis  delays in diagnosis and unnecessary testing may occur when a patient presents with a normal erythrocyte sedimentation rate and a clinical history consistent with this condition  we describe a patient with giant cell arteritis who presented with a normal erythrocyte sedimentation rate and who subsequently developed devastating central nervous system complications  
class10	p300 brain activity in seizure patients preceding temporal lobectomy  event related potentials were recorded over occipital and parietal scalp from 20 patients suffering from intractable partial complex seizures prior to undergoing a temporal lobectomy  subjects were presented with language and nonlanguage visual stimuli using a divided field   odd ball  paradigm  although behavioral performance  button press accuracy  reaction time  and running counts  was comparable across all groups  although accuracy was worse for those in the left temporal group   patients showed tremendous variability in both the amplitude and latency of the p300 response  particularly notable was the observation that more slow wave activity was present among the patients than among the control subjects  and those scheduled for a left temporal resection evinced more amplitude reduction than those scheduled for a right temporal resection  in addition  a number of patients appeared not to show a p300 response at all  these results are discussed in the context of the utility of using noninvasive event related potential measures to examine both memory impairment and the integrity of the neural structures that mediate memory functioning in certain patient populations  
class10	age at onset of alzheimer s disease  relation to language dysfunction  a later age at onset of alzheimer s disease  ad  was found to be related to diminished language performance in 86 patients with probable ad  a hierarchical linear model was constructed to assess effects of age at onset and disease duration on the performance of patients with ad on four language tasks  naming  reading  auditory comprehension  and writing to dictation  after controlling for disease severity  results of univariate analysis  in which the dependent variable was the averaged language task performances  revealed a significant effect for age at onset of ad  but not for disease duration  to assess the possibility that the relationship between the age at onset of ad and language performance reflects effects of normal aging  the language tasks were given to 33 normal subjects of similar ages who scored perfectly on dementia severity measures  a convincing relationship was not found between test score and age  
class10	the distribution of cerebral muscarinic acetylcholine receptors in vivo in patients with dementia  a controlled study with 123iqnb and single photon emission computed tomography  a high affinity muscarinic receptor antagonist  123iqnb  3 quinuclidinyl 4 iodobenzilate labeled with iodine 123   was used with single photon emission computed tomography to image muscarinic acetylcholine receptors in 14 patients with dementia and in 11 healthy controls  high resolution single photon emission computed tomographic scanning was performed 21 hours after the intravenous administration of approximately 5 mci of iqnb  in normal subjects  the images of retained ligand showed a consistent regional pattern that correlated with postmortem studies of the relative distribution of muscarinic receptors in the normal human brain  having high radioactivity counts in the basal ganglia  occipital cortex  and insular cortex  low counts in the thalamus  and virtually no counts in the cerebellum  eight of 12 patients with a clinical diagnosis of alzheimer s disease had obvious focal cortical defects in either frontal or posterior temporal cortex  both patients with a clinical diagnosis of pick s disease had obvious frontal and anterior temporal defects  a region of interest statistical analysis of relative regional activity revealed a significant reduction bilaterally in the posterior temporal cortex of the patients with alzheimer s disease compared with controls  this study demonstrates the practicability of acetylcholine receptor imaging with 123iqnb and single photon emission computed tomography  the data suggest that focal abnormalities in muscarinic binding in vivo may characterize some patients with alzheimer s disease and pick s disease  but further studies are needed to address questions about partial volume artifacts and receptor quantification  
class10	widespread functional effects of discrete thalamic infarction  in order to investigate functional effects of various thalamic structures on metabolism in remote  morphologically intact cerebral regions  we used positron emission tomography of  18f  2 fluoro 2 deoxy d glucose to study regional cerebral metabolic rates of glucose  rcmrglu  in 11 patients with chronic unilateral or bilateral infarcts strictly confined to the thalamus  patients were grouped according to computed tomographic scans showing anterior  three   medial  four   or posterior  four  lesions  compared with a matched group of 11 healthy subjects  hemispheric cmrglu 35 2     3 49 mumol 100 g per minute   glucose metabolism was significantly lower in the hemisphere ipsilateral to the infarction  31 2     2 97 mumol 100 g per minute   patients with bilateral infarcts had lower hemispheric cmrglu  29 9     2 74 mumol 100 g per minute  than those with unilateral lesions  32 2     2 97 mumol 100 g per minute   depending on infarct location within the thalamus  there was differential depression of rcmrglu  with the largest effects on frontal and occipital areas in medial infarctions  except for ipsilateral thalamic deactivation  metabolic patterns with anterior thalamic infarcts were close to normal  while posterior infarcts mostly depressed rcmrglu in the visual and in the inferior limbic cortex  cerebellar metabolic rates were within normal limits in most cases  these patterns of regional cerebral deactivation may be related to categories of thalamic projections  intrathalamic  to limbic system and basal ganglia  diffuse to most cortical areas  and specific to defined neocortical areas  even small brain lesions may have widespread functional sequelae  potentially demonstrable by positron emission tomography  
class10	spectral analysis of heart rate in diabetic autonomic neuropathy  a comparison with standard tests of autonomic function  power spectral analysis of the heart rate was compared with standard tests of autonomic function performed on 15 insulin dependent diabetic patients with symptoms of autonomic dysfunction  the high frequency power  low frequency power  and total power of the heart rate power spectrum measured in the supine position  possible measures of parasympathetic nervous system function  were significant predictors of the expiratory inspiratory ratio  the beat to beat heart rate difference on deep respiration  the standard deviation of the resting heart rate  the 30 15 ratio  and the valsalva ratio  the change in low frequency power on moving from the supine to upright position  a possible measure of sympathetic nervous system function  was a modest predictor of the systolic and diastolic blood pressure fall in response to postural change  but a poor predictor of the blood pressure response to isometric exercise and a cold stimulus  this study supports the role of heart rate power spectral analysis as a clinical test of autonomic function in patients with known or suspected autonomic failure  
class10	alterations in brain phosphate metabolite concentrations in patients with human immunodeficiency virus infection  human immunodeficiency virus  hiv  infected individuals often demonstrate neuropsychiatric impairment  however  it is unclear how brain metabolism may be altered in such patients  we used in vivo phosphorus 31 magnetic resonance spectroscopy to noninvasively assess brain energy and phospholipid metabolism by measuring brain concentrations of adenosine triphosphate  atp   phosphocreatine  pcr   and inorganic phosphate  pi   as well as phospholipid compounds and intracellular ph  in study 1  17 hiv seropositive men with varying degrees of neuropsychiatric impairment and six control subjects were studied  localized spectra were obtained from a heterogeneous 5 x 5 x 5 cm volume of interest  voi   patients with hiv infection had a significantly lower atp pi ratio and a trend for a lower pcr pi ratio than did the control group  in addition  the atp pi and pcr pi ratios were both significantly negatively correlated with overall severity of neuropsychiatric impairment  in study 2  three hiv seropositive men with neuropsychiatric impairment were compared with 11 hiv seronegative men  localized phosphorus 31 magnetic resonance spectra were obtained from two relatively homogeneous vois   1  a predominantly white matter voi  and  2  a predominantly subcortical gray matter voi  the three hiv infected patients demonstrated significantly decreased atp and pcr concentrations in the white matter voi  these results suggest that hiv infection of the brain may impair brain cellular oxidative metabolism and that the degree of metabolic compromise may be related to the severity of neuropsychiatric impairment  
class10	the effect of sleep on the dyskinetic movements of parkinson s disease  gilles de la tourette syndrome  huntington s disease  and torsion dystonia  the effect of sleep on the involuntary movements or dyskinesias in parkinson s disease  huntington s disease  primary and secondary torsion dystonia  and gilles de la tourette syndrome was studied in a total of 52 patients and 10 normal subjects using video electroencephalographic telemetry  movements typical of the wake pattern were seen occasionally during unequivocal sleep in all but two completed studies  and in each condition reappeared under similar circumstances  the movements were most likely to occur after awakenings or lightenings of sleep  or in stage one sleep  the movements were very rare during the deeper phases of sleep  those movements that occurred during sleep without awakenings were usually preceded by arousal phenomena and  rarely  by sleep spindles or slow waves  the control group showed normal  semipurposeful  movements under the same conditions during sleep  the rare appearance of the different dyskinesias and normal movements under similar circumstances during sleep could be a result of common effects on the generator systems or changes in the excitability of the final common motor pathway  
class10	intravenous immunoglobulin treatment in patients with chronic inflammatory demyelinating polyneuropathy  clinical and laboratory characteristics associated with improvement  of 52 patients fulfilling the criteria of chronic inflammatory demyelinating polyneuropathy  20  38   did not improve after intravenous immunoglobulin treatment  two  4   had a short lasting improvement and subsequent infusions had no effect  nine  17   reached a spontaneously or therapeutically induced complete remission  and 21 patients  40   needed intermittent infusions to maintain improvement  all patients who improved initially had symptoms that significantly interfered with life style  after treatment  90  of these patients were independent in their daily activities  significantly associated with improvement were disease duration of less than 1 year  progression of weakness until treatment  absence of discrepancy in weakness between arms and legs  areflexia of the arms  and slowed nerve conduction velocity of the motor median nerve  the probability of improvement if all these features are present in 93   
class10	posttraumatic torticollis  we report six cases of torticollis precipitated by neck trauma  the dystonia began 1 to 4 days after the trauma and differed clinically from idiopathic torticollis by marked limitation of range of motion  lack of improvement after sleep   honeymoon period    and absence of geste antagonistique  worsening with action was not present  nor was there improvement with support as seen with idiopathic torticollis  onset of pain immediately after the trauma and marked spasms of the paracervical muscles were other predominant features  anticholinergic therapy was without benefit  however  some improvement occurred with botulinum toxin injection  it is concluded that torticollis can be caused by peripheral trauma and that it has unique clinical characteristics  
class10	an early description of slowly progressive aphasia  slowly progressive aphasia without generalized dementia has become an important issue of present day neuropsychological research  historically  credit for the first description is usually given to pick  another german speaking author who has published a vivid description of a pertinent cases is pick s contemporary  max rosenfeld  this author has also observed a patient with slowly progressive spatial disorientation and visual recognition deficit  and he has discussed these patients in a remarkably modern way in the context of partial atrophy of the brain  
class10	frontal impairment and hypoperfusion in neuroacanthocytosis  cerebral blood flow tomography  by xenon 133 inhalation or hmpao  99mtc d  l hexamethyl propylene amine oxime  technetium tc 99m injection  revealed a severe hypoperfusion in both frontal lobes of a 40 year old woman with confirmed neuroacanthocytosis  this finding occurred in conjunction with neuropsychological deficits consistent with selective frontal lobe dysfunction  this observation is the first documentation of this type of dementia in neuroacanthocytosis  
class10	visual evoked potentials and visual prognosis following perinatal asphyxia  twenty five children born at term with perinatal asphyxia were studied at age 2 5 to 4 5 years to evaluate visual function and to determine the prognostic value of postnatal assessments of visual outcome  postnatal assessments included several visual evoked potentials and electroretinograms in the first week of life  follow up assessments included flash and pattern visual evoked potentials  visual evoked potential threshold measurements  and clinical eye examinations  nineteen children had normal visual function  three were visually impaired  and three remained blind  a strong association was found between normal  abnormal  or absent visual evoked potentials in the early postnatal period and long term visual outcome  p less than  0001   other perinatal indicators of asphyxia  including neurologic status  apgar scores  and arterial ph values  were poor predictors of visual outcome  the risk of visual impairment was limited to those survivors with neurodevelopmental deficits  
class10	trial of brief intermittent neuroleptic prophylaxis for selected schizophrenic outpatients  clinical and social outcome at two years  objective  to evaluate a novel approach to the prophylaxis of schizophrenic relapse characterised by administration of brief courses of neuroleptic for the earliest non psychotic signs of relapse  prodromal symptoms   design  two year follow up of subjects randomised  double blind  to receive either active  control group  or placebo  intermittent group  depot neuroleptic medication  both groups received brief courses of oral neuroleptic when prodromal symptoms or relapse occurred  setting  psychiatric outpatient department  charing cross hospital  london  subjects  54 stable patients in remission who met the american psychiatric association s dsm iii criteria for schizophrenia on the basis of case notes  main outcome measures  survival without relapse  survival without hospitalisation  point prevalence of extrapyramidal side effects and tardive dyskinesia  structured assessment of social functioning  social adjustment scale ii   and frequency of prodromal symptoms  results  of 19 relapses recorded over two years  10  53   were preceded by non psychotic prodromal signs  survival rates for both relapse and hospitalisation were worse with intermittent treatment than continuous treatment over the two year follow up  92  of controls and only 54  of patients given intermittent treatment survived the two year period without hospitalisation  prolonged or frequent relapses as well as episodes of prodromal symptoms were more frequent with intermittent treatment  lower scores for extrapyramidal side effects were recorded in the intermittent treatment group  but periodic assessments of social functioning failed to show any social advantages from this  conclusion  the findings are at variance with a previous report of one year follow up in this cohort and attest to the superiority of continuous depot neuroleptic prophylaxis in preventing both psychotic and neurotic or dysphoric morbidity in schizophrenia  
class10	prevalence of acute mountain sickness in the swiss alps  objective  to assess the prevalence of symptoms and signs of acute mountain sickness of the swiss alps  design  a study using an interview and clinical examination in a representative population of mountaineers  positive symptoms and signs were assigned scores to quantify the severity of acute mountain sickness  setting  four huts in the swiss alps at 2850 m  3050 m  3650 m  and 4559 m  subjects  466 climbers  mostly recreational  47 at 2850 m  128 at 3050 m  82 at 3650  and 209 at 4559 m  results  in all  117 of the subjects were entirely free of symptoms and clinical signs of acute mountain sickness  191 had one or two symptoms and signs  and 158 had more than two  those with more than two symptoms and signs were defined as suffering from acute mountain sickness  at 4559 m 11 climbers presented with high altitude pulmonary oedema or cerebral oedema  or both  men and women were equally affected  the prevalence of acute mountain sickness correlated with altitude  it was 9  at 2850 m  13  at 3050 m  34  at 3650 m  and 53  at 4559 m  the most frequent symptoms and signs were insomnia  headache  peripheral oedema  and scanty pulmonary rales  severe headache  vomiting  dizziness  tachypnoea  and pronounced pulmonary rales were associated with other symptoms and signs and therefore characteristic of acute mountain sickness  conclusion  acute mountain sickness is not an uncommon disease at moderately high altitude  that is  above 2800 m  severe headache  vomiting  dizziness  tachypnoea  and pronounced pulmonary rales indicate severe acute mountain sickness  and subjects who suffer these should immediately descend to lower altitudes  
class10	prognosis of wilsonian chronic active hepatitis  twenty of 320 patients with wilson s disease initially presented with chemical and laboratory features of chronic active hepatitis  confirmed histologically in 17  when first seen  cirrhosis was present in all 20 and was complicated by ascites and or jaundice in 11  within 1 week to 8 years of the onset of over liver disease the diagnosis of wilson s disease was established  and treatment with d penicillamine was promptly initiated in 19 patients  one man refused treatment and died 4 months later  treated patients received d penicillamine or trientine for a total of 264 patient years  median  14 patient years   abnormal water retention  for which salt restriction and diuretics were added to penicillamine or trientine  disappeared in all but 1 of the patients so affected  symptomatic improvement and virtually normal levels of serum albumin  bilirubin  aspartate aminotransferase  and alanine aminotransferase followed within 1 year in the majority of subjects  one woman died after 9 months of treatment  two patients  who became noncompliant with the therapeutic regimen after 9 and 17 years of successful pharmacological treatment  required liver transplants  these results indicate that the prognosis of specifically treated wilsonian chronic active hepatitis is very good in spite of the presence of cirrhosis  
class10	hereditary internal anal sphincter myopathy causing proctalgia fugax and constipation  a newly identified condition  a newly identified myopathy of the internal anal sphincter is described  in the affected family  at least one member from each of five generations had severe proctalgia fugax  onset was usually in the third to fifth decades of life  three members of the family have been studied in detail  each had severe pain intermittently during the day and hourly during the night  constipation was an associated symptom  in particular difficulty with rectal evacuation  clinically the internal anal sphincter was thickened and of decreased compliance  the maximum anal canal pressure was usually increased with marked ultraslow wave activity  anal endosonography confirmed a grossly thickened internal anal sphincter  two patients were treated by internal anal sphincter strip myectomy  one showed marked improvement and one was relieved of the constipation but had only slight improvement of the pain  the hypertrophied muscle in two of the patients showed unique myopathic changes  consisting of vacuolar changes with periodic acid schiff positive polyglycosan bodies in the smooth muscle fibers and increased endomysial fibrosis  in vitro organ bath studies showed insensitivity of the muscle to noradrenaline  isoprenaline  carbachol  dimethylpiperazinium  and electrical field stimulation  immunohistochemical studies for substance p  calcitonin gene related peptide  galanin  neuropeptide y  and vasoactive intestinal peptide showed staining in a similar distribution to that in control tissue  a specific autosomal dominant inherited myopathy of the internal anal sphincter that causes anal pain and constipation has been identified and characterized  
class10	management of pseudarthrosis after arthrodesis of the spine for idiopathic scoliosis  sixty three first  second  or third time repairs of one or more pseudarthroses were done in fifty one patients who had had an arthrodesis for idiopathic scoliosis  forty five of the patients were female and six were male  the average age was 30 2 years  the indications for the sixty three repairs were pain  twenty five repairs   progression of the curve  sixteen   both pain and progression of the curve  twelve   and radiographic changes only  ten   failure of the implant was identified before 27 per cent of the sixty three procedures  the pseudarthroses were diagnosed an average of 2 8 years after the initial arthrodeses  sixty eight per cent of the defects were visible on plain radiographs preoperatively and 32 per cent were identified at operation  during the time between the original arthrodeses and the repairs of the pseudarthroses  the scolioses increased by a mean of 7 degrees and the kyphoses  by a mean of 10 degrees  harrington distraction was the most commonly used instrumentation  twenty six  41 per cent  of the sixty three procedures   and autogenous iliac bone was the most commonly used material for the graft  thirty three  52 per cent  of the procedures   
class10	valgus deformities of the feet and characteristics of gait in patients who have rheumatoid arthritis  to investigate the cause of valgus deformity of the hindfoot in patients who have rheumatoid arthritis and to characterize the effects of the deformity on gait  two groups of patients were evaluated clinically  radiographically  and with gait analysis in the laboratory  group 1 consisted of seven patients who had seropositive rheumatoid arthritis and normal alignment of the feet and group 2  of ten patients who had rheumatoid arthritis and valgus deformity of the hindfoot  in group 2  the disease was of longer duration and the feet were more painful than in group 1  there was no evidence of muscular imbalance  equinus contracture  valgus deformity of the tibiotalar joint  or isolated deficiency of the tibialis posterior  such as weakness  tenosynovitis  or rupture of the tendon  that could have contributed to the development of the valgus deformity  in the patients who had valgus deformity  quantitated electromyography demonstrated that the intensity and duration of activity of the tibialis posterior was significantly increased  apparently in an effort to support the collapsing longitudinal arch of the foot  gait studies revealed decreases in velocity  stride length  and single limb support time  as well as delayed heel rise in both groups  but the decreases were more marked in the patients who had valgus deformity  the results of this study suggest that valgus deformity of the hindfoot in rheumatoid patients results from exaggerated pronation forces on the weakened and inflamed subtalar joint  these forces are caused by alterations in gait secondary to symmetrical muscular weakness and the effort of the patient to minimize pain in the feet  radiographs also suggested an association between the valgus deformity of the feet and valgus deformity of the knees in patients who have rheumatoid arthritis  
class10	reconstruction of the chronically insufficient anterior cruciate ligament with the central third of the patellar ligament  the results of reconstruction of the anterior cruciate ligament with the central third of the patellar ligament as a free  autogenous  non vascularized graft were retrospectively reviewed at our institution  eighty reconstructions in seventy nine patients were evaluated after a minimum of two years  in forty eight  60 per cent  of the knees  the reconstruction was augmented with an extra articular lateral sling of iliotibial band  the patients were evaluated with a physical examination  a kt 1000 arthrometer  radiographs  a subjective questionnaire  and a revision of the scale of the hospital for special surgery for rating ligaments  postoperatively  seventy six  95 per cent  of the eighty knees no longer gave way  and the pivot shift test was negative in sixty seven  84 per cent  of the knees  the average score on the ligament rating scale was 93 points  all of the patients who had clinical instability at the time of the most recent follow up had associated ligamentous instability that had not been appreciated or addressed at the time of reconstruction  arthrometric evaluation revealed that the laxity differed by three millimeters or less from that of the untreated knee in sixty  76 per cent  of the treated knees  in the patient who had bilateral reconstruction  the laxity was the same in both knees  seventeen patients  who had more than three millimeters of translation  also had additional related ligamentous instability  most commonly posterolateral instability and insufficiency of the medial collateral ligament  we think that major associated ligamentous instability predisposes the reconstruction to failure and should be corrected in conjunction with the reconstruction  
class10	the automatic implantable cardioverter defibrillator  effect of patch polarity on defibrillation threshold  an automatic implantable cardioverter defibrillator  aicd  was implanted in 40 patients with sudden cardiac arrest  n   29   sustained monomorphic ventricular tachycardia  n   10  or recurrent syncope  n   1  who were unsuitable for direct ablative surgery or had had unsuccessful medical therapy  the effect of patch electrode polarity on the defibrillation threshold was prospectively evaluated  two large epicardial patches were used  initial polarity was selected at random  ventricular fibrillation was induced by direct current and a preestablished defibrillation protocol employed to assess the minimal energy that would reproducibly defibrillate the heart  nineteen patients had a lower defibrillation threshold with the inferior left ventricular patch as an anode and nine patients had a lower defibrillation threshold with this patch as a cathode  in general  the defibrillation threshold was lower when this patch was used as an anode than when it was used as a cathode  18     10 versus 22 6     12 2 j  p less than 0 01   no preoperative variable predicted optimal polarity  therefore  the effect of patch polarity on defibrillation threshold should be assessed in each patient at the time of aicd implantation so that the safety margin for satisfactory device function can be maximized  
class10	comparison of motor response to apomorphine and levodopa in parkinson s disease  the magnitude and pattern of motor responses to single doses of subcutaneous apomorphine and oral levodopa were compared in 14 patients with parkinson s disease  although apomorphine produced much shorter motor responses than levodopa  the quality of response to the two drugs was virtually indistinguishable  these clinical observations support the notion that integrity of striatal post synaptic dopamine receptors is a key determinant of responsiveness to dopaminergic treatment in parkinson s disease  
class10	evaluation of vigabatrin as an add on drug in the management of severe epilepsy  the effects of the addition of vigabatrin  a new anti epileptic drug  to the therapy of 128 patients with severe medically refractory epilepsy is reported  forty two  33   of patients experienced side effects  which were predominantly neurotropic  in 28  22    the drug was withdrawn because of these side effects  the commonest side effects were drowsiness and behavioural change  the remaining 100 patients were followed for a mean of 30 weeks  range 12 75   forty one of these patients showed a marked improvement in seizure frequency  a 50  or more reduction when compared with the pre trial period   and nine  7   were rendered seizure free  apparent tolerance to the effects of the drug were noted in five patients  an exacerbation of seizures may occur if the drug is withdrawn too quickly  vigabatrin appears to be a promising new anti epileptic drug  
class10	early onset dementia and extrapyramidal disease  clinicopathological variant of gerstmann straussler scheinker or alzheimer s disease  a case of progressive dementia and extrapyramidal signs beginning at age 29  with a ten year course until death  is presented  necropsy examination showed an assortment of plaque types  including striatal plaques   neurofibrillary tangles  granulovacuolar degeneration  and depigmentation of the substantia nigra and locus ceruleus  this case had pathological features found in both gerstmann straussler scheinker disease and in alzheimer s disease  while somewhat similar to several other cases with features of both diseases  it differs in the presence of dystonia and striatal plaques  although such cases may be difficult to categorize at present  they must be considered in the differential diagnosis of early onset dementia  
class10	diagnostic value of anti neuronal antibodies for paraneoplastic disorders of the nervous system  the diagnostic value of the presence of anti neuronal antibodies in serum was examined in 21 patients suspected of paraneoplastic disorders of the nervous system  ns   group 1  and was compared to three control groups  group 2  25 patients with a neurological disease  without cancer and no sign of paraneoplastic disorder  group 3  27 patients with neurological disease and cancer and no signs of a paraneoplastic disorder  group 4  94 patients with cancer and without neurological disease  in group 1  anti neuronal nuclear antibodies were detected in eight patients  38    in titres from 1 1000 to 1 32 000  a small cell lung cancer was present in six patients  ovarian cancer in one patient and in one patient no tumour could be detected  the neurological symptoms preceded a diagnosis of cancer in five out of eight patients  anti neuronal antibodies were found in the serum of two out of 94 patients  2   from control group 3 but not in serum from any of the other control groups  these data indicate a moderate sensitivity of 38   but a high specificity of 98 6   95  confidence interval 95 5 99 8   for the presence of anti neuronal nuclear antibodies if a paraneoplastic ns disorder is suspected  
class10	diurnal differences in response to oral levodopa  diurnal differences in duration and quality of motor response to levodopa are frequently described by patients  the quality and duration of motor responses were objectively assessed to morning and afternoon oral levodopa doses in five patients with parkinsonian motor fluctuations who complained of diurnal variation in response to their normal levodopa medication  results suggest that under controlled conditions which eliminated the effects of diet and overlapping levodopa effects the response to levodopa remained unchanged throughout the day  and that the duration of response could be predicted by plasma levodopa levels  
class10	vitamin b12 and folate concentrations in serum and cerebrospinal fluid of neurological patients with special reference to multiple sclerosis and dementia  vitamin b12 and folate concentrations were measured in serum and cerebrospinal fluid  csf  in 293 neurological patients  serum and csf vitamin b12 concentrations showed a positive correlation  in individual patients csf b12 concentrations varied considerably for a given serum concentration  the median serum vitamin b12 concentration of the alzheimer s type dementia group was significantly lower compared with that of a control group  lower median csf vitamin b12 concentrations were found in groups of patients with multiple sclerosis and alzheimer s type dementia  five patients with heterogeneous clinical pictures had unexplained low serum and csf b12 concentrations without macrocytosis  two patients had very high serum b12 and low normal csf concentrations which could be explained by a blood brain barrier transport defect  serum and csf folate concentrations did not show significant differences between the various groups  
class10	clinical diagnosis of binswanger s disease  to aid in the prospective study of binswanger s disease  a poorly understood form of vascular dementia  a standardised criteria for its antemortem diagnosis was proposed  these criteria include dementia  bilateral radiological abnormalities on computed tomography  ct  or magnetic resonance imaging  mri   and at least two of the following three clinical findings  a  a vascular risk factor or evidence of systemic vascular disease  b  evidence of focal cerebrovascular disease  and c  evidence of  subcortical  cerebral dysfunction  these criteria were validated in two ways  first  by retrospectively applying them to a series of 30 demented patients with various pathological diagnoses  second  by prospectively applying them to a series of 184 patients with clinically typical alzheimer s disease  the sensitivity and specificity of the criteria appear adequate for use in clinical research  
class10	a simple method to improve the accuracy of non invasive ultrasound in selecting tia patients for cerebral angiography  a prospective study is reported of the ability of b mode ultrasound imaging and continuous wave doppler flow studies to detect different degrees of stenosis of the extracranial internal carotid artery  ica  in 186 arteries in 99 patients with transient ischaemic attacks  tia  and minor ischaemic stroke  a simple mathematical equation has been developed which combines the image and flow data to provide a single predictor of the degree of angiographic stenosis which has advantages over either ultrasonic modality used alone  the sensitivity and specificity of the predictive model in the detection of stenosis greater than or equal to 25  was 73  and 98   of stenosis greater than or equal to 50  was 90  and 93   of stenosis greater than or equal to 75   65  and 99  and occlusion 100  and 94  respectively  the principal clinical value of ultrasound screening is to spare patients with  non significant  stenosis the risk of unnecessary angiography  thus a simple measure of the duplex screening tests  performance is the proportion of all strokes occurring as a complication of angiography that are avoided by changing the investigation policy from  angiograms for all carotid tia and minor ischaemic stroke patients  to  angiograms for all patients with abnormal ultrasound results   if duplex scanning were used to select patients most likely to have a significant abnormality on angiography  depending on the degree of stenosis to be detected  52 85  of angiographic strokes might be avoided  if the predictive equation were used 62 88  of angiographic strokes might be avoided  
class10	the accuracy of predictions about progress of patients on a stroke unit  the aim of the study was to check the accuracy of predictions about the factors which affect the progress  in physical abilities and activities of daily living  of patients admitted to a stroke unit  a series of 60 patients admitted consecutively to a stroke unit were assessed on tests of motor  functional and cognitive abilities at admission  on the basis of these assessments predictions were made about the abilities of the patients at discharge  patients were assessed for level of motor abilities and activities of daily living at discharge and the accuracy of the predictions checked  predictions were found to be significantly correlated with outcome but the relationships were not so close as to be useful for the clinical management of individual patients  
class10	spectral analysis of tremor  understanding the results  spectral analysis of a tremor record can sometimes produce a spectrum with multiple components of significant amplitude  the problem is to determine whether the presence of several peaks represents the coexistence of separate tremor mechanisms or be a consequence of fluctuations in the frequency or amplitude of a single tremor  the spectrum of a tremor whose frequency or amplitude vary and are independent has the recognisable pattern of a central carrier frequency with sidebands of equal amplitudes distributed symmetrically around the carrier  however  if tremor amplitude and frequency fluctuate and are not independent   frequency proportional to amplitude or frequency inversely proportional to amplitude   the spectrum has a pattern of sidebands which are asymmetrical in amplitudes and may resemble the spectrum of the combined signal from different independent oscillators  the investigation of sidebands in spectra has been neglected in tremor studies and multiple irregular peaks on a tremor spectrum have sometimes been used wrongly as evidence for the coexistence of multiple tremor mechanisms or frequency components assumed to be concurrent  
class10	shy drager syndrome  effect of fludrocortisone and l threo 3 4 dihydroxyphenylserine on the blood pressure and regional cerebral blood flow  in nine cases of shy drager syndrome  the changes in blood pressure and cerebral blood flow on sitting up from a supine position were studied  the influence of fludrocortisone  a synthetic mineralocorticoid  and l threo 3 4 dihydroxyphenylserine  dops   a precursor of norepinephrine  on these changes was examined  on sitting up  the regional cerebral blood flow  rcbf  measured by xe133 inhalation showed a tendency to decrease  fludrocortisone reduced the fall of the mean blood pressure significantly  dops reduced the fall of both the diastolic blood pressure and rcbf significantly  
class10	hydromyelic hydrocephalus  correlation of hydromyelia with various stages of hydrocephalus in postshunt isolated compartments  the clinical features and pathophysiology of specific forms of hydromyelia are analyzed in this report together with the chronological changes of associated hydrocephalus  nine patients were studied  all had hydromyelia with varying degrees of associated hydrocephalus  clinically applicable classification systems were used to evaluate the progression of hydrocephalus  stages i to iv  and to define the compartment isolated after shunting in the previously communicating cerebral ventricles  types i to iv   four patients had stage iv disease  holoneural canal dilatation   one had stage ii and four had stage i disease  both stages i and ii with supratentorial hydrocephalus   all patients were initially treated by ventriculoperitoneal shunting at an average age of 9 9 years  five patients had progressive spinal symptoms before or after treatment of their hydrocephalus  two patients had type iii isolation  an isolated rhombencephalic ventricle  with a functioning ventricular shunt  ventriculography confirmed a communication between the fourth ventricle and the hydromyelia  and both patients improved after placement of a shunt in the fourth ventricle  the remaining patients had type iv isolation  isolated central canal dilatation  with a functioning ventricular shunt  this study indicates that in some cases the pathophysiology of hydromyelia is closely related to associated hydrocephalus  a new concept of the development of an isolated compartment after shunting is proposed to explain the progression of hydromyelia in these cases  
class10	functional outcomes following selective posterior rhizotomy in children with cerebral palsy  the recent increase in popularity of selective posterior rhizotomy demands objective documentation of surgical outcome  for this reason  the authors have analyzed the status of 25 children with spastic cerebral palsy before and after rhizotomy to determine the effects of this therapy on muscle tone  range of movement  and motor function  postoperative tests showed a reduction in muscle tone compared with preoperative assessments  range of motion in the lower extremities was significantly increased and improvements in functional gross motor skills were noted  an increase in range of motion in the knees and thighs during gait was detected in 18 ambulatory patients studied with computerized two dimensional motion analysis  preliminary findings indicate that selective posterior rhizotomy reduced spasticity  thereby increasing range of motion and contributing to improvements in active functional mobility  
class10	spontaneous neuronal hyperactivity in the medial and intralaminar thalamic nuclei of patients with deafferentation pain  electrical activity was recorded from single cells in the thalamus of 10 patients with chronic pain associated with deafferentation  under local anesthesia  these patients underwent either electrode implantation or thalamotomy for treatment of their pain  in eight of the 10 patients  single units were identified as discharging spontaneously in high frequency  often rhythmic  bursts  the discharges were of two types  short bursts comprised of two to six spikes with a burst frequency of one to four per second  and long trains of 30 to 80 spikes of similar frequency  reconstruction of electrode trajectories indicated that recordings were made from the region corresponding to the lateral aspect of the mediodorsal thalamic nucleus  the central lateral nucleus  a small part of the central median nucleus  and the parafascicular nucleus  in the eight patients in whom spontaneous neuronal burst activity was exhibited  it was impossible to study activity evoked by natural cutaneous stimulation due to the continuous spontaneous neuronal discharges  both animal and human studies have suggested that pain related to deafferentation is accompanied by spontaneous hyperactivity in the dorsal horn of the spinal cord and in the ventral posterior thalamic nuclei  the authors present evidence of spontaneous neuronal hyperactivity in the intralaminar thalamic nuclei of patients with pain related to deafferentation  the findings suggest that spontaneous neuronal discharge in patients with pain related to deafferentation is more widespread in the central nervous system than has been previously appreciated  the results have important implications for the surgical treatment of chronic pain  
class10	radical intracapsular removal of acoustic neurinomas  long term follow up review of 11 patients  historically  the neurosurgical treatment of large acoustic neurinomas has developed with two principal goals  complete tumor removal and preservation of facial nerve function  a recent goal for small tumors is the preservation of hearing  out of a personal series of 124 acoustic neurinomas treated over the past 35 years  the senior author has undertaken a radical intracapsular approach in 12 patients with large tumors  greater than 3 cm in diameter   surgical indications for intracapsular removal included advanced age  five cases   the patient s wish to avoid any risk of facial paralysis  six cases   contralateral facial palsy  one case   and contralateral deafness  one case   eleven of these 12 patients were available for follow up review  tumor recurrence developed in two patients  18   at 2 and 3 years postoperatively  there were no late recurrences  four patients died of unrelated causes  10 to 19 years after surgery  the remaining five patients have survived a mean of 12 years since surgery without recurrence  range 3 to 22 years   facial function was preserved in nine patients  82    the results suggest that radical intracapsular removal may be the procedure of choice under certain circumstances and may offer an alternative to focused high energy radiation  
class10	radiation induced optic neuropathy  a magnetic resonance imaging study  optic neuropathy induced by radiation is an infrequent cause of delayed visual loss that may at times be difficult to differentiate from compression of the visual pathways by recurrent neoplasm  the authors describe six patients with this disorder who experienced loss of vision 6 to 36 months after neurological surgery and radiation therapy  of the six patients in the series  two had a pituitary adenoma and one each had a metastatic melanoma  multiple myeloma  craniopharyngioma  and lymphoepithelioma  visual acuity in the affected eyes ranged from 20 25 to no light perception  magnetic resonance  mr  imaging showed sellar and parasellar recurrence of both pituitary adenomas  but the intrinsic lesions of the optic nerves and optic chiasm induced by radiation were enhanced after gadolinium diethylenetriaminepenta acetic acid  dtpa  administration and were clearly distinguishable from the suprasellar compression of tumor  repeated mr imaging showed spontaneous resolution of gadolinium dtpa enhancement of the optic nerve in a patient who was initially suspected of harboring recurrence of a metastatic malignant melanoma as the cause of visual loss  the authors found the presumptive diagnosis of radiation induced optic neuropathy facilitated by mr imaging with gadolinium dtpa  this neuro imaging procedure may help avert exploratory surgery in some patients with recurrent neoplasm in whom the etiology of visual loss is uncertain  
class10	relationship between body and brain temperature in traumatically brain injured rodents  recent work has shown that mild to moderate levels of hypothermia may profoundly reduce the histological and biochemical sequelae of cerebral ischemic injury  in the present study  the authors examined the effect of fluid percussion injury on brain temperature in anesthetized rats and the effect of anesthesia on brain temperature in uninjured rats  the relationship between the brain  rectal  and temporalis muscle temperatures during normothermia  hypothermia  and hyperthermia was studied following a moderate magnitude of fluid percussion brain injury  2 10 to 2 25 atmospheres  in rats  the results showed that mean brain temperature in 10 anesthetized injured rats  in 21 anesthetized uninjured rats  and in 10 unanesthetized uninjured rats was a mean      standard error of the mean  of 36 04 degrees     0 20 degrees c  36 30 degrees     0 08 degrees c  and 37 95 degrees     0 09 degrees c  respectively  there was no significant difference in temperature under general anesthesia between injured and uninjured rats  p greater than 0 05   in the absence of brain injury  mean brain temperature was significantly lower in anesthetized rats than in unanesthetized rats  p less than 0 001   in anesthetized brain injured rats  temporalis muscle temperature correlated well with brain temperature over a 30 degrees to 40 degrees c range  even when brain temperature was rapidly changed during induction of hypothermia or hyperthermia  r   0 9986  p less than 0 0001   in contrast  rectal temperature varied inconsistently from brain temperature  these observations indicated that  1  brain injury itself does not influence brain temperature in this model  2  anesthesia alone decreases brain temperature to levels producing cerebral protection in this model  and 3  external monitoring of temporalis muscle temperature can provide a reliable indirect measure of brain temperature in the course of experimental brain injury  the authors believe that it is essential to monitor or control brain temperature in studies of experimental brain injury  
class10	tethered cord syndrome from a choristoma of mullerian origin  case report  the authors report a case of tethered cord syndrome due to a choristoma of mullerian origin located in the spinal cord at the lumbosacral junction  two similar cases were found upon review of the literature  the embryology of this lesion is discussed  
class10	intradural chordoma of the tentorium cerebelli  case report  a rare case of intradural chordoma is described  the literature contains seven examples of intradural extraosseous chordoma  all reported in a ventral location  this is the first reported case of a primary intradural chordoma distant from the clivus and involving both the supra  and infratentorial compartments  
class10	a vascular malformation mimicking an intracanalicular acoustic neurilemoma  case report  a patient with an enhancing  completely intracanalicular mass on magnetic resonance imaging was operated on for a presumed acoustic neurilemoma  but was found at surgery to have an intracanalicular vascular malformation  this rare lesion should be distinguished from angiomatous change within an acoustic neurilemoma and in the past has been termed  vascular tumor    hemangioma   or  fibro angioma   the clinical distinctions between intracanalicular acoustic neurilemomas and intracanalicular vascular malformations and the ability of magnetic resonance imaging to distinguish between the two are discussed  
class10	anticonvulsant and behavioral effects of two novel competitive n methyl d aspartic acid receptor antagonists  cgp 37849 and cgp 39551  in the kindling model of epilepsy  comparison with mk 801 and carbamazepine  the orally active competitive n methyl d aspartate  nmda  receptor antagonists cgp 37849  dl  e  2 amino 4 methyl 5 phosphono 3 pentenoic acid  and its ethyl ester cgp 39551 were evaluated in amygdala kindled rats  a model for complex partial and secondarily generalized seizures  anticonvulsant and behavioral effects of these novel compounds were compared with those of the noncompetitive nmda receptor antagonist mk 801      5 methyl 10 11 dihydroxy 5h dibenzo a d cyclohepten 5 10 imin e  and the antiepileptic drug carbamazepine  one of the major drugs for treatment of partial and generalized seizures in humans  for comparative evaluation  the compounds were injected i p  at the following doses  1 to 10 mg kg  cgp 37849 or cgp 39551   0 05 to 0 3 mg kg  mk 801  and 20 to 40 mg kg  carbamazepine   respectively  in contrast to carbamazepine  cgp 37849  cgp 39551 and mk 801 exerted only weak anticonvulsant effects in fully kindled rats and did not increase the focal seizure threshold  the weak anticonvulsant effects of the nmda receptor antagonists in kindled rats were associated with profound untoward behavioral effects  the behavioral syndrome induced by the nmda receptor antagonists in kindled rats was characterized by marked ataxia  hyperactivity and  in case of cgp 37849 and mk 801  stereotypies  such as head weaving  the low or absent effectiveness of the novel nmda receptor antagonists against kindled seizures suggests that these compounds will not be clinically useful antiepileptics against partial and secondarily generalized seizures  furthermore  in view of the recent clinical findings on psychotomimetic effects of mk 801 in epileptic patients  the similarities in the excitatory effects produced by cgp 39551  cgp 37849 and mk 801 in kindled rats may indicate that competitive nmda receptor antagonists may also produce psychotomimetic effects in humans  
class10	combined hemorrhagic shock and head injury  effects of hypertonic saline  7 5   resuscitation  hypertonic saline resuscitation was compared to isotonic fluid resuscitation in a large animal model combining hemorrhagic shock with head injury  sheep were subjected to a freeze injury of one cerebral hemisphere as well as 2 hours of hypotension at a mean arterial pressure  map  of 40 mm hg  resuscitation was then carried out  map   80 mm hg  for 1 hour with either lactated ringer s  lr  n   6  or 7 5  hypertonic saline  hs  n   6   hemodynamic parameters and intracranial pressure  icp  were followed  at the end of resuscitation brain water content was determined in injured and uninjured hemispheres  no differences were detected in cardiovascular parameters  however  icps were lower in animals resuscitated with hs  4 2     1 5 mm hg  compared to lr  15 2     2 2 mm hg  p less than 0 05   additionally  brain water content  ml h2o gm dry weight  in uninjured brain hemispheres was lower after hs resuscitation  hs   3 3     0 1  lr   4 0     0 1  p less than 0 05   no differences were detected in the injured hemispheres  we conclude that hypertonic saline abolishes increases in icp seen during resuscitation in a model combining hemorrhagic shock with brain injury by dehydrating areas where the blood brain barrier is still intact  hypertonic saline may prove useful in the early management of multiple trauma patients  
class10	optimal escort for interhospital transport of pediatric emergencies  the charts of 130 seriously ill or injured children transported to tertiary level intensive care were examined to determine the incidence of secondary insults incurred  as a function of escort training  of all insults incurred  approximately 8  occurred with specialized pediatric transport escorts who were accompanied by a tertiary care physician  group iii  n   52   20  with specialized pediatric transport escorts alone  group ii  n   44   and 72  with escorts who had not received specialized pediatric transport training  group i  n   34   based on our results  we recommend that all transport coordinators review the qualifications and experience of their transport team members and all potential escorts to assess their ability to provide optimal care for the children they transport  particularly during long journeys  transfer by air  and when serious illness or injury is involved  
class10	relative effects of brain and non brain injuries on neuropsychological and psychosocial outcome  based on the 242 consecutive surviving head injury cases and 132 general trauma cases  this study examined the contribution of brain and non brain injuries to cognitive and psychosocial outcome 1 month postinjury  the study also examined the relationships among various head injury severity indices  the head injury severity indices were all correlated but patients with glasgow coma scale scores in the mild range had broadly ranging scores on the other head injury severity indices  abbreviated injury scale and time to follow commands   neuropsychological outcome was related to brain injury severity  but was not independently influenced by severity of other systems injuries  psychosocial outcome related to both brain and non brain injuries independently  when evaluating trauma outcome  it is important to consider the contributions of both brain and other system injuries  
class10	timing of osteosynthesis of major fractures in patients with severe brain injury  a retrospective study was performed to assess the effects on outcome of early osteosynthesis of major extremity fractures in patients with severe brain injury  gcs less than or equal to 7   in a consecutive series of 58 patients  early osteosynthesis was performed on the day of injury in 15 patients   group a   in 43 patients no major fractures were present or no early osteosynthesis was performed  group b   the severity of brain injury as seen on ct scan was similar in both groups  mortality was significantly lower in group a  despite a significantly higher iss  as to the functional end result of brain injury  an indication of a better outcome was present in group a  
class10	reflex sympathetic dystrophy after clavicle fracture  case report  reflex sympathetic dystrophy  rsd  of the anterior chest wall is a rare entity  a medline search in all languages of the world s literature from 1966 to the present yielded no report of the association of clavicle fracture with this pain syndrome  two cases are presented and the anatomic variations of the supraclavicular nerves in relation to the clavicle are discussed  
class10	rediscovering tactile agnosia  eighty four patients with damage to various levels of the nervous system  ranging from the peripheral nerves to the cerebral cortex  underwent somesthetic assessment in order to determine the degree to which basic and complex perceptual and motor disorders affect tactile object recognition  tor  and to determine whether tor can be impaired in the absence of more basic sensorimotor imperception  the results suggest that  1  basic and intermediate disorders of somesthetic function impair tor but are commensurately more severe for any given degree of tor impairment in patients with peripheral lesions than in patients with cortical lesions   2  neither hemiparesis nor hemianopia alone precludes normal tor   3  hemineglect contributes substantially to tor impairment   4  impairment of tor can occur in the absence of more basic somesthetic dysfunction and constitutes tactile agnosia   5  tactile agnosia is a subtle  nondisabling disorder that should be distinguished from the nonagnosic  severe and disabling disorder  astereognosis  and  6  tactile agnosia results from unilateral damage to parietotemporal cortices  possibly including the second somatosensory cortex  in either hemisphere  
class10	snow skiing for the physically disabled  the sport of snow skiing by the physically disabled  which originated in europe in 1935 and first received attention in the united states in the 1940s  is reviewed in terms of opportunities available  instructions  adaptive equipment necessary  and benefits provided  persons with a wide variety of disabilities  such as cerebral palsy  multiple sclerosis  spinal cord injury  hemiplegia  amputation  blindness  spina bifida  and muscular dystrophy  can participate  accordingly  a wide range of adaptive equipment is available  including outrigger skis  flip skis  canting wedges  ski bras   toe spreaders   sit skis  and mono skis  to allow safe enjoyment of the sport  programs for instruction of the disabled skier are increasing in number and popularity  and numerous opportunities are available to enter competitive events sponsored by national handicapped sports  both the participants and the instructors relate the numerous physical and psychologic benefits that can be derived from skiing  the sport provides an almost universal enjoyment of the sense of freedom and independence  snow skiing is an enjoyable  beneficial  outdoor cold weather activity that the disabled population can safely learn with proper instruction  
class10	traumatic intracranial aneurysms caused by missiles  their presentation and management  only 30 cases of traumatic intracranial aneurysm  tica  secondary to missile injury have been reported to date  to these we add 15 more cases  missile ticas are often seen on a secondary branch of the middle cerebral artery and are usually accompanied by a intracerebral hematoma  80   or by an acute subdural hematoma  26    fourteen of our cases were secondary to shrapnel injuries and only one was secondary to a bullet  none of the injuries was through and through  ticas may enlarge in time and  seemingly inoffensive  may rupture and lead to death  all seven ticas studied histologically proved to be false aneurysms  ticas are best treated through trapping and excision  the outcome depends on the patient s status and level of consciousness before surgery  indications for angiography are discussed  
class10	progressive coma after the transsphenoidal decompression of a pituitary adenoma with marked suprasellar extension  report of two cases  two cases of neurological deterioration and coma after the transsphenoidal decompression of a pituitary adenoma with marked suprasellar extension and invasion of the 3rd ventricle are presented  emergency ventricular shunting led to prompt neurological improvement  which  supplemented by radiation therapy  allowed long term amelioration of symptoms  three possible explanations for this complication are offered  1  traction of the attached 3rd ventricle into the decompression site  causing increased obstructive hydrocephalus  2  vasopressin release by surgical manipulation of the pituitary stalk and circumventricular organs causing cerebral edema  and 3  edema in the residual tumor secondary to surgical manipulation causing further hydrocephalus  subsequent patients with similar clinical and imaging criteria will have a planned perioperative ventricular shunting procedure performed  
class10	ectopic retinoblastoma within the 3rd ventricle  case report  ectopic intracranial retinoblastomas are rare  these tumors usually occur in the pineal  parasellar  or suprasellar regions several years after the successful treatment of ocular retinoblastomas with no evidence of direct extension or distant metastasis  we report here a case of ectopic retinoblastoma occurring within the third ventricle  the tumor was surgically excised by the transventricular approach  ectopic retinoblastomas exhibit greater differentiation than one would expect to observe in a metastatic lesion of this tumor  the distinction of ectopic retinoblastomas and metastasis from ocular retinoblastomas is important  since ectopic retinoblastomas  unlike metastasis  can be successfully managed by intensive therapy including radical excision  
class10	monitoring of cortical blood flow during temporary arterial occlusion in aneurysm surgery by the thermal diffusion method  during aneurysm surgery  regional cortical blood flow  cobf  was continuously monitored in 12 patients with a thermal diffusion flow probe in an attempt to assess the effects of temporary major arterial occlusion on blood flow and outcome  when the cobf was above 30 ml 100 g min  the safe period for temporary clipping applied distal to the perforators was 15 minutes  the occlusion time should be shortened when the cobf is below 30 ml 100 g min  two patients suffered basal infarction  which was not detected by cobf monitoring  attention should be paid to the blood flow in the deep structures when a temporary clip is applied at a site proximal to the perforating branches  direct measurement of cobf may be of value in estimating the time that temporary occlusion of a major vessel can be tolerated  
class10	the effect of continuous drainage of cerebrospinal fluid in patients with subarachnoid hemorrhage  a retrospective analysis of 108 patients  the effects of continuous drainage of cerebrospinal fluid  csf  on vasospasm and hydrocephalus were analyzed retrospectively in 108 patients with subarachnoid hemorrhage  sah  who were operated on for ruptured aneurysms within 48 hours of their onset  ninety two of these patients underwent a procedure for csf drainage  cisternal drainage  ventricular drainage  lumbar drainage  or a combination of these   the duration  the total volume  and the average daily volume of csf drainage were 10 4     7 0 days  mean     sd   2034     1566 ml  and 190     65 3 ml  respectively  patients with a greater drainage volume at a lower height of drainage in the early period after sah developed more cerebral infarctions later  p less than 0 025   the relationship between the total volume of csf removed and shunt dependent hydrocephalus was determined to be statistically significant  p less than 0 005   cerebral infarction and hydrocephalus after sah were also found to be statistically associated  p less than 0 001   thus  continuous cerebrospinal fluid drainage should not be performed too readily in patients with sah  because the removal of a large amount of csf can induce cerebral vasospasm as well as hydrocephalus  
class10	spinal cord stimulation  a contemporary series forty three patients with chronic pain disorders of different causes were selected for spinal cord stimulation  all underwent implantation of a ribbon electrode through a small laminotomy  under general anesthesia  thirteen patients  30   failed to obtain significant pain relief during a period of trial stimulation  and their electrodes were removed  the remainder underwent a definitive implant and were followed for a mean of 13 months  range  3 33 months   nineteen of them  63   continued to experience pain relief  a detailed analysis of this series  as well as a literature review  is presented  
class10	chronic headache associated with a functioning shunt  usefulness of pressure monitoring  chronic headaches in a shunt dependent patient with small ventricles has long been treated with little or no regard to intracranial pressure  in this study  pressure monitoring on 12 such patients demonstrated that they fell into three distinct categories  3 had headaches caused by intracranial hypertension  2 had headaches from hypotension  and 7 showed no relation of symptoms to pressure  as therapeutic procedures for treating these three categories are entirely different and sometimes opposing  it is clear that intracranial pressure monitoring is essential to successful management of this complaint  
class10	the transoral approach for the management of intradural lesions at the craniovertebral junction  review of 7 cases  the main difficulty in dealing with intradural lesions located ventrally in the region of the craniovertebral junction  cvj  is related to their relative inaccessibility  posterolateral approaches involve some manipulation of the brain stem and provide limited access because of the necessity of working between the cranial nerves  even then  the view of the ventral midline and across is limited  the transoral approach  which has been widely used for the management of extradural lesions in this area  is also useful for the treatment of intradural lesions  it provides an unimpeded although somewhat restricted  view of the ventral aspect of the cvj without the need for brain retraction  the cranial nerves and vertebral arteries are not interposed between the surgeon and the lesion  the risks of cerebrospinal fluid leakage and infection are greatly diminished by the use of fibrin adhesive and prolonged diversion of the cerebrospinal fluid  the use of this approach  together with its technical difficulties and results  in the management of seven purely intradural lesions located ventrally at the cvj  is discussed  
class10	improved access to lesions of the central skull base by mobilization of the zygoma  experience with 54 cases  improved access to lesions at the medial end of the sphenoid wing or in the interpeduncular cistern after mobilization of the zygoma has been a subject of growing interest in recent years  this study describes the operative technique we have adopted and records our experience with 55 operations in 54 patients who underwent the procedure in the past 3 years  seven patients had vascular lesions  44 had tumors  and 3 had miscellaneous lesions  the majority of the tumors were medial meningiomas  and particular note is made of those arising from the cavernous sinus with respect to their resectability  sixteen of these tumors were encountered  and total excision was possible in 11 cases  access to the infratemporal fossa is facilitated  and in 2 cases we were able to excise completely trigeminal neuromas that had extended there  the extra maneuver adds little to the overall operating time  and complications relating to it are uncommon  mild in degree  and usually self limiting  we conclude that the operation is extremely valuable in appropriate circumstances  
class10	diabetic amyotrophy without pain  a puzzling clinical picture  a patient with weight loss and weakness presents a diagnostic challenge  drs moeser and kent describe an unusual case of diabetic amyotrophy that required extensive workup to arrive at the diagnosis and rule out more serious disease  symptoms were dramatic  and recovery was spontaneous following conservative treatment  
class10	intracranial aneurysms  interventional neurovascular treatment with detachable balloons  results in 215 cases patients with complex or surgically difficult intracranial aneurysms are being treated with interventional neurovascular techniques  with neuroleptic anesthesia and a transfemoral femoral approach  a silicone micro balloon can be flow directed through the intracranial circulation  guided directly into the aneurysm  and detached  the aneurysm is thus eliminated from the circulation  and the parent artery is preserved  for broad based or ectatic aneurysms  test occlusion followed by permanent occlusion of the aneurysm and parent vessel can be performed  since 1981  211 patients with 215 aneurysms  including 177 cases involving the anterior and 38 cases involving the posterior circulation  have been treated with this technique  in 127 cases  59 1    the parent vessel was occluded  in 88 cases  40 9    primary occlusion of the aneurysm was achieved with preservation of the parent artery  therapy related complications included 21 deaths  9 8   and 16 strokes  7 4    follow up examinations were performed at 1  3  and 12 months after treatment  and follow up ranged from 5 months to 9 years  in patients in whom standard surgical therapy fails or for aneurysms in surgically inaccessible anatomic locations  interventional techniques that make use of detachable balloons may be a useful therapeutic alternative  
class10	nerve root avulsion of birth palsy  comparison of myelography with ct myelography and somatosensory evoked potential  findings at myelography and computed tomographic  ct  myelography were reviewed in 21 patients  22 limbs  with birth palsy  nerve root shadows were the focus of this study  myelography demonstrated 51 completely avulsed roots  78   and 14 incompletely avulsed roots  22    a traumatic meningocele was detected at 38 roots on myelograms and 51 roots on ct myelograms  thirteen avulsed roots  eight completely and five incompletely avulsed roots   20   were not associated with a meningocele  in nine patients who underwent brachial plexus exploration  myelographic findings were compared with root somatosensory evoked potential  sep   sep was not induced at 22 of 25 completely avulsed roots and was induced at all seven incompletely avulsed roots  myelography and sep were consistent in 29 of 32 roots  91    it is concluded that myelography is indispensable for preoperative evaluation of cervical nerve root avulsion of birth palsy  because ct myelography is not sensitive to nerve root avulsion without a traumatic meningocele  and sep cannot enable one to discriminate incomplete avulsion from intact roots  
class10	mapping the distribution of amobarbital sodium in the intracarotid wada test by use of tc 99m hmpao with spect  the intracarotid amobarbital sodium  or wada  test has been used to localize speech and memory function prior to surgical treatment of temporal lobe seizures  the authors mixed technetium 99m hexamethyl propyleneamine oxime  hmpao  with amobarbital sodium and injected the mixture in 25 patients with epilepsy  single photon emission computed tomography  spect  of the brain was then performed to determine intracerebral distribution of the amobarbital sodium  results of spect were compared with those of conventional and digital subtraction angiography  dsa   the distribution of tc 99m hmpao and  presumably  amobarbital sodium varied from patient to patient  spect revealed a statistically different distribution from that predicted with conventional angiography  the distribution also often differed from that of dsa  although the difference was not significant  spect revealed infrequent delivery to mesial temporal lobe structures  this emphasizes the need for caution in the use of the intracarotid amobarbital sodium test to predict the outcome of removal of these areas  
class10	osteonecrosis of the knee after arthroscopic surgery  diagnosis with mr imaging  spontaneous osteonecrosis about the knee typically is a disease of the elderly characterized by an acute onset of pain  the exact cause of this condition has long been debated  although a causative relationship between meniscal tears and spontaneous osteonecrosis about the knee has been postulated  seven patients with knee pain  meniscal tears  and chondromalacia without initial evidence of osteonecrosis at magnetic resonance  mr  imaging underwent arthroscopic surgery with meniscal recontouring or repair and cartilage shaving  these patients returned within 2 14 months with recurrent pain in the treated knee  mr imaging then demonstrated abnormalities consistent with osteonecrosis  osteonecrosis of the femoral condyle or tibial plateau may be a late sequela of meniscal injury in association with chondromalacia and arthroscopic surgery  this diagnosis should be suspected in patients with recurrent knee pain after arthroscopic repair of meniscal tears  the precise relationship of this pattern of osteonecrosis to that previously described as spontaneous requires further investigation  
class10	the prolonged burner syndrome  over the course of a single football season  six players evaluated by the medical staff had burners that displayed a prolonged neurologic recovery  these players were examined and subsequently evaluated with isokinetic testing and electrodiagnostic studies to elucidate better the short term natural history of the prolonged burner syndrome  evidence of muscular weakness at 72 hours postinjury best correlated with positive electrodiagnostic findings  no correlation was found between the initial physical examination findings and the results of electrodiagnostic testing  isokinetic strength evaluation demonstrated many relative strength differences that were difficult to discern with manual muscle testing  the return of a player to athletic competition following this injury should largely be based on the clinical examination  
class10	cauda equina syndrome after continuous spinal anesthesia  four cases of cauda equina syndrome occurring after continuous spinal anesthesia are reported  in all four cases  there was evidence of a focal sensory block and  to achieve adequate analgesia  a dose of local anesthetic was given that was greater than that usually administered with a single injection technique  we postulate that the combination of maldistribution and a relatively high dose of local anesthetic resulted in neurotoxic injury  suggestions that may reduce the potential for neurotoxicity are discussed  use of a lower concentration and a  ceiling  or maximum dose of local anesthetic to establish the block should be considered  if maldistribution of local anesthetic is suspected  as indicated by a focal sensory block   the use of maneuvers to increase the spread of local anesthetic is recommended  if such maneuvers prove unsuccessful  the technique should be abandoned  
class10	continuous postoperative regional analgesia by nerve sheath block for amputation surgery  a pilot study  a pilot study of continuous postoperative regional analgesia by nerve sheath block for lower limb amputation is presented  at the time of exposure of sciatic or posterior tibial nerve trunks during above  or below knee amputations in 11 patients with asa physical status iii or iv  a catheter was introduced directly into the transected nerve sheath for continuous infusion of 0 25  bupivacaine at a rate of 10 ml h for 72 h  effective amputation stump analgesia was obtained  significantly reducing the need for on demand narcotic analgesics during this time to a mean dose equivalent of 1 4 mg of morphine compared with a retrospective control group who received the equivalent of a mean dose of 18 4 mg of morphine  p less than 0 0001   no complications related to the technique were observed  a follow up of the group receiving continuous postoperative regional analgesia for up to 12 mo showed a total absence of phantom pain despite the presence of preoperative limb pain  
class10	intestinal permeability in patients with chronic urticaria angioedema with and without arthralgia  we evaluated the clinical response to oligoallergenic dietary treatment and the intestinal absorption of a protein antigen  cow milk beta lactoglobulin  blg  in 24 patients with chronic urticaria angioedema syndrome 13 of whom also suffered from joint symptoms  sixteen patients  77  of those with arthralgia  responded to diet  rd  with marked reduction of symptoms  the others did not respond  nr   ten  all but one rd with arthralgia  had increased permeability to blg after oral administration of cow milk  four with high titers of igg to blg showed the highest absorption of blg and the groups with arthralgia showed higher blg levels than those without arthralgia  in all cases  specific ige to cow milk was absent  these data suggest that the symptoms of a subgroup of patients with chronic urticaria  and especially patients with joint complaints that subside with diet  are related to excess intestinal permeability  the measurement of gut permeability to food proteins may be useful to define those who may benefit from dietary restriction  
class10	effect of parenterally administered gold therapy on the course of adult rheumatoid arthritis objective  to describe the course of rheumatoid arthritis over 5 years in adults and to evaluate the effect of parenterally administered gold salts on that course  design  a prospective observational study of adults with rheumatoid arthritis  data derived from annual interviews with patients from 1983 to 1988 and from physician surveys in 1983 and 1987  setting  rheumatology practices in the community  patients  the study began in 1982 with 822 adults who had rheumatoid arthritis and were under the care of rheumatologists  interventions  those selected by rheumatologists in the management of their patients  measurements  information describing sociodemographic and clinical characteristics  course  and therapy was collected from patients and verified by physician reports  functional status  measured by the health assessment questionnaire  and the number of painful joints were used as outcome variables  outcome variables were adjusted for age  sex  disease duration  baseline values of the outcome variable  and the use of four disease remittive agents other than gold  main results  multivariate repeated measures analysis of variance showed no change in the course of rheumatoid arthritis over 5 years  the use of parenteral gold for at least 2 consecutive years at the start of the observation period produced  on average  no change in the course over 5 years in the two outcome variables  conclusion  in our study of a community based population of adults with rheumatoid arthritis who were under the care of community rheumatologists  we found that there was  on average  no statistically significant change in function or number of painful joints between 1983 and 1988  patients receiving parenteral gold therapy for at least 2 consecutive years did not show a statistically significant difference in outcome when compared with those not receiving such therapy  
class10	lyme disease  recommendations for diagnosis and treatment the incidence and the endemic range of lyme disease in the united states have increased steadily since the disease was originally recognized in lyme  connecticut  in 1975  because of the varied clinical manifestations of this illness and the use of unstandardized serologic testing methods  diagnosis is often uncertain and treatment outcomes are often difficult to evaluate  the antibiotic regimens that are commonly used in clinical practice have changed rapidly  they show much regional variation with little critical comparison of treatment results  the clinical diagnosis and the literature on the treatment of the various stages of lyme disease are reviewed  the reported data are supplemented with recommendations based on 15 years of clinical experience with this illness  
class10	developmental dyslexia in women  neuropathological findings in three patients  brains from male cases with dyslexia show symmetry of the planum temporale and predominantly left sided cerebrocortical microdysgenesis  we now report on three women with dyslexia  in all brains  the planum temporale was again symmetrical  also  in two of the brains  multiple foci of cerebrocortical glial scarring were present  in both women  many of the scars were myelinated  suggesting origination during late intrauterine or early postnatal life  in one  scars were mainly left perisylvian and involved portions of the vascular border zone of the temporal cortex  in the other  scars were more numerous and occurred in the border zone of the anterior  middle  and posterior cerebral arteries symmetrically  all three cases showed to a variable extent brain warts  molecular layer ectopias  and focal architectonic dysplasia identical to those seen in the male cases  two women had primary brain neoplasms  an oligodendroglioma and a low grade astrocytoma  respectively  and two women showed small angiomas  reexamination of previously reported male cases disclosed one with myelinated glial scars  two control brains with asymmetrical plana temporale showed myelinated glial scars as well  the significance of the anatomical findings is discussed  and possible etiological factors are considered with known effects of autoimmune diseases on the nervous system  
class10	cerebrospinal fluid immune complexes in patients exposed to borrelia burgdorferi  detection of borrelia specific and  nonspecific complexes  we analyzed cerebrospinal fluid  csf  from 32 patients with neurological symptoms and evidence of borrelia burgdorferi infection  29 were seropositive as determined by enzyme linked immunosorbent assay  2 were cell mediated immune positive  and 1 had been seropositive as shown by enzyme linked immunosorbent assay 9 months previously   csf immune complexes were found in 22  69   of 32 patients  in 18  there was sufficient sample to isolate immune complexes  by enzyme linked immunosorbent assay  isolated immune complexes from 10 of these 18 patients contained antibody specific for b  burgdorferi antigens  the isotypes were igg  n   8   igm  n   3   and iga  n   2   by immunoblot  these antibodies were directed against b  burgdorferi 41 kda antigen and occasionally against the 33  and 17 kda antigens  anti b  burgdorferi igm was present in patients with acute neurological symptoms  was predominantly complexed rather than free  and decreased with clinical recovery in the one serial study  three patients were nonreactive for free csf antibodies  but had complexed antibodies to the organism  the preliminary finding of specific b  burgdorferi components in immune complexes in csf suggests an active process triggered by the organism  even in the absence of other csf abnormalities  
class10	cerebellar and frontal hypometabolism in alcoholic cerebellar degeneration studied with positron emission tomography  local cerebral metabolic rate for glucose was studied utilizing 18f 2 fluoro 2 deoxy d glucose and positron emission tomography  pet  in 14 chronically alcohol dependent patients and 8 normal control subjects of similar age and sex  nine of the 14 patients  group a  had clinical signs of alcoholic cerebellar degeneration  and the remaining 5  group b  did not have signs of alcoholic cerebellar degeneration  pet studies of group a revealed significantly decreased local cerebral metabolic rates for glucose in the superior cerebellar vermis in comparison with the normal control subjects  group b did not show decreased rates in the cerebellum  both groups a and b showed decreased local cerebral metabolic rates for glucose bilaterally in the medial frontal area of the cerebral cortex in comparison with the normal control subjects  the severity of the clinical neurological impairment was significantly correlated with the degree of hypometabolism in both the superior cerebellar vermis and the medial frontal region of the cerebral cortex  the degree of atrophy detected in computed tomography scans was significantly correlated with local cerebral metabolic rates in the medial frontal area of the cerebral cortex  but not in the cerebellum  the data indicate that hypometabolism in the superior cerebellar vermis closely follows clinical symptomatology in patients with alcoholic cerebellar degeneration  and does not occur in alcohol dependent patients without clinical evidence of cerebellar dysfunction  hypometabolism in the medial frontal region of the cerebral cortex is a prominent finding in alcohol dependent patients with or without alcoholic cerebellar degeneration  
class10	normal proprioceptive trigeminal afferents in patients with sjogren s syndrome and sensory neuronopathy  a pure sensory neuropathy due to neuronal damage in the gasserian and spinal ganglia has been described in patients with sjogren s syndrome  conventional electromyographic  emg  studies can demonstrate the selective involvement of the sensory pathways but they do not provide definite evidence for the site of the lesion  noting that the trigeminal sensory neurons carrying cutaneous and muscular afferents are differentially located in the gasserian and mesencephalic nuclei  respectively  we carried out an electrophysiological study of the trigeminofacial and trigeminotrigeminal reflexes in 5 patients with sjogren s syndrome and pure sensory neuropathy  in 10 patients with sensory motor neuropathies of other causes  and in 10 healthy subjects  our results show that patients with sjogren s syndrome and pure sensory neuropathy who exhibited abnormal blink reflexes and an abnormal  cutaneous induced masseter silent period had normal jaw jerks  whereas patients with sensory motor neuropathies who exhibited abnormal cutaneous responses had abnormal jaw jerks  these findings suggest that the lesion in pure sensory neuropathy involves damage to the neurons of the gasserian ganglia and not to the trigeminal axons  since an axonal lesion would be expected to involve the large axons from muscle spindle receptors  
class10	timing and topography of cerebral blood flow  aura  and headache during migraine attacks  ten years of study has resulted in considerable but fragmented knowledge about regional cerebral blood flow in migraine with aura  classic migraine   in the present study  the number of repeatedly studied patients  n   63  was large enough to determine statistically significant sequences of events and statistically significant spatial relations  the first observable event was a decrease of regional cerebral blood flow posteriorly in one cerebral hemisphere  further development of this pathological process was accompanied by the aura symptoms  thereafter headache occurred while regional cerebral blood flow remained decreased  during the headache phase  regional cerebral blood flow gradually changed from abnormally low to abnormally high without apparent change in headache  in some patients headache disappeared while regional cerebral blood flow remained increased  although regional cerebral blood flow reduction and aura symptoms in the great majority of patients were unilateral  one third had bilateral headache  unilateral headache usually localized to the side on which regional cerebral blood flow was reduced and from which the aura symptoms originated  i e   aura symptoms were perceived to occur contralaterally but presumably originated in the hypoperfused hemisphere   our results suggest a simple model for migraine attacks  a pathological disturbance in one cerebral hemisphere causes the aura symptoms and after a time delay  it also causes the headache by stimulating local vascular nociceptors  bilateral headache caused by a unilateral cerebral disturbance may be explained by recent neuroanatomical and neurophysiological findings  
class10	general assay for phosphoproteins in cerebrospinal fluid  a candidate marker for paraneoplastic cerebellar degeneration  the components of protein phosphorylation systems  protein kinases  protein phosphatases  and their phosphoprotein substrates  are highly enriched in neuronal cells compared with other cell types  we exploited this relative neuronal enrichment of protein phosphorylation system components to develop a general assay technique for putative protein kinase substrates  phosphoproteins  in human cerebrospinal fluid  using this cerebrospinal fluid phosphoprotein assay  we have detected a putative protein kinase c substrate protein of apparent mr 60 kd in 6 of 14 patients with paraneoplastic cerebellar degeneration but not in any of 55 patients with a variety of other neurological diseases  phosphoproteins in cerebrospinal fluid may provide novel and unique markers for the diagnosis or staging of neuronal diseases as well as offer potential insights into the biochemical characterization of affected neuronal populations  
class10	ataxia and peripheral neuropathy  a benign variant of peroxisome dysgenesis  a 5 year old boy with panperoxisomal dysfunction is described  clinical features included hypotonia  areflexia  and ataxia  cognition  vision  hearing  and hepatic function were normal  a panel of peroxisomal markers  including very long chain fatty acids  phytanic acid  pipecolic acid  and catalase compartmentalization  were abnormal  this is a uniquely benign syndrome of disordered peroxisome biogenesis  
class10	okt3 encephalopathy  okt3 therapy for induction immunosuppression in a patient who underwent renal transplantation produced obtundation and quadriparesis associated with computed tomographic scan evidence of brain edema  these findings resolved over 3 days with supportive therapy and okt3 withdrawal  
class10	orocaecal transit time in duchenne muscular dystrophy  smooth muscle degeneration may occur in duchenne muscular dystrophy  we measured fasting orocaecal transit time in patients with advanced duchenne muscular dystrophy and other muscular dystrophies and in healthy controls  no significant differences were found  in contrast to reports of gastric hypomotility in duchenne muscular dystrophy  we found no evidence of impaired small intestinal motility  
class10	cardiac echinococcosis with fatal intracerebral embolism  a previously well 7 year old boy presented with sudden loss of consciousness and fitting  no evidence of trauma or space occupying lesion was identified  death occurred the next day due to cerebral infarction caused by embolised fragments from a ruptured left ventricular hydatid cyst that was found at necropsy  
class10	temporal arteritis with normal erythrocyte sedimentation rates presenting as occipital neuralgia  a retrospective review of 46 patients with biopsy proven giant cell  temporal  arteritis revealed 8  17   whose initial presentation was occipital pain  the most likely etiology of occipital pain in these patients was occipital artery inflammation  a westergren erythrocyte sedimentation rate less than 40 mm hour was noted at presentation in 6 of these 8 patients  giant cell arteritis should be considered in the differential diagnosis of elderly patients who present with occipital pain and demonstrate a normal erythrocyte sedimentation rate  
class10	risk monitoring of randomized trials in emergency medicine  experience of the brain resuscitation clinical trial ii  risk monitoring for the brain resuscitation clinical trial ii  a multicenter  placebo controlled trial to evaluate the efficacy of the calcium entry blocker lidoflazine in the amelioration of brain damage in comatose cardiac arrest survivors  posed unexpected challenges  concern arose when monitoring of adverse reactions showed an excess of dangerous cardiac arrhythmias  including rearrest  in the lidoflazine group  to ascertain the cause of this problem and determine whether it was ethical for the trial to continue  an in depth review of data was conducted  outside experts were consulted  and additional data were collected  these efforts suggested possible causes for the problem  existing drug administration protocols for blood pressure control were reinforced  resulting in lower subsequent arrhythmia rates  thus  through an efficient monitoring system  an important problem was uncovered and resolved  allowing the trial to be completed without major changes  
class10	early diagnosis and survival of ruptured abdominal aortic aneurysms  the hospital records of patients treated with ruptured abdominal aortic aneurysm in a recent 5 year period were reviewed to collect data on factors which may be associated with mortality  overall mortality was 62   patients with intraperitoneal rupture had a higher mortality  97   than patients with retroperitoneal rupture  25    patients at increased risk were older than 80 years  presented with syncope  experienced a short duration of symptoms prior to emergency department  ed  arrival  had initial systolic blood pressure less than 90 mm hg  and or initial hemoglobin level less than eight on arrival at the ed and delay in beginning surgery  multivariate analysis demonstrated preoperative blood pressure  preoperative hemoglobin  presence of syncope  and the amount of blood transfused were largely reflections of the type of rupture and had only slight independent relationship to mortality  the authors concluded that treating emergency physicians and surgeons have little control over the most important risk factors for mortality after aneurysm rupture  but may improve the prognosis by expediting diagnosis in the ed and surgical therapy  
class10	cerebral circulation and metabolism in patients with septic encephalopathy  cerebral circulation and metabolism in septic encephalopathy have not been well documented  the authors measured cerebral blood flow  cbf  and metabolic rate for oxygen  cmro2  in six patients with septic encephalopathy associated with multiple organ failure  three to five organs   they found that cbf and cmro2 were significantly lower than awake control values of 46     2 to 28     3 ml 100g min  mean     sem  and 3 1     0 2 to 1 2     0 2 ml 100g min  respectively  cerebral vascular resistance  cvr  and cerebral circulatory index  cci cbf cmro2  were significantly higher than the control values of 2 0     0 1 to 3 0     0 4 mm hg ml 100g min and 15 1     0 8 to 24 2     3 3  respectively  at the time of cerebral circulatory and metabolic measurements  their consciousness varied between 4 and 10 as evaluated by the glasgow coma scale  the electroencephalogram showed diffuse slow wave activity and the latency of the auditory brain stem evoked response was prolonged in four of six patients  computed brain tomography showed either no abnormality or mild atrophy  it is concluded that cbf and cmro2 are disproportionally decreased during septic encephalopathy in association with dysfunction of the cns and decreased electrical activity  
class10	the effect of ph buffering on reducing the pain associated with subcutaneous infiltration of bupivicaine  published erratum appears in am j emerg med 1991 jul 9 4  410  the authors propose that ph buffering of bupivicaine with sodium bicarbonate reduces the pain associated with its local subcutaneous infiltration  in a double blind  prospective study  62 healthy adult volunteers received a 0 5 ml subcutaneous infiltration of 0 5  buffered bupivicaine into the dorsum of a randomly chosen hand  the ph was adjusted to 7 0 by adding 0 05 ml of sodium bicarbonate  1 meq l  corrected   to 10 ml vials of commercially available bupivicaine  1 200 dilution   the control hand was injected with the same amount of unbuffered agent  pain was scored after each infiltration using a nonsegmented visual analogue scale  student s t test for paired measurements was used to analyze intergroup pain score differences  forty three subjects  69   reported less pain with buffered bupivicaine and only 17  27   noted a modest increase  two subjects  3   reported no difference  the mean pain score for the buffered agent was 22 mm compared with 30 mm for the control  the mean difference  control experimental  was 8 mm  t   4 64  df   61  p less than  001   the authors conclude that the addition of sodium bicarbonate to bupivicaine reduces the pain associated with its local infiltration  
class10	evaluation of minor head trauma in children younger than two years  the recent medical literature emphasizes the limitations of skull films in the evaluation of minor head trauma  however  the emergency medicine literature places little emphasis on the particular risks in children younger than 2 years old with blunt head injury  these children have immature bone and unfused sutures that may increase risk of cranial injury and delayed complications  a case is presented to illustrate this point  unlike severe head trauma  where evaluation is directed toward computed tomography  the literature continues to be controversial regarding the indications for skull radiographs and computed tomography in minor head trauma  the authors recommend a low threshold for radiographic imaging in blunt heat injuries in children younger than 2 years  
class10	new approaches in the rehabilitation of the traumatic high level quadriplegic  the use of noninvasive alternatives to tracheostomy for ventilatory support have been described in the patient management of various neuromuscular disorders  the use of these techniques for patients with traumatic high level quadriplegia  however  is hampered by the resort to tracheostomy in the acute hospital setting  twenty traumatic high level quadriplegic patients on intermittent positive pressure ventilation  ippv  via tracheostomy with little or no ability for unassisted breathing were converted to noninvasive ventilatory support methods and had their tracheostomy sites closed  four additional patients were ventilated by noninvasive methods without tracheostomy  these methods included the use of body ventilators and the noninvasive intermittent positive airway pressure alternatives of ippv via the mouth  nose  or custom acrylic strapless oral nasal interface  soni   overnight end tidal pco2 studies and monitoring of oxyhemoglobin saturation  sao2  were used to adjust ventilator volumes and to document effective ventilation during sleep  no significant complications have resulted from the use of these methods over a period of 45 patient years  elimination of the tracheostomy permitted significant free time by glossopharyngeal breathing for four patients  two of whom had no measurable vital capacity  we conclude that noninvasive ventilatory support alternatives can be effective and deserve further study in this patient population  
class10	research in physical medicine and rehabilitation  xii  measurement tools with application to brain injury  there are basic principles and techniques of measurement that are relevant across biomedical disciplines  the purpose of this article is to explain some of the most important of these for medical rehabilitation  to illustrate how to use them to choose assessment instruments and to describe the nature of measurement in medical rehabilitation by examples in brain injury rehabilitation  reliability is basic to any scientific measure  validity  the ultimate criterion  is closely associated with the purpose of the measure  content validity  criterion validity and construct validity are explained  sensitivity to rehabilitative interventions and significance in patients  real lives  ecological validity  are emphasized  measures of functional outcomes  disability  may show improvement after rehabilitation even when impairment measures do not  an extensive but selected list of measures of coma  global status  disabilities  communicative and cognitive impairments  and handicaps is presented  and their main uses are illustrated  examples illustrate how to choose measures to study comprehensive program level outcomes  to study learning based interventions and to develop a general purpose database  although there are many measures of activities of daily living and mobility  little published evidence of reliability and validity could be found even for some well known scales  ecologically valid and sensitive outcome measures are especially needed  studies of the clinical utility of measures were also scarce  many of these gaps can be spanned by clinical researchers with limited resources  physical medicine and rehabilitation will benefit from formal studies of the reliabilities and validities of both its old and its new measurement instruments and by increased sophistication in choice of measures  
class10	recovery time of independent function post stroke  stroke patients undergoing physical rehabilitation were monitored daily to determine the length of time needed to recover independent function  of the 93 patients admitted  there were 45 who could not attain the sitting position independently  75 who could not walk independently and 75 who could not negotiate the stairs independently  by discharge  25 of 45 patients  55 6   were able to attain sitting from supine independently  35 of 75 patients  46 7   achieved the ability to walk independently but only 25 of 75 patients  33 3   learned to negotiate stairs independently  the time from admission to achievement of independent function and the time from onset of stroke to achievement of independent function was modeled in relation to explanatory variables  age  sex  side of lesion  comorbidity  the presence of depression and the extent of impairment in perception  cognition  auditory comprehension and verbal expression  four variables were found to influence recovery time  age influenced the rate of recovery of walking and stair climbing  perceptual impairment influenced the rate of achieving independent sitting and stair climbing  and depression and comprehension influenced walking  
class10	a case of cerebrotendinous xanthomatosis  ii  the sterol content of a cataractous lens  the cholestanol content of a cataractous lens nucleus from a patient with cerebrotendinous xanthomatosis  ctx  was quantified by gas chromatography mass spectrometry and found to be 0 27 micrograms per mg freeze dried lens tissue  the cholestanol cholesterol ratio of 1 7  in the lens nucleus was similar to that in the serum of the ctx patient  the cholestanol content and cholestanol cholesterol ratio in the ctx lens were approximately four fold and six fold greater respectively than the mean levels found in three senile cataractous lens nuclei analysed simultaneously for comparative purposes  
class10	outcome of cataract surgery in central india  a longitudinal follow up study  an epidemiological follow up study of patients who had intracapsular cataract extraction in a voluntary hospital and its associated eye camps in central india has for the first time evaluated the outcome one year after surgery in terms of visual acuity  use of spectacles  and improvement in income and mobility  the findings indicate that under these fairly typical conditions  92  of the cases have adequate vision of 6 18 or better one year after surgery  information on high usage of spectacles and on considerable improvements in income and mobility after cataract surgery is also reported  the outcome for patients operated upon in eye camps was almost as favourable as for those operated upon in hospital  although the small differences are not statistically significant  the comparative findings require cautious interpretation and give rise to the epidemiological issues which are briefly discussed in this paper  
class10	corneal sensitivity and correlations between decreased sensitivity and anterior segment pathology in ocular leprosy  leprosy is one of the leading causes of corneal hyposensitivity  in this article the corneal sensitivity of 143 leprosy patients was examined  and correlations between corneal hyposensitivity and anterior segment pathology were detected  twenty four healthy volunteers were examined as controls  various degrees of corneal loss of sensitivity were found in 46 2  of leprosy patients  lagophthalmos  chronic lepromatous granulomatous uveitis  iris atrophy  and social blindness were found 4 5 16 6 times more frequently in eyes which developed severe corneal hyposensitivity  
class10	flecked retina associated with ring 17 chromosome  we report the case of a mentally retarded male with a ring 17 chromosome who had subretinal drusen like deposits in each eye  this is the second report of flecked retina in a patient with ring 17 chromosome  suggesting that there may be a causal relationship between abnormalities of chromosome 17 and retinal pigment epithelial or photoreceptor dysfunction  
class10	ocular defects in infants of extremely low birth weight and low gestational age  the eyes of 49 babies who weighed less than 1 000 g at birth or who were born at or before 28 weeks gestation were examined at the age of 4 years  twenty one children were normal  the remaining 29 children  59   had ocular abnormalities which ranged from mild amblyopia to blindness from retinopathy of prematurity  the need to examine children at risk is stressed  
class10	magnetic resonance imaging of the head and spine  effective for the clinician or the patient  objectives  to test how the results of magnetic resonance imaging influence clinicians  diagnoses and management plans for patients with cranial and spinal problems and to assess changes in the quality of life of these patients  design  survey of patients undergoing cranial and spinal magnetic resonance imaging with questionnaires about diagnoses and intended management plans before and after imaging and quality of life questionnaires at the time of imaging and again four months later  setting  regional magnetic resonance imaging and spectroscopy unit  subjects  100 consecutive patients referred for cranial imaging in early 1989  100 similar patients referred for spinal imaging  main outcome measures  changes in clinicians  leading diagnoses after magnetic resonance imaging and their confidence in these diagnoses  changes in intended management plans  assessment of the contribution to the future management of the patient  changes in patients  quality of life  results  magnetic resonance imaging altered the clinicians  leading diagnoses in 35 of 169  21   cases  the clinicians became more confident about their leading diagnoses in 90 of 167  54    there was a change in management plan in 113 of 182  62    the clinicians considered that magnetic resonance imaging made an important contribution to management in 119 of 162  73   patients  overall  the patients  quality of life was unchanged at the four month assessment  conclusions  magnetic resonance imaging of patients with cranial and spinal problems influences clinicians  diagnoses and management plans  but the quality of life of these patients remains unchanged  
class10	ventilatory function as a predictor of fatal stroke  objective  to investigate the relation between ventilatory function and subsequent mortality due to cerebrovascular disease  design  prospective longitudinal study  subjects  a total of 18 403 male civil servants aged 40 64 years at entry examination for the whitehall study  main outcome measure  mortality from cerebrovascular disease  icd8 430 438  after 18 years of follow up  results  in all  262 men with sinus rhythm at entry died due to stroke during the 18 years of follow up  compared with men with a forced expiratory volume in one second of greater than or equal to 3 5 litres those with a value of less than 3 0 litres were almost twice as likely to die of cerebrovascular disease  rate ratio adjusted for age and systolic blood pressure   1 88  95  confidence interval 1 32 to 2 69   this increased risk occurred within each tertile of systolic blood pressure  nested case control analyses were used to control precisely for confounding effects of age  height  and smoking  by matching  and employment grade and physiological risk factors  by modelling   the effect of forced expiratory volume in one second was independent of age  height  smoking habits  employment grade  blood pressure  weight  cholesterol concentration  glucose tolerance  electrocardiographic abnormalities  history of chest pain  and history of intermittent claudication  conclusions  measurements of ventilatory function may assist clinical decisions about whether to treat mild hypertension  impaired ventilatory function and stroke may share common causes  
class10	availability of transplantable organs from brain stem dead donors in intensive care units  objective  by audit from january to june 1989 to quantify  separately for hearts  kidneys  liver  lungs and corneas  the possible increases in transplantable organs from brain stem dead potential donors in intensive care units and to compare them with the increases achieved in october november 1989  during intense  national publicity about transplantation  design  prospective audit of all deaths in intensive care units in england from 1 january to 30 june 1989 and subsequent case study of the impact of publicity on offers and donations during october november 1989  setting  15 regional and special health authorities in england  patients  5803 patients dying in intensive care units  of whom 497 were confirmed as brain stem dead and had no general medical contraindication to organ donation  main outcome measures  organ specific suitability for transplantation  as reported by intensive care units   consent for donation of specific suitable organs  and procurement of specific organs reported as suitable for transplantation and offered  results  in the 497  8 6   brain stem dead potential donors were estimated the organ specific suitability for heart as 63   kidneys 95   liver 70   lungs 29   and corneas 91   refusal of relatives  30   accounted for major losses of suitable organs of all types  for kidneys the loss was equivalent to 44  of brain stem dead actual kidney donors  no discussion of organ donation was the second most important reason for missed kidney donors  the loss being equivalent to 10  of brain stem dead actual donors  non procurement or difficulties with allocating organs was the second most notable cause of missed suitable liver and lung donors  29   55  of the offered total of 189 liver donors and 27   21  of 78 offered suitable lung donors in six months  non procurement of suitable  offered organs was rare for kidneys and modest  of the order of 13  and 10  respectively  for heart and corneas  corneal donation from brain stem dead potential donors might be improved nearly as much  that is  a 78  increase in brain stem dead actual corneal donors  by specific measures to promote corneal donation when other organs are offered as by reducing the overall refusal rate  restricted offers  non procurement  and no discussion of donation accounted for nearly equal numbers of lost donations of hearts  each equivalent to 15  of donated hearts   during october november 1989 when there was intense  positive publicity about transplantation the rates of refusal and non discussion fell compared with during january june  22   36 163 v 30   138 460  7   33 497 v 2   4 167 respectively   offers of suitable donors increased significantly  p less than 0 02  compared with the first six months of 1989  most notably for heart donors  80 v 60 1 expected  and kidney donors  122 v 102 1 expected  but only for kidneys was there a noticeable 17  increase in actual donors  118 actual audited donors v 100 8 expected donors  p   0 09   conclusions  four strategies to increase the supply of transplantable organs from brain stem dead potential donors in intensive care units were identified   a  reducing refusal of relatives  b  avoiding non procurement of actually suitable organs  by logistical initiatives  and deterioration of initially suitable organs  by donor care initiatives    c  converting restricted offers to unrestricted offers  and  d  ensuring discussion with families  early referral to the transplant team or coordinator gives time for discussion about donor care and agreement on medical suitability for donation of specific organs  solving some of the logistical problems of non procurement may be a prerequisite for increased offers to be translated into increased donations  the impact of publicity therefore needs to be measured on offers of suitable donors as well as by actual donations  
class10	reinforcement of incontinent stools in the treatment of encopresis  in this paper  fecal incontinence and constipation were treated in two mentally retarded individuals using a novel intervention wherein incontinent stools were first rewarded in order to increase the frequency of bowel movements  this intervention was implemented only after more traditional pediatric and behavioral treatments were unsuccessful  the reinforcement of incontinent stools procedure resulted in an increase in both the frequency and the number of continent stools for both individuals  hypotheses regarding the failure of previous treatments and the success of the current treatment are discussed as well as directions for future research  
class10	relative validity of self reported snoring as a symptom of sleep apnea in a sleep clinic population the purpose of this study was to evaluate the relative validity of responses to three different questions about snoring as indicators for sleep apnea in a population referred to a sleep clinic  secondary goals were to evaluate the meaning of a  don t know  response to these questions and to examine how the associations between snoring and sleep apnea are influenced by demographics  results from 1 409 patients in a sleep clinic indicated that nearly all levels of estimated snoring frequency were associated with a greater likelihood of sleep apnea  in addition  a  don t know  response indicated a likelihood of sleep apnea  in the sample from this clinic  sensitivities approximating 90 percent were obtained in men  and specificities approximating 90 percent were obtained in women  but high diagnostic accuracy  high specificity in men  high sensitivity in women  could not be achieved with the three snoring questions used here  generally  associations between snoring and sleep apnea were independent of age and sex  single persons  persons living alone  and persons customarily sleeping alone of both sexes all showed associations between self reported snoring and the presence of sleep apnea  
class10	dacron woven pacemaker pouch  influence on long term pacemaker mobility  pacemaker migration can interfere with correct pacing system function and patient comfort  a dacron pouch has been developed which may prevent these problems  to assess the efficacy of the pouch  we measured various factors of pacemaker mobility in 100 patients after long term follow up  the patients were divided into three groups on the basis of their dictated operative reports  group 1  no pouch or anchoring stitch  group 2  pouch only  group 3  anchoring stitch to pacemaker header or pouch  the average age of the study population was 74 3     11 years  total follow up time was 42     28 months  group i  53     32 months  group 2  36     23 months  group 3  34     25 months   there were no significant differences when pacemakers were measured for movement in the inferosuperior and lateromedial directions  nor was there any difference in the distance between the incision scar and the pacemaker header in any group  there was a significant difference between group 1 and groups 2 and 3 when the degree of tilt of the pacemaker off the chest wall was compared  this was 46 degrees     34 degrees for group 1 and 27 degrees     26 degrees and 26 degrees     27 degrees for groups 2 and 3  respectively  p less than 0 02 for both   these data suggest that the dacron pouch does not restrict pacemaker mobility parallel to the chest wall during long term follow up but does reduce the angle to which the pacemaker can be tilted relative to the chest wall  
class10	sleepwalking precipitated by treatment of sleep apnea with nasal cpap  a 33 year old man with a long history of snoring  observed apneic episodes  and excessive daytime sleepiness  underwent all night polysomnography  which demonstrated severe obstructive sleep apnea  during the nasal cpap trial  two episodes of sleepwalking were observed during a period of delta sleep rebound  
class10	potentially fatal asthma and syncope  a new variant of munchausen s syndrome in sports medicine  we report a case of munchausen s syndrome in a 19 year old female college athlete who presented with potentially fatal asthma and recurrent syncopal episodes  failure to control her asthma with the appropriate medications and the lack of objective findings on both physical examination and diagnostic testing raised the possibility of factitious disease  munchausen s syndrome  although not described with any frequency in asthmatic patients  should be considered in the differential diagnosis of those patients refractory to aggressive medical management  
class10	natural killer cell activity in patients with liver cirrhosis relative to severity of liver damage  to evaluate the role of severe liver damage on natural killer cell activity  29 patients with liver cirrhosis were examined  the natural killer cell activity was measured with a 4 hr chromium release assay  and the k562 cell line was employed as target cells  the natural killer cell activity was significantly decreased in cirrhotic patients compared with normal controls and patients with chronic active hepatitis  cirrhotic patients with pugh s c grade of severity of liver disease had lower natural killer cell activity  the depression of natural killer cell activity in cirrhotic patients was inversely correlated with prothrombin time ratios  and the natural killer cell activity in cirrhotic patients with hepatic encephalopathy was lower than in patients without hepatic encephalopathy  thus  the diminished natural killer cell activity in cirrhotic patients might be related to the severity of liver damage  
class10	alzheimer s disease and related disorders in state mental hospitals  data from a nationwide survey  notwithstanding three decades of transferring of the elderly to nursing homes  geriatric patients continue to reside in state mental hospitals  many of these patients  perhaps one third or more  are thought to suffer from alzheimer s disease and related disorders  adrd   this study reports data from a nationwide survey of state hospitals that provides an exploratory look at the adrd patients currently served in state hospitals  admission trends  reasons for admission  and sources of referral are described  civil commitment of nursing home patients with dementing illnesses and the place of the state hospital in the continuum of care for adrd patients are discussed  
class10	elevated intracranial pressure and computed tomography of the brain in fulminant hepatocellular failure  cerebral herniation is a leading cause of death in patients with fulminant hepatocellular failure  classical signs of elevated intracranial pressure are often absent in these patients  a reliable noninvasive method by which the presence of cerebral edema could be determined is much needed  to assess the efficacy of computed tomography of the brain in this setting  we compared the radiographic findings to the intracranial pressure measured by an epidural monitor in patients with fulminant hepatic failure  unfortunately  a considerable difference existed between the presence of cerebral edema diagnosed by computed tomography of the brain and elevation of the intracranial pressure  our observations suggest that in patients with fulminant hepatic failure and advanced hepatic encephalopathy  computed tomography of the brain is of little value in detecting cerebral edema  pressure monitoring is most important to establish the presence and guide the therapy of intracranial hypertension  
class10	differences in the membrane interaction of scrapie amyloid precursor proteins in normal and scrapie  or creutzfeldt jakob disease infected brains  the membrane interaction and hydrophobicity of the normal  prpc  and infectious isoform  prpsc cjd  of scrapie and creutzfeldt jakob disease amyloid precursor proteins was studied  the normal isoform of hamster and human scrapie amyloid precursor protein was found on the microsomal synaptosomal membranes anchored solely by the c terminal glycolipid  glycolipid cleavage resulted in dissociation from the membranes and change of behavior from a highly hydrophobic to a hydrophilic protein  susceptible to proteases  in contrast  the prpsc cjd isoform was resistant to release by glycolipid cleaving enzymes  a part of prpsc cjd was released from the membranes after prolonged trypsin treatment  yielding a further protease resistant product of 27 30 kda  the results demonstrate the proteolytic resistance of the membrane bound prpsc cjd isoform and also indicate the presence of a different  apparently disease induced mechanism of membrane interaction in the scrapie  and cjd infected microsomal and synaptosomal membranes  
class10	effect of indomethacin on the pathophysiology of experimental meningitis in rabbits  the effects of indomethacin on central nervous system abnormalities in rabbits with experimental pneumococcal meningitis were studied  as expected  prostaglandin e2 levels in cerebrospinal fluid were significantly lower in the indomethacin treated group  indicating that the drug effectively reduced prostaglandin synthesis  brain edema was markedly attenuated in the indomethacin treated group  however  cerebrospinal fluid white blood cell counts  lactate and protein concentrations  and intracisternal pressure were not significantly different between groups  it seems that indomethacin  while effective in reducing brain edema  does not significantly affect other important pathophysiologic alterations in experimental pneumococcal meningitis  
class10	sudden death and sleeping history among finnish men  an autopsy was performed in 460 consecutive cases of sudden death among 35  to 76 year old men  the closest cohabiting individual known to each decreased subject was interviewed  snoring history was obtained in 321 of the 371 interviews  in 86 cases there was a history of  habitual   almost always or always  snoring  and 88 men snored  often   the mean age of subjects was 55 4 years  the mean body mass index  bmi  was 26 3 kg m 2  among the obese snorers  n   82   apnoeas had been observed  occasionally    often   or  habitually  in 49 cases  death was classified as cardiovascular in 186  40 4   cases  cardiovascular cause of death was more common among those who snored habitually or often than among those who snored occasionally or never  p less than 0 05    habitual  snorers died more often while sleeping  p less than 0 05   habitual snoring was found to be a risk factor for morning death  p less than 0 01   the possibility of obstructive sleep apnoea as a cause of sudden death should at least be considered if the decreased is known to have been a habitual snorer  
class10	long term follow up of the use of nonporous hydroxyapatite for augmentation of the alveolar ridge  particulate hydroxyapatite  ha  was used in the augmentation of 18 mandibular and four maxillary ridges in 21 patients whose cases were followed postoperatively for 5 to 7 years  patients were evaluated clinically  radiographically  and through questionnaires  prosthodontic assessment of retention and stability of dentures showed improvement 5 years postoperatively  patients receiving ha rated their dentures favorably using parameters of the cornell medical index  the results of this study show that particulate ha alone can be used as a satisfactory material for augmentation of the alveolar ridge  
class10	creutzfeldt jakob disease from allogeneic dura  a review of risks and safety  surgeons and the lay public have recently expressed concern over the safety of allogeneic dura as it relates to the transmission of creutzfeldt jakob disease  indeed  two cases have resulted from use of tissue procured from a commercial agency that did not adhere to criteria accepted by the american association of tissue banks or the southeast organ procurement foundation  this review discusses the risks and safety of allogeneic dura  the findings should reassure the surgeon of the safety of allogeneic dura when it is properly processed and catalogued by a bona fide  reputable tissue bank  to date  there have been no documented cases reported to the center for disease control in which creutzfeldt jakob disease was transmitted from allogeneic dura obtained from a registered tissue bank  
class10	clinical diagnostic considerations on cocaine abuse  following a review of the research literature on the psychophysiological effects of cocaine  a study is described of a group of 120 cocaine addicts  of the 120 patients  10  8 33   exhibited fleeting  unformed  organic delusions and hallucinations  case reports of the 10 cases are presented  the quality of the adverse subjective effects of cocaine is emphasized  and the differential diagnosis between cocaine delusional disorder and paranoid schizophrenia is discussed  guidelines for a more accurate differential diagnosis are provided  
class10	medicare peer review organization preprocedure review criteria  an analysis of criteria for three procedures the medicare peer review organization  pro  program includes preprocedure review using explicit criteria to assess the appropriateness of specific procedures  this study evaluates the variability in the pro preprocedure criteria for the three procedures most frequently reviewed by pros  carotid endarterectomy  cataract removal  and cardiac pacemaker implants  in august 1989  the pro review criteria were received from the health care financing administration  to provide a reference point for reviewing the pro criteria  national practice guidelines for these three procedures were identified  wide variability was demonstrated in the pro procedure specific carotid endarterectomy and cataract removal review criteria among pros  and the criteria differed significantly from the identified practice guidelines  the criteria for cardiac pacemaker implants were somewhat less variable  and were based  to varying degrees  on practice guidelines developed by the american college of cardiology  acc   greater attention is needed to improve the development of review criteria  including the use of relevant practice guidelines  to ensure that review criteria are optimal  
class10	neurobehavioral effects of phenytoin prophylaxis of posttraumatic seizures in order to determine potential negative neurobehavioral effects of phenytoin given to prevent the development of posttraumatic seizures  244 subjects were randomized to phenytoin or placebo  they received neurobehavioral assessments at 1 and 12 months postinjury while receiving their assigned drug and at 24 months while receiving no drugs  in the severely injured  phenytoin significantly impaired performance at 1 month  no significant differences were found as a function of phenytoin in the moderately injured patients at 1 month or in either severity group at 1 year  patients who stopped receiving phenytoin according to protocol between 1 and 2 years improved more than corresponding placebo cases on several measures  we conclude that phenytoin has negative cognitive effects  this  combined with lack of evidence for its effectiveness in preventing posttraumatic seizures beyond the first week  raises questions regarding its use for long term prophylaxis  our findings do not negate phenytoin s proven efficacy in controlling established seizures nor do they indicate that its cognitive effects are worse than other anticonvulsant drugs  
class10	physical and pharmacologic restraint of nursing home patients with dementia  impact of specialized units this case control study of 31 specialized dementia units and 32 traditional units in five states investigated use of physical and pharmacologic restraints among 625 patients with the diagnosis of dementia  physical restraints were observed in use on 18 1  of dementia unit patients and on 51 6  of comparison unit patients who were out of bed during the day  adjusted odds ratio  0 283 95  confidence interval  0 129 to 0 619   pharmacologic restraints were routinely given to 45 3  of dementia unit patients and 43 4  of comparison unit patients  adjusted odds ratio  0 950  95  confidence interval  0 611 to 1 477   we used multivariate logistic regression to identify residence in a nonspecialized nursing home unit  nonambulatory status  transfer dependency  mental status impairment  hip fracture history  and a high nursing staff to patient ratio  which we found to be independent predictors of physical restraint use  physically abusive behavior  severe mental status impairment  and frequent family visitation were found to be significant predictors of pharmacologic restraint use  while advanced patient age  large nursing home size  and patient nonambulatory status were protective against such use  these results support the conclusion that physical and pharmacologic restraint constitute separate treatment modalities with different risk factors for use  and indicate that specialized dementia units are successful in reducing the use of physical but not pharmacologic restraints  
class10	retrovirus induced spongiform myeloencephalopathy in mice  regional distribution of infected target cells and neuronal loss occurring in the absence of viral expression in neurons  the cas br e murine leukemia virus  mulv  induces a spongiform myeloencephalopathy resulting in a progressive hindlimb paralysis  we have used in situ hybridization with a cas br e mulv specific probe to study viral expression in the central nervous system  infected cells were concentrated in regions where spongiform lesions and gliosis are detected  lumbosacral spinal cord  brainstem  deep cerebellar regions   suggesting a causative link between the level of virus expression and the degree of pathological changes in this disease  however  viral expression was not in itself sufficient to cause disease  since significant viral expression was observed in regions that did not exhibit pathological changes  cerebellar cortex  hippocampus  corpus callosum  peripheral nervous system   in both diseased and nondiseased regions  endothelial and glial cells were identified as the main target cells  neurons in diseased regions did not show viral expression  the regional distribution of the spongiform changes appears to be laid down very early following infection  since expression could be detected at 10 days postinfection in regions that become diseased  these results indicate that nonneuronal cells have distinct properties in various regions of the central nervous system and suggest an indirect mechanism of neuronal loss consequent to viral expression in nonneuronal cells  
class10	tumoral thrombosis of cerebral venous sinuses  preoperative diagnosis using magnetic resonance phase imaging  intracranial  dural based neoplasms will not infrequently invade adjacent venous sinuses  therefore  the preoperative diagnosis of venous invasion is important  as it will alter the surgical approach to the lesion  magnetic resonance imaging is a noninvasive means of visualizing the cerebral venous sinuses  the preoperative diagnosis of venous thrombosis can  however  be difficult and confusing with conventional spin echo magnetic resonance imaging because of variable appearances produced by blood clot degradation products as well as flowing blood  phase magnetic resonance imaging is a simple method that can be acquired simultaneously with conventional spin echo sequences  and is based primarily on whether protons are stationary or moving  in the context of venous sinus occlusion  phase imaging can demonstrate the presence or absence of blood flow more easily than spin echo imaging  three cases of dural based neoplasms are presented that demonstrate the utility of phase imaging in diagnosing tumoral occlusion of the venous sinuses  
class10	hydrocephalus  overdrainage by ventricular shunts  a review and recommendations  selected literature review of the clinical course of patients with ventricular shunts for hydrocephalus shows that the effects of cerebrospinal fluid overdrainage are subdural hematoma  craniosynostosis  slit ventricle syndrome  and low intracranial pressure syndrome  these occur sequentially at different age groups  but approximate averages of incidence and time of occurrence after first shunt reveal an overall incidence of 10  12  for at least one of these appearing at 6 5 years after shunting  the basic etiology  diagnosis  and variety of treatment modalities available are reviewed  including the need for shunt closing intracranial pressure control  included is a hydrocephalus program designed to minimize the need for long term extracranial shunts and to maximize therapeutic intracranial procedures for hydrocephalus  
class10	unusually late onset of cerebrospinal fluid rhinorrhea after head trauma  two cases of acute meningitis and cerebrospinal fluid rhinorrhea  in which the head trauma responsible occurred 10 and 30 years before  are presented  intraoperatively  the brain parenchyma was found to be plugged into the fractured anterior fossa  by debridement and duraplasty from an intradural approach  both patients were cured  several precipitating factors could be responsible for this unusually late reopening of the fistula  the possible accidental causes could be coughing or undetected microtraumas  but in the long run  atrophy of tissues and consequent changes in brain compliance with aging may play a role  
class10	angiotropic intravascular large cell lymphoma  malignant angioendotheliomatosis   report of a case and review of the literature  we present a case of angiotropic large cell lymphoma and review the literature in order to define the neurologic features of this rare disorder  this is the first report of gadolinium dtpa imaging in angiotropic large cell lymphoma that demonstrates infarcts of multiple ages  as well as striking meningeal enhancement  angiotropic large cell lymphoma should be suspected in patients with clinical evidence of small and large cerebral vessel disease and diagnosis requires skin  liver  renal  meningeal  or brain biopsy  single modality treatment  using either radiation therapy or steroids  has been ineffective  and new findings of a lymphomatous origin of this neoplasm suggest that combination chemotherapy may be indicated  
class10	treatment of leptomeningeal carcinomatosis with continuous intraventricular infusion of recombinant interleukin 2  a 42 year old man developed leptomeningeal carcinomatosis 6 years after treatment of a malignant melanoma  he was treated with two courses of recombinant interleukin 2  administered as a continuous intraventricular infusion  6 x 10e5 u 24 h  during 5 days  during the first day of the first course he also received 5 x 10e9 lymphokine activated killer cells intraventricularly  this gave rise to a severe elevation of intracranial pressure  with headaches and meningismus  during the second course no lak cells were administered  this course was tolerated much better  the neurological status did not change during the treatment  recombinant interleukin 2 levels were maintained at about 300 u ml during both courses  
class10	antivenom therapy in russell s viper bite  bleeding and renal failure are the two main manifestations responsible for the high morbidity and mortality in untreated russell s viper bite victims  this study was an effort to find prognostic factors and a practical therapeutic approach for the care of such patients  early detection of abnormalities in the clot quality test and or evidence of systemic bleeding followed by immediate correction of the clotting defects using specific antivenom can reduce morbidity in russell s viper envenomation  
class10	midazolam induced benzodiazepine withdrawal syndrome a case history of a patient who developed severe anxiety and agitation on two occasions after discontinuation of a midazolam infusion is presented  the withdrawal symptoms interfered with effective mechanical ventilation and the patient required the reintroduction of a long acting benzodiazepine to treat the withdrawal state and to facilitate weaning from mechanical ventilation  
class10	response to suxamethonium in a myasthenic patient during remission  a cumulative dose followed by an infusion was used to determine the dose response to suxamethonium in a patient with diagnosed myasthenia gravis who was in true remission  asymptomatic while receiving no therapy   the ed50 and ed90 values for suxamethonium were 0 08 mg kg and 0 20 mg kg  and an infusion rate of 3 2 mg kg hour was required to maintain a 90 95  depression of the single twitch response as monitored by integrated electromyography  these values are within the range for normal patients  and we conclude that myasthenic patients during a true remission may not demonstrate resistance to suxamethonium  
class10	non drug related asystole associated with anaesthetic induction  a patient is presented where routine venepuncture associated with anaesthetic induction resulted in bradycardia and asystole  the case highlights the need for special caution with  and ecg monitoring throughout induction for  patients with a history of syncope  it also demonstrates the need for caution when attributing cardiovascular events during induction to the effect of the induction agents used  
class10	modification of pain on injection of propofol  a comparison between lignocaine and procaine  pain on injection of propofol was assessed in a controlled  randomised study of 273 patients  they received either lignocaine 10 mg  procaine 10 mg or isotonic saline 0 5 ml  15 seconds before the injection of propofol into a vein on the back of the hand  the incidence of pain on injection in the control group  51   was comparable with other studies  lignocaine and procaine both significantly reduced the pain  35  and 34  respectively  p less than 0 05  but there was no statistical difference between these two groups  
class10	flexion extension views in the evaluation of cervical spine injuries  study objective  to determine the efficacy of flexion extension  f e  cervical spine radiographs in detecting acute cervical spine instability in emergency patients  design  we retrospectively reviewed the charts of 141 consecutive trauma patients who had f e views performed after a routine cervical spine series  three views  was obtained in the emergency department  interpretations of the routine series were compared with those of the f e views to determine if additional useful information was provided by the latter  the charts also were reviewed to determine if any variables were associated with an increased use of f e views  an increased likelihood of these views demonstrating instability  or any neurologic sequelae resulted from these studies  setting  an urban level i adult trauma center  measurements  the interpretations of the routine series were noted to be either normal  abnormal but without demonstrable fracture dislocation  or demonstrating a fracture dislocation  the f e views were categorized as stable  unstable  or uninterpretable  results  cervical spine instability was demonstrated by f e views in 11 of the 141 patients  8    four of whom had normal routine cervical spine films  three of these four patients required surgical stabilization  prolonged neck pain  more than 24 hours   an initially abnormal spine series  and a neurosurgical consult were all associated with an increased use of f e views  ten of 11 patients with radiographic instability had significant neck pain by history  the remaining patient was intoxicated  no neurologic sequelae resulted from performing f e studies  there was one false negative f e study  which raises concern about the reliability of this procedure in the ed  conclusion  we believe that a large prospective study is required to determine which patients warrant f e views  
class10	lidocaine potentiation of cocaine toxicity  study hypothesis  the toxic effects of cocaine are enhanced in the presence of lidocaine  study population  male sprague dawley rats weighing 200 to 300 g  methods  animals received intraperitoneal injections of cocaine  10  20  35  or 50 mg kg   lidocaine  30 or 40 mg kg   or a combination of all doses of cocaine given simultaneously with 30 or 40 mg kg lidocaine  the incidence and time to seizure and death were recorded in these groups and compared by chi 2 and analysis of variance analyses  respectively  results  at doses of 30 or 40 mg kg  lidocaine does not induce seizures or death  the effect of simultaneous injection of both cocaine and lidocaine was to dramatically increase the incidence of both seizures and death over that of cocaine alone  the incidence of seizures in animals receiving 35 mg kg cocaine alone was 10   this increased to 50  and 80  with the addition of 30 and 40 mg kg lidocaine  respectively  p less than or equal to  05  p less than or equal to  01   death did not occur in animals receiving 35 mg kg cocaine alone  the addition of 30 and 40 mg kg lidocaine resulted in death in 30  and 60  of animals  respectively  p less than or equal to  01 each group   similarly  in rats receiving 50 mg kg cocaine  the incidence of death increased from 0  to 60  and 80  with 30 and 40 mg kg lidocaine  respectively  p less than or equal to  01   conclusion  in the rat  overall toxicity of cocaine is significantly increased with simultaneous exposure to lidocaine  
class10	phenytoin administration by constant intravenous infusion  selective rates of administration  study objectives  to determine the adequacy of seizure control and the adverse effects of administering an iv loading dose of phenytoin by constant infusion pump  design  a prospective study of patients presenting with acute onset of seizures  patients were divided into two groups  group 1 comprised all patients 50 years of age or younger without a history of atherosclerotic cardiovascular disease  ascvd   group 2 comprised all patients older than 50 years or with a history of ascvd  setting  a rural community hospital emergency department  type of participants  forty two adult patients  interventions  both groups received an iv loading dose of phenytoin at 15 mg kg  infusion rates were 50 mg min and 25 mg min for groups 1 and 2  respectively  cardiac rhythm and vital signs were monitored throughout and after infusion  measures and main results  group 2 demonstrated significantly more cardiovascular side effects  hypotension and bradycardia  than did group 1  fisher s exact test  p less than  05   conclusion  phenytoin provided adequate seizure control in both groups  for individuals with ascvd  iv phenytoin administration rates should not exceed 25 mg min  for individuals without ascvd  phenytoin administration at 50 mg min appears safe and without significant cardiovascular side effects  
class10	poisoning with equine phenylbutazone in a racetrack worker  phenylbutazone is a potent nonsteroidal  anti inflammatory drug often used by veterinarians to treat racetrack animals  its use in human beings is limited because of significant adverse effects and the availability of newer  safer drugs  we report the case of a 24 year old man who ingested 17 g of equine phenylbutazone over a 24 hour period to treat the pain of a toothache  he developed grand mal seizures  coma  hypotension  respiratory and renal failure  and hepatic injury  serum phenylbutazone concentration obtained approximately eight hours after presentation was 900 micrograms ml  the patient recovered during six weeks of intensive supportive care and repeated hemodialysis  
class10	multiple cranial nerve deficits after ethylene glycol poisoning  we report the cases of two patients who developed cranial nerve palsies after drinking ethylene glycol  a 33 year old man developed multiple cranial nerve deficits nine days after the ingestion of ethylene glycol in a suicide attempt  clinical findings included profound bilateral cranial nerve vii palsies and severe dysfunction of cranial nerves ix and x  the neuropathy occurred despite treatment with hemodialysis  the dysphagia completely cleared within two weeks  but at six months a severe bilateral cranial nerve vii dysfunction persisted  a 22 year old man undergoing hemodialysis for ethylene glycol induced renal failure developed bilateral cranial nerve vii dysfunction 14 days after ingestion  at a three month follow up  the patient demonstrated only moderate functional recovery  the etiology of the cranial nerve deficits is unknown but may be related to oxalate crystal deposition of ethylene glycol induced pyridoxine dysfunction  
class10	genetic cause of a juvenile form of tay sachs disease in a lebanese child  abnormality in the beta hexosaminidase alpha gene underlying the clinical phenotype of a lebanese patient with a juvenile form of tay sachs disease has been studied  clinical features were progressive spasticity  ataxia  and cognitive decline  the protein coding sequence of several beta hexosaminidase alpha chain complementary dnas isolated by polymerase chain reaction was completely normal except for a g to a transition at nucleotide position 1511 within exon 13  which resulted in substitution of the normal arginine 504  cgc  with histidine  cac   although the patient was from a first cousin marriage  she was heterozygous for this mutation  the abnormality in the other allele  which is carried by the father  was not identified  except that it is neither of the two mutations responsible for the infantile jewish tay sachs disease  biosynthetic and immunoprecipitation studies in cultured fibroblasts showed synthesis of the alpha chain precursor  but the mature form of the alpha subunit was not detected  
class10	elevated alpha tumor necrosis factor levels in spinal fluid from hiv 1 infected patients with central nervous system involvement  to assess the role of alpha tumor necrosis factor in the pathogenesis of central nervous system involvement during human immunodeficiency virus type 1 infection  we recorded clinical data and measured alpha tumor necrosis factor levels in serum and cerebrospinal fluid samples from 45 patients infected with human immunodeficiency virus type 1  classified as group ii iii  10   group iv a  5   group iv b  10   and group iv c 1  20  of the centers for disease control acquired immunodeficiency syndrome classification system and 42 controls  alpha tumor necrosis factor was above the limit of detection in only 3 of 15 sera and 3 of 15 cerebrospinal fluid samples from patients in group ii iii and group iv a  whereas it was detected in 17 of 30 sera  p less than 0 05  and 22 of 30 cerebrospinal fluid  p less than 0 0002  samples from clinically more advanced patients  group iv b and group iv c 1   alpha tumor necrosis factor mean values were 21 5 pg ml in sera and 50 0 pg ml in cerebrospinal fluid from group iv b patients and 30 4 pg ml in sera and 24 pg ml in cerebrospinal fluid from group iv c 1 patients  
class10	neuroanatomy of fragile x syndrome  the posterior fossa  the occurrence and specificity of posterior fossa abnormalities as measured from magnetic resonance images of the brain were investigated in a group of 14 males with fragile x syndrome and comparison groups consisting of 17 males with other causes of developmental disability and 18 males with normal iqs  the size of the posterior cerebellar vermis was significantly decreased and the fourth ventricle significantly increased in the group of males with fragile x syndrome compared with males in both comparison groups  these neuroanatomical abnormalities appeared to be secondary to hypoplasia rather than atrophy  
class10	visual dysfunction in alzheimer s disease  relation to normal aging  published erratum appears in ann neurol 1991 mar 29 3  271  in patients with alzheimer s disease  ad   compared with age matched and young healthy control subjects  visual deficits in the following functions were observed  color  stereoacuity  contrast sensitivity  and backward masking  homogeneous and pattern   critical flicker fusion thresholds were normal  relative to age matched healthy subjects  for color  the majority of the errors were tritanomalous  blue axis   color and stereoacuity deficits were unrelated to severity of dementia  in accordance with models of vision that describe these functions as modular rather than diffuse for cortical localization  although contrast sensitivity was depressed throughout the frequency range in ad  more patients were impaired at low than at high spatial frequencies  contrasting with the observed normal aging pattern of high frequency loss  healthy elderly subjects showed depressed critical flicker fusion thresholds and reduced contrast sensitivity at high frequencies  relative to the young group  differences between these groups were not found for the other vision tests  a subset of the ad group received detailed neuro ophthalmological examination  and no abnormalities were found  this finding  taken together with normal thresholds for critical flicker fusion  suggests that the widespread visual dysfunction reported here is more likely to be related to known pathological changes in primary visual and association cortex in ad than to changes in the retina or optic nerve  
class10	the functional anatomy of motor recovery after stroke in humans  a study with positron emission tomography  we have studied regional cerebral blood flow changes in 6 patients after their recovery from a first hemiplegic stroke  all had a single well defined hemispheric lesion and at least a brachial monoparesis that subsequently recovered  each patient had 6 measurements of cerebral blood flow by positron tomography with 2 scans at rest  2 during movement of fingers of the recovered hand  and 2 during movement of fingers of the normal hand  when the normal fingers were moved  regional cerebral blood flow increased significantly in contralateral primary sensorimotor cortex and in the ipsilateral cerebellar hemisphere  when the fingers of the recovered hand were moved  significant regional cerebral blood flow increases were observed in both contralateral and ipsilateral primary sensorimotor cortex and in both cerebellar hemispheres  other regions  namely  insula  inferior parietal  and premotor cortex  were also bilaterally activated with movement of the recovered hand  we have also demonstrated  by using a new technique of image analysis  different functional connections between the thalamic nuclei and specific cortical and cerebellar regions during these movements  our results suggest that ipsilateral motor pathways may play a role in the recovery of motor function after ischemic stroke  
class10	lymphoma  motor neuron diseases  and amyotrophic lateral sclerosis  we studied 9 patients with motor neuron disease and lymphoma  the following several observations have not been recognized in the past   1  motor neuron syndromes are associated with either hodgkin s disease or non hodgkin s lymphoma   2  the syndromes are not restricted to lower motor neuron disorders  8 of 9 patients had definite or probable upper motor neuron signs as well  qualifying for the diagnosis of amyotrophic lateral sclerosis  corticospinal tracts were affected in both postmortem examinations   3  the combination of motor neuron disease and lymphoma is often accompanied by paraproteinemia  3 of 7 patients studied   increased cerebrospinal fluid protein content  6 of 9 patients   and cerebrospinal fluid oligoclonal bands  3 of 9 patients    4  in 2 patients  asymptomatic non hodgkin s lymphoma was found only because the discovery of paraproteinemia gave impetus to examine the bone marrow   5  patients with both upper and lower motor neuron signs  amyotrophic lateral sclerosis  may show physiological evidence of conduction block in peripheral nerves or autopsy abnormalities in peripheral nerves  the cause of this syndrome is not known  both lymphoma and motor neuron disease could have a common cause  possibly a retroviral infection  the frequency of paraproteinemia suggests that an immunological disorder may play a role in the pathogenesis of the neurological disorder  
class10	nerve growth factor prevents toxic neuropathy in mice  taxol is a promising new antitumor drug with therapeutic use that is limited by a toxic sensory neuropathy  taxol is also cytotoxic to dorsal root ganglion neurons in vitro  but this effect is prevented by cotreatment with the trophic protein  nerve growth factor  we sought to develop an animal model and then to determine whether nerve growth factor can prevent taxol neuropathy in vivo  administration of taxol to mice resulted in a profound sensory neuropathy characterized by decreases in dorsal root ganglion content of the peptide neurotransmitter  substance p  elevated threshold to thermally induced pain  and diminished amplitude of the compound action potential in the caudal nerve  coadministration of nerve growth factor prevented all of these signs of neurotoxicity  these findings suggest that administration of nerve growth factor may prevent certain toxic sensory neuropathies  
class10	localization of 3h dihydroergotamine binding sites in the cat central nervous system  relevance to migraine  dihydroergotamine  dhe  is the treatment of choice in aborting the acute attack of migraine  although its efficacy has been known for 40 years  its mechanism of action is still disputed  data regarding the site of action of dihydroergotamine may provide an insight into its mechanism of action and thus identify a locus of potentially abnormal pathophysiology in migraine  by using in vitro and ex vivo autoradiographic techniques  the localization of specific binding sites for 3h dihydroergotamine in the cat brain has been examined  binding was seen in the dorsal horn of the cervical spinal cord  in the medulla  associated with the nucleus of the tractus solitarius  area postrema  and descending spinal trigeminal nucleus  and in the mesencephalon and the cerebral cortex  the highest density of binding sites was found in the dorsal and medial raphe nuclei of the midbrain  furthermore  these same brain regions were also labeled after intravenous administration of 3h dihydroergotamine  it is important that the brain areas specifically labeled are key nuclei involved in cranial pain transmission  suggesting that dihydroergotamine may act at these central sites in migraine  
class10	acceleration of scrapie in trisomy 16    diploid aggregation chimeras  we studied the susceptibility to prion infection of the trisomy 16    diploid chimeric mouse  a putative model of down syndrome  when weanling chimeras were inoculated intracerebrally with scrapie prions  the time until appearance of the first symptoms of scrapie was reduced by 17 days  from a mean control time of 153 days  and the time to death was reduced by 30 days  from control time of 170 days   our results with trisomy 16 chimeras argue that the susceptibility to central nervous system degeneration caused by prions can be modulated by chromosome imbalance  
class10	muscle biopsy for diagnosis of malignant hyperthermia susceptibility in two patients with severe exercise induced myolysis  muscle biopsy and in vitro contracture tests for diagnosis of susceptibility to malignant hyperthermia  mh  were performed in two patients who had developed fever and severe myolysis during exercise  mh susceptibility was confirmed in one patient  but in the other  exercise induced heat stroke proved to be the correct diagnosis  clinical presentation and epidemiology of exercise induced mh and its relation to the heat stroke syndrome are discussed  
class10	traumatic subarachnoid pleural fistula in a child  a case report  a seven year old girl sustained a gunshot wound to the chest and spine  evaluation of a persistent pleural effusion demonstrated a subarachnoid pleural fistula  surgical closure of the dural defect resulted in resolution of the fistula  traumatic subarachnoid pleural fistulae are rare  the diagnosis is reached by an awareness of fistula formation from penetrating or blunt trauma to the chest  
class10	total knee arthroplasty in patients after patellectomy  twenty six total knee arthroplasties  tkas  were evaluated in 22 patients who had had a patellectomy  fourteen knees  12 patients  had a primary tka  and 12 patients had a revision tka  two patients in the revision group  whose prostheses failed  were from the primary tka group  the mean follow up time was 8 5 years in the primary tka group and 7 6 years in the revision tka group  a group of 14 control knees with patellae was randomly generated but matched for prosthesis  diagnosis  surgeon  age  and time of surgery  this group was similarly evaluated with an average follow up time of 6 9 years  the primary tka group had seven knees that were rated as good or excellent  two as fair  and three as poor  the control group had a significantly higher average rating than the primary tka group  in this group  there were 12 good or excellent knees  three fair  and none poor  postoperative pain  flexion contracture  extension lag  and range of motion all contributed significant information to the final score  whereas other variables  walking  function  strength  and instability  did not contribute any additional information  although higher overall scores may have been expected if the patients had patellae  the results during the follow up examination were satisfactory and justified tka in these patients  in general  however  patients without patellae may be at a higher risk for failure of the prosthesis  as seen in five patients having primary tka and another ten patients with failed tka requiring revision  
class10	magnetic resonance imaging for ineffectual tarsal tunnel surgical treatment  tarsal tunnel syndrome  tts  is an entrapment neuropathy caused by compression of the posterior tibial nerve beneath the ankle flexor retinaculum  treatment of tts consists of surgical release of the retinaculum  the failure rate is 10  20   magnetic resonance  mr  imaging was used to evaluate a patient with an unsatisfactory response  mr imaging demonstrated incompleteness of the surgical release of the flexor retinaculum  
class10	neurologic status of spina bifida patients and the orthopedic surgeon  the purpose of this paper is to review recent developments in the neurologic assessment of spina bifida patients  determination of the neurosegmental level of the lesion  recognition of spasticity and progressive paralysis  the potential for deformity  and functional expectations are described  the status of the neurologic deficit remains the most important factor in determining the myelomeningocele patient s ultimate functional abilities  accurate neurologic assessment will assist in meeting the aims of orthopedic management  which include preventing joint contracture  correcting deformity  preventing skin sores  and obtaining the best possible locomotor function  
class10	gait analysis in the treatment of the ambulatory child with cerebral palsy  surgical treatment of children with cerebral palsy has changed from staged  single joint procedures to comprehensive simultaneous bony and soft tissue corrections  this regimen of treating multiple joint levels and planes of abnormality is subject to error when based solely on the clinical examination  a more scientific evaluation can be provided by the use of clinical gait analysis  both preoperative and postoperative analyses provide the clinician with information from which neurologic patterns can be determined and surgical protocols can be judged  
class10	impact of day care on dementia patients  costs  well being and relatives  views  forty seven patients in psychogeriatric day centre were analysed regarding use of resources  costs and well being  the level of well being was based on interviews with staff and relatives and related to the economic outcome  a cost utility analysis  a 6 month period prior to day care was compared with the first 6 months in such care  the use of resources at home increased by 20  while the use of institutional care was reduced by 22   fifty three percent of the patients improved in their well being after participation in day care  when the cost of utility analysis was applied  the cost for a well year was 4293 pounds  
class10	a comparison of the efficacy and safety of pergolide and bromocriptine in the treatment of hyperprolactinemia  pergolide is a synthetic ergoline derivative with highly potent long acting prl lowering activity  allowing therapy of hyperprolactinemia with a once daily administration of the drug  the results of two open label  randomized controlled multicenter clinical trials are reported  pergolide  taken once a day   was compared with bromocriptine  taken two to four times daily  regarding efficacy and safety in the reduction of prl levels  the cessation of galactorrhea and amenorrhea  the improvement in sexual function  and tumor shrinkage in hyperprolactinemia without  trial i  61 patients  and with radiologically evident pituitary tumors  trial ii  96 patients   both drugs were equally effective in lowering prl levels in both trials  a median optimal dose of 50 micrograms pergolide and 5 mg bromocriptine day suppressed prl levels in the 61 patients of trial i by more than 80   during the 24 week investigational period galactorrhea disappeared in 96  and 87  of patients  whereas menstruation returned in 90  and 96  of patients  respectively  an equally high efficacy  optimal median dose  75 100 micrograms pergolide  7 5 10 mg bromocriptine daily  was observed in trial ii  although the resumption of menses was less frequent than in the patients of trial i  50  and 58  of patients  respectively   sexual dysfunction improved similarly on both drugs in about half the patients  in addition  tumor shrinkage occurred to a similar extent with both drugs  a high incidence of adverse events was noted especially at the initiation of therapy with both compounds  nausea  dizziness  vomiting  asthenia  headache  and decrease in blood pressure occurred at a similar incidence and extent during the use of pergolide and bromocriptine  patients in trial i treated with pergolide reported a slightly higher incidence of fever  vasodilatation  and flu syndrome  conclusions  in these 24 week studies comprising a total of 157 hyperprolactinemic patients  a once daily administration of pergolide was shown to be as safe and effective as the two to four times daily ingestion of bromocriptine  longer acting dopamine agonists like pergolide that can be taken once daily  are likely to increase the ease to adherence to the therapeutic regimen  this might result in a higher compliance to medical treatment of hyperprolactinemia  
class10	immunoassay of p2 protein in cerebrospinal fluid in neurological disorders  cerebrospinal fluid samples were obtained at lumbar puncture from 53 patients with a wide variety of neurological disorders  cerebrospinal fluid samples were tested for the presence of p2 protein  a constituent of myelin  with an enzyme linked immunosorbent assay technique using a specific polyclonal antibody  high concentrations of p2 in the cerebrospinal fluid paralleled a raised igg index  clearance ratio   the presence of oligoclonal bands  as well as raised white cell counts or depressed albumin igg ratios  twenty one patients had been diagnosed as having definite or probable multiple sclerosis and the remaining 32 had other conditions  of the 13 patients with high positive p2  12  92   were in the multiple sclerosis category  of the 40 patients with low  12  or undetectable  28  p2 concentrations  only nine  23   were diagnosed as having multiple sclerosis  in this patient population the presence of high immunoreactive p2 concentrations in cerebrospinal fluid was closely associated with evidence of intrathecal immunoglobulin synthesis and with the clinical diagnosis of multiple sclerosis  on this basis it is suggested that immunoassay of p2 concentration in the cerebrospinal fluid may be of potential value in the investigation of patients with demyelinating disorders  
class10	the role of pain in the last year of life of older persons  a random sample of 200 decreased older community residents was studied with a focus on the role of pain in the last year of life  interviews with a surviving close person elicited retrospective reports  pain increased over the final year  one month before death 66  felt pain frequently or all of the time  substantially higher than a matched comparison group of living persons  24    for both groups across the year  pain was associated with most measures of behavioral competence  perceived quality of life  and psychological well being  hierarchical multiple regressions indicated that background and health variables explained 28  to 32  of the variance of pain over the year  controlling for background variables and health  pain contributed significantly to lowered happiness and to depression  but had no independent impact on hope and interest in the world  after controlling for physical health  the older old were judged to have less pain than the younger old  
class10	mechanical ventilation in medical and neurological diseases  11 years of experience  mechanical ventilation  mv  is imperative in many forms of acute respiratory failure  arf   the aim of this work was to review all episodes of mv in a medical intensive care unit  micu  during the 11 year period 1976 1986  four per cent  n   1008  of 24 899 admissions to the micu were treated with mv  the mean age of ventilator treated patients was 53     18 years  and obviously it increased during the period of study  the average duration of mv was 4 7 d  micu mortality  hospital mortality and 2 year mortality rates for patients subjected to mv were 33   38  and 46   respectively  the mortality rate did not change during the study period  cerebrovascular and malignant diseases carried the highest mortality rates  75 and 79   respectively  whereas mortality in patients ventilated because of drug overdose  n   313  was only 2   the results of this study confirm previously published findings concerning the outcome of mv  and we conclude that the effects of mv remain discouraging in medical and neurological patients  improved quality of ventilator therapy and monitoring  as well as continued research directed at the causes of arf  are equally important in reducing the mortality in arf  
class10	serum creatinine  an independent predictor of survival after stroke  we prospectively studied the relationship between serum creatinine and survival among 492 elderly subjects admitted for stroke and monitored for a mean period of 18 months post stroke  in multivariate proportional hazards models  serum creatinine remained an independent predictor of mortality  p   0 0001  after accounting for other important predictors such as level of consciousness  mini mental state score  age  leucocyte count  presence of heart disease  diabetes  heart failure  atrial fibrillation and use of cardiovascular medication  this association between elevated serum creatinine and mortality was also found in patient subgroups with ct proven infarction and intracerebral haematoma  it is concluded that serum creatinine is an independent predictor of survival after stroke  further studies are required to confirm this relationship and to elucidate the underlying mechanism  
class10	familial hypobetalipoproteinaemia complicated by cerebellar ataxia and steatocystoma multiplex  a 55 year old man with cerebellar ataxia and steatocystoma multiplex was found to have reduced serum concentrations of total cholesterol  betalipoprotein and apolipoprotein b  computed tomography revealed atrophy of the cerebellum and brain stem  of the six family members examined  four had hypobetalipoproteinaemia  and one had mild ataxia  similar skin lesions were noted in five male relatives  this case represents a rare combination of familial hypobetalipoproteinaemia  cerebellar ataxia and steatocystoma multiplex  
class10	patterns of neuropsychological impairment after severe blunt head injury  a consecutive series of 100 subjects with severe blunt head injuries was followed up 6 years after trauma  neuropsychological test performances of 82 subjects and of a noninjured control group were analyzed by two principal components analyses  pcas   each pca extracted 15 factors relating to a range of cognitive impairments  as well as neuropsychological features consistent with posttraumatic personality changes  measures identified by the pcas were applied to 85 head injured subjects in the series to examine the incidence of impairment in four neuropsychological areas  disorders of learning and memory  neuropsychological features consistent with posttraumatic personality change  slowness in rate of information processing  and a range of basic neuropsychological skills  overall  impairments occurred in 70  of the series  disorders of learning and memory were the most common type of deficit  56 5    with disturbances in basic neuropsychological skills the least frequent  16 5    variability among subjects with respect to the types and combinations of neuropsychological impairments was a characteristic feature of this clinical group  but the largest proportion  one third  demonstrated isolated impairments  the implications of the incidence and selectivity of neuropsychological impairments are discussed  
class10	fibromyalgia in human immunodeficiency virus infection  tenderness was assessed by point count and by scored palpation in 51 patients with human immunodeficiency virus  hiv  infection as well as 51 patients with rheumatoid arthritis  ra  and 50 patients with psoriatic arthritis  psa   fifteen of 51  29   patients with hiv infection met criteria for fibromyalgia  based on the presence of 10 tender  of 14   fibrositic  points  similar results were observed among patients with psa  24    the prevalence of fibromyalgia was higher among patients with ra  57    patients with hiv and psa were less tender than patients with ra  fibromyalgia in patients with hiv was significantly associated with myalgia and arthralgia  but not with age  duration of hiv infection  stage of hiv disease  or zidovudine therapy  
class10	an objective score to predict upper tract deterioration in myelodysplasia  bladder dysfunction in myelodysplasia may present a significant hazard to the upper tract and a threat to kidney function  urodynamic features of high leak pressure and detrusor sphincter dyssynergia have been associated with an increased risk  we have developed an objective score to describe urodynamic findings in myelodysplasia  the score includes consideration of bladder compliance  detrusor contractility and reflux  in addition to leak pressure and sphincter behavior  in 171 myelodysplastic patients a significant correlation was demonstrated between the score and upper tract studies at the time of urodynamics and the score and the management decision  of 73 myelodysplasia patients with normal upper tracts at the first urodynamics study hydronephrosis later developed in 14  the score was a potent predictor of outcome  p   0 0006   
class10	thigh muscle function after partial tear of the medial ligament compartment of the knee  the purpose of the study was to assess the isokinetic and isometric strength and power profile of the knees of 48 patients who had a previous second degree sprain  partial tear  of the medial ligament compartment  the most common knee ligament injury in sports  the cybex ii isokinetic dynamometer was used in the measurements  on an average of 8 yr after the injury  the mean strength deficit of the injured knees was minimal  4     5   range 0 28   in extension and 2     4   0 20   in flexion  the average strength score  max  100 points  was 90     11  56 100   representing an excellent classification  in hamstrings  the relative strength deficit increased significantly with a higher speed of isokinetic movement  p less than 0 05   compared with the strength parameters  peak torques   the other functional parameters of the injured knees  total work  average power  and peak torque acceleration energy  showed some but not significantly greater deficits  hamstrings 9 11   quadriceps 6 8    in conclusion  the general thigh muscle function in knees with old second degree sprain of the medial ligament compartment appears good and acceptable  but the strength deficits are systematically greater in higher speeds of isokinetic movement  therefore  rehabilitation utilizing high speed extension and flexion exercises is recommended  
class10	magnetic resonance imaging in the preoperative evaluation of cervical radiculopathy  forty patients with cervical radiculopathy were examined preoperatively with magnetic resonance imaging  mri   mri was used alone in 27  68   of the 40 patients  the remainder also had computed tomography in conjunction with myelography  the primary criterion on mri for a clinically significant lesion was asymmetrical narrowing of the subarachnoid space in the region of the nerve root  surgical confirmation of the abnormality was obtained in all 40 cases  the operative findings were a herniated nucleus pulposus  32 of 40 patients   spondylosis  2 of 40 patients   or a combination of the two  6 of 40 patients   mri identified a surgical lesion  herniated nucleus pulposus  spondylosis  or both  in 37 of the 40  92   patients  we think mri is the only preoperative imaging examination necessary in most cases of cervical radiculopathy  
class10	intracranial hypertension in relation to memory functioning during the first year after severe head injury  the relationship between intracranial hypertension and residual memory deficit after closed head injury was evaluated using the 6 month and 1 year neurobehavioral outcome data obtained by the traumatic coma data bank  intracranial pressure was analyzed using the percentage of time that it exceeded 20 mm hg and the maximum value recorded during the first 72 hours after injury  memory measures included recall of word lists  prose recall  and visual memory for designs that were obtained 6 months  n   149  and 1 year  n   132  after injury  intracranial hypertension occurred in more than half of the traumatic coma data bank cohort who met the criteria for the neurobehavioral follow up study  linear regression analysis disclosed an effect of elevated intracranial pressure on some  but not all  measures of memory at 6 months  whereas the results were negative for the 1 year follow up examination  we conclude that the elevation of intracranial pressure exerts little if any effect on later memory functioning  and that any effect it does have diminishes over 1 year in survivors of severe head injury  
class10	localization of stereotactic targets by microrecordings of thalamic somatosensory evoked potentials  to improve the localization of stereotactic targets  somatosensory evoked potentials  seps  were recorded from the thalamus and subthalamic area using a specially designed semimicroelectrode in 61 patients and a conventional  macroelectrode  in 17 patients  by means of the semimicroelectrode  median nerve stimulation evoked two distinct seps  consisting of a diphasic wave with a huge positivity restricted to the nucleus ventrocaudalis  vc  and a triphasic wave of lower amplitude with a major negativity in the ventral part of the nucleus ventrointermedius  vim  and nucleus ventrooralis posterior  vop  as well as the subthalamic lemniscal pathway  the vim vc junction could thus be clearly delineated by an abrupt transition of seps from one type to the other with a precision of 1 mm  the parvicellular part of the vc  vcpc   situated in its basal region  was distinguishable from the vc proper by a significant reduction of the positivity elicited by stimulation of the median nerve and by a rapid growth of a diphasic seps to stimulation of the posterior tibial nerve  in the other thalamic nuclei  stimulation of the median nerve elicited triphasic seps of a very small amplitude  suggesting a volume conduction current from the lemniscal pathway  with the macroelectrode  the positivity in the vc was sensitive to electrode manipulation and the thalamic nuclei could not be distinctly outlined  sep monitoring using the semimicroelectrode significantly improved the precision of target localization  which allowed minimizing of the volume of the therapeutic lesion without losing surgical effectiveness  while avoiding complications associated with increased penetration of the coagulating electrode  it is suggested that recording serial thalamic seps with the semimicroelectrode is a practical method to refine stereotactic targets in the thalamus  
class10	definition of the role of contemporary surgical management in cisternal and parenchymatous cysticercosis cerebri  with increasing immigration from endemic regions  the incidence of neurocysticercosis in north america is rising  this retrospective study was undertaken to examine the role of surgery in those cases presenting with large cystic parenchymal and cisternal lesions in the current era of anthelminthic agents administered orally  a total of 237 patients presented with newly diagnosed neurocysticercosis to our institution over a recent 5 year period  mean age  31 2 years   among those who presented with cystic mass lesions predominantly affecting the brain parenchyma and cisternal spaces  20  8 4   mean age  40 2 years  with large cystic lesions subsequently underwent surgical intervention  either because of an emergent presentation or because they were refractory to medical management  clinical presentation included increased intracranial pressure  focal neurological deficit  and seizure  radiographic imaging  computed tomography and or magnetic resonance imaging  demonstrated 12 cases with cisternal lesions  7 with parenchymal lesions  and 1 involving both compartments  based on imaging guidelines  30 operative procedures  excluding shunt revisions  were performed  14 craniotomies  8 cerebrospinal fluid diversions  7 stereotactic procedures  and 1 burr hole drainage   fifteen  75   showed neurological or symptomatic improvement over a median follow up period of 36 4 months  there were three surgery related complications and no deaths  
class10	cerebrospinal fluid flow dynamics in children with external ventricular drains  fifty five children had 64 external ventricular drains  evds  placed predominantly  95   for cerebrospinal fluid  csf  shunt infections  in 9 children  a computer monitoring system measured the csf output each second continuously for up to 24 hours  the monitoring was repeated daily for up to 9 days  the state of arousal of the patients was recorded simultaneously  in all children  daily evd outputs were related to age  sex  weight  method of establishing the evd  height of the drip chamber  time since insertion  and type of infecting organism  computer monitoring revealed wide fluctuations in flow rate  with peak rates frequently greater than 20 ml h and periods of flow arrest  these changes were usually associated with increased arousal  but also occurred with sleep  the mean evd flow rate for all children was 6 3 ml h  evd output increased with age and weight  evd output decreased with gram negative or multiple organism infections and with elevation of the drip chamber  resolution of the infection  sex of the patient  and method of establishing the evd had no effect on output  these results predict that csf production increases with brain growth in humans  that csf production is depressed by gram negative and multiple organism infections  that implanted csf shunts with standard valves flow at equivalent rates to an evd in the supine position  and that the csf drainage requirements in this group are approximately equal to their evd outputs  
class10	the influence of the calcium antagonist nimodipine and induced hypertension on the behavior of the cerebral pial arteries  the blood brain barrier  cerebral edema  and cerebral infarction in cats with one hour occlusion of the middle cerebral artery  thirty anesthetized cats were randomly assigned to one of three groups of 10 cats each  nimodipine treatment  nimodipine treatment combined with induced hypertension  or a control group  the behavior of the cerebral pial arteries was measured by means of microscopic observation through a cranial window  the middle cerebral artery of each cat was clipped for 1 hour via the transorbital approach  five hours after circulation was reestablished in the middle cerebral artery  evans blue dye was injected intravenously  30 minutes later  the animal was killed  administration of nimodipine or saline in the treated or control group was started 5 minutes before the middle cerebral artery was clipped and maintained until the end of the experiment  induced hypertension was produced by administration of dopamine during the occlusion  damage to the blood brain barrier  bbb  was judged by extravasation of evans blue dye  cerebral edema and infarction were evaluated from histological findings  they were most prominent in the control group  the extent of hemisphere affected was as follows  mean     standard error   extravasation  40 5     8 8   edema  43 2     5 7   infarction  35 5     9 6   on the other hand  the extravasation of evans blue dye and cerebral edema were significantly more extensive in the group treated with nimodipine and induced hypertension  extravasation  28 2     9 6  of the hemisphere  edema  30 3     7 1   than in the group treated with nimodipine alone  extravasation  18 5     8 7  of the hemisphere  edema  19 4     6 3    but the infarction size was similar in both groups  16 6     4 9  of the hemisphere in the former  17 0     6 2 in the latter   
class10	kenneth mckenzie  harvey cushing  and the early neurosurgical treatment of spasmodic torticollis  in 1923  dr  kenneth mckenzie trained at the peter bent brigham hospital under dr  harvey cushing  at that time  a patient with spasmodic torticollis came to cushing and was treated with an innovative operation for this disorder with good results  this case sparked an interest in dr  mckenzie  who published the case 1 year later  in reviewing the surgical histories from the peter bent brigham hospital  we have found the original records of this well documented case  the record includes postoperative drawings of the intraoperative field by dr  cushing  a sketch by dr  mckenzie illustrating the postoperative sensory examination  and pre  and postoperative photographs of the patient  
class10	isolated trigeminal sensory loss secondary to a distal anterior inferior cerebellar artery aneurysm  case report  a previously healthy 25 year old woman suddenly developed right sided facial numbness and a headache  the neurological examination was within normal limits with the exception of meningismus and right sided facial sensory loss  a computed tomographic scan and a magnetic resonance imaging study demonstrated an acute hematoma in the right cerebellopontine angle  a 4 vessel cerebral angiogram revealed no abnormalities  posterior fossa exploration disclosed a large  partially thrombosed  fusiform anterior inferior cerebellar artery aneurysm  which indented the pons at the trigeminal root entry zone  the aneurysm was excised  and the patient made an excellent recovery  she was left with a persistent trigeminal sensory deficit  anterior inferior cerebellar artery aneurysms are rare lesions that generally present with a cerebellopontine angle syndrome  occasionally  facial sensory loss is also a feature  isolated trigeminal sensory findings  as illustrated in this case  are extremely unusual in posterior fossa vascular lesions  
class10	iatrogenic saphenous neuralgia  successful therapy with neuroma resection  we report the case of a patient with saphenous neuralgia secondary to iatrogenic trauma resulting from bypass surgery in the femoral popliteal region  early symptoms of this condition were medial calf and ankle pain  with no findings of motor and reflex abnormalities  exploration of the thigh 2 years later revealed a neuroma of the nerve in the distal dissection site  medial to the knee  resection of the neuroma alleviated this condition  it is noted that saphenous neuropathy is seen as a spontaneous entrapment syndrome as well as a complication of orthopedic and vascular procedures performed on the medial area of the knee  saphenous neuralgia is often not recognized by neurosurgeons  if the condition is intractable  it does respond to surgical therapy  
class10	spinal man after declaration of brain death complex spinal automatism in a patient who was declared brain dead is described  these movements tend to appear once cerebrospinal shock has abated  we postulate that these manifestations are a reflection of the physiological potential of the isolated spinal cord  these spinal movements should be included in the revised guidelines for the determination of cerebral death  
class10	reversible hearing loss from cerebellopontine angle tumors  we report two patients who presented with a dramatic recovery from severe sensorineural hearing loss after total surgical removal of cerebellopontine angle tumors  meningioma and jugular foramen neurinoma   the factors that differentiate these  non acoustic tumors  in relation to the prognosis for hearing are discussed  a surgical approach that maintains the labyrinthine structure and preserves the arachnoid membrane of the superior cerebellopontine angle cistern during tumor removal is stressed  
class10	adult peripheral neuroepithelioma in meckel s cave  a case of peripheral neuroepithelioma arising from the trigeminal nerve in meckel s cave is presented  the discussion emphasizes the pathological criteria for the diagnosis of a peripheral neuroepithelioma and the current controversy about the classification of this and related tumors  
class10	a comparison of midazolam with and without nalbuphine for intravenous sedation  the introduction of nalbuphine to intravenous sedation with midazolam added little to the quality of sedation for short operative procedures  there was a greater tendency for patients who received nalbuphine and midazolam to sleep in the afternoon after treatment compared with those who received only midazolam  significantly more patients had nausea and vomiting in the midazolam nalbuphine group than did patients in the midazolam only group  
class10	presentation and management of an acute caffeine overdose  a one year old white female ingested approximately two to three grams of caffeine  200 300 mg kg   the patient survived the ingestion with a maximum caffeine concentration of 385 micrograms ml four hours postingestion  the child developed ventricular arrhythmias  seizures  metabolic disturbances  and severe pulmonary edema  she survived without apparent long term sequelae despite having reached a serum caffeine concentration that is the second highest reported level in a survivor  
class10	selective myectomy for postparetic facial synkinesis  synkinetic movements are secondary to facial palsy because they appear like a late sequela to spontaneously healing facial nerve injury  they are produced by an involuntary contraction of a muscle group simultaneous with contraction of other homologous muscle groups  the disorderly regeneration of severed axons is responsible for these movements  according to the lippschitz theory  the regenerating nerve fibers sprout into the wrong peripheral branches  between 1975 and 1986  71 patients with facial paralysis were evaluated  spontaneous recovery from the facial paralysis occurred in 28 of these patients  14  50 percent  developed synkinetic movements  and surgical treatment was sought by only 6 patients  in all patients  the lesion of the facial nerve was in the trunk  proximal to the principal ramification  the most frequent clinical finding was simultaneous activation between the orbicularis oculi and the elevators of the corner of the mouth  12 patients  or the elevators of the upper lip  2 patients   in 8 patients  in whom the slight synkinesis was not noticed by the patients  surgical correction was not necessary  but in the other 6 patients with severe aesthetic disturbances  surgical treatment for  disconnection  of the wrong impulses was realized  i obtained this  disconnection  through resection of the involved perioral muscle groups instead of paralysis of the orbicularis oculi  follow up of the 6 patients operated with the surgical treatment proposed herein for between 4 and 8 years has shown good aesthetic results without functional or aesthetic sequelae  
class10	intrapalatine resection  ipr  in the treatment of sleep apnea and snoring  a conservative surgical technique is proposed as an alternative to the classical uvulopalatopharyngoplasty  uppp  for the treatment of obstructive sleep apnea and snoring  the resection is strictly intrapalatine  and careful suturing in three planes seems to lead to complete disappearance of the often unbearable postoperative pain  the soft palate is shortened but nonetheless still resembles a normal soft palate  uvulopalatopharyngoplasty  uppp  was described by ikematsu in 1952  this method has taken on a new lease of life in recent years  its efficacy is generally accepted  and its use  especially in cases of obstructive sleep apnea syndrome  is the only treatment of the palatal velum at present practiced  in addition to aesthetic problems  this method generally gives rise to complications in the shape of temporary  but sometimes considerable  pain  nasal regurgitation  and a nasal voice  in a small percentage of patients  some of these disorders may prove irreversible  in my series of eight patients  five were obese and presented with hypertension  three of them also were suffering from obstructive sleep apnea syndrome  the three others were ordinary snorers who caused considerable inconvenience to sleeping partners  
class10	radiographic manifestations of anomalies of the brain  congenital brain anomalies are classified as developmental anomalies  effects of teratogens  errors of histogenesis  or sequelae of infections  the imaging options for delineation of these anomalies are many  a basic understanding of the disorder is central to the effective choice of imaging modality  this review begins with a brief overview of embryogenesis then reviews the common congenital brain anomalies encountered in infants  
class10	genetic mapping of new dna probes at xq27 defines a strategy for dna studies in the fragile x syndrome  the fragile x syndrome is the most common cause of familial mental retardation and is characterized by a fragile site at the end of the long arm of the x chromosome  the unusual genetics and cytogenetics of this x linked condition make genetic counseling difficult  dna studies were of limited value in genetic counseling  because the nearest polymorphic dna loci had recombination fractions of 12  or more with the fragile x mutation  fraxa  five polymorphic loci have recently been described in this region of the x chromosome  the positions of these loci in relation to fraxa were defined in a genetic linkage study of 112 affected families  the five loci  dxs369  dxs297  dxs296  ids  and dxs304  had recombination fractions of 4  or less with fraxa  the closest locus  dxs296  was distal to fraxa and had a recombination fraction of 2   the polymorphisms at these loci can be detected in dna enzymatically digested with a limited number of restriction endonucleases  a strategy for dna studies which is based on three restriction endonucleases and on five probes will detect one or more of these polymorphisms in 94  of women  this strategy greatly increases the utility of dna studies in providing genetic advice to families with the fragile x syndrome  
class10	mtdna depletion with variable tissue expression  a novel genetic abnormality in mitochondrial diseases  we studied two related infants with a fatal mitochondrial disease  affecting muscle in one and liver in the other  quantitative analysis revealed a severe depletion of mtdna in affected tissues  this genetic abnormality was also observed in muscle of an unrelated infant with myopathy and in muscle and kidney of a fourth child with myopathy and nephropathy  biochemistry  immunohistochemistry  and in situ hybridization showed that the depletion of mtdna in muscle fibers was correlated with a respiratory chain defect and with lack of mitochondrially translated proteins  although the differential tissue involvement in these infants suggests mtdna heteroplasmy  sequence analysis of mtdna replication origins did not reveal any abnormality that could account for the low copy number  
class10	deficiency of complex iii of the mitochondrial respiratory chain in a patient with facioscapulohumeral disease  facioscapulohumeral disease  fshd   an inherited neuromuscular disorder  is characterized by progressive wasting of specific muscle groups  particularly the proximal musculature of the upper limbs  the primary defect in this disorder is unknown  we studied a patient with fshd to determine whether the mitochondrial respiratory chain was functionally abnormal  muscle biopsy revealed fiber atrophy with patchy staining for oxidative enzymes  electron microscopy of a liver section showed many enlarged mitochondria with paracrystalline inclusions  decreased oxidation of the respiratory substrates alanine and succinate in skin fibroblasts suggested a deficiency of complex iii of the electron transport chain  cytochrome c oxidase activity  complex iv  was in the normal range  biochemical analysis of liver supported the fibroblast data  since succinate oxidase activity  electron transport activity through complexes ii iv  was reduced  whereas complex iv activity was normal  furthermore  analysis of the cytochrome spectrum in liver revealed typical peaks for cytochromes cc1 and aa3  whereas cytochrome b  a component of complex iii  was undetectable  southern blot analysis of fibroblast mtdna revealed no major deletions or rearrangements  our study provides the first documentation of a specific enzyme complex deficiency associated with fshd  
class10	intermediate hyperhomocysteinemia resulting from compound heterozygosity of methylenetetrahydrofolate reductase mutations  four subjects with thermolabile methylenetetrahydrofolate reductase  mthfr  were discovered among 16  obligate  heterozygotes for severe mthfr deficiency and their family members  all four subjects had less than 25  of normal mean mthfr specific activity in lymphocyte extracts  three of them with normal serum folate and cyanocobalamin had intermediate hyperhomocysteinemia  and one with high serum folate and cyanocobalamin had no excessive accumulation of serum homocysteine  the biochemical features in these four subjects are distinguishable from subjects homozygous for the thermolabile mthfr  whose specific activity is approximately 50  of the normal mean  and from heterozygotes for severe mthfr deficiency  in whom the enzyme is thermostable and has a specific activity of about 50  of the normal mean  we propose that these four subjects are genetic compounds of the allele for the severe mutation and the allele for thermolabile mutation of the mthfr gene  it is postulated that subjects with this genetic compound are more susceptible to the development of intermediate hyperhomocysteinemia despite normal folate and b12 levels  nonetheless  hyperhomocysteinemia due to this compound heterozygosity is correctable by oral folic acid therapy  
class10	distribution of three alpha chain beta hexosaminidase a mutations among tay sachs carriers  dna from 176 carriers of the tay sachs gene was tested for the presence of the three mutations most commonly found among ashkenazi jews  the so called insertion  splice junction  and adult mutations  among 148 ashkenazi jews tested  108 had the insertion mutation  26 had the splice junction mutation  five had the adult mutation  and nine had none of the three  among 28 non jewish carriers tested  most of whom were obligate carriers  four had the insertion mutation  one had the adult mutation  and the remaining 23 had none of the three  
class10	nasal midline masses in infants and children  dermoids  encephaloceles  and gliomas  nasal dermoids  gliomas  and encephaloceles are uncommon congenital lesions that result from aberrant embryologic development  we have treated 46 children with these nasal lesions  in view of the potential intracranial connection  patients are at risk for intracranial infection  and early surgical correction is thus imperative  neuroimaging studies may help to predict intracranial involvement  
class10	postcardiotomy mechanical circulatory support in the elderly  the role of mechanical circulatory support after cardiac operations in elderly patients is not clearly established  between november 1985 and july 1989  18 patients 65 years of age or older  mean age  71 years  range  65 to 82 years  were treated after cardiotomy with a centrifugal vortex or pneumatic mechanical ventricular assist device  this group comprised 1 9  of the 926 patients 65 years of age or older undergoing cardiac surgical procedures and 69  of the 26 patients requiring postcardiotomy support during this interval  before institution of mechanical support  all patients were receiving maximal inotropic support and 16 patients had intraaortic balloon pumps inserted  univentricular support was used in 9 patients  6 left  3 right  and biventricular support in 9 patients  the mean duration of support was 45 hours  range  8 to 118 hours   twelve patients  67   were successfully weaned  8  44   were discharged from the hospital  and 6  33   remain alive 11 to 31 months postoperatively  four of the 6 survivors are in new york heart association class i  1 is in class ii  and 1 is in class iv  the combined registry for ventricular assist device support has recently reported an overall survival rate of 12  in patients 65 to 70 years of age and 6  in those older than 70 years  our results are comparable with those reported for younger patients and justify the use of postcardiotomy ventricular assist device support in the elderly  
class10	muscle rehabilitation in impaired elderly nursing home residents  based on observations of changes in muscle function associated with aging  and the exacerbation of these changes with frailty  a program of muscle strengthening has been developed to correct specific defects in muscles  this pilot study was undertaken on 18 functionally impaired nursing home residents  age range 60 to 90 years  with markedly deteriorated muscle function  50   secondary to age  disuse  and multiple chronic illnesses  fourteen of the subjects completed the six week program without adverse effects  in 75  of the patients  there was improved muscle function  with endurance  strength  and speed increasing 35   15   and 10   respectively  after the program  many subjects increased their spontaneous activity and decreased their dependency  the improvements were still evident four months after rehabilitation  these results suggest that it may be possible  through a carefully supervised  short term program of muscle rehabilitation  for nursing home residents to achieve an enhanced level of physical functioning  
class10	evaluation of treatment protocols on minimal to moderate spasticity in multiple sclerosis  thirty men and women diagnosed with definite multiple sclerosis  ms  were treated for ten weeks in a blinded  cross over study  patients with minimal to moderate spasticity were randomized to one of three sequences to evaluate the effects on ms related spasticity of baclofen alone  stretching regimen with placebo  placebo alone  and stretching regimen with baclofen  the cybex ii isokinetic unit  timed gait  ashworth scale  and subject s assessment of function were objective and subjective measures used to evaluate changes in hypertonicity  there was significant correlation between the cybex and ashworth as methods of measuring spasticity  overall  treatment with baclofen alone significantly improved moderate quadriceps spasticity as measured by cybex flexion scores  a trend  indicative of enhancing the beneficial effects of baclofen  was noted when stretching exercises were added to the treatment  
class10	anemia after traumatic spinal cord injury  the incidence and natural history of anemia in patients with spinal cord injuries  sci  were investigated in a prospective study of 68 patients consecutively admitted to a regional acute sci unit  fifty had sci and 18 had spine injuries  si  without neurologic deficit  thirty six of 41 males  88   and six of nine females  67   with sci were anemic on at least one occasion  in the first two weeks after injury  in females and in males  there was no significant difference in mean hemoglobin level between si and sci patients  at six weeks  no male with si was anemic  and males with sci had significantly lower mean hemoglobin levels than those with si  121 6 g l vs 145 4 g l  p less than  001   identified early causes of anemia were blood loss due to bony soft tissue or visceral injury  gastrointestinal bleeding  and surgery  in the postacute phase  more than six weeks after injury   anemia occurred in 25 of 41 male and three of nine female sci patients  and its occurrence was associated with the presence of an identified chronic disease  especially urinary tract infection  
class10	sexual changes in hemiparetic patients  eighty six patients  each with hemiparesis caused by a single stroke  were studied to assess the changes in sexual life experienced after the onset of the illness  clinical data were collected  and a questionnaire concerning both sexual behavior and feelings about sexuality was administered to the patients and their spouses  twenty four couples were eliminated from further analysis because of a discrepancy between husband and wife in the answers concerning sexual behavior after stroke  a marked decline in sexual activity after stroke was found in both genders  other aspects of sexual behavior underwent fewer changes  the feeling of an overall change in sexual life was reported more frequently by male patients  most patients  spouses reported the feeling of an overall psychological change in their partners and the feeling of an overall change in sexual life after the onset of the illness  no significant associations were found between clinical features and changes in sexual life  this study confirms that cerebrovascular accidents are generally followed by some important alterations in sexual life  clinical factors do not seem to play a crucial role in determining these changes  which may be better explained in terms of maladjustment attributable to psychologic and interpersonal factors  
class10	recurrent thoracic outlet syndrome after first rib resection  seventy seven patients with 84 operated limbs participated in a follow up examination on an average of about six years after the resection of the first rib for thoracic outlet syndrome  tos   forty two limbs  50   were totally asymptomatic one month after the operation and remained so for at least half a year postoperatively  in the follow up examination  31 limbs were still asymptomatic  whereas 11 limbs had the same symptoms as before the operation  of the nine patients with recurrent tos  two with bilateral resection   seven were women and two were men  these nine patients were on average 38 years old  range   19 to 51 years  and their jobs consisted of monotonous desk work  seven of 11 stumps of the first rib were subluxated disclosed by the cervical rotation lateral flexion test  the occurrence of a subluxated stump of the first rib in the group of asymptomatic patients was far lower  only 3   p less than  001   of the 42 patients with persistent problems  a subluxated stump was encountered in seven  17    results of this follow up examination suggest that monotonous desk work is an important factor causing kinesiologic abnormalities in the thoracic aperture  this abnormal kinesiology contributes to the recurrence of tos symptoms even after the resection of the first rib  
class10	wrist flexion as an adjunct to the diagnosis of carpal tunnel syndrome  the effects of five minutes of wrist flexion on median motor and sensory evoked potential latencies in 87 individuals were studied  nineteen subjects had carpal tunnel syndrome  cts  as diagnosed by increased median nerve latencies across the wrist  and 68 had values in the normal range and were assigned to the control group  a slight prolongation of up to 0 5m sec of evoked potential latencies was observed in both groups after flexion  but the differences between the two groups were not significant to establish the value of adding wrist flexion to conventional screening methods  
class10	detecting lower motor neuron dysfunction of the pharynx and larynx with electromyography  this study assessed the utility of clinical electromyography  emg  for detecting lower motor neuron  lmn  or upper motor neuron  umn  dysfunction affecting the intrinsic muscles of the larynx and pharynx  twenty nine subjects were examined  their clinical diagnoses included perioperative nerve injury  cerebral infarction  and lateral medullary infarction  resting activity  motor unit action potential  muap  morphology  and muap recruitment were evaluated in every case  medical records  excluding emg data  were analyzed for clinical evidence of lmn or umn dysfunction in the intrinsic muscles of the larynx and pharynx  the diagnosis of lmn dysfunction rested on clinical data consistent with cranial nerve injury  poliomyelitis  wallenberg syndrome  or unilateral bulbar palsy  criteria for umn dysfunction included previous cerebral  not brainstem  infarction or mass lesion or the presence of hemiparesis  electromyographic abnormalities were significantly associated with lmn dysfunction  p less than  05   but they were not significantly associated with umn dysfunction  of the parameters tested  muap recruitment was the most sensitive  82   and specific  92    
class10	neurobehavioral effects of phenytoin  carbamazepine  and valproic acid  implications for use in traumatic brain injury  due to the risk of posttraumatic epilepsy  phenytoin  carbamazepine  and valproic acid are often prescribed for patients with traumatic brain injury  tbi   in this review the literature is examined for evidence of neurobehavioral impairment due to carbamazepine  phenytoin  and valproic acid  no comparative studies have been performed in the tbi population  making if difficult to determine if one of these medications is preferable  direct inference from studies on epilepsy patients to tbi patients is hazardous due to underlying differences in the two populations  reported findings for epilepsy patients are subtle and not consistent across studies  all three drugs appear to exert some effect on cognitive and motor functions in epileptic patients  and these impairments worsen at increasing serum levels  the varied length of experience with each drug makes it difficult to assign relative weight to the evidence for or against each  a comparative assessment of cognitive and behavioral effects of anticonvulsants should be done in the tbi population  
class10	a cellist with arm pain  thermal asymmetry in scalenus anticus syndrome  we report on a cellist with pain and coldness of the upper extremity  abnormal thermographic studies were instrumental in uncovering intermittent compression of the subclavian artery  and this prompted us to study the effects of cello playing on skin temperature asymmetry  temperature asymmetry was defined as the temperature difference  delta t  from one hand to the other  in 57 controls  mean delta t at rest was  309      254c  exercising the upper extremities by prolonged elbow flexion or by movements mimicking cello playing in controls did not significantly affect delta t  in our patient  delta t was ten times control  3 6c   angiography showed extrinsic compression of the subclavian artery occurring only after cello playing  sympathetic ganglion block relieved the pain  our patient s abnormal skin temperature may have reflected sympathetic vasomotor hyperactivity  intermittent neurovascular compression and sympathetic hyperactivity appear to be factors in scalenus anticus syndrome  
class10	candida pyelonephritis complicating traumatic c5 quadriplegia  diagnosis and management  we present the first reported case of candida pyelonephritis in a spinal cord injured patient  in addition to multiple courses of empiric antibiotics  the neurogenic bladder and alteration in cell mediated immunity found in spinal cord injured patients may have increased this patient s susceptibility to fungal disease  a 50 year old patient with c5 motor functional quadriplegia developed candid albicans pyelonephritis while undergoing rehabilitation  the patient had several surgical procedures and multiple courses of antibiotic therapy during acute hospitalization  he continued to have a hectic fever curve  leukocytosis with increased band forms  lethargy  and progressive uremia during rehabilitation  successful investigation of the patient s condition included assessment of serologic tests for candida precipitin antigen  multiple blood and urine cultures  exclusion of other causes of hectic fever  abdominal computerized tomogram  which revealed a left kidney hypodensity with irregular margins  and a retrograde pyelogram  which demonstrated multiple renal pelvic filling defects  cystoscopically placed ureteral stents  which relieved the genitourinary obstruction  drained gross pus from which candida albicans was cultured  the patient was treated with amphotericin b and showed clinical improvement  pathogenesis  presentation  diagnosis  and treatment of candida pyelonephritis are reviewed  
class10	spinal accessory nerve palsy  an unusual complication of coronary artery bypass the neurologic complications of coronary artery bypass surgery have been well documented  with a reported incidence of 61  in one large study  most injuries to the peripheral nervous system involve the brachial plexus  we report the first case of a spinal accessory nerve lesion after coronary bypass surgery  the patient presented with progressive right shoulder weakness  electrodiagnostic studies revealed a partial lesion of the right spinal accessory nerve  physical therapy  including strengthening  range of motion  and electric stimulation to the right shoulder  was prescribed to assist recovery of strength and function  repeat electrodiagnostic studies confirmed nerve regeneration  prompt recognition of spinal accessory nerve damage after coronary bypass surgery is essential  early rehabilitation will improve the chances of a better functional outcome  
class10	ratio of immunochemically determined amniotic fluid acetylcholinesterase to butyrylcholinesterase in the differential diagnosis of fetal abnormalities  a total of 111 amniotic fluid samples  clear or blood stained  with elevated levels of alpha fetoprotein and acetylcholinesterase was analysed by immunoassays specific for acetylcholinesterase and butyrylcholinesterase and the acetylcholinesterase butyrylcholinesterase ratios determined  samples from 40 pregnancies associated with anencephaly  47 pregnancies associated with open spina bifida or encephalocele and six pregnancies with fetal intrauterine death or miscarriage all had ratios of greater than 0 14  all 11 pregnancies with fetal ventral wall defects had ratios less than 0 14 as had four pregnancies with normal outcome and elevated levels of alpha fetoprotein and acetylcholinesterase  three fetuses with both open spina bifida and ventral wall defects were associated with ratios above 0 14  these results suggest that immunochemical determination of acetylcholinesterase and butyrylcholinesterase can be used to distinguish pregnancies complicated by anencephaly  open spina bifida  encephalocele and miscarriage from those with ventral wall defects and samples with false positive elevated levels of alpha fetoprotein and acetylcholinesterase  the procedure is accurate and simple to carry out and well suited to routine use in a clinical chemistry laboratory  
class10	the neck eye reflex in patients with reduced vestibular and optokinetic function  it is accepted that the neck eye loop  cervico ocular reflex  cor  is enhanced following loss of vestibular function and that this helps to restore gaze stability during head movements  in this paper we address the question of which structures and or mechanisms may participate in such plastic enhancement by investigating the cor in 2 patients with absent vestibular function and reduced smooth pursuit optokinetic eye movements  sp okn   the patients had multisystem atrophy involving the vestibular system and the cerebellum  the cor  elicited by angular motion of the trunk relative to the fixed head and angular motion of the head relative to the fixed trunk  was not enhanced in these 2 patients when compared with normal subjects  in contrast to previous findings in a group of patients with absent vestibular function alone  measurements of slow phase eye movement velocity during sp okn stimuli and during combined cor okn stimulation  head oscillation relative to the stationary trunk in the light  showed identical values in these two conditions  which indicates that the neck eye loop did not contribute to gaze stability during head movements  the absence of plastic enhancement of the cor in these patients may be secondary to interruption of sp okn pathways at various possible sites and or to involvement of the vestibulocerebellum  which is known to mediate adaptive plasticity in the vestibulo ocular reflex  
class10	neuroacanthocytosis  a clinical  haematological and pathological study of 19 cases  nineteen cases are described  including 12 cases from three different families and 7 nonfamilial cases  in which multisystem neurological disease was associated with acanthocytosis in peripheral blood and normal plasma lipoproteins  mild acanthocytosis can easily be overlooked  and scanning electron microscopy may be helpful  some neurologically asymptomatic relatives with significant acanthocytosis were identified during family screening  including some who were clinically affected  the mean age of onset was 32  range 8 62  yrs and the clinical course was usually progressive but there was marked phenotypic variation  cognitive impairment  psychiatric features and organic personality change occurred in over half the cases  and more than one third had seizures  orofaciolingual involuntary movements and pseudobulbar disturbance commonly caused dysphagia and dysarthria that was sometimes severe  but biting of the lips or tongue was rarely seen  chorea was seen in almost all symptomatic cases but dystonia  tics  involuntary vocalizations and akinetic rigid features also occurred  two cases had no movement disorder at all  computerized tomography often demonstrated cerebral atrophy  caudate atrophy was seen less commonly  and nonspecific focal and symmetric signal abnormalities from the caudate or lentiform nuclei were seen by magnetic resonance imaging in 3 out of 4 cases  depression or absence of tendon reflexes was noted in 13 cases and neurophysiological abnormalities often indicated an axonal neuropathy  sural nerve biopsies from 3 cases showed evidence of a chronic axonal neuropathy with prominent regenerative activity  predominantly affecting the large diameter myelinated fibres  serum creatine kinase activity was increased in 11 cases but without clinical evidence of a myopathy  postmortem neuropathological examination in 1 case revealed extensive neuronal loss and gliosis affecting the corpus striatum  pallidum  and the substantia nigra  especially the pars reticulata  the cerebral cortex appeared spared and the spinal cord showed no evidence of anterior horn cell loss  two examples of the mcleod phenotype  an x linked abnormality of expression of kell blood group antigens  were identified in a single family and included 1 female  the genetics of neuroacanthocytosis are unclear and probably heterogeneous  but the available pedigree data and the association with the mcleod phenotype suggest that there may be a locus for this disorder on the short arm of the x chromosome  
class10	idiopathic intracranial hypertension  a prospective study of 50 patients  management of patients with idiopathic intracranial hypertension  iih  should be based on the presence and progression of visual loss  to characterize the clinical course of iih more completely  we monitored the clinical status  especially visual function  in 50 consecutive newly diagnosed patients over a period of 2 to 39 months  average follow up 12 4 months   the mean age at onset of symptoms was 31  range 11 58  yrs  46  92   were women and 47  94   were obese  mean weight 90 kg   common symptoms were headache  92    transient visual obscurations  72   and intracranial noises  60    13 of the patients  26   initially had complaints of sustained visual loss  there was visual loss as determined by goldmann perimetry in 96  and by automated perimetry in 92   contrast sensitivity testing was abnormal in 50  and snellen acuity in 22   two patients  4   became blind in both eyes  the goldmann visual field grade improved in 60  of patients but visual function deteriorated in 5  10    deterioration of visual field grade was significantly associated only with weight gain during the year before diagnosis  visual loss in patients with iih is common and is often reversible  patients should be evaluated by perimetry using an appropriate strategy and contrast sensitivity testing  along with careful examination of the optic discs  
class10	dual task performance and processing resources in normal subjects and patients with parkinson s disease  in recent years  there has been a growing consensus among investigators that the presence or absence of external cues guiding behaviour and attention is an important factor in determining whether or not deficits are found in patients with parkinson s disease  pd   in an earlier study  the authors suggested that the pattern of impaired and intact performance could be explained in terms of differential resource demands of the tasks  combined with depleted levels of central processing resources in pd patients  two experiments are reported  both employing dual task paradigms  the first assessed  in normal subjects  the relative processing demands of a cued and an uncued version of the stroop task  the results supported the proposal that the noncued task made greater demands on the subject s limited processing resources  further  performing a resource demanding secondary task concurrently with the stroop test produced  in normal subjects  the same pattern of impaired performance as that reported previously in pd patients  in the second experiment the same dual task paradigm was employed with a group of pd patients and normal aged matched controls  only the patients showed an increase in reaction time on the stroop task when performing a resource demanding secondary task  the patients also showed an interfering effect with concurrent foot tapping but not with an articulatory suppression task  the results were taken to support the hypothesis that pd patients have depleted central processing resources  in considering the present data  alternative explanations for the results are considered  in particular the possibility that they represent a deficit in switching processing resources between two tasks as the combined demands outweigh available resources  
class10	reversed lateralization of cognitive functions in right handers  exceptions to classical aphasiology  most current and past research on the cerebral organization of cognitive functions has presupposed certain specialized hemisphere operations  at least for right handers  language and praxis are to be organized in the left hemisphere  while affective prosody  configurational spatial capacity  and global attention are lateralized in the right hemisphere  deviations from these presuppositions  as in crossed aphasics and perhaps left handers  are generally considered to be  exceptions  and either to disprove the rules or to be irrelevant to the rule  we report 4 very  exceptional  cases  right handers with almost entirely reversed lateralization of functions  analysis of the intrahemispheric relationships between functions suggests that there may be a specific neurobiology to the interrelationships between and among cognitive functions  handedness  and the intrahemisphere localization of the function  
class10	short term memory and sentence comprehension  an investigation of a patient with crossed aphasia  the relationship between short term memory impairment and sentence comprehension is explored in a right handed patient with a focal temporoparietal lesion of the right hemisphere  the general clinical profile  as well as characteristics of the patient s immediate memory for word lists  suggests the occurrence of a  mirror image  crossed aphasia  detailed analysis of the patient s ability to repeat and to comprehend sentences  however  indicates some important differences between this case and previously reported patients with short term memory impairment  it is suggested that these differences  which may be related to an unusual pattern of neuroanatomical organization of cognitive functions  involve symptom dissociations with implications for models of normal language memory interactions  
class10	task dependent variations in parkinsonian motor impairments  studies of visually guided arm movements in patients with parkinson s disease  pd  have suggested a relationship between slowness of movement and a reduction in the ratio of movement amplitude and peak velocity  recent studies indicate  however  that pd impairments may be different for well learned  natural movements performed without visual guidance  or movements associated with sequential motor behaviours such as speech  to address this issue  pd subjects and age sex matched controls were compared on the performance of three tasks  all of which required lowering the jaw   1  single  rapid  visually guided movements   2  equivalent movements associated with a single speech syllable  inherently without visual guidance   and  3  well learned speech movements produced in a natural sequence  pd subjects manifested similar deficits for visually guided jaw lowering as those previously reported for arm movements  namely reduced velocity amplitude ratios and increased movement durations  by contrast  analogous jaw movements during the sequential speech tasks were unimpaired on these measures  these results suggest that pd motor impairments are influenced by a variety of factors  including the degree to which tasks are familiar and natural  and the availability of visual information  
class10	effects of anticonvulsant treatment and low levels of folate and thiamine on amine metabolites in cerebrospinal fluid  a total of 157 epileptic patients were studied with respect to  1  biogenic amine precursors and metabolites in the csf   2  levels of folate and thiamine in the blood and csf   3  length of treatment with phenytoin  pht    4  pht intoxication   5  cns atrophy  alterations in csf amine metabolite levels were related primarily to pht intoxication  and low csf folate and thiamine levels  but not to length of treatment or cns atrophy  pht intoxication increased csf 5 hydroxyindoleacetic acid  5hiaa   low folate levels were associated with decreased csf 5hiaa and homovanillic acid  while low thiamine levels were associated with decreased csf 5hiaa and 3 methyoxy 4 hydroxyphenylethylene glycol  it remains to be seen to what extent these alterations in biogenic amine metabolism  mediated by low cns vitamin levels  also lead to deficits in cerebral function  
class10	the stroke syndrome of striatocapsular infarction  striatocapsular infarction has recently been described as a distinct stroke entity and forms an important subgroup of subcortical infarctions  in a prospective study of 50 consecutive patients over a 10 yr period with this syndrome  clinical and neuropsychological features  pathogenesis and outcome were studied to provide information concerning management and prognosis  the most common clinical presentation was that of a stroke affecting mainly the upper limb with cortical signs such as dysphasia  neglect or dyspraxia  evidence from eeg  angiographic and neuropsychological data supported a vascular haemodynamic basis for the presence of the acute neuropsychological changes  while the chronic changes were more likely to be due to diaschisis  a study of risk factors and cerebral angiography enabled 4 pathophysiological subgroups to be identified   1  cardiac emboli to the origin of the middle cerebral artery   2  severe extra cranial cranial carotid artery occlusive disease with presumed embolism to the same site and or involvement of haemodynamic factors   3  proximal middle cerebral artery abnormalities causing occlusion of multiple lateral striate arteries at their origins   4  normal angiography where pathogenesis was uncertain  the risk factors of cardiac disease and smoking were significantly increased as compared with age and sex matched controls with other forms of ischaemic stroke  stroke or vascular death rate was 2 7  per yr during a mean follow up period of 2 25 yrs  predictors of an excellent recovery with return to normal lifestyle were younger age  only brachial or brachiofacial weakness with absence of cortical signs at presentation and minimal change on angiography  this stroke entity deserves particular recognition in the spectrum of subcortical infarctions because of its specific pathogenesis  distinct neuropsychological features and reasonable prognosis  
class10	human olfactory discrimination after unilateral frontal or temporal lobectomy  olfactory discrimination and detection was studied in 106 patients with unilateral cerebral excision in the right or left temporal lobe  right or left frontal lobe  left parietal lobe  or right frontal and temporal lobes  and in 20 normal control subjects  detection thresholds for n butyl alcohol  measured separately in each nostril  did not differ across subject groups or across nostrils  thus excluding any primary sensory loss  the discrimination task involved monorhinal presentation of repairs of unfamiliar odorants  which the subjects judged as same or different in quality  the results showed a significant deficit in discrimination confined to the nostril ipsilateral to the lesion in patients with temporal lobe removals  patients with frontal lobe excisions were also impaired and  for patients with right frontal lesions including the orbital cortex  the impairment was found in both nostrils  patients with left parietal lesions did not demonstrate any significant deficits  normal subjects showed consistently better performance in the right than in the left nostril  the results are interpreted as reflecting the importance of the orbitofrontal cortex in olfactory discrimination  temporal lobe lesions may disrupt the input to the orbitofrontal cortex  thereby producing poorer performance  the nostril difference in the normal subjects  together with the birhinal impairment in patients with right orbitofrontal damage  suggest a relative advantage of the right orbital region in olfactory processing  
class10	sequencing in parkinson s disease  abnormalities in programming and controlling movement  central programming deficits in parkinson s disease  pd  were studied in two reaction time  rt  experiments  in experiment 1  pd patients and controls performed sequences of hand postures that varied in length  the number of different postures  repetitive vs heterogeneous   and the delay interval before movement  before movement  the pd group planned repetitive movements like controls whereas for heterogeneous sequences rt increased less with sequence length for the pd group  implying less preprogramming  the interresponse time  irt  data from repetitive sequences showed that the pd group had difficulty controlling movement such that irts were faster when sequences were longer  thus allowing more time to schedule the termination of the sequence during the course of movement  for heterogeneous sequences  the pd group made more errors and were slower than controls when changing hand postures  suggesting a deficit in switching between different responses  while rt decreased with a longer delay similarly for both groups  irt1 continued to improve only for the pd group but similarly for both types of sequences  suggesting a deficit specific to programming the first response  in experiment 2  subjects made decisions about the number of different hand postures contained within a sequence  pd patients  decision times improved more with a longer delay only for heterogeneous sequences  suggesting a problem in identifying the number of different hand postures  the results have implications for levels of motor dysfunction in pd which emphasize the influence of sequence length and complexity  
class10	clinical features and treatment of obstructive sleep apnea  objective  to review the clinical features and treatment of obstructive sleep apnea  osa   data source and selection  all articles on osa published in french and english between 1970 and 1990 and indexed in index medicus were reviewed  studies addressing the epidemiologic features and clinical aspects of osa were selected  and special emphasis was given to articles reporting the effects of treatment on morbidity and mortality rates  main results  osa is characterized by episodes of upper airway obstruction during sleep that result in repetitive hypoxemia and sleep disruption  osa leads to various neuropsychologic and cardiovascular complications  including daytime hypersomnolence  cognitive impairment  systemic and pulmonary hypertension and cardiac arrhythmias  there is suggestive evidence that the death rate among affected people is increased  the true incidence of osa is unknown  but estimates have varied from 1  upwards among men  the current treatment with the greatest overall effectiveness and acceptability is nasal continuous positive airway pressure  conclusion  this common  readily treatable disorder is associated with serious complications and therefore must be widely recognized by health professionals  
class10	diagnosis of obstructive sleep apnea  the diagnosis of obstructive sleep apnea is frequently made by taking a meticulous history coupled with a high index of suspicion  snoring and hypersomnolence are clinical features common to individuals with sleep apnea  since snoring is said to be a  disease of listeners   it is not uncommon that bed partners reported an increased incidence of depression and marital displeasure  it is for this reason that the spouse or bed partner should be interviewed  since the patient may not be aware of any sleeping problems  physicians should also be alert to complaints of excessive daytime somnolence  because studies have shown that patients with obstructive sleep apnea are at increased risk for automobile crashes  it has been estimated that approx 58 000 motor vehicle accidents involving people with sleep apnea will occur in the us each yr  by proper diagnosis and treatment  the physician is in a unique position to prevent at least some of the automobile accidents that result from falling asleep while driving  polysomnography is the only definitive way to obtain a diagnosis of sleep apnea  this allows the physician not only to diagnosis the disorder  but also helps in the evaluation of the severity of the syndrome and selection of therapy  an ent evaluation is also important in ruling out anatomic disorders that can cause upper airway obstruction  certain factors  such as alcohol and sedative ingestion  may aggravate the condition in a person predisposed to sleep apnea  and subtle changes  such as unexplained hypertension  polycythemia  and cor pulmonale  should lead one to investigate the possibility of sleep apnea as the etiology  
class10	pain control in the ambulatory elderly  pain control in the elderly  no matter what the etiology or setting  can be a major clinical challenge  aging causes unique physiologic changes  eg  a decreased perception of pain and an enhanced sensitivity to opioid analgesics  principles regarding evaluation of patients with pain are reviewed  including the use of an objective instrument for pain assessment from the viewpoint of both physician and patient  good pain control can be achieved with the nonopioids  such as acetaminophen and the nonsteroidal anti inflammatory drugs  the opioid analgesics  and  in some cases  adjuvant agents  discussed also are the concerns for patient addiction and the who cancer pain relief program  
class10	the role of methanethiol in the pathogenesis of hepatic encephalopathy  mixed disulfides of methanethiol represent a relative estimate for an exposure to methanethiol  the concentrations of methanethiol mixed disulfides  methionine  4 methylthio 2 oxobutyrate and ammonia were measured in patients with different stages of hepatic encephalopathy  in patients with chronic kidney failure and in healthy subjects  in patients with hepatic encephalopathy  the mean serum concentrations of all these compounds were elevated  however  the elevations of methanethiol mixed disulfides were small and partly caused by decreased renal function  in addition  the levels of methanethiol mixed disulfides did not differ significantly between the different grades of hepatic encephalopathy  the concentrations of methanethiol mixed disulfides were substantially lower than those previously observed in healthy subjects after an oral methionine load or in a patient with a deficiency in methionine adenosyltransferase  the latter without causing encephalopathy  we concluded that the role of methanethiol in the pathogenesis of hepatic encephalopathy is probably minor  if not insignificant  in the patients with hepatic encephalopathy  a significant correlation was found between the concentrations of methionine and 4 methylthio 2 oxobutyrate and between 4 methylthio 2 oxobutyrate and methanethiol mixed disulfides  supporting the theory that methanethiol is formed by way of the methionine transamination pathway  evidence is provided that  besides the methionine transsulfuration pathway  the transamination pathway is also impaired in patients with hepatic encephalopathy  
class10	effects of antihypertensive therapy on mechanics of cerebral arterioles in rats  the purpose of this study was to examine effects of antihypertensive treatment on structure and mechanics of cerebral arterioles and the incidence of stroke in stroke prone spontaneously hypertensive rats  shrsp   treatment of hypertension was begun at 3 months of age with cilazapril  45 mg kg day   an angiotensin converting enzyme  ace  inhibitor  or with hydralazine  18 mg kg day   cilazapril and hydralazine reduced systolic arterial pressure  from 195     8 to 125     5 and 148     3 mm hg  respectively  mean     sem   p less than 0 05   to examine structure and mechanics of cerebral arterioles  we measured pressure  servonull   external diameter  and cross sectional area of the vessel wall  histologically  in pial arterioles of normotensive wistar kyoto  wky  rats and shrsp that were untreated or that were treated for 3 months with cilazapril or with hydralazine  arterioles were maximally dilated with edta  in wky rats  cilazapril and hydralazine did not alter pial arteriolar pressure  external diameter  or cross sectional area of the vessel wall  in shrsp  both cilazapril and hydralazine reduced cross sectional area of the vessel wall to levels not significantly different from wky rats  from 1 911     155 to 1 244     101 and 1 388     59 microns 2  respectively  compared with 1 405     95 microns 2 for untreated wky rats   cilazapril was more effective than hydralazine in reducing pial arteriolar pressure  from 110     6 to 62     2 mm hg with cilazapril versus 79     5 mm hg for hydralazine compared with 60     4 mm hg for untreated wky rats   cilazapril  but not hydralazine  attenuated reductions in external diameter of pial arterioles  from 91     4 to 100     4 microns for cilazapril versus 91     3 microns for hydralazine compared with 107     3 microns for untreated wky rats   
class10	plasticity of integrin expression by nerve derived connective tissue cells  human schwann cells  perineurial cells  and fibroblasts express markedly different patterns of beta 1 integrins during nerve development  neoplasia  and in vitro  strikingly selective expression patterns of beta 1  alpha 2  alpha 3  and alpha 5 integrin subunits were revealed in endoneurium  perineurium  and epineurium of fetal and adult human peripheral nerve by immunostaining with specific antibodies  the alpha 2 subunit was expressed only on schwann cells both in fetal and adult nerve  whereas the alpha 3 epitopes were expressed exclusively in the adult tissue and were primarily present on perineurial cells  the alpha 5 epitopes were expressed only on the innermost cell layer of perineurium of fetal and adult nerve  the tumor cells within schwannomas and cutaneous neurofibromas expressed both alpha 2 and alpha 3 subunits  indicating that schwann cells have the potential to express also the alpha 3 subunit in vivo  cell cultures established from human fetal nerve and neurofibromas revealed expression of the alpha 2 and alpha 5 epitopes on schwann cells  perineurial cells  and fibroblasts  whereas only schwann cells contained the alpha 3 epitopes which were occasionally concentrated on the adjacent schwann cells at cell cell contacts  our findings emphasize that nerve connective tissue cells change their profiles for expression of extracellular matrix receptors under conditions which have different regulatory control signals exerted by  for example  axons  humoral factors  or the extracellular matrix of the peripheral nerve  this plasticity may play an important role during nerve development and in neoplastic processes affecting the connective tissue compartments of peripheral nerve  
class10	differential diagnosis of mut and cbl methylmalonic aciduria by dna mediated gene transfer in primary fibroblasts  methylmalonic aciduria can be caused by mutations in the gene encoding the methylmalonyl coenzyme a mutase apoenzyme  mut  or genes required for the provision of cofactor b12  cbl   the mut and cbl forms are classically differentiated by somatic cell complementation  we describe a novel method for differential diagnosis of mut and cbl methylmalonic aciduria using dna mediated gene transfer of a methylmalonyl coa mutase cdna clone  gene transfer of a functional methylmalonyl coa mutase cdna clone into mut fibroblasts reconstitutes holoenzyme activity measured by metabolism of  14c  propionate in culture  identical gene transfers into cbl fibroblasts have no effect  this method is used for the differential diagnosis of mut and cbl genotypes in cells from patients with a clinical diagnosis of methylmalonic aciduria and is shown to be a facile  sensitive  and specific method for genetic diagnosis  this work establishes the principle of using dna mediated gene transfer to identify the genotype of diseases which can result from mutations at several different genetic loci  this type of differential genotypic diagnosis will be particularly important for establishing the applicability of somatic gene therapy in individual patients  
class10	trichothiodystrophy with chronic neutropenia and mild mental retardation  trichothiodystrophy is a feature of several diseases that consist of characteristic hair shaft abnormalities and a wide spectrum of other developmental defects  detection of sulfur deficient hairs identifies this disorder and separates it from other similar ectodermal dysplasias with normal sulfur content  detection of low sulfur hair syndrome is also important for genetic counseling  because the disease appears to be an autosomal recessive trait  we report a patient with chronic neutropenia  mild mental retardation  and low sulfur content in hair  our case expands the spectrum of disorders associated with trichothiodystrophy  
class10	modifying the translabyrinthine approach to preserve hearing during acoustic tumour surgery  removing an acoustic schwannoma using the translabyrinthine approach has previously been considered incompatible with hearing preservation  by modifying the approach and preventing the loss of endolymph  we have successfully removed an intracanalicular acoustic schwannoma  which originated from the inferior vestibular nerve  and preserved hearing in the operated ear  this report represents the preliminary findings using this particular technique in the management of an intracanalicular acoustic tumour  
class10	unusual presentation of squamous cell carcinoma of the middle ear and mastoid  an unusual case of squamous cell carcinoma of the middle ear and mastoid in which syncope was a major presenting feature is reported  no such case has been reported in the literature  a possible explanation is offered  
class10	radiation induced cranial nerve palsy  hypoglossal nerve and vocal cord palsies  cranial nerve palsies are an unexpected complication of radiotherapy for head and neck tumours  we present a case of this radiation induced cranial palsy  an 18 year old female with nasopharyngeal carcinoma developed a right hypoglossal nerve palsy 42 months after cancericidal doses of radiotherapy  in addition  she developed a bilateral vocal cord palsy 62 months after therapy  follow up over four years has demonstrated no evidence of tumour recurrence and no sign of neurological improvement  
class10	life events and difficulties preceding stroke  life events and difficulties were recorded for the year before stroke  using a standardised semi structured interview  in 113 surviving patients seen after their first ever in a lifetime stroke  an age and sex matched control group  n   109  was also interviewed about the preceding year  the stroke patients reported fewer non threatening events and events with only a short term threat  while difficulties were reported with equal frequency by the two groups  however  events which were severely threatening in the long term were significantly more common in the stroke patients  in the 52 weeks before stroke 26  versus 13   odds ratio 2 3  95  confidence interval 1 1 4 9   the increased rate was apparent throughout the year and not just in the weeks immediately before stroke onset  the number of stroke patients experiencing severe events in the follow up year fell to the level found in the control group  recognised risk factors for stroke were found equally in those patients with and without severe events before onset  except that hypertension was rather less common in the patients who had experienced a severe event  it therefore appears that severe life events may be one of the determinants of stroke onset  
class10	transient ischaemic attacks in young patients  a thromboembolic or migrainous manifestation  a 10 year follow up study of 46 patients  forty six patients aged 18 39 years with transient ischaemic attacks  tia  were studied  two thirds were women  twenty five patients had attacks accompanied by headache  and seven gave a history of common migraine  only four of 27 angiograms were abnormal  no operable carotid lesion was demonstrated  over a mean follow up period of 10 years stroke or myocardial infarction  ami  occurred in all four patients who presented major cerebrovascular risk factors  but in only two of the remaining 42 patients  thus irrespective of age thromboembolic tia is a harbinger of stroke or ami  however  most tias under the age of 40 years are caused by a non embolic benign vascular disorder  the clinical characteristics  long term prognosis  and possible pathogenesis  for such attacks are often indistinguishable from those of classical migraine  in the absence of cardiovascular risk factors  arteriography does not provide much diagnostic and prognostic information  
class10	idiopathic and symptomatic trigeminal pain  the trigeminal reflexes  corneal reflex  blink reflex  masseter inhibitory periods  jaw jerk  and far field scalp potentials  nerve  root  brainstem  subcortical  evoked by percutaneous infraorbital stimulation were recorded in 30 patients with  idiopathic  trigeminal neuralgia  itn  and 20 with  symptomatic  trigeminal pain  stp   seven postherpetic neuralgia  five multiple sclerosis  four tumour  two vascular malformation  one tolosa hunt syndrome  and one traumatic fracture  all the patients with stp and two of those with itn had trigeminal reflex abnormalities  80  of patients with stp and 30  of those with itn had evoked potential abnormalities  the results indicate that 1  trigeminal reflexes and evoked potentials are both useful in the examination of patients with trigeminal pain  and in cases secondary to specific pathologies provide 100  sensitivity  2  in  symptomatic  and  idiopathic  paroxysmal pain the primary lesion affects the afferent fibres in the proximal portion of the root or the intrinsic portion in the pons  3  primary sensory neurons of the a beta fibre group are involved in both paroxysmal and constant pain  but in the latter the damage is far more severe  
class10	clinical features and associations of 560 cases of motor neuron disease  in 560 cases of motor neuron disease  studied retrospectively from their case notes in three teaching centres  the age at onset ranged from 13 to 87 years  mean 56 years   and the mean duration of illness until death was 2 6 years  in the subgroup of the disease presenting with progressive bulbar palsy presenting after age 59 years  there was a previously unrecognised excess of females sufficient to equalize the sex ratio of incidence of the disease in this age group  no potentially causative clinical associations emerged  no relation was noted between occupational exposure to leather products  trauma or surgical procedures and the disease  there was a trend for patients with motor neuron disease to give a history of abstention from alcohol  
class10	progressive degeneration of the right temporal lobe studied with positron emission tomography  a 79 year old man with a twelve year progressive history of prosopagnosia and recent naming difficulty  in whom other intellectual skills were preserved  is described  positron emission tomography  pet  revealed an area of right temporal lobe hypometabolism  with an additional area of less severe hypometabolism at the left temporal pole  this may represent an example of progressive focal cortical degeneration similar to that associated with primary progressive dysphasia  but affecting the right temporal lobe  
class10	vigabatrin  rational treatment for chronic epilepsy  vigabatrin is a selective  irreversible suicide inhibitor of gaba transaminase and thus increases brain and csf gaba  in 33 adult patients with long standing refractory epilepsy on treatment with one or two standard anti convulsant drugs  the addition of vigabatrin up to 3g daily for eight weeks was associated with a 48 2  reduction in seizure frequency  twenty patients who had exhibited a 50  or more reduction in frequency of one or more seizure types entered an eight week double blind placebo controlled phase  patients on vigabatrin maintained a 54 7  reduction of seizure frequency  whereas those on placebo showed an 18 6  increase in seizure frequency  a highly significant difference between the two groups  in the open phase  seven patients were withdrawn due to unacceptable and reversible adverse events  the commonest side effects were drowsiness  depression and mood instability  and headaches  vigabatrin is a potentially valuable new treatment for chronic epilepsy  especially partial seizures with or without secondary generalisation  
class10	correlation between essential tremor and migraine headache  the relationship between essential tremor  et  and migraine was investigated in a prospective study  in a group of 74 et patients 36 5  had migraine compared with 17 7  of 102 control subjects without tremor  in a group of 58 patients with migraine 17 2  had et compared with 1 2  of 85 controls without migraine  the prevalence of et in migraine controls was greater than controls without migraine  22  compared with 1   p   0 002   it is concluded that there is an association between essential tremor and migraine  
class10	cyclosporin associated akinetic mutism and extrapyramidal syndrome after liver transplantation  three patients developed akinetic mutism on the third day after the introduction of intravenous cyclosporin a  given for immunosuppression after liver transplantation  one patient in addition developed a florid orofacial dyskinesia  which resolved completely  as did the akinetic mutism  after withdrawal of cyclosporin  in these patients the time course of the akinetic mutism and extrapyramidal syndrome  which developed in the absence of any other identifiable cause  suggests cyclosporin a was the precipitating factor  subsequently  two of the patients showed signs of pseudobulbar palsy with abnormalities in the pons on mri scanning  suggesting central pontine myelinolysis  cpm   none of the patients had experienced significant fluctuations in serum sodium or other risk factors for central pontine myelinolysis and the exact relationship to the earlier cyclosporin related mutism was not clear  
class10	cauda equina syndrome associated with multiple lumbar arachnoid cysts in ankylosing spondylitis  improvement following surgical therapy  a case of cauda equina syndrome with multiple lumbar arachnoid cysts complicating ankylosing spondylitis  as  is described  the value of computerised tomography  ct  and magnetic resonance imaging  mri  as a non invasive means of establishing the diagnosis is emphasised  in contrast to previously reported cases the patient showed neurological improvement following surgical therapy  surgery may be indicated in some patients  particularly when there is nerve root compression by the arachnoid cysts and when the patient is seen early before irreversible damage to the cauda equina has occurred  
class10	grading white matter lesions on ct and mri  a simple scale  we developed and tested a simple three point scale for grading white matter lesions in anterior and posterior regions of the brain  twenty four ct scans and 24 mri scans were separately judged by 11 and five observers  respectively  on the presence and severity of white matter lesions  the observers were radiologists and neurologists  for ct scans  these periventricular changes were graded according to their extent as absent  or partly involving the white matter  or extending up to the subcortical region  the mri lesions were graded as no lesion or only a single one  multiple focal lesions  and multiple confluent lesions  the pairwise agreements of all possible combinations of observers for each scan were corrected for chance  kappa statistics  maximal agreement 1 0   the weighted kappa value  for anterior and posterior regions combined  was 0 63 for ct scans  and 0 78 for mri scans  this three point scale for two separate regions seems suitable as a basis for cross sectional or longitudinal studies of large series of patients  
class10	hypothalamic obesity due to hydrocephalus caused by aqueductal stenosis  a case is presented of 14 year old female with hypothalamic obesity due to hydrocephalus caused by aqueductal stenosis  evidence of hypothalamic obesity included 1  acute hyperphagia and weight gain  2  neuroradiology showed hydrocephalus with focal enlargement of the third ventricle  3  endocrinological studies revealed hyperinsulinaemia and impaired growth hormone  gh  response to arginine  but normal gh response to growth hormone releasing factor  grf  and 4  torkildsen s ventriculo cisternal shunting resulted in improvement in hyperphagia and obesity  
class10	the community hospital based stroke programs in north carolina  oregon and new york  v  stroke diagnosis  factors influencing the diagnostic evaluation of patients following acute stroke  among the 4129 patients of the community hospital based stroke program  30  had an unspecified stroke diagnosis  since specific diagnosis and  perhaps  eventual treatment  derives in part from diagnostic testing  we examined the effect of clinical condition  geographic and demographic factors on the incidence of certain diagnostic tests after acute stroke  in this multivariable analysis  race  sex  history of hypertension and history of diabetes did not influence the chance of having any test  but older age strongly reduced the chances of receiving extensive evaluation  when ct scanning was available  the utilization of a ct as well as other diagnostic studies including cerebral angiography  radionuclide brain scan  eeg and ekg was increased  the odds of receiving a ct scan increased if the patient was married  and decreased with a history of previous stroke  a history of previous tia increased the chance of having a cerebral angiogram while a history of cardiac disease decreased the chance  there were striking regional geographic differences in the use of ct  radionuclide brain scanning and cerebral angiography which may  in part  reflect differences between the availability of these technologies in urban and rural hospitals  these results indicate that evaluation of stroke patients remains heterogenous  
class10	bone metastases  pathophysiology and management policy  the pathophysiology and options for management of bone metastases as well as criteria for determining response to therapy are reviewed  bone metastases are frequently one of the first signs of disseminated disease in cancer patients  in the majority of patients  the primary tumor is in the breast  prostate  or lungs  although almost all patients will die of their disease  a proportion of the patients will survive for several years  treatment is primarily palliative  the intention is to relieve pain  prevent fractures  maintain activity and mobility  and  if possible  to prolong survival  therapeutic options include local treatment with radiotherapy and or surgery  and systemic treatment using chemotherapy  endocrine therapy  radioisotopes  agents such as diphosphonates  which inhibit resorption of bone  as well as analgesic and antiinflammatory drugs  the mechanisms by which pain is relieved by several of these therapies remain unclear but actions beyond a simple tumoricidal effect appear to be important  there have been few randomized trials comparing the therapeutic options  and the criteria for assessing response to therapy have  in general  been poorly defined  there is a need for rigorous clinical investigations that assess the efficacy of the various therapeutic possibilities by using well defined and validated criteria of response  
class10	high risk of recurrent stroke after discontinuance of five to twelve years of transfusion therapy in patients with sickle cell disease  although long term transfusion therapy is at least 90  effective in preventing recurrent strokes after an initial cerebrovascular accident in patients with sickle cell disease  it is unknown how long transfusion therapy should be continued  to address this question  we prospectively discontinued transfusions in 10 patients with sickle cell disease whose median duration of transfusion therapy after an initial stroke was 9 1 2 years  range 5 to 12 years   before the transfusions were discontinued  patients were examined by cerebral angiography  magnetic resonance imaging of the head  neuropsychologic testing  electroencephalography  and a complete neurologic examination  within 12 months after transfusion therapy was stopped  5 of 10 patients had had an ischemic event  three events caused relatively mild deficits in the same areas as those originally affected  two were associated with massive intracranial hemorrhage  including one on the contralateral side of original involvement  an additional patient died suddenly of unknown causes  of the four remaining patients  three declined to resume transfusion and are relatively well at greater than or equal to 18 months after therapy was stopped  the studies performed before transfusions were stopped were not predictive of recurrent stroke  the risk of recurrent cerebrovascular accident in this group was significantly greater than the estimated risk of 10  in patients who are receiving long term transfusion therapy  p   0 002   this adverse outcome suggests that patients with sickle cell disease who have had a stroke must receive long term transfusion indefinitely or a suitable therapeutic alternative must be devised  
class10	fundoplication and gastrostomy in familial dysautonomia  fundoplication with gastrostomy has become a frequent treatment for patients with familial dysautonomia  so we evaluated the use of both procedures in 65 patients  although patients differed widely in presenting signs and age  from 5 weeks to 40 years  gastroesophageal reflux was documented in 95  of patients by cineradiography or ph monitoring  panendoscopy was a useful adjunct  preoperative symptoms of gastroesophageal reflux included vomiting  respiratory infections  and exaggerated autonomic dysfunction  severe oropharyngeal incoordination frequently coexisted and resulted in misdirected swallows with aspiration  dependence on gavage feedings  or poor weight gain and dehydration  follow up after surgical correction ranged from 3 months to 11 years  55 patients  85   were available for a 1 year postoperative assessment  we had no instances of surgical death  the long term mortality rate was 14   primarily related to severe preexisting respiratory disease  beyond the first postoperative year  30 patients had pneumonia attributed to continued aspiration  exacerbation of preexisting lung disease  or recurrence of gastroesophageal reflux  of 11 patients who vomited postoperatively  six had recurrence of reflux  recurrence of gastroesophageal reflux was documented in eight patients  12    and we revised the fundoplication in three patients  the number of patients with cyclic crises was reduced from 18 to 7  retching replaced overt vomiting in all but two of these seven patients  neither of whom had recurrence of reflux  because oropharyngeal incoordination was prominent  concomitant use of gastrostomy and an antireflux procedure was especially effective in the treatment of younger patients with familial dysautonomia  before the development of severe respiratory disease  despite the development of severe morning nausea in 15 patients  the combination procedure resulted in significantly improved nutritional status  decreased vomiting  and decreased respiratory problems  appropriate use of gastrostomy feedings also contributed to success of the operation  the generally good outcome of fundoplication with gastrostomy confirms the benefit of this procedure in familial dysautonomia  
class10	is it correct to correct  developmental milestones in 555  normal  preterm infants compared with term infants  to determine whether correction for preterm birth should be applied during developmental assessment  we conducted a prospective national survey of very premature infants  born at less than 32 weeks of gestation   neurodevelopment in the first 2 years was studied with the dutch child health care developmental assessment  in 555 preterm children who had no evidence of handicap at 2 years of age  the age at which developmental milestones were reached was established  the results were compared with the results of the same assessment in dutch children born at term  during the first year  the development of the very premature children equaled the development of normal children when full correction was applied  at 2 years of age  development was equal to or better than normal children s development without correction  we conclude that full correction for prematurity should be applied in the first year to avoid overreferral for developmental stimulation  whereas at 2 years of age correction is not necessary  
class10	relationships of somatic symptoms to behavioral and emotional risk in young adolescents  junior high students  n   1508  from a midwestern community completed a health behavioral questionnaire that asked the frequency of headache and abdominal pain and of a number of behavioral and emotional risk indicators  headache  24   and abdominal pain  13   were frequently reported among these young adolescents  particularly among girls  those reporting frequent somatic complaints also reported significantly more behavioral and emotional symptoms indicative of risk  p less than 0 001   further  the interaction between somatic complaint and gender significantly affected risk status  p less than 0 01   this interaction was greater with behavioral risk  boys with both abdominal pain and headaches reported higher behavioral risk than all other groups  p less than 0 0001   somatic symptoms continued to account for a significant amount of variance in behavioral risk after the effects of emotional risk and age were removed  this suggests that behavioral risk and emotional risk are independently associated with somatic complaints  the evaluation of persistent somatic complaints in adolescents  particularly in boys with abdominal symptoms  should include careful examination of emotional risk factors and other health endangering behaviors such as substance use  early sexual activity  and delinquency  
class10	influence of preservation or perfusion of intraoperatively identified spinal cord blood supply on spinal motor evoked potentials and paraplegia after aortic surgery  permanent ligation of arteries supplying blood to the spinal cord in operations for aortic aneurysm can lead to spinal cord ischemia  which can result in either paraparesis or paraplegia  this report describes a rapid method of intraoperative identification of those arteries that supply the spinal cord by use of an intrathecal platinum electrode to detect hydrogen in solution that has been injected into the aortic ostia  preservation or perfusion of those identified arteries supplying the spinal cord may decrease the rate of postoperative neurologic complications  of 28 porcine experiments with postoperative observation for 24 hours  there were 3 initial pilot experiments in which saline saturated with hydrogen was injected into the temporarily cross clamped aorta  twenty animals were then randomized to  1  preservation of only the vessels sequentially identified to supply blood to the spinal cord from t 13 to l 5  n   10    2  division of the vessels supplying the spinal cord  n   10   a further five animals underwent perfusion experiments wherein the identified cord arteries were perfused by a shunt  the other nonsupply arteries were divided  and the aorta was kept clamped for 45 minutes  spinal motor evoked potentials were elicited with an intrathecal electrode and were highly sensitive for paralysis  paralysis occurred in 0 3 pilot  p less than 0 013 vs division   8 10 division  1 10 preservation  p less than 0 0017 vs division   and perfusion 1 5  p less than 0 025 vs division   results of a pilot study in eight humans shows that the technique can be used to rapidly identify segmental arteries supplying the spinal cord  to determine if distal perfusion is supplying the spinal cord with blood flow  and if reattached segmental arteries are patent  
class10	limitations of electroencephalographic monitoring in the detection of cerebral ischemia accompanying carotid endarterectomy  an analysis was undertaken of 458 consecutive carotid endarterectomies performed over 6 years with the patient under general anesthesia and with electroencephalographic monitoring  seventy patients  15   had electroencephalographic changes suggestive of ischemia with carotid clamping and had shunts placed  ischemic encephalographic changes occurred in 26  of patients with an occluded contralateral carotid artery  21  of patients with a prior stroke history  and 12  of patients with no stroke history and a patent contralateral carotid artery  nineteen strokes  4 1    nine transient deficits  2 0    and one death  0 2   occurred in the 458 endarterectomies in this experience  ten of the 19 strokes and five of nine transient deficits were immediately apparent when patients awoke from anesthesia  five of 10 patients with immediate strokes and all five patients with immediate transient deficits had no ischemic electroencephalographic changes during the procedure  two other patients with immediate strokes initially had ischemic electroencephalographic changes after carotid clamping that reversed with increased blood pressure or shunting  therefore 7 of 10 patients with immediate strokes and all 5 patients with immediate transient deficits had electroencephalographs unchanged from baseline at completion of the procedure  and thus deficits not manifest by operative electroencephalographic changes developed  our data do not support the tenet that electroencephalographic monitoring will always predict neurologic deficits accompanying carotid endarterectomy  
class10	intrathecal baclofen for spasticity in cerebral palsy seventeen patients with congenital spastic cerebral palsy and six patients with other forms of spasticity were injected intrathecally with doses of placebo or baclofen  25 micrograms  50 micrograms  or 100 micrograms  in a randomized  double blind manner  muscle tone in the upper and lower extremities was assessed by ashworth scores both before the injections and every 2 hours afterward for 8 hours  function of the upper extremities was evaluated before the injections and 4 hours afterward  muscle tone in the lower extremities was significantly decreased within 2 hours after baclofen injection and remained lower than baseline 8 hours afterward  upper extremity tone and function were not significantly affected by these single doses  confusion and drowsiness occurred in two of the youngest children in the study after the 50 micrograms dose  but cleared within 2 hours  our findings indicate that intrathecal baclofen reduces spasticity in children with cerebral palsy  as it does in adults with spasticity of spinal origin  
class10	no confirmation of visual evoked potential diagnostic test for migraine  we have attempted to replicate the results of studies on a diagnostic test reported to have 90  sensitivity and 89 96  specificity for migraine  the technique is based on peak to peak measurements of fast background electroencephalographic activity during a visual evoked potential  vep  study  vep latencies and amplitudes did not differ significantly  and showed substantial overlap  between a group of eight migraine patients and ten age matched healthy controls  we could not recognise previously described fast activity or measure it objectively by peak to peak measurements  we cannot confirm that measurement of fast wave activity in the vep background is useful in diagnosis of migraine  
class10	intracranial pressure in african children with cerebral malaria opening lumbar cerebrospinal fluid  csf  pressure was measured with a paediatric spinal fluid manometer in 26 of 61 kenyan children  mean age 39 months  with cerebral malaria  in all cases pressure was above normal  mean  sd 22 6  7 4  cm csf  range 10 5 36   clinical features of our patients suggest that intracranial hypertension is important in the pathogenesis of cerebral malaria in children  especially as a cause of death  we suggest that raised intracranial pressure is secondary to increased cerebral blood volume  lowering intracranial pressure may significantly reduce the mortality and morbidity of cerebral malaria  the potential risks and benefits of lumbar puncture should be considered carefully in patients with suspected cerebral malaria  
class10	intracranial complications of paranasal sinusitis  a combined institutional review  intracranial complications of paranasal sinusitis constitute true surgical and medical emergencies  the charts of all patients  n   649  admitted for acute or chronic sinusitis to the university of minnesota hospital and to the university of michigan medical center during a 13 year period  1975 to 1988  were retrospectively reviewed to determine the incidence of complications  the clinical presentation  bacteriology  involved sinuses  influencing host factors  white blood cell count on presentation  length of hospitalization  and postinterventional complications are presented  twenty four patients with intracranial complications from paranasal sinusitis are studied for an incidence of 3 7   aggressive medical and semi emergent surgical intervention are required to prevent excessive morbidity and or mortality  intracranial complications included subdural empyema  frontal lobe abscesses  intrahemispheric abscesses  cavernous and superior sagittal sinus thrombosis  and osteomyelitis  
class10	polyglucosan body disease  adult polyglucosan disease has been described in 15 cases  all had signs of peripheral neuropathy  upper motor neuron signs  and 12 of the 15 had sphincter problems  dementia was prominent in 8 of 15 cases  we reported 2 cases that contained these clinical features  electrophysiological studies showed axonal neuropathy  somatosensory evoked potentials on the second patient were abnormal  sural nerve biopsy showed clusters of polyglucosan bodies  although the presence of polyglucosan bodies in biopsy is nonspecific  the number as well as the clinical features are necessary to make the diagnosis  branching enzyme activity in muscle extracts of the muscles were normal  hence  a specific enzyme abnormality is not yet known  
class10	aaem case report  1  ulnar neuropathy at the elbow  a patient with bilateral cubital syndrome complicated by anomalous innervation is presented  the electrodiagnostic approach to patients with this neuropathy is reviewed emphasizing new developments  the interpretation of the findings in this patient centers around issues of pathophysiology and methodology  
class10	abnormal pattern detected in fragile x patients by pulsed field gel electrophoresis  the fragile x syndrome is the most frequent inherited form of mental retardation  with an incidence of 1 in 1 500 males  it is characterized by the presence of a fragile site at xq27 3 induced in vitro by folate deprivation or by inhibitors of deoxynucleotide synthesis  its mode of inheritance is unusual for an x linked trait  with incomplete penetrance in both males and females  some phenotypically normal males transmit the mutation to all their daughters who rarely express any symptoms  but penetrance is high in sons and daughters of these carrier women  genetic and physical mapping of the xq27 q28 region has confirmed that the disease locus is located at or very near the fragile site  hypotheses proposed to account for the abnormalities in the inheritance of the disease include sequence rearrangements by meiotic recombination or a mutation that affects reactivation of an inactive x chromosome during differentiation of female germ cells  to detect such rearrangements  or methylation changes that may reflect a locally inactive x chromosome  we used pulsed field gel analysis of dna from fragile x patients with probes close to the fragile x locus  the probe do33  dxs465  detected abnormal patterns in fragile x patients  but not in normal controls or in non expressing male transmitters  
class10	lexical organization of nouns and verbs in the brain  the analysis of neuropsychological disorders of lexical processing has provided important clues about the general organization of the lexical system and the internal structure of the processing components  reports of patients with selective dysfunction of specific semantic categories such as abstract versus concrete words  living things versus inanimate objects  animals  fruits and vegetables  proper names and so forth  support the hypothesis that the neural organization of the semantic processing component is organized in these categories  there are reports of selective dysfunction of the grammatical categories noun and verb  suggesting that a dimension of lexical organization is the grammatical class of words  but the results reported in these studies have not provided unambiguous evidence concerning two fundamental questions about the nature and the locus of this organization within the lexical system  is the noun verb distinction represented in the semantic or in the phonological and orthographic lexicons  is grammatical class knowledge represented independently of lexical forms or is it represented separately and redundantly within each modality specific lexicon  here we report the performance of two brain damaged subjects with modality specific deficits restricted principally  h w   or virtually only  s j d  to verbs in oral and written production  respectively  the contrasting performance suggests that grammatical class distinctions are redundantly represented in the phonological and orthographic output lexical components  
class10	the nature of opioid responsiveness and its implications for neuropathic pain  new hypotheses derived from studies of opioid infusions  in recent years  the observation that the response of patients to opioid drugs may be influenced by properties inherent in the pain or pain syndrome  such as its pathophysiology  has evolved into the belief that certain types of pain  e g   neuropathic pains  may be unresponsive to these drugs  this concept has important implications for both clinical practice and basic understanding of opioid mechanisms  we critically evaluate opioid responsiveness  particularly as it relates to neuropathic pain  and propose a clinically relevant definition and a paradigm for its investigation  the paradigm is illustrated by analgesic responses to opioid infusion in 28 patients with neuropathic pains and by a detailed presentation of the pharmacokinetic and pharmacodynamic relationships in one of these patients  whose central pain responded promptly to an infusion of hydromorphone  from this analysis  we hypothesize that  1  opioid responsiveness in man can be defined by the degree of analgesia achieved during dose escalation to either intolerable side effects or the occurrence of  complete  or  adequate  analgesia   2  opioid responsiveness is a continuum  rather than a quantal phenomenon   3  opioid responsiveness is determined by a diverse group of patient characteristics and pain related factors  as well as drug selective effects  and  4  a neuropathic mechanism may reduce opioid responsiveness  but does not result in an inherent resistance to these drugs  given the complexity of factors contributing to opioid responsiveness and the observation that outcome cannot be reliably predicted  opioids should not be withheld on the assumption that pain mechanism  or any other factor  precludes a favorable response  both the clinical use of opioids and paradigms to investigate opioid responsiveness should include dose escalation to maximally tolerated levels and repeated monitoring of analgesia and other effects  
class10	chronic musculoskeletal pain and depressive symptoms in the general population  an analysis of the 1st national health and nutrition examination survey data  chronic pain and depression frequently occur together  a selection bias afflicts all hospital clinic and family practice populations in which this relationship has been examined  we report here some of the results from civilian populations outside institutions  examined in the united states in national surveys  the findings are based upon the recollection of individuals with respect to the period of 12 months prior to interview and upon the occurrence of depression in the previous week as indicated by the answers to the depression scale of the centre for epidemiologic studies  ces d   they indicate that 14 4  of the united states population between the ages of 25 74 suffer from definite chronic pain related to the joints and musculoskeletal system  another 7 4  have some pain of uncertain duration  eighty three percent of the definite pain group received treatment  chronic pain subjects scored significantly higher than normals on the ces d  10 68     s e m  0 76 vs  8 05     0 23  p less than 0 01  with subjects with pain of uncertain duration scoring similar to the definite chronic pain population  11 13     0 76   using a high cut off score for depression  18  of the population with chronic pain were found to have depression  this is in contrast to 8  of the population who did not have chronic pain  
class10	codeine plus paracetamol versus paracetamol in longer term treatment of chronic pain due to osteoarthritis of the hip  a randomised  double blind  multi centre study  this randomized  double blind  multi centre study was undertaken to evaluate the efficacy and safety of treatment for 4 weeks with codeine plus paracetamol versus paracetamol in relieving chronic pain due to osteoarthritis of the hip  a total of 158 outclinic patients entered the study  eighty three patients  mean age 66 years  were treated with codeine 60 mg plus paracetamol 1 g 3 times daily  and 75 patients  mean age 67 years  with paracetamol 1 g 3 times daily  ibuprofen 400 mg was prescribed as rescue medication  due to an unexpected high rate of adverse drug reactions  the study was closed before the planned 400 patients had entered  over weeks 1 4  87   64   61  and 52  of patients in the codeine plus paracetamol group  and 38   31   22  and 29  of patients in the paracetamol group had one or more adverse drug reactions  significantly more patients in the codeine plus paracetamol group had adverse drug reactions in each of the 4 weeks  nausea  dizziness  vomiting and constipation were predominant adverse reactions in the codeine plus paracetamol group  during the first week of treatment  30 patients  36   in the codeine plus paracetamol group and 9  12   in the paracetamol group dropped out  as evaluated from patients completing the first week of treatment  the pain intensity during that week compared to their baseline pain was significantly lower in the codeine plus paracetamol group than in the paracetamol group  moreover  during the first week the paracetamol group received rescue medicine significantly more frequently  in conclusion  when evaluated after 7 days of treatment  the daily addition of codeine 180 mg to paracetamol 3 g significantly reduced the intensity of chronic pain due to osteoarthritis of the hip joint  however  several adverse drug reactions  mainly of the gastrointestinal tract  and the larger number of patients withdrawing from treatment means that the addition of such doses of codeine cannot be recommended for longer term treatment of chronic pain in elderly patients  
class10	pain  memories  in phantom limbs  review and clinical observations  this paper reviews reports of phantom limb sensations which resemble somatosensory events experienced in the limb before amputation  it also presents descriptions of this phenomenon in 68 amputees who took part in a series of clinical studies  these somatosensory memories are predominantly replicas of distressing pre amputation lesions and pains which were experienced at or near the time of amputation  and are described as having the same qualities of sensation as the pre amputation pain  the patients who experience these pains emphasize that they are suffering real pain which they can describe in vivid detail  and insist that the experience is not merely a cognitive recollection of an earlier pain  reports of somatosensory memories are less common when there has been a discontinuity  or a pain free interval  between the experience of pain and amputation  among the somatosensory memories reported are cutaneous lesions  deep tissue injuries  bone and joint pain and painful pre amputation postures  the experience of somatosensory memories does not appear to be related to the duration of pre amputation pain  time since amputation  age  gender  prosthetic use  level of amputation  number of limbs amputated  or whether the amputation followed an accident or illness  the results suggest that somatosensory inputs of sufficient intensity and duration can produce lasting changes in central neural structures which combine with cognitive evaluative memories of the pre amputation pain to give rise to the unified experience of a past pain referred to the phantom limb  implications for pre  and post operative pain control are discussed  
class10	assessment of the components of observed chronic pain behavior  the checklist for interpersonal pain behavior  chip   this article describes the development of the checklist for interpersonal pain behavior  chip   an observation scale which assesses overt pain behavior  the study is an extension of an earlier study in which the dimensions and components of observed chronic pain behavior were examined  a broad definition of pain behavior is chosen  interpersonal pain behavior   namely the interaction between the pain patient and his her direct environment  the list of pain behaviors  taken from the earlier study  has been transformed into a 78 item global rating scale to be used by nurses to quantify observed pain behavior in a clinical setting  six studies examine the factor structure and the psychometric properties of this behavioral observation method  in the first study  6 internally reliable factors are derived using factor analytic techniques from a sample of 152 chronic pain patients  they are labeled as   distorted mobility    verbal complaints    non verbal complaints    nervousness    depression  and  day sleeping   internal consistency of all factors  except  day sleeping  was excellent  the following studies show that the chip is sufficiently reliable and valid  after a discussion on the advantages of this observation scale  the conclusion seems justified that the chip is a useful tool in pain assessment that can easily be used by nurses  
class10	diphtheria tetanus pertussis vaccine and serious neurologic illness  an updated review of the epidemiologic evidence  a widespread impression that dtp vaccine does cause brain damage has been based first on historical precedent  smallpox and rabies vaccines were recognized as sometimes causing devastating neurologic illness  analogy to pertussis  the disease can cause encephalopathy  and more recently on anecdotal evidence  particularly case series  a noncausal relationship  coincidence  could explain the temporal relation between dtp vaccine and neurologic illness  inasmuch as dtp vaccine is given at the age of emergence of idiopathic neurologic disease  the relationship between dtp vaccine and neurologic illness lacks specificity  case series have had an impact on both physicians  and the lay public s impression of the safety of pertussis vaccine greatly out of proportion to their scientific importance  case series can be useful for generating hypotheses but cannot provide evidence that pertussis vaccine is causally related to acute neurologic illness or brain damage  observational studies using cohort and ecologic designs did not find an association between dtp vaccine and serious neurologic illness  but they were not powerful enough to detect an association as rare as that observed by the nces investigators  the case control design offers the best chance of providing causal evidence regarding dtp vaccine and serious neurologic illness  the nces is the only published case control study of this issue  this study found a rare association between dtp vaccine and some types of acute neurologic illness  bias and chance are unlikely to account entirely for the association demonstrated by the nces  however  the association has not yet been replicated by other case control studies  the nces does not demonstrate that dtp vaccine causes permanent brain damage  
class10	can clinical judgment detect children with speech language problems  pediatricians often rely on clinical judgment derived from observation or parental concern to identify children with developmental problems  the less popular but recommended alternative is to repeatedly administer standardized screening tests  such tests are time consuming but  unlike clinical judgment  have known detection rates  preliminary research concerning clinical judgment showed that clusters of parental concerns related to their childrens  performances on screening tests  in the present study  previous research was refined by assessment of the meaning of parents  concerns about their childrens  speech language development  in this study of 157 families seeking pediatric care  72  of children whose speech language screening yielded positive results had parents who were concerned about their speech language development  of children with negative screening results  83  had parents with no concerns about their speech language development  although standardized screening tests should be used occasionally in the developmental surveillance process  the findings show that the problems of most children with developmental problems were detected through clinical judgment based on parental concern  
class10	location of port wine stains and the likelihood of ophthalmic and or central nervous system complications  of 310 patients with port wine stains  68  had more than one dermatome involved  85  had unilateral and 15  had a bilateral distribution of their port wine stain  at the time of examination  8  of all patients with trigeminal port wine stains had evidence of eye and or central nervous system  cns  involvement  extensive involvement  with port wine stain over the trunk and extremities as well as the head and neck  was observed in 12   patients who did not have port wine stains on the areas served by branches v1 and v2 of the trigeminal nerve had no signs or symptoms of eye and or cns involvement  port wine stains of the eyelids  bilateral distribution of the birthmark  and unilateral port wine stains involving all three branches of the trigeminal nerve were associated with a significantly higher likelihood of having eye and or cns complications  twenty four percent of those with bilateral trigeminal nerve port wine stains had eye and or cns involvement compared with 6  of those with unilateral lesions  all those who had eye and or cns complications had port wine stain involvement of the eyelids  in 91  both upper and lower eyelids were involved  whereas in 9  only the lower eyelid was involved  none of those with upper eyelid port wine stains alone had eye and or cns complications  in addition  3  75   of the 4 subjects with seizures alone had bilateral port wine stain involvement  a third group  these with unilateral v1  v2  and v3 port wine stains  had eye and or cns complications in 3  19   of 16 subjects  
class10	hypoglycemia  hypotonia  and cardiomyopathy  the evolving clinical picture of long chain acyl coa dehydrogenase deficiency  inherited defects in fatty acid oxidation  which have been described and diagnosed with increasing frequency in the last decade  are most commonly attributed to a deficiency in the activity of medium chain acyl coa dehydrogenase  few cases of the related enzyme defect of long chain acyl coa dehydrogenase activity have been reported  an infant with documented long chain acyl coa dehydrogenase deficiency is described with a detailed metabolic profile  long term clinical follow up  and response to treatment  this patient is compared with the seven previously published cases of this disorder in order to stress the unique features of the initial presentation  more subtle late manifestations of the disease  and clinical and biochemical differentiation from the more common medium chain acyl coa dehydrogenase deficiency  this report stresses the enlarging spectrum of the clinical presentation and natural history of this defect in fatty acid oxidation  
class10	tilt test for diagnosis of unexplained syncope in pediatric patients  thirty five teenage patients with a history of presyncope or syncope underwent a passive head up tilting to reproduce symptoms of syncope  if tilting alone did not induce syncope  isoproterenol infusion was given to increase heart rate to 150 to 160 beats per minute  in 80  of patients with a history of syncope  identical symptoms could be reproduced during tilting  an abrupt fall in blood pressure combined with profound nodal bradycardia  ranging from 32 to 86 beats per minute  these symptoms were quickly reversed by returning the patient to the supine position  for patients with frequent occurrences of syncope  especially when there was a history of trauma sustained during these episodes  a therapeutic regimen of either beta blockers or 9 alpha fluorocortisol was begun  the mechanisms of this common cause of syncope in childhood is neurocardiogenic in response to venous pooling and catecholamine induced tachycardia  the tilt test is an excellent and cost effective test for the workup of unexplained syncope in childhood  
class10	pain management in the orthopedic patient  pain is a familiar phenomenon to all orthopedic nurses  as dunwoody said   few things we do for patients are more fundamental to the quality of life than relieving pain   we as orthopedic nurses are in a position to contribute to the positive management of pain by using a comprehensive approach to pain management that involves the participation of the patient  we need to believe the patient s pain  try new approaches  and help our patients achieve pain relief  
class10	help for the hurting elderly  safe use of drugs to relieve pain  pharmacologic management of pain in elderly patients is a common and difficult clinical problem  because of altered drug metabolism and pharmacodynamics in the elderly  the drugs of choice are different than in younger patients and side effects occur more often  however  with judicious use and monitoring for toxicity  oral medications given as part of a multimodality approach can achieve adequate analgesia in most elderly patients  
class10	chronic pain  assessment of orthopedic physical therapists  knowledge and attitudes  orthopedic physical therapists  knowledge of pain mechanisms and methods of pain management and their attitudes toward working with patients with benign chronic pain were studied  a random sample of 500 members of the american physical therapy association s section on orthopaedics received by mail a 36 item questionnaire  statistical analysis of scores  using frequencies  means  and correlations was performed on the 119  23 8   usable returns  all but 4  of the respondents preferred to work with patients who are not likely to have chronic pain  seventy two percent believed their entry level education in pain management and theory was very inadequate or less than adequate to deal with an orthopedic patient population  pain knowledge scores were low  35 8 out of 46 points   and the scores on positive attitudes toward treating patients with benign chronic pain were lower  20 5 out of 36 points   the study suggests specific deficiencies in orthopedic physical therapists  knowledge of clinical pain mechanisms and management and potentially undesirable attitudes toward treating patients with chronic pain  
class10	movement analysis  an aid to early diagnosis of cerebral palsy  the purpose of this article is to review research related to the use of clinical analysis of movement as an aid to the early diagnosis of cerebral palsy  a historical perspective of clinical techniques used by physicians and physical therapists in the early diagnosis of cerebral palsy will be presented first  including recent research findings on clinical signs that were most predictive of this movement disorder  predictive neuromotor behaviors common across several recent studies will be highlighted  future trends in the use of movement analysis  including digitized kinematic analysis of term and preterm infants and fetal ultrasound techniques  will be discussed as well  
class10	implications of a dynamical systems approach to understanding infant kicking behavior  implications of the dynamical systems approach to understanding movement dysfunction in infants are discussed  traditional theories of motor development attribute changes in movement to the hierarchical maturation of the central nervous system  the dynamical systems approach emphasizes that movement self organizes as the result of the interaction of the participating subsystems in developmental and real time  in this article  i discuss  from the theoretical perspective of the dynamical systems approach  the organization of leg movements in low  and high risk preterm and full term infants  developmental changes in movement in low risk preterm infants from 34 weeks  gestational age to 40 weeks  postgestational age  and differences in movement between low risk preterm infants at 40 weeks  postgestational age and full term infants  preliminary data on high risk preterm infants are presented  based on these data  the necessity to review and reinterpret traditional concepts of motor development is explored  suggestions are offered and questions posed on how the dynamical systems perspective may influence the practice of physical therapy in the evaluation  and treatment of infants at risk for movement dysfunction  
class10	cognitive strategies during coincident timing tasks  research findings suggest that experience and cognitive strategies contribute to successful performance during perceptual motor tasks  this article critically reviews selected literature on the effects of information processing skills  preferred movement time  experience  and task difficulty on performance during coincident timing tasks  theoretical information and research findings are discussed  and their applications to clinical practice are considered  clinical recommendations include assessment of coincident timing skills and use of functional activities that provide opportunities to explore and dynamically interact with the environment  
class10	measurement and treatment in cerebral palsy  an argument for a new approach  this article describes the need for a shift in our therapeutic strategies for patients with cerebral palsy  changes in functional abilities must be stressed in therapy  coincident with this emphasis must be the development of functional assessments to be used when documenting intervention outcomes  research on functional arm movement using kinematic analysis is described for this patient group  
class10	dorsal rhizotomy for children with cerebral palsy  support for concepts of motor control  the results from selective dorsal rhizotomy research suggest that therapists need to question some common clinical assumptions about movement dysfunction  the rationale for performing a selective dorsal rhizotomy is based on the clinical assumptions that spasticity is the underlying cause of disordered movement and that reducing or eliminating the spasticity will improve movement  this article reviews the literature related to movement dysfunction  the effects of selective dorsal rhizotomy  and the evidence for disordered motor control in children with spastic cerebral palsy  selective dorsal rhizotomy appears to reduce spasticity and increase joint range of motion  abnormal movement patterns  however  persist after the spasticity is reduced  well coordinated movement patterns are acquired slowly and appear to be related to an intense period of physical therapy  i argue that these results provide evidence that the presence of spasticity alone is an insufficient explanation for abnormal movement patterns  i propose that physical therapists redirect their efforts from developing methods for reducing spasticity to developing adequate assessment  treatment  and measurement techniques for assessing motor control in children with cerebral palsy  i believe we can maximize the functional potential of children with cerebral palsy by identifying problems related to motor control and applying sound principles of motor learning to treatment  
class10	spinal cord injury after subclavian flap aortoplasty  an experimental study in piglets  paraplegia is a rare but much feared complication of corrective surgery for coarctation of the aorta  the problem was studied in 31 newborn pigs submitted to subclavian flap aortoplasty  the aortic cross clamping time ranged from 9 25 min  twenty three piglets with clamping times 9 18 min were neurologically intact  whereas eight with aortic clamping for 18 25 min became paraplegic  the clinical implications for newborn children with symptomatic aortic coarctation are discussed with regard to these experimental findings  
class10	long term medical consequences of incest  rape  and molestation  one hundred thirty one patients who gave a history of childhood sexual abuse were seen in a general medical practice decades after the event and were compared with a control group  the subject patients were found to be distinct for chronic depression  morbid obesity  marital instability  high utilization of medical care  and certain psychosomatic symptoms  particularly chronic gastrointestinal distress and recurrent headaches  it is clear that these remote events can underlie difficult chronic medical problems  questions about childhood sexual abuse must become part of the practitioner s review of systems in these difficult cases  if not routinely  
class10	scalp pilomatrix carcinoma as an extra axial mass  we report the ct  mri  and angiographic findings in a case of pilomatrix carcinoma that had invaded the temporal bone and presented itself as an extra axial mass  even though bone destruction was better shown with ct  the tumor mass with its meningeal and tentorial extension was seen more clearly with mri  the arteriogram demonstrated a unique vascular supply from the external carotid artery  
class10	cerebral falciparum malaria mimicking thrombotic thrombocytopenic purpura  we have described a patient with cerebral falciparum malaria who had rapidly progressive cns deterioration  renal failure  hemolytic anemia associated with striking and varied erythrocyte morphologic changes  and thrombocytopenia  the initial diagnosis was thrombotic thrombocytopenic purpura  ttp  of unknown origin  reexamination of the peripheral smear of this comatose patient led to correct diagnosis and effective treatment in this case of cerebral falciparum malaria  another of medicine s great mimickers  
class10	management of arginine monohydrochloride extravasation in the forearm  we initially observed our patient  who had subcutaneous arginine monohydrochloride extravasation in the volar forearm  until his wound demarcation was complete  after wound demarcation  we proceeded with debridement and partial thickness skin grafting  upper extremity function was totally normal 3 months after this therapy  this is the first case report in the literature that describes a child with an arginine monohydrochloride induced extravasation necrosis  
class10	cerebellar degeneration and meige s syndrome  we have reported a case of meige s syndrome in a middle aged man who eventually had a cerebellar degeneration syndrome  the extrapyramidal symptoms preceded cerebellar signs and symptoms by 5 years  most patients with idiopathic meige s syndrome show some improvement with high dose anticholinergic therapy  our patient s lack of response to such agents and his subsequent cerebellar symptoms are reminiscent of the situation seen with parkinsonian patients who do not respond to medications  indicating a more widespread degenerative disease  the association of extrapyramidal symptoms with some spinocerebellar disorders  and the pathologic changes seen in the one reported autopsy case  should place the group of spinocerebellar disorders high on the differential list  
class10	profound papilledema due to cryptococcal meningitis in acquired immunodeficiency syndrome  successful treatment with fluconazole  although cryptococcal meningitis is a frequent infection in patients with aids  papilledema is rarely reported  we have reported a case of profound papilledema associated with cryptococcal meningitis in a patient with aids  after treatment failure with amphotericin b  the patient was successfully treated with fluconazole  and the papilledema resolved  
class10	acute oculogyric crisis after administration of prochlorperazine  we report a case of acute oculogyric crisis due to prochlorperazine administration in a young black woman with a concomitant viral infection  neuroleptic medications are the most common cause of drug induced acute dystonic reactions such as oculogyric crisis  prochlorperazine is an antiemetic agent with a phenothiazine type chemical structure and is known to cause dystonic reactions  drug induced acute dystonic reactions are most common in young adults and in men  viral infections may also predispose patients to these adverse reactions  caution is warranted when this drug is used in patients who have other risk factors for an acute dystonic reaction  
class10	experience with surgical treatment of takayasu s disease  we reviewed 28 patients with takayasu s disease to determine the incidence of stroke and its relationship to the involvement of the thoracic aortic arch and its branches  we describe surgical experiences with 10 of the 28 patients who required 21 vascular surgical procedures for critical thoracic aortic arch arterial stenoses  upper and lower extremity ischemia  and renal artery stenoses  four of the 28 patients initially had a stroke caused by occlusion of one or more thoracic aortic arch arteries  six of the 10 patients underwent 7 bypass procedures for critical thoracic arch stenoses  all have remained free of stroke for 5 or more years  four patients had five anastomotic stenoses or graft occlusions in late follow up  the development of these stenoses did not relate to disease activity at the time of the operative procedure  all bypass grafts originating from the subclavian axillary artery developed anastomotic stenoses  no anastomotic stenoses occurred in bypass grafts originating from the ascending aorta  in contrast to other reports  no anastomotic false aneurysms occurred  occlusions of major aortic arch arteries in takayasu s disease cause stroke  bypass of critically stenoses aortic arch arteries protects against stroke and is best performed with grafts originating from the ascending aorta  anastomotic stenoses but not anastomotic aneurysms are common  this study suggests that aggressive surgical treatment can be performed with good results  
class10	interstitial cystitis  successful management by increasing urinary voiding intervals  a variant of the interstitial cystitis  ic  syndrome  minimal or no pain or significant pain that has been lessened by another therapy  can be clinically improved by retraining of the individual s voiding pattern  patients with greater pain but capable of completing this protocol also may be helped  while this group of patients fills the diagnostic criteria of ic and has many of the classic changes  many differ in that they have minimal or no pain  while simultaneously they have a dysfunctional bladder as expected from long term low volume voiding  all patients were placed on a protocol which focused on progressively increasing intervals between voids  fifteen to thirty minutes initially were added to their present voiding time  the same increase was added to the voiding pattern every three or four weeks until an interval of three to four hours between voids was achieved  twenty one patients fit the criteria to be entered into this study  overall 71 percent  15 21  had successful management of their symptoms and reported a 50 percent decrease in their symptoms of urinary urgency  frequency  and nocturia  nineteen percent  4 21  reported 25 percent decrease in symptoms and 10 percent had no change  presence of significant pain adversely affects outcome  3 7  with pain  improvements versus 12 14  without pain   for all patients there was a significant increase in bladder capacity  92 ml average before study and 179 ml after  and average daily voids  13 2 day prestudy and 7 4 post therapy   these differences in voided profiles were statistically significant  p value less than 0 01   
class10	methamphetamine  stimulant of the 1990s  during the past several years  the use of a smokable form of methamphetamine hydrochloride called  ice  has increased rapidly  the heaviest use has occurred on the west coast and in hawaii  many regional emergency departments treat more methamphetamine users than cocaine intoxicated patients  the ease of synthesis from inexpensive and readily available chemicals makes possible the rampant abuse of a dangerous drug that can produce a euphoria similar to that induced by cocaine  clinicians should be familiar with the medical effects and treatment of acute methamphetamine toxicity  
class10	outpatient management of schizophrenia  as effective antipsychotic pharmacotherapy has become available  patients with schizophrenia are increasingly managed in an outpatient setting by primary care physicians  pharmacotherapy is generally effective in treating  positive   or psychotic  symptoms and lessening the risks of relapse  but ineffective in improving  negative   or deficit  symptoms  aggressive attempts to totally control positive symptoms and to ameliorate negative symptoms tend to increase side effects and may be detrimental to the patient  intensive psychotherapeutic and rehabilitative approaches are generally unproductive  attempting to obtain a cure is unrealistic  a moderate approach is recommended  taking into consideration the limitations of existing treatments  achieving control of extreme symptoms and minimizing social and occupational limitations  
class10	neuromuscular disease of the gastrointestinal tract  gastrointestinal motility is the function of gastrointestinal smooth muscle  it is controlled by both the intrinsic and extrinsic nerves of the gastrointestinal tract and  to a lesser degree  the gastrointestinal hormones  therefore  any abnormality of the above factors  theoretically  can cause gastrointestinal dysmotility  in a clinical situation  commonly seen is gastrointestinal dysmotility caused by either smooth muscle or intrinsic and extrinsic nerves dysfunction  diseases that cause smooth muscle dysfunction include familial visceral myopathies  nonfamilial visceral myopathies  collagen disease  muscular dystrophies  amyloidosis  thyroid disease  and so on  diseases that cause enteric nerve dysfunction include familial visceral neuropathies  nonfamilial visceral neuropathies  diabetes mellitus  chagas  disease  ganglioneuromatosis of the intestine  visceral neuropathy of carcinomatosis  parkinson s disease  and so on  the patients with neuromuscular disease of the gastrointestinal tract have a wide range of clinical manifestations regardless of the underlying cause  at one end of the spectrum  the patients may be asymptomatic  and at the other end of the spectrum  the patients may have functional obstruction of the gastrointestinal tract  plain abdominal x rays  upper gastrointestinal  ugi  and small bowel x rays  enteroclysis  barium enema  and manometric studies are useful for the work up of these patients  enteroclysis is especially helpful in ruling out mechanical obstruction of the small intestine in patients with chronic intestinal pseudo obstruction  treatment is mainly symptomatic and supportive  there is no effective drug to improve gastrointestinal motility  surgery may be helpful in selected cases of severe gastrointestinal dysmotility  
class10	murine retroviral neurovirulence correlates with an enhanced ability ofvirus to infect selectively  replicate in  and activate resident microglial cells  published erratum appears in am j pathol 1991 may 138 5  1058  to determine the biologic basis of ts1 momulv neurovirulence in vivo  newborn cfw d mice were inoculated with neurovirulent ts1 momulv and nonneurovirulent wt momulv and the temporal response to virus infection in the central nervous system  cns   spleen  and thymus was studied comparatively  experimental procedures included single and double labeling in situ immunohistochemistry with selective morphometric analyses  and steady state immunoblotting of viral proteins  cellular targets for virus infection were identical for both ts1 and wt momulv and consisted sequentially of 1  splenic megakaryocytes  2  splenic and thymic lymphocytes  3  cns capillary endothelial cells  and 4  cns pericytes and microglia  resident microglial cells served as the major reservor and amplifier of virus infection in the cns of ts1 momulv infected mice  a similar but much less significant role was played by microglia in wt momulv infected mice  the genesis and progression of severe spongiform lesions in ts1 momulv infected mice were both temporally and spatially correlated with amplified virus infection of microglia  and hyperplasia and hypertrophy of both virus infected and nonvirus infected microglial cells  direct virus infection of neurons was never observed  the development of clinical neurologic disease and spongiform lesions in ts1 momulv infected mice correlated with the accumulation of both viral gag and env gene products in the cns  there was no selective accumulation of env precursor polyprotein pr80env  when compared to wt momulv infected mice  the neurovirulence of ts1 momulv infected mice occurred by an enhanced ability to replicate in the cns and to infect and activate more microglia  rather than by a fundamental change in cellular tropism or topography of virus infection  
class10	secondary deposition of beta amyloid within extracellular neurofibrillary tangles in alzheimer type dementia  the hippocampal areas of 34 autopsy specimen brains from aged demented and nondemented subjects were examined using double staining of bodian and beta protein  in 18 cases  75 5     7 4 years old   none of the extracellular neurofibrillary tangles  e nfts  were immunoreactive with beta protein  in 16 cases  82 9     5 4 years old   the minority of e nfts were immunoreactive with beta protein antiserum  these beta immunoreactive e nfts frequently appeared in the areas having senile plaques  while they were not observed in the area lacking beta immunoreactive senile plaques  the ultrastructure of beta immunoreactive e nfts revealed that they consisted of extracellular amyloid fibrils  extracellularly located bundles of paired helical filaments  astroglial processes and degenerating neurites  these findings suggest that the beta immunoreactivity of e nfts comes from secondary deposition of amyloid fibrils  
class10	effect of thiopental on neurologic outcome following coronary artery bypass grafting to determine if thiopental reduces the incidence of neurologic sequelae after coronary artery surgery  we prospectively studied 300 patients undergoing coronary artery bypass grafting  patients who had no history of neurologic or psychiatric illness were randomly assigned to receive either a thiopental infusion or a saline placebo infusion beginning with the administration of heparin and ending just after aortic decannulation  the patients received an opioid relaxant anesthetic administered by an anesthesiologist who was not involved in this investigation and who was blinded to the test infusion  one of the investigators infused either saline or thiopental to produce an isoelectric electroencephalogram with 30 45 s between bursts  standardized neurologic examinations were performed preoperatively and on the 2nd and 5th postoperative days by one of the blinded investigators  the group of patients receiving thiopental required a longer time for awakening  6 4     3 9 vs  4 0     2 4 h  mean     sd  p less than 0 05  and for tracheal extubation  22 4     18 4 vs  17 4     9 6 h  p less than 0 05   and a greater number of these patients were lethargic on the 2nd postoperative day  more patients receiving thiopental required vasoconstrictors during the thiopental loading and cardiopulmonary bypass  cpb  periods  while a greater number of patients receiving placebo required vasodilators  a greater number of patients receiving thiopental required inotropic drugs during separation from cpb  despite the above differences  only 2 of the 151 patients in the placebo group  1 3   and 5 of the 149 patients in the thiopental group  3 3   experienced strokes  p   0 2535   
class10	recovery profile after desflurane nitrous oxide versus isoflurane nitrous oxide in outpatients  thirty eight healthy outpatients undergoing elective surgical procedures lasting 1 3 h were randomly assigned to receive either desflurane 3   approximately 0 5 mac  or isoflurane 0 6   approximately 0 5 mac  for maintenance of general anesthesia with nitrous oxide 60  in oxygen after a standardized induction sequence consisting of fentanyl 3 micrograms kg 1  thiopental 4 mg kg 1  and succinylcholine 1 1 5 mg kg 1  intravenously  although anesthetic conditions were similar during operations in the two treatment groups  significant differences were noted in the recovery profiles as measured by elimination kinetics  psychometric testing  and visual analog scales  to assess subjective feelings   the time required for the end tidal concentration to decrease by 50  was 2 5     0 8 min for desflurane vs  9 5     3 4 min for isoflurane  mean     standard deviation  sd    times to awakening and ability to follow simple commands were significantly shorter after desflurane than after isoflurane  5 1     2 4 vs  10 2     7 7 min 6 5     2 3 min vs  11 1     7 9 min  respectively   postoperatively  patients who received desflurane exhibited less impairment of cognitive function  as measured using the digit symbol substitution test  than did those who received isoflurane  furthermore  visual analog scores indicated that patients receiving desflurane experienced significantly less discomfort  pain   drowsiness  fatigue  clumsiness  and confusion in the early postoperative period  we conclude that desflurane may offer clinical advantages over isoflurane when used for maintenance of anesthesia during outpatient surgical procedures  
class10	the induction dose of propofol in infants 1 6 months of age and in children 10 16 years of age  the propofol dose needed for satisfactory induction of anesthesia was determined in 22 infants 1 6 months of age and 22 children 10 16 yr of age  a single bolus of propofol was given over 10 s  thirty seconds after injection the lid reflex was tested and the anesthesia mask was applied  the patient was considered to be asleep if there were no gross movements during the next 30 s while the patient breathed o2  the dose required for satisfactory induction in 50  of patients  ed50       se  was 3 0     0 2 mg kg in infants and 2 4     0 1 mg kg in older children  p less than 0 02   pain on injection occurred in 50  of the infants and 18  of the children  
